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  • 51.
    Konrad, David
    et al.
    Anestesiologi och Intensivvård, Karoliska Institutet, Stockholm.
    Haney, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Wanecek, Michael
    Anestesiologi och Intensivvård, Karoliska Institutet, Stockholm.
    Weitzberg, Eddie
    Anestesiologi och Intensivvård, Karoliska Institutet, Stockholm.
    Oldner, Ander
    Anestesiologi och Intensivvård, Karoliska Institutet, Stockholm.
    Cardiac effects of endothelin receptor antagonism in endotoxemic pigs.2007In: Am J Physiol Heart Circ Physiol, ISSN 0363-6135, Vol. 293, no 2, p. H988-96Article in journal (Refereed)
    Abstract [en]

    Myocardial depression in sepsis is frequently encountered clinically and contributes to morbidity and mortality. Increased plasma levels of endothelin-1 (ET-1) have been described in septic shock, and previous reports have shown beneficial effects on cardiovascular performance and survival in septic models using ET receptor antagonists. The aim of the current study was to investigate specific cardiac effects of ET receptor antagonism in endotoxicosis. Sixteen domestic pigs were anesthetized and subjected to endotoxin for 5 h. Eight of these pigs were given tezosentan (dual ET receptor antagonist) after 3 h. Cardiac effects were evaluated using the left ventricular (LV) pressure-volume relationship. Endotoxin was not associated with any effects on parameters of LV contractile function [end-systolic elastance (Ees), preload recruitable stroke work (PRSW), power(max)/end-diastolic volume (PWR(max)/EDV) and dP/dt(max)/end-diastolic volume (dP/dt(max)/EDV)] but with impairments in isovolumic relaxation (time constant for pressure decay, tau) and mechanical efficiency. Tezosentan administration decreased Ees, PWR(max)/EDV, and dP/dt(max)/EDV, while improving tau and LV stiffness. Thus, dual ET receptor antagonism was associated with a decline in contractile function but, in contrast, improved diastolic function. Positive hemodynamic effects from ET receptor antagonism in acute endotoxemia may be due to changes in cardiac load and enhanced diastolic function rather than improved contractile function.

  • 52.
    Konrad, David
    et al.
    Karolinska Institutet, Anestesiologi och Intensivvård, Stockholm.
    Oldner, Anders
    Karolinska Institutet, Anestesiologi och Intensivvård, Stockholm.
    Wanecek, Michael
    Karolinska Institutet, Anestesiologi och Intensivvård, Stockholm.
    Rudehill, Anders
    Karolinska Institutet, Anestesiologi och Intensivvård, Stockholm.
    Weitzberg, Eddie
    Karolinska Institutet, Anestesiologi och Intensivvård, Stockholm.
    Biber, Björn
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Häggmark, Sören
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Haney, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Positive inotropic and negative lusitropic effects of endothelin receptor agonism in vivo.2005In: American Journal of Physiology, Heart and Circulatory Physiology, ISSN 0363-6135, Vol. 289, no 4, p. H1702-9Article in journal (Refereed)
    Abstract [en]

    The endothelin (ET) system is involved in the regulation of myocardial function in health as well as in several diseases, such as congestive heart failure, myocardial infarction, and septic myocardial depression. Conflicting results have been reported regarding the acute contractile properties of ET-1. We therefore investigated the effects of intracoronary infusions of ET-1 and of the selective ET(B) receptor-selective agonist sarafotoxin 6c with increasing doses in anesthetized pigs. Myocardial effects were measured through analysis of the left ventricular pressure-volume relationship. ET-1 elicited increases in the myocardial contractile status (end-systolic elastance value of 0.94 +/- 0.11 to 1.48 +/- 0.23 and preload recruitable stroke work value of 68.7 +/- 4.7 to 83.4 +/- 7.2) that appear to be mediated through ET(A) receptors, whereas impairment in left ventricular isovolumic relaxation (tau = 41.5 +/- 1.4 to 58.1 +/- 5.0 and t(1/2) = 23.0 +/- 0.7 to 30.9 +/- 2.6, where tau is the time constant for pressure decay and t(1/2) is the half-time for pressure decay) was ET(B) receptor dependent. In addition, intravenous administration of ET-1 impaired ventricular relaxation but had no effect on contractility. Intracoronary sarafotoxin 6c administration caused impairments in left ventricular relaxation (tau from 43.3 +/- 1.8 to 54.4 +/- 3.4) as well as coronary vasoconstriction. In conclusion, ET-1 elicits positive inotropic and negative lusitropic myocardial effects in a pig model, possibly resulting from ET(A) and ET(B) receptor activation, respectively.

  • 53.
    Lehtipalo, Stefan
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Biber, Björn
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Fröjse, Rolf
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Surgery.
    Arnerlov, Conny
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Surgery.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Effects of dopexamine and positive end-expiratory pressure on intestinal blood flow and oxygenation: the perfusion pressure perspective2003In: Chest, Vol. 124, no 2, p. 688-98Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate the net effects of the concomitant use of positive end-expiratory pressure (PEEP) and dopexamine on intestinal tissue perfusion and oxygenation during predefined artificial reductions in intestinal perfusion pressure (IPP). DESIGN: Prospective, self-controlled, experimental study. SETTING: University hospital research laboratory. SUBJECTS: Seven female pigs. MEASUREMENTS: In barbiturate-anesthetized pigs, we measured mesenteric blood flow (QMES) [by transit-time ultrasonic flowmetry], jejunal mucosal perfusion (by laser Doppler flowmetry), and tissue PO(2) (by microoximetry). Based on blood sampling, we calculated the intestinal net lactate production and oxygenation. INTERVENTIONS: These measurements and calculations were performed at three predefined and controlled IPP levels, which were obtained by an adjustable clamp around the superior mesenteric artery. At each IPP level, measurements were performed prior to and during PEEP (10 cm H(2)O), both with and without simultaneous dopexamine infusions (at 0.5 and 1.0 microg/kg/min). RESULTS: Within the IPP range of 77 to 33 mm Hg, intestinal perfusion and oxygenation were maintained irrespective of whether PEEP and/or dopexamine were applied or not. At IPP < 33 mm Hg, QMES and intestinal oxygenation deteriorated, resulting in regional net lactate production. At this IPP range, tissue oxygen perfusion was entirely pressure-dependent, and even small reductions in IPP led to prominent increases in intestinal net lactate production. Dopexamine did not modify this pattern. CONCLUSIONS: We describe maintained intestinal tissue oxygen perfusion within a wide perfusion pressure range. Within this perfusion pressure range, PEEP did not induce any adverse regional circulatory effects. Below the perfusion pressure range for effective autoregulation, intestinal tissue oxygen perfusion deteriorated, and regional ischemia occurred. In this situation, dopexamine was unable to counteract IPP-dependent decreases in intestinal tissue oxygen perfusion. The regional ischemic threshold can be defined either as an IPP of < 33 mm Hg or as an intestinal tissue PO(2) of < 45 mm Hg.

  • 54.
    Lehtipalo, Stefan
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Biber, Björn
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Fröjse, Rolf
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Arnerlöv, Conny
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Surgery.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Does dopexamine influence regional vascular tone and oxygenation during intestinal hypotension?2002In: Acta Anaesthesiol Scand, Vol. 46, no 10, p. 1217-26Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Local effects of dopexamine on intestinal vascular tone and oxygenation were investigated during intestinal hypotension. To this end, we employed an experimental model, in which the superior mesenteric arterial pressure (PSMA) was controlled by an adjustable perivascular clamp. This approach enabled us to keep the intestinal perfusion pressure (IPP) constant in the face of any systemic circulatory alterations. METHODS: In 11 barbiturate-anesthetized pigs, we instrumented the superior mesenteric circulation for assessments of vascular resistance (RMES), IPP, jejunal mucosal perfusion (Laser Doppler) and intestinal tissue oxygenation (microoximetry). Measurements were carried out before and during dopexamine infusions (0.5 and 1.0 micro g.kg-1.min-1) at a freely variable PSMA (i.e. the perivascular clamp fully open) and at a PSMA of 50 mmHg and 30 mmHg. RESULTS: At a constant PSMA of 50 mmHg, dopexamine had no significant intestinal vascular effects. However, at a constant PSMA of 30 mmHg, both doses of dopexamine were associated with decreases in RMES. Effects of dopexamine on intestinal oxygen delivery and extraction were minimal during these procedures, while a minor decrease in intestinal tissue oxygen tension was observed during dopexamine administration at the lowest IPP level. CONCLUSION: At very low intestinal perfusion pressures (approximately 30 mmHg) dopexamine produces intestinal vasodilation in excess of what is produced by intrinsic autoregulation. This suggests that there is a vasodilatory reserve in the intestine under such conditions and that a pharmacological vasodilator like dopexamine may improve intestinal circulation during regional severe hypotension.

  • 55.
    Lehtipalo, Stefan
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Biber, Björn
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Fröjse, Rolf
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Surgery.
    Arnerlöv, Conny
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Surgery.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Effects of positive end-expiratory pressure on intestinal circulation during graded mesenteric artery occlusion2001In: Acta Anaesthesiol Scand, Vol. 45, no 7, p. 875-84Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Reduced gut perfusion is associated with multiple organ failure. Positive end-expiratory pressure (PEEP) reduces cardiac output (CO) and portal blood flow, and might be detrimental in a situation of already compromised intestinal circulation. The aim of this study was to investigate regional circulatory and metabolic effects of PEEP during graded regional hypoperfusion. METHODS: In 12 barbiturate-anesthetized pigs, we measured systemic and regional blood flows (superior mesenteric arterial, QSMA and portal venous, QPORT), jejunal mucosal perfusion (LDF), tissue oxygenation (PO2TISSUE) and metabolic parameters at PEEP (0, 4, 8 and 12 cm H2O) in a randomized order. Measurements were performed at unrestricted intestinal perfusion pressures (IPP) and at IPP levels of 50 and 30 mmHg. RESULTS: During unrestricted IPP, PEEP decreased MAP, CO, QSMA and QPORT, while systemic, and preportal (RPORT) vascular resistances and jejunal mucosal perfusion were not significantly changed. Preportal tissue oxygen delivery and PO2TISSUE decreased, while preportal tissue oxygen uptake was unaltered. During restricted IPP, PEEP produced the same pattern of hemodynamic alterations as when IPP was not restricted. QPORT and QSMA were lowered by the reductions in IPP, and QPORT was further reduced during PEEP. At an IPP of 30 mmHg, this reduction in QPORT decreased preportal tissue oxygen uptake. Consequently, intestinal ischemia, as indicated by increased net lactate production, occurred. Simultaneously, jejunal mucosal perfusion and PO2TISSUE declined. CONCLUSION: At IPP levels below 50 mmHg, even moderate levels of PEEP impaired local blood flow enough to cause intestinal ischemia. Our data underscore the importance of considering regional circulatory adaptations during PEEP ventilation.

  • 56.
    Lehtipalo, Stefan
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Koskinen, Lars Ove
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Kolmodin, Jane
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Biber, Björn
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Continuous interscalene brachial plexus block for postoperative analgesia following shoulder surgery1999In: Acta Anaesthesiol Scand, Vol. 43, no 3, p. 258-64Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Severe postoperative pain is a well-known problem following shoulder surgery. This study evaluates the clinical efficacy of continuous interscalene brachial plexus block, patient-controlled analgesia, and morphine (i.v. and i.m.) for postoperative analgesia in this setting. METHODS: Thirty patients, scheduled for acromioplasty during general anesthesia, were randomly allocated to one of three different postoperative pain management groups. Group MO received morphine (5 mg i.m. and 2 mg i.v.) when visual analogue pain score (VAS) > 3, group PL received a continuous interscalene brachial plexus block with bupivacaine (1.25 mg kg-1 + 0.25 mg kg-1 h-1) and group PCA received patient-controlled analgesia with morphine (bolus 1 mg). Postoperative pain relief was assessed (24 h) by VAS, circulatory and respiratory stress parameters (heart rate, systemic arterial pressure and respiratory rate) and stress metabolites (glucose, lactate, glycerol by abdominal subcutaneous microdialysis). RESULTS: Pain relief in the PL group was effective (VAS < 3) and significantly more potent than in groups MO and PCA, except at 16 and 20 h. Lactate was significantly increased in the PL group, glucose was significantly increased in all groups, while glycerol showed a variable pattern. There were no significant stress metabolite differences among groups. VAS showed no statistical correlation with microdialysate, respiratory or circulatory data. CONCLUSION: Successful continuous interscalene brachial plexus block provides very good pain relief following shoulder surgery and is superior to the other methods studied. However, we were unable to demonstrate a correlation between VAS pain scores and stress indicators in metabolic, circulatory and respiratory parameters.

  • 57.
    Lehtipalo, Stefan
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Biber, Björn
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Cutaneous sympathetic vasoconstrictor reflexes for the evaluation of interscalene brachial plexus block2000In: Acta Anaesthesiol Scand, Vol. 44, no 8, p. 946-52Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Although signs of sympathetic blockade following interscalene brachial plexus block include Horner's syndrome, increased skin temperature and vasodilatation, the degree of sympathetic blockade is not easily determined. The aim of this study was, therefore, to use activation of cutaneous finger pad vasoconstrictor reflexes for description and quantification of the degree of sympathetic blockade following unilateral interscalene brachial plexus block. METHODS: Eight patients scheduled for acromioplasty under general anesthesia were studied. An interscalene plexus catheter was inserted preoperatively on the side to be operated upon and used postoperatively for administration of bupivacaine, given as a bolus (1.25 mg kg(-1)) followed by a continuous infusion (0.25 mg kg(-1) h(-1)). Skin blood flow (SBF) in the pad of the index finger was assessed by the laser Doppler technique, and regional skin vascular resistance (RVR) was calculated. The inspiratory gasp test (apnea at end-inspiration) or a local heat provocation were used as provocations of the cutaneous microcirculation. RESULTS: Interscalene brachial plexus block increased SBF and decreased RVR at rest, and produced satisfactory sensory and motor block. The inspiratory gasp test decreased SBF and increased RVR in the unblocked arm, while the opposite, increased SBF and decreased RVR, were observed during local heat provocation. In the blocked arm, these gasp-induced cutaneous vasoconstrictor and heat-induced vasodilator responses were attenuated. CONCLUSIONS: Interscalene brachial plexus block reduces regional sympathetic nervous activity, illustrated by increases in skin blood flow, skin temperature and attenuated vasoconstrictor responses to an inspiratory gasp. The inspiratory gasp vasoconstrictive response is a powerful and sensitive indicator for monitoring the sympathetic blockade following interscalene brachial plexus block.

  • 58.
    Nath, Sherdil
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Häggmark, Sören
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Reiz, Sebastian
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Differential depressant and electrophysiologic cardiotoxicity of local anesthetics: an experimental study with special reference to lidocaine and bupivacaine1986In: Anesth Analg, Vol. 65, no 12, p. 1263-70Article in journal (Refereed)
    Abstract [en]

    In 15 pigs lidocaine and bupivacaine were injected into the left anterior descending (LAD) coronary artery to investigate the cardiotoxic effects of these drugs. Anesthesia was maintained by a continuous intravenous pentobarbital infusion and ventilation was controlled. Aortic, pulmonary arterial, right atrial, and left ventricular pressures, a standard 12 lead ECG, cardiac output, and great cardiac venous blood flow were recorded. The local anesthetics were administered at body temperature over approximately 10 sec in a random, crossover fashion at the following equipotent anesthetic doses: bupivacaine, 0.25, 0.5, 1, 2, and 4 mg; lidocaine, 1, 2, 4, 8, and 16 mg. The hemodynamic effects were short-lived, peaking about 5 sec after drug infusion. At the highest dose, both drugs decreased left ventricular dP/dT by 28% (P less than 0.001) and aortic blood pressure by 12% (lidocaine) and 8% (bupivacaine) (P less than 0.001 and P less than 0.01). Heart rate, cardiac output, and coronary venous blood flow did not change. Thus, the cardiodepressant ratio between the two drugs was comparable with their local anesthetic the two drugs was comparable with their local anesthetic potency ratio (bupivacaine/lidocaine, 4:1). Seven animals died in ventricular fibrillation within 1 min after 4 mg bupivacaine dose. All animals given 16 mg lidocaine survived. Ventricular fibrillation was preceded by progressive widening of the QRS complexes recorded over the area perfused by the LAD. The ECG changes after 16 mg lidocaine were of the same magnitude as those recorded after 1 mg bupivacaine. In five of the surviving animals 32 and 64 mg lidocaine were injected intracoronarily after termination of the crossover study.(ABSTRACT TRUNCATED AT 250 WORDS)

  • 59.
    Näslund, Ulf
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Häggmark, Sören
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Marklund, Stefan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Reiz, Sebastian
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    A closed-chest myocardial occlusion-reperfusion model in the pig: techniques, morbidity and mortality1992In: Eur Heart J, Vol. 13, no 9, p. 1282-9Article in journal (Refereed)
    Abstract [en]

    Extensive preparative surgery and lengthy experimentation may lead to high rate of complications and mortality in myocardial ischaemia studies. These problems are particularly common when pigs are used as the subject as they are prone to develop lethal ventricular arrhythmias. Here, a closed-chest model is presented, in which the trauma of major preparative surgery is avoided. One-hundred and twelve pentobarbital-anaesthetized, mechanically ventilated pigs were used. Coronary occlusion was produced by injection of a 2 mm diameter ball via a modified coronary angiography catheter. Reperfusion was induced by retraction of the ball via a thin filament attached to the ball. The amount of the myocardium at risk (MAR) was 8.23 +/- 2.41% (mean +/- SD) of the left plus right ventricular weight. It was possible to carry out scheduled 24 h experiments in 87 out of 93 animals (93.5%). Preparative mortality was 1.8% and 24 h mortality 6.5%. Ventricular fibrillation (VF) occurred during preparation in 3.6%, during coronary occlusion in 7.3% and during reperfusion in 5.0% of the animals. VF was significantly related to a large zone of MAR and insufficient premedication. Catheter- or ball-induced complications were found in 10.7%. Mortality and incidence of VF are considerably lower in this closed-chest model than in a previously reported open-chest pig preparation.

  • 60.
    Näslund, Ulf
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Häggmark, Sören
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Marklund, Stefan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Reiz, Sebastian
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Limitation of myocardial infarct size by superoxide dismutase as an adjunct to reperfusion after different durations of coronary occlusion in the pig1990In: Circ Res, Vol. 66, no 5, p. 1294-301Article in journal (Refereed)
    Abstract [en]

    Superoxide dismutase (SOD) has been documented to limit myocardial infarct size in the richly collateralized dog heart. This study was designed to explore this concept in a low-collateralized animal model. A blind, randomized, placebo-controlled protocol was used in 65 pentobarbital-anesthetized pigs subjected to closed-chest left anterior descending coronary artery occlusion for 30 (n = 22), 60 (n = 22), and 90 (n = 14) minutes followed by reperfusion up to 24 hours from the start of occlusion. Another seven control pigs were subjected to 24 hours of permanent occlusion. A total dose of 9 mg/kg bovine CuZn SOD was administered as a bolus injection immediately before reperfusion followed by a 1-hour infusion. Infarct size was assessed by tetrazolium staining. Myocardium at risk and collateral flow were determined by using cerium-141-labeled microspheres (15 microns) during the occlusion. After 30 minutes of occlusion, infarct sizes in placebo versus SOD-treated animals were 45.5 +/- 15.7% vs. 23.8 +/- 15.6% of myocardium at risk (p = 0.007). The corresponding values after 60 minutes of occlusion were 78.6 +/- 9.3% vs. 66.9 +/- 14.6% (p = 0.035). SOD administered after 90 minutes of occlusion did not limit infarct size (88.5 +/- 4.8% vs. 92.3 +/- 5.2%). Twenty-four hours of coronary occlusion resulted in infarction of 92.4 +/- 4.2% of myocardium at risk. (All values are mean +/- SD.) Ventricular fibrillation occurred in only nine pigs distributed equally between SOD and placebo. The results indicate that CuZn SOD has the potential to further improve the myocardial salvage established by reperfusion of an ischemic pig heart territory. However, the narrow time window for limiting infarct size in the pig by reperfusion is not much extended by SOD.

  • 61.
    Näslund, Ulf
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Häggmark, Sören
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Marklund, Stefan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Reiz, Sebastian
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Öberg, Agneta
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Superoxide dismutase and catalase reduce infarct size in a porcine myocardial occlusion-reperfusion model1986In: J Mol Cell Cardiol, Vol. 18, no 10, p. 1077-84Article in journal (Refereed)
    Abstract [en]

    We investigated if superoxide dismutase and catalase could reduce myocardial infarct size in an open chest occlusion-reperfusion model. Thirty pigs were used for the experiment. The left anterior descending artery was ligated for 60 min followed by a 5 h reperfusion period. After randomisation and blinding the two enzymes or placebo were injected into the left atrium as a bolus immediately before and at the end of the occlusion and as a continuous infusion over the first hour of the reperfusion period. The total dose for each enzyme was 8 mg/kg bw. Tetrazolium staining was used to determine infarct size. The study code was not broken until all calculations and exclusions had been made. Nine animals died from intractable ventricular fibrillation, most commonly during the occlusion. Another three were excluded for technical reasons. We found that superoxide dismutase and catalase reduced infarct size in relation to myocardium at risk from a mean of 89% to 63% (P less than 0.01). Initial plasma half life for the two enzymes after the bolus infusions were calculated to be 30 min.

  • 62.
    Näslund, Ulf
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Häggmark, Sören
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Pennert, Kjell
    Reiz, Sebastian
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Marklund, Stefan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Effects of reperfusion and superoxide dismutase on myocardial infarct size in a closed chest pig model1992In: Cardiovasc Res, Vol. 26, no 2, p. 170-8Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim was to study the effects on myocardial infarct size of reperfusion alone or of CuZn superoxide dismutase (SOD) as an adjunct to reperfusion. METHODS: Occlusion was induced in closed chest, pentobarbitone anaesthetised, mechanically ventilated pigs by injection of a 2 mm ball into a preselected coronary artery. Reperfusion was achieved by retraction of the ball via an attached filament. Twenty nine placebo treated and 25 SOD treated animals were subjected to 30 (n = 21), 60 (n = 21), and 90 (n = 12) min of coronary occlusion followed by reperfusion to 24 h; a control group of 24 pigs was subjected to a sustained occlusion for 24 h. Infarct size was assessed by tetrazolium staining and plasma creatine kinase (CK), aspartate aminotransferase (ASAT), and lactate dehydrogenase (LD). In the CuZn SOD group, 200 mg bovine CuZn SOD was given as a bolus intravenously immediately before reperfusion followed by a continuous infusion (100 mg) for 60 min. The size of the ischaemic myocardium at risk was measured from post mortem autoradiograms. RESULTS: Infarct size as percent of myocardium at risk was 46.0(SD 15.5)%, 80.1(9.9)%, and 88.9(5.0)% respectively in placebo animals with 30, 60, and 90 min occlusion, and 94.2(5.1)% in pigs with 24 h sustained occlusion. Compared to 24 h sustained occlusion, limitation of infarct size by reperfusion was only demonstrated in the 30 (p less than 0.001) and 60 min groups (p less than 0.001). Plasma values of CK, ASAT, and LD at 90 min post-reperfusion correlated closely with infarct size as assessed by tetrazolium staining and were related to occlusion duration. No myocardial salvage, as assessed by plasma ASAT, CK, or LD, was shown in the SOD treated groups. CONCLUSIONS: Early reperfusion resulted in myocardial salvage as assessed by tetrazolium staining and peak ASAT, CK, and LD at 90 min after the reperfusion. No limitation of infarct size by SOD could be demonstrated from analyses of plasma CK, ASAT, or LD.

  • 63.
    Näslund, Ulf
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Häggmark, Sören
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Reiz, Sebastian
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Ischaemia and reperfusion induced transient QRS vector changes: relationship to size of the ischaemic territory1993In: Cardiovasc Res, Vol. 27, no 2, p. 327-33Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim was to investigate QRS vector changes during the first 30 min of coronary occlusion or the early phase of reperfusion with special reference to location and size of myocardium at risk. METHODS: 24 h experiments were performed in closed chest anaesthetised pigs. QRS vectors were studied by computerised vectorcardiography via Frank leads. Occlusion of the left anterior descending coronary artery followed by reperfusion was induced in 23 pigs and a sustained occlusion in 20 pigs: left anterior descending coronary artery in seven, right coronary artery in eight, and left circumflex coronary artery in five. Myocardium at risk was measured in postmortem autoradiograms. Eight animals were excluded. RESULTS: Four minutes after occlusion, QRS(mean) deviated towards the ischaemic region in 34/35 animals and returned thereafter at varying speeds. In half of the reperfused animals, deviation of QRS vectors towards the ischaemic territory was also observed during the first minutes of reperfusion. A paradoxical increase in QRS vector changes, "reperfusion peak", was recorded during the initial minutes of reperfusion in 12/19 animals. Maximum spatial QRS vector magnitude increased in all right coronary or left circumflex coronary occlusion animals compared to 6/25 in left anterior descending coronary occlusion animals. QRS vector difference, change in spatial QRS vector angle, and maximum change in QRS azimuth 4 min after occlusion correlated significantly with extent of myocardium at risk. CONCLUSIONS: Marked directional and quantitative QRS vector changes, with significant relation to size and location of myocardium at risk, were recorded during the initial minutes of ischaemia. The transient increase in QRS vector changes during the first minutes of reperfusion deserves further exploration as a new indicator of reperfusion.

  • 64.
    Näslund, Ulf
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Häggmark, Sören
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Reiz, Sebastian
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Quantification of myocardium at risk and detection of reperfusion by dynamic vectorcardiographic ST segment monitoring in a pig occlusion-reperfusion model1993In: Cardiovasc Res, Vol. 27, no 12, p. 2170-8Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim was to investigate whether continuous computerized vectorcardiographic monitoring of absolute spatial ST vector magnitude (ST-VM) and spatial ST change vector magnitude (STC-VM) during coronary occlusion could be used to estimate the size of myocardium at risk; and also to test whether reperfusion could be distinguished from sustained occlusion by continuous monitoring of ST vector alterations. METHODS: Computerised vectorcardiographic monitoring via Frank leads was applied in a closed chest occlusion-reperfusion pig model. Coronary occlusion over 24 h was produced in 20 animals by injecting a 2 mm ball into the left anterior descending coronary artery (n = 7), the right coronary artery (n = 8), and the left circumflex coronary artery (n = 5). Another 31 pigs were reperfused by retraction of the ball after 30 (n = 10), 60 (n = 15), or 90 (n = 6) min of left anterior descending artery occlusion. The extent of the myocardium at risk was measured by autoradiography. RESULTS: Seven animals were excluded. Irrespective of occluded coronary artery the relative parameters STC-VM over the first 30 min of occlusion correlated closely with area at risk, that is, the mean STC-VM between 10 and 30 min of occlusion (r = 0.78 p < 0.001). The absolute parameter ST vector magnitude (ST-VM) did not reflect ischaemia in 16/44 animals and did not correlate significantly with area at risk. The weight of myocardium at risk (MAR) was predictable from STC-VM: MAR weight (measured) = 0.97 x MAR weight (predicted) + 0.26 (g), r = 0.81, p < 0.001. STC-VM decline rate, time to STC-VM plateau, and cumulated sum plots of STC-VM were all able to distinguish reliably between reperfused animals and those with permanent occlusion. A paradoxical increase in STC-VM - "reperfusion peak" - was detected in 17/31 (55%) of the animals. This phenomenon was related to large amount of myocardium at risk or to a long occlusion time. CONCLUSION: Dynamic vectorcardiographic ST monitoring provides adequate estimation of myocardium at risk and enables detection of reperfusion in experimental myocardial ischaemia.

  • 65.
    Reiz, Sebastian
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Häggmark, Sören
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Nath, Sherdil
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Cardiotoxicity of ropivacaine--a new amide local anaesthetic agent1989In: Acta Anaesthesiol Scand, Vol. 33, no 2, p. 93-8Article in journal (Refereed)
    Abstract [en]

    Anaesthetically equipotent doses of lidocaine, bupivacaine and a new bupivacaine-like local anaesthetic agent, ropivacaine, were injected into the left anterior descending coronary artery of pentobarbital-anaesthetized pigs. The aim was to study the cardiotoxicity of ropivacaine in relation to the two other drugs. A random, crossover, dose response study design was used. The following doses of the drugs were administered: lidocaine (L): 1,2,4,8 and 16 mg, bupivacaine (B): 0.25, 0.5, 1,2 and 4 mg and ropivacaine (R): 0.33, 0.66 1.33, 2.66 and 5.33 mg. Systemic haemodynamics, left ventricular dP/dT and a 12-lead electrocardiogram were recorded continuously during the study period. The drugs depressed cardiac contractility in relation to their local anaesthetic potency on the isolated nerve-4:3:1 (B:R:L). The prolongation of the ECG QRS-interval was regarded as a measure of electrophysiologic toxicity. Comparable prolongation of the QRS-interval was recorded after 2 mg of bupivacaine, 4.5 mg of ropivacaine and 30 mg of lidocaine. Thus, the electrophysiological toxicity ratio was 15:6.7:1 (B:R:L). Provided local anaesthetic potency data can be extrapolated from the isolated nerve preparation to regional anaesthesia in humans, ropivacaine appears to provide a greater margin of safety than bupivacaine, if inadvertently injected into the venous circulation.

  • 66. Seeman‐Lodding, Helen
    et al.
    Häggmark, Sören
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Jern, Christina
    Jern, Sverker
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Biber, Björn
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Systemic levels and preportal organ release of tissue‐type plasminogen activator are enhanced by PEEP in the pig1999In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 43, no 6, p. 623-633Article in journal (Refereed)
  • 67. Seeman-Lodding, Helene
    et al.
    Biber, Björn
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Häggmark, Sören
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Jern, Christina
    Jern, Sverker
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Anesthesia and surgery influences regional net release and uptake rates of tissue-type plasminogen activator. An experimental study in the intact pig1997In: Acta Anaesthesiol Scand Suppl, Vol. 110, p. 151-3Article in journal (Refereed)
  • 68. Seeman-Lodding, Helene
    et al.
    Häggmark, Sören
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Jern, Christina
    Jern, Sverker
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Biber, Björn
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Aortic cross-clamping influences regional net release and uptake rates of tissue-type plasminogen activator in pigs1997In: Acta Anaesthesiol Scand, Vol. 41, no 9, p. 1114-23Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The key regulator of intravascular fibrinolysis, tissue-type plasminogen activator (t-PA), is released from a dynamic endothelial storage pool. The aim of the study was to investigate regional t-PA net release and uptake rates in response to infra-renal aortic cross-clamping (AXC) and declamping (DC). METHODS: Anesthetized pigs were studied during 5 min of AXC, followed by a 35-min declamping (DC) period. Arterio-venous concentration gradients of total and active t-PA, as well as respective plasma flows, were simultaneously obtained across the preportal, hepatic, coronary and pulmonary vascular beds. Plasma levels of total t-PA (ELISA with purified porcine t-PA as standard), and active t-PA (spectrophotometric functional assay) were determined. RESULTS: Prior to AXC, we found a high net release rate of total t-PA across the preportal vascular bed (1700 ng.min-1 P < 0.001), and a high hepatic net uptake (4900 ng.min-1, P < 0.001), while coronary and pulmonary t-PA net fluxes were small and variable. AXC per se did not induce significant alterations in net fluxes of t-PA. Following DC, preportal and coronary net releases of total t-PA increased (to 2900 ng.min-1 and 60 ng.min-1, respectively). Despite an increase in hepatic net uptake of total t-PA (to 6100 ng.min-1) after DC, a significant increase in hepatic venous total t-PA occurred. CONCLUSIONS: The release and uptake of t-PA is indicated to be dynamic and organ-specific. DC induces an acute profibrinolytic reaction in preportal organs. The high hepatic t-PA uptake capacity restricts preportal profibrinolytic events to affect the systemic circulation.

  • 69.
    Sehlin, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Sandkvist Törnell, Siv
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Öhberg, Fredrik
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Pneumatic performance of the boussignac CPAP system in healthy humans2011In: Respiratory care, ISSN 0020-1324, E-ISSN 1943-3654, Vol. 56, no 6, p. 818-826Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The Boussignac CPAP has been found to effectively treat acute pulmonary oedema. However, data on airway pressure in association with the Boussignac CPAP are sparse. We therefore designed this study to evaluate the stability of the Boussignac CPAP in terms of maintaining adequate inspiratory and expiratory pressure levels. We also wanted to evaluate the perceived exertion when breathing with the Boussignac CPAP.

    METHODS: Continuous recordings of airway pressure and airflow were made in 18 healthy volunteers during breathing with the Boussignac CPAP at 5, 7.5 and 10 cm H₂O for three sessions of 10 minutes at each CPAP level. Participants were blinded for the sequential order of the investigated CPAP levels. They terminated each session, at the respective CPAP level, by taking 10 forced breaths.

    RESULTS: During 10 minutes normal breathing periods, when participants breathed at 20 % of their VC with a peak expiratory airflow of 14 % of FEV₁, the maximal pressure difference was 4.0 cm H₂O between inspiration and expiration at CPAP 10 cm H₂O. Changes in airway pressure were never large enough to reduce airway pressure below zero. When taking forced breaths, expiratory volume was 38-42 % of VC and peak expiratory airflow was 49-56 % of FEV ₁. As airflow increased, both the drop in inspiratory airway pressure and the increase in expiratory airway pressure were enhanced.

    CONCLUSIONS: Pressure changes during breathing with CPAP are considered to be associated with increased work of breathing. The pneumatic performance of the Boussignac CPAP is adequate during normal breathing with low airflow. However, during forced breathing resulting in increased airflow, the Boussignac CPAP is unable to maintain stable airway pressure levels, possibly resulting in increased work of breathing and respiratory fatigue. Thus, the Boussignac CPAP system might be less suitable for patients breathing at a higher frequency.

  • 70.
    Sehlin, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Öhberg, Fredrik
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Physiological responses to positive expiratory pressure breathing: a comparison of the PEP bottle and the PEP mask2007In: Respiratory care, ISSN 0020-1324, E-ISSN 1943-3654, Vol. 52, no 8, p. 1000-1005Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In the intensive care unit we have observed that patients have different adherence to 2 commonly used positive-expiratory-pressure (PEP) therapy devices: the PEP bottle and the PEP mask. The reason for this difference is not clear. METHODS: In a randomized prospective study, we made continuous recordings of airway pressure and airflow, with 20 healthy volunteers, with the PEP bottle and the PEP mask. The measurement sequence consisted of 3 sessions of 10 breaths with the PEP bottle and the PEP mask, in a randomized crossover design. A rest period of 15 min separated the PEP bottle and PEP mask measurements. RESULTS: With the PEP bottle the expiratory phase began with a zero-flow period of 0.39 s, during which airway pressure rose 11.9 cm H2O. With the PEP bottle the mean expiratory pressure was 11.7 cm H2O, and end-expiratory pressure was 9.5 cm H2O. With the PEP mask the initial expiratory zero-flow period was almost nonexistent (0.04 s) and without any change in airway pressure. With the PEP mask the shape of the expiratory pressure curve was different; mean expiratory pressure was 8.6 cm H2O, and end-expiratory pressure was zero. With the PEP bottle the inspiration also began with a zero-flow period of 0.43 s, during which airway pressure decreased 9.6 cm H2O from the end-expiratory airway pressure. With the PEP mask the initial inspiratory zero-flow period was only 0.01 s and there was no concomitant change in airway pressure. CONCLUSIONS: The PEP bottle and the PEP mask showed major differences in the relationship between airflow and airway pressure. These findings might explain the observed differences in patient adherence to these therapies.

  • 71. Sellgren, Johan
    et al.
    Söderstrom, Stefan
    Johansson, Göran
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Biber, Björn
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Häggmark, Sören
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Pontén, Johan
    Preload changes by positive pressure ventilation can be used for assessment of left ventricular systolic function2003In: Acta Anaesthesiol Scand, Vol. 47, no 5, p. 541-8Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Assessment of preload independent left ventricular function with conductance volumetry is traditionally accomplished by inflating a balloon in the inferior caval vein. Our aim was to investigate if a similar change in preload could be achieved by positive pressure ventilation with large tidal volume. METHODS: Conductance volumetry generating left ventricular pressure-volume loops was used in seven pentobarbital-anesthetized pigs. Changes in preload recruitable stroke work were studied, comparing the effects of inferior vena cava occlusion (IVCO) or large tidal volume (LTV). Cardiodepression was induced by halothane anesthesia and halothane + phenylephrine, and stimulation by epinephrine infusion. RESULTS: Although the decreasis in left ventricular end diastolic volume was slightly less with LTV (16.5 +/- 1.7 ml, mean +/- SEM) than with IVCO (22.4 +/- 1.7 ml) (P < 0.0001) the PRSW-slopes showed a high degree of correlation (r=0.80, P < 0.0001). Although peak tracheal pressures increased significantly to 27.8 +/- 0.9 mmHg during LTV, esophageal pressures (used as an indicator of pericardial pressure) were unchanged. CONCLUSIONS: Positive pressure ventilation with LTV is similar to IVCO in creating transient changes in preload, necessary for assessment of left ventricular systolic function. This observation was valid also during drug-induced cardiac depression and stimulation. The preload recruitable stroke work used for this validation was shown to be a reliable and stable method.

  • 72.
    Sharma, Rajiv
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Axelsson, H.
    Öberg, Åke
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Jansson, Erica
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Clergue, F.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Reiz, Sebastian
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Diaphragmatic activity after laparoscopic cholecystectomy1999In: Anesthesiology, Vol. 91, no 2, p. 406-13Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Laparoscopic cholecystectomy is presumed to induce a reduction in diaphragmatic activity. Indirect indices of diaphragmatic function based on tidal changes in pressures and cross-section area measurements can be unreliable in the postoperative phase. The present study evaluates diaphragmatic activity by directly recording diaphragmatic EMG (EMGdia) data, along with indirect indices. METHODS: Thirteen adult patients (American Society of Anesthesiologists physical status I or II) undergoing laparoscopic cholecystectomy were examined preoperatively for inspiratory tidal changes in gastric (Pgas-insp) and esophageal (Peso-insp) pressures, and tidal changes in ribcage (Vthor) and abdominal (Vabd) cross-section areas and then again at 1, 6, and 24 h postoperatively combined with EMGdia recordings. Variations in inspiratory gastric (deltaPgas-insp) and inspiratory transdiaphragmatic (deltaPdi-insp) pressures were derived from the above. RESULTS: Laparoscopic cholecystectomy induced a significant reduction in mean deltaPgas-insp, mean deltaPdi-insp, and mean Vabd indicating a reduction of diaphragmatic activity postoperatively. DeltaPdi-insp decreased from 11.8+/-4.0 cm H2O preoperatively to 5.7+/-5.7 cm H2O at 1 h and 6.6+/-5.1 cm H2O at 6 h postoperatively (mean +/- SD; P < 0.05). Vabd decreased from 327.0+/-113.0 ml preoperatively to 174.0+/-65.0 ml at 1 h and 175.0+/-98.0 ml at 6 h postoperatively (mean +/- SD; P < 0.05). These values had partially recovered at 24 h. CONCLUSION: The direct and indirect indices of diaphragmatic activity taken together confirm the presence of reduction in diaphragmatic activity after laparoscopic cholecystectomy followed by its partial recovery at 24 h.

  • 73. Sundeman, Henrik
    et al.
    Haney, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Broomé, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Häggmark, Sören
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Biber, Björn
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    The effects of desflurane on cardiac function as measured by conductance volumetry in swine1998In: Anesth Analg, Vol. 87, no 3, p. 522-8Article in journal (Refereed)
    Abstract [en]

    The purpose of the investigation was to assess the effects of desflurane (DES) on left ventricular heart function during basal barbiturate anesthesia in a closed-pericardium, closed-chest acute swine model. The study was performed in 11 normoventilated adult pigs. Hemodynamic measurements were obtained using arterial, central venous, and pulmonary artery catheters, as well as a conductance volumetry and tip manometry catheter placed in the left ventricle. Hemodynamic measurements were recorded during basal pentobarbital anesthesia and with the addition of 1%, 2%, 4%, and 6% DES. DES dose-dependently decreased mean arterial pressure, systemic vascular resistance, left ventricular end-systolic pressure, dP/dtMAX and dP/dtMIN. At doses >1%, decreases in CO, stroke volume, ejection fraction, end-systolic elastance, preload recruitable stroke work, preload adjusted maximal power, and peak filling rate were observed. Heart rate decreased at 4% and 6% DES. Isovolumetric relaxation time increased only at 6% DES. We conclude that smaller doses of DES have a significant cardiodepressive effect in the setting of barbiturate infusion, as measured by conductance volumetry. IMPLICATIONS: Desflurane, in very small doses, depressed cardiac function during pentobarbital anesthesia with ketamine and benzodiazepine premedication in swine, as assessed by conductance volumetry and left ventricular pressure and volume relationship analysis. These results suggest that desflurane, in combination with certain anesthetics, can be cardiodepressive even in very small doses.

  • 74. Sundeman, Henrik
    et al.
    Åneman, Anders
    Broomé, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Haney, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Häggmark, Sören
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Biber, Björn
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Effects of desflurane on the pig intestinal circulation during hypotension1999In: Acta Anaesthesiol Scand, Vol. 43, no 10, p. 1069-77Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The aim of the present study was to analyze the perfusion pressure dependency for the splanchnic vascular effects of desflurane (DES). METHODS: We measured portal blood flow (QPORT, perivascular ultrasound) and jejunal mucosal perfusion (JMP; laser Doppler) in pentobarbital-anesthetized pigs (n=10). Experimentally, decreases in mean arterial pressure (MAP) were produced by pericardial infusions of dextran. The protocol included sets of measurements at incremental doses of DES (1, 2, 4 and 6%) prior to and during pericardial infusions. RESULTS: Although QPORT and JMP decreased significantly during pericardial infusions, DES, irrespective of dose, did not reduce QPORT until MAP had decreased below 65-70 mm Hg. In higher MAP ranges, vasodilation in pre-portal tissues was powerful enough to maintain QPORT in spite of concurrent decreases in driving arterial pressure, as produced by either DES or pericardial infusion, or by a combination of both. We found no effects of DES on JMP even at very low MAP (about 40 mm Hg during pericardial infusion), indicating that the normal physiological response of the small intestine to redistribute blood flow from deeper to more superficial layers during hypotension was unimpaired by DES. CONCLUSIONS: Our data suggest a wide dose-tolerability of DES as regards the splanchnic circulation during hypotensive states.

  • 75.
    Svanström, M C
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Biber, B
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Hanes, M
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, G
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Näslund, U
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Bålfors, E M
    Signs of myocardial ischaemia after injection of oxytocin: a randomized double-blind comparison of oxytocin and methylergometrine during Caesarean section.2008In: British journal of anaesthesia, ISSN 1471-6771, Vol. 100, no 5, p. 683-9Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: ECG changes, similar to those seen during myocardial ischaemia, together with symptoms of chest pain, are common during Caesarean section (CS). We hypothesized that oxytocin administration has cardiovascular effects leading to these symptoms and ECG changes. METHODS: Forty women undergoing elective CS under spinal anaesthesia were given an i.v. bolus of either 10 IU of oxytocin (Group OXY-CS, n=20) or 0.2 mg of methylergometrine (Group MET-CS, n=20), in a double-blind, randomized fashion after delivery. Ten healthy, non-pregnant, non-anaesthetized women were used as normal controls (Group OXY-NC, n=10) and were given 10 IU of oxytocin i.v. Twelve-lead ECG, on-line, computerized vectorcardiography (VCG), and invasive arterial pressure were recorded. RESULTS: Oxytocin produced a significant increase in heart rate, +28 (SD 4) and +52 (3) beats min(-1) [mean (SEM); P<0.001], decreases in mean arterial pressure, -33 (2) and -30 (3) mm Hg (P<0.001), and increases in the spatial ST-change vector magnitude (STC-VM), +77 (12) and +114 (8) microV (P<0.001), in CS patients and controls, respectively. Symptoms of chest pain and subjective discomfort were simultaneously present. Methylergometrine produced mild hypertension and no significant ECG changes. CONCLUSIONS: Oxytocin administered as an i.v. bolus of 10 IU induces chest pain, transient profound tachycardia, hypotension, and concomitant signs of myocardial ischaemia according to marked ECG and STC-VM changes. The effects are related to oxytocin administration and not to pregnancy, surgical procedure, delivery, or sympathetic block from spinal anaesthesia.

  • 76.
    Svenmarker, Staffan
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Häggmark, Sören
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Axelsson, B.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Haney, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Regional changes in cerebral blood flow oxygenation can indicate global changes in cerebral blood flow during coronary artery occlusion in juvenile pigs2014In: Physiological Measurement, ISSN 0967-3334, E-ISSN 1361-6579, Vol. 35, no 7, p. 1439-1450Article in journal (Refereed)
    Abstract [en]

    Near infrared spectroscopy (NIRS) is a widely employed method for assessment of regional cerebral oxygenation (R(c)StO(2)). RcStO(2) values are expected to vary with changes in the relative amount of oxyhaemoglobin. The present experimental study aimed to assess the response of RcStO(2) to controlled alterations of carotid blood flow (CQ). Landrace pigs were anesthetized followed by surgical preparation. Cyclic variations in cardiac output were accomplished by intermittently occluding the main stem of the left coronary artery. A flow measurement probe for assessing CQ was placed around the left carotid artery. One NIRS probe was placed on the left ipsilateral forehead to assess regional cerebral oximetry. Simultaneous registration of CQ and RcStO(2) was conducted. There was a strong correlation for variation in CQ and RcStO(2) signal values. Based on coherence analysis the fraction of power of the RcStO(2) that was coherent with the CQ signal reached 0.84 - 0.12 (P < 0.05) for frequencies lower than 0.1 Hz. The agreement of the sampleto- sample co-variation, as assessed by the Pearson correlation coefficient, was 0.83 +/- 0.08 (P < 0.05). One explanatory component for variations in cerebral oxygenation verified by NIRS should be attributed to variations in the cerebral blood flow.

  • 77.
    Svennerholm, Kristina
    et al.
    Anestesiologi, Sahlgrenska akademin, Göteborg.
    Bergh, Niklas
    Wallenberg lab, Sahlgrenska akademin, Göteborg.
    Larsson, Pia
    Wallenberg lab, Sahlgrenska akademin, Göteborg.
    Jern, Sverker
    Wallenberg lab, Sahlgrenska akademin, Göteborg.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Biber, Björn
    Anestesiologi, Sahlgrenska akademin, Göteborg.
    Haney, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Histone Deacetylase Inhibitor Treatment Increases Coronary t-PA Release in a Porcine Ischemia Model2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 5, p. e97260-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The expression of the tissue plasminogen activator gene can be affected by histone deacetylation inhibition and thus appears to be under epigenetic control.

    OBJECTIVES: The study aimed to test if in vivo pharmacological intervention by valproic acid treatment would lead to increase in tissue plasminogen activator release capacity. METHODS: In an anaesthetized pig model, a controlled transient coronary occlusion was used to stimulate coronary tissue plasminogen activator release in a valproic acid treated (one week) and a non-treated group. Coronary venous blood samples from the ischemic region were collected, great cardiac vein thermodilution flow measurements were performed, and trans-coronary tissue plasminogen activator fluxes were calculated. Plasminogen activator inhibitor-1 was also measured.

    RESULTS: Adequate sampling from the affected area after the 10 minute ischemic period was confirmed by lactate measurements. Fluxes for tissue plasminogen activator at minutes 1, 3, 5, 7 and 10 were measured and then used to present cumulative net tissue plasminogen activator release for the whole measurement period for both groups. Area under the curve was higher for the valproic acid treated group at 10 minutes; 932+/-173 nanograms (n = 12) compared to the non-treated group, 451+/-78 nanograms (n = 10, p = 0.023). There was no difference in levels of plasminogen activator inhibitor-1 between groups.

    CONCLUSIONS: These findings support a proof of concept for histone deacetylation inhibition positive effect on tissue plasminogen activator expression in an in vivo setting. Further studies are needed to find an optimal way to implement histone deacetylation inhibition to achieve desired clinical changes in tissue plasminogen activator expression.

  • 78.
    Talsi, Oskar
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Berggren, Ritva Kiiski
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Swedish National Quality Registry for Intensive Care (SIR), Karlstad, Sweden.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    A national survey on routines regarding sedation in Swedish intensive care units2019In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 37, no 23, p. 3088-3096Article in journal (Refereed)
    Abstract [en]

    Background: Previous studies concerning sedation in Swedish intensive care units (ICU) have shown variability in drug choices and strategies. Currently, there are no national guidelines on this topic. As an update to a Nordic survey from 2004, and as a follow-up to a recently introduced quality indicator from the Swedish Intensive Care Registry, we performed a national survey.

    Methods: A digital survey was sent to the ICUs in Sweden, asking for sedation routines regarding hypnosedatives, analgosedatives, protocols, sedation scales, etc.

    Results: Fifty out of 80 ICUs responded to the survey. All units used sedation scales, and 88% used the RASS scale; 80% used written guidelines for sedation. Propofol and dexmedetomidine were the preferred short-term hypnosedatives. Propofol, dexmedetomidine, and midazolam were preferred for long-term hypnosedation. Remifentanil, morphine, and fentanyl were the most frequently used agents for analgosedation.

    Conclusions: All ICUs used a sedation scale, an increase compared with previous studies. Concerning the choice of hypno- and analgosedatives, the use of dexmedetomidine, clonidine, and remifentanil has increased, and the use of benzodiazepines has decreased since the Nordic survey in 2004.

  • 79.
    Waldenström, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Ronquist, Gunnar
    Åberg, Anna-Maja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Ahlstrom, Katarina
    Hauck, Philip
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Abrahamsson, Pernilla
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Biber, Björn
    Haney, Michael F.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Ischaemic preconditioning reduces myocardial calcium overload in coronary-occluded pig hearts shown by continuous in vivo assessment using microdialysis2012In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 32, no 2, p. 133-138Article in journal (Refereed)
    Abstract [en]

    During ischaemia, ATP depletion leads to insufficient fuelling for Na+/K+ ATPase, decreased electrochemical potential and increased influx of calcium ions. This study demonstrated a means to assess the effects of ischaemic preconditioning (IP) on the free intracellular Ca2+ pool during prolonged ischaemia. In a porcine myocardial ischaemia model, microdialysis (MD) was used for sampling of metabolic and injury markers in IP and non-IP (control) groups. 45Ca2+ was delivered in microperfusate locally to ischaemic myocardium, with distribution and uptake assessed by 45Ca2+ recovery in microdialysate. Cardiomyocytes in vitro were exposed to a Ca2+ ionophore and tested for 45Ca2+ uptake. An accentuated myocardial calcium ion influx (observed as an increased microdialysate 45Ca2+ recovery in the extracellular milieu) was noted in control pigs compared with IP pigs during ischaemia. Suspended cardiomyocytes preincubated with a Ca2+ ionophore to increase the intracellular calcium ion pool and subsequently incubated with 45Ca2+, displayed lower 45Ca2+ uptake in cells compared with control cells not exposed to the ionophore, corroborating the idea of a strong relationship between degree of intracellular calcium overload and microdialysate 45Ca2+ recovery. The ischaemic insult was differentially verified by metabolic and injury markers. We introduce an in vivo method for serial assessment of myocardial calcium overload during ischaemia, using a MD technique and 45Ca2+ inclusion. IP leads to relatively less calcium overload as assessed by this new method, and we interpret this to mean that reduction in calcium overload is an important part of the IP protective effect.

  • 80.
    Winsö, Ola
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Kral, Josef
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Wang, Wanzhong
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Kralova, Ivana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Abrahamsson, Pernilla
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Blind, Per-Jonas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Thoracic epidural anaesthesia reduces insulin resistance and inflammatory response in experimental acute pancreatitis2018In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 4, p. 207-215Article in journal (Refereed)
    Abstract [en]

    AIMS: The activity of the sympathetic nervous system (SNS) is crucial at an early stage in the development of an inflammatory reaction. A study of metabolic events globally and locally in the early phase of acute pancreatitis (AP), implying hampered SNS activity, is lacking. We hypothesized that thoracic epidural anaesthesia (TEA) modulates the inflammatory response and alleviates the severity of AP in pigs.

    MATERIAL AND METHODS: The taurocholate (TC) group (n = 8) had only TC AP. The TC + TEA group (n = 8) had AP and TEA. A control group (n = 8) underwent all the preparations, without having AP or TEA. Metabolic changes in the pancreas were evaluated by microdialysis and by histopathological examination.

    RESULTS: The relative increase in serum lipase concentrations was more pronounced in the TC group than in TC + TEA and control groups. A decrease in relative tissue oxygen tension (PtiO2) levels occurred one hour later in the TC + TEA group than in the TC group. The maintenance of normoglycaemia in the TC group required a higher glucose infusion rate than in the TC + TEA group. The relative decrease in serum insulin concentrations was most pronounced in the TC + TEA group.

    CONCLUSION: TEA attenuates the development of AP, as indicated by changes observed in haemodynamic parameters and by the easier maintenance of glucose homeostasis. Further, TEA was associated with attenuated insulin resistance and fewer local pathophysiological events.

  • 81.
    Åberg, Anna-Maja
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Abrahamsson, Pernilla
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Haney, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Larsson, Jan Erik
    Does carbon monoxide treatment alter cytokine levels after endotoxin infusion in pigs?: A randomized controlled study2008In: Journal of Inflammation, ISSN 1476-9255, Vol. 5, p. 13.-Article in journal (Refereed)
    Abstract [en]

    ABSTRACT: BACKGROUND: Carbon monoxide (CO) has recently been suggested to have anti-inflammatory properties, but data seem to be contradictory and species-specific. Thus, in studies on macrophages and mice, pretreatment with CO attenuated the inflammatory response after endotoxin exposure. On the other hand, human studies showed no effect of CO on the inflammatory response. Anti-inflammatory efficacy of CO has been shown at concentrations above 10% carboxyhaemoglobin. This study was undertaken to elucidate the possible anti-inflammatory effects of CO at lower CO concentrations. METHODS: Effects of CO administration on cytokine (TNF-alpha, IL-6, IL-1beta and IL-10) release were investigated in a porcine model in which a systemic inflammatory response syndrome was induced by endotoxin infusion. Endotoxin was infused in 20 anaesthetized and normoventilated pigs. Ten animals were targeted with inhaled CO to maintain 5% COHb, and 10 animals were controls. RESULTS: In the control group, mean pulmonary artery pressure increased from a baseline value of 17 mmHg (mean, n = 10) to 42 mmHg (mean, n = 10) following 1 hour of endotoxin infusion. Similar mean pulmonary artery pressure values were found in animals exposed to carbon monoxide. Plasma levels of all of the measured cytokines increased in response to the endotoxin infusion. The largest increase was observed in TNF-alpha, which peaked after 1.5 hours at 9398 pg/ml in the control group and at 13395 pg/ml in the carbon monoxide-exposed group. A similar peak was found for IL-10 while the IL-6 concentration was maximal after 2.5 hours. IL-1beta concentrations increased continuously during the experiment. There were no significant differences between carbon monoxide-exposed animals and controls in any of the measured cytokines. CONCLUSION: Our conclusion is that 5% COHb does not modify the cytokine response following endotoxin infusion in pigs.

  • 82.
    Åberg, Anna-Maja
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Ahlström, K
    Department of Anaesthesiology and Intensive Care Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Abrahamsson, Pernilla
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Ronquist, Gunnar
    Department of Medical Sciences, Clinical Chemistry, University Hospital of Uppsala, Uppsala, Sweden.
    Hauck, Philip
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Biber, B
    Department of Anaesthesiology and Intensive Care Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Haney, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Ischaemic pre-conditioning means an increased adenosine metabolism with decreased glycolytic flow in ischaemic pig myocardium2010In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 54, no 10, p. 1257-1264Article in journal (Refereed)
    Abstract [en]

    This association between increased adenosine turnover and decreased glycolytic flow during prolonged ischaemia in response to IP can possibly be explained by the competitive effect for the metabolites from both glucose and adenosine metabolism for entering glycolysis. We conclude that this study provides support for an energy-metabolic explanation for the protective mechanisms of IP.

  • 83.
    Åberg, Anna-Maja
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Nilsson Sojka, Birgitta
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Abrahamsson, Pernilla
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Larsson, Jan Erik
    Carbon monoxide concentration in donated blood: relation to cigarette smoking and other sources2009In: Transfusion, ISSN 0041-1132, E-ISSN 1537-2995, Vol. 49, no 2, p. 347-353Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Carbon monoxide (CO) is normally present in the human body due to endogenous production of CO. CO can also be inhaled by exposure to external sources such as cigarette smoke, car exhaust, and fire. The purpose of this study was to investigate CO concentrations in blood from 410 blood donors at the blood center in Umea, Sweden. To further evaluate the effects of cigarette smoking on CO concentrations, the elimination time for CO was examined in six volunteer smokers after a smoked cigarette. STUDY DESIGN AND METHODS: Blood samples from whole blood donors were obtained during the blood center's routine operation. In connection with blood donations, demographic and behavioral data were collected from the donors. The CO concentration was determined using gas chromatography. RESULTS: The majority of blood donors had approximately the same CO concentration (mean, 84.5 micromol/L). In 6 percent of the samples, the concentrations were higher than 130 micromol per L. The highest CO concentration was 561 micromol per L. The main source for these high CO concentrations appeared to be cigarette smoking. In the volunteer smokers, the elimination time after a smoked cigarette varied significantly, with elimination half-lives from 4.7 to 8.4 hours. CONCLUSION: These results show that blood bank red blood cell bags may have CO concentrations above the physiologic level. The time interval between cigarette smoking and blood donation seems to be a particularly important factor for elevated CO concentrations.

  • 84.
    Åkesson, Oscar
    et al.
    Dept of Clinical Scienses, Lund University.
    Abrahamsson, Pernilla
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Blind, Per-Jonas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Surface microdialysis on small bowel serosa in monitoring of ischemia2016In: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 204, no 1, p. 39-46Article in journal (Refereed)
    Abstract [en]

    Background: Ischemic injury of an organ causes metabolic change from aerobic to anaerobic metabolism. It has been shown in experimental studies on the heart and liver that such conversion may be detected by conventional microdialysis probes placed intraparenchymatously, as well as on organ surfaces, by assaying lactate, pyruvate, glucose, and glycerol in dialysate. We developed a microdialysis probe (S-mu D) intended for use solely on organ surfaces. The aim of this study was to assess whether the newly developed S-mu D probe could be used for detection and monitoring of small bowel ischemia. Methods: In anesthetized normoventilated pigs, a control S-mu D probe was applied on the jejunal serosa 50 cm downstream from the duodenojejunal junction (DJJ). Starting 100 cm from DJJ, a 100-cm long ischemic segment was created by division of all mesenteric vessels. S-mu Ds were applied at 2.5, 5, 20, and 50 cm from the starting point of ischemia by serosal sutures. A standard mu D probe was placed in the abdominal cavity as a further control. Dialysate was harvested before inducing ischemia and subsequently every 20 min for 4 h. Central venous blood was drawn every hour to monitor systemic lactate, C-reactive protein, and white blood cell count. Results: Microdialysis lactate levels were significantly higher than baseline from 20 min on into protocol time in the ischemic segment and in the control S-mu D probe. The peritoneal cavity probe showed no significant elevation. Lactate levels from the ischemic segment reached a plateau at 60 min. Courses of pyruvate, glucose, and glycerol levels were in accordance with transition from an aerobic to anaerobic metabolism in the bowel wall. No statistically significant changes in hemoglobin, white blood cell count, or lactate values in central venous blood were recorded. Conclusions: Assaying the aforementioned compounds in dialysate, harvested by the newly developed S-mu D probe, allowed detection and monitoring of small bowel ischemia from 20 min on following its onset.

  • 85.
    Åkesson, Oscar
    et al.
    Institutionen för Klinisk Vetenskap, Lunds Universitet.
    Falkenback, Dan
    Institutionen för Klinisk Vetenskap, Lunds Universitet.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Abrahamsson, Pernilla
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Surface Microdialysis Detects Ischemia After Esophageal Resection: An Experimental Animal Study2019In: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 245, p. 537-543Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: After an esophageal resection, continuity is commonly restored by a gastric tube reconstruction and an intrathoracic anastomosis to the remaining proximal esophagus. Ischemia of the anastomotic region is considered to play a pivotal role in anastomotic leakage. Microdialysis (μD) is an excellent method to measure local biochemical substances and parameters in a specific organ or compartment aiming at early detection of ischemia. This animal study evaluates ischemia of the gastric tube reconstruction using a novel method-μD on organ surfaces. This promising method may have the potential to detect an anastomotic leakage before clinical symptoms develop.

    METHODS: Anesthetized normoventilated pigs were used. Surface microdialysis (S-μD) catheters and an intraparenchymal oxygen tension catheter were placed on the stomach. A gastric tube was made and the gastroepiploic artery was divided halfway along the greater curvature to produce severe ischemia at the top of the gastric tube. μD data from four locations (gastric tube, ileum and peritoneal cavity) were recorded every 20 min during the experiment. Tissue samples from all catheter sites underwent histopathological analysis. Intraparenchymal oxygen partial pressure, systemic blood tests, and hemodynamic parameters were recorded.

    RESULTS: S-μD data showed values indicating severe ischemia at the top of the gastric tube and intermediate ischemia at the level of transection of the gastroepiploic artery. Ischemia was verified by histopathological analysis of tissue samples and intraparenchymal oxygen tension data.

    CONCLUSIONS: S-μD can detect and grade severity of local ischemia in real time, in an animal model.

  • 86.
    Österlund, Barbro
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Andersson, Bengt
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Surgery.
    Häggmark, Sören
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Jern, Christina
    Johansson, Göran
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Seeman-Lodding, Helen
    Biber, Björn
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Myocardial ischemia induces coronary t-PA release in the pig2002In: Acta Anaesthesiol Scand, Vol. 46, no 3, p. 271-8Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Tissue-type plasminogen activator (t-PA) is the key factor in initiating endogenous fibrinolysis in the vascular compartment. Regulated release of t-PA from endothelial stores is rapidly induced by several humoral factors as well as coagulation activation products. The aim of the present study was to test the hypothesis that regional myocardial ischemia induces regulated release of t-PA in the coronary vasculature in vivo. METHODS: Healthy anesthetized (pentobarbital) pigs (n=8) were studied before and after a 10-min left anterior descending region coronary artery occlusion (LAD). Coronary fluxes of lactate, total t-PA antigen (ELISA, detecting both complex bound and free fraction) and active t-PA (functional assay detecting biological free fraction) were determined at 1, 3, 5 and 10 min of reflow. RESULTS: Coronary occlusion induced myocardial lactate production in all animals. Net coronary release of total t-PA, which was 21 ng/min during control, increased rapidly during reflow with a peak after only 1 min (136 ng/min), and returned to baseline within 3 min. Net release of active t-PA mirrored the overall net release response, but fell short of statistical significance. CONCLUSION: Data indicate a local myocardial profibrinolytic response following regional ischemia, which may serve as a prompt defence against coronary thromboembolic events.

  • 87.
    Österlund, Barbro
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Gedeon, Andreas
    Krill, Paul
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Reiz, Sebastian
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    A new method of using gas exchange measurements for the noninvasive determination of cardiac output: clinical experiences in adults following cardiac surgery1995In: Acta Anaesthesiol Scand, Vol. 39, no 6, p. 727-32Article in journal (Refereed)
    Abstract [en]

    New mathematical algorithms have been applied to a computer controlled closed breathing circuit system for non-invasive measurement of cardiac output (COniv). This system has been described in an animal study. Forty patients were studied 5 and 18 hours after cardiac surgery using the thermodilution technique as the reference (COtd). The variables entered into the algorithms for COniv were oxygen uptake, carbon dioxide elimination, end-tidal carbon dioxide partial pressure, tidal volume and arterial oxygen saturation. Mixed venous carbon dioxide partial pressure was obtained from an automatically implemented short rebreathing manoeuvre. Pulmonary perfusion was calculated by a modified Fick equation for carbon dioxide and the shunt flow added to obtain COniv. During mechanical ventilation, there was a good agreement between COtd and COniv (r = 0.8). The bias was -0.14 l/min and the precision was 0.77 l/min. The reproducibility of COniv was 0.03 l/min and for COtd -0.03 l/min with a standard deviation of the difference being 0.35 l/min for COniv and 0.31 l/min for COtd. In awake, but sedated extubated patients, the method proved unsatisfactory on account for uneven tidal volumes and difficulties with leakage around the mouth piece. We conclude that this new technique provides reliable and reproducible measures of cardiac output in sedated, ventilated patients.

  • 88.
    Österlund, Barbro
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Surgery.
    Häggmark, Sören
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Jern, Christina
    Johansson, Göran
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Seeman-Lodding, Helen
    Biber, Björn
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Surgical stress induces acute coronary release of tissue-type plasminogen activator in the pig2000In: Acta Anaesthesiol Scand, Vol. 44, no 10, p. 1226-31Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Tissue-type plasminogen activator (t-PA) is an endothelium derived key enzyme in the initiation of endogenous fibrinolysis. Acute regulated release of active t-PA occurs within minutes in response to threatening thrombotic vessel occlusion. The aim of this study was to investigate the impact of surgical stimulation on the kinetics of t-PA release in the coronary vascular bed in the pig. METHODS: In anaesthetised pigs (n=16), arterio-venous concentration gradients of t-PA, and plasma flows (retrograde thermodilution) were obtained across the coronary vascular bed before (control) and at 1, 3, 5 and 10 min after sternotomy. RESULTS: At control, no significant coronary net flux (release or uptake) of t-PA was observed, while sternotomy induced a rapid net release of total t-PA (132.6 ng x min(-1)), with an associated increase in active t-PA (93.6 ng x min(-1)). This response, evident already after 1 min, showed a peak at 5 min and returned towards baseline levels within 10 min. No concurrent alterations in aortic levels of active t-PA were found and haemodynamic variables were unaltered. CONCLUSION: The rapidly increasing and transient net coronary release of t-PA after sternotomy suggests that the endothelium actively promotes local endogenous fibrinolysis during surgery. Such events could reflect a dynamic responsiveness to protect the coronary circulation during stress.

  • 89.
    Österlund, Barbro
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Jern, Christina
    Seeman-Lodding, Helen
    Johansson, Göran
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Häggmark, Söran
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Broomé, Michael
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Biber, Björn
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Intracoronary beta2 receptor activation induces dynamic local t-PA release in the pig2003In: Thromb Haemost, Vol. 90, no 5, p. 796-802Article in journal (Refereed)
    Abstract [en]

    To investigate beta2 -adrenergic agonist-mediated effects on coronary fluxes of local fibrinolytic factors, healthy anaesthetised and instrumented pigs (n=10) were studied during infusion of isoprenaline (IPR) into the left main coronary artery. Coronary net fluxes of total t-PA antigen, active t-PA and total PAI-1 antigen were determined at baseline and at 3, 5, 7 and 10 minutes of IPR infusion. During IPR, net release of total t-PA increased in a biphasic pattern with transiently high levels at 3 (+440 %) and 7 minutes (+620%) and returned towards baseline at 10 minutes. Net coronary release of active t-PA increased with maximum levels at 3 minutes (+50%). Baseline coronary net flux of total PAI -1 showed a decrease which was most pronounced at 10 minutes. To conclude, a fast beta2 agonist-mediated local release of t-PA into the coronary vasculature was demonstrated. For total t-PA, this response was characterised by a biphasic release profile.

  • 90.
    Österlund, Barbro
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Jern, Sverker
    Jern, Christina
    Seeman-Lodding, Helen
    Östman, Margareta
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Biber, Björn
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Impaired myocardial t-PA release in patients with coronary artery disease2008In: Acta Anaesthesiol Scand, Vol. 52, no 10, p. 1375-84Article in journal (Refereed)
    Abstract [en]

    AIMS: Myocardial ischemia remains a significant perioperative complication in coronary artery disease (CAD) patients. We hypothesized that noxious stimuli during major surgery are associated with an acute release of tissue-type plasminogen activator (t-PA) into the coronary circulation, and that this response is reduced by CAD. METHODS AND RESULTS: Two patient groups, with (n=14) and without (n=8) CAD, were studied during the initial phase of heart surgery. After retrograde great cardiac vein catheterizations during closed-chest conditions, coronary arterial-venous concentration gradients of t-PA and plasminogen activator inhibitor type-1 (PAI-1) were measured together with coronary blood flow measurements, allowing derivation of coronary net release rates. Pre-surgery atrial pacing, performed to evaluate the influence of increases in heart rate (+ 40 beats/min) and coronary blood flow (+ 80 ml/min), did not significantly alter coronary net release of t-PA or PAI-1 in either patient group. Sternotomy induced a prominent increase in coronary net release of both total and active t-PA in the non-CAD group. This response was considerably reduced in the CAD group. CONCLUSIONS: This study provides the first analysis of coronary t-PA release during major surgery and demonstrates a deficient local endothelial t-PA release in patients with CAD. This suggests a reduced local fibrinolytic capacity in CAD patients, which may explain the increased risk for coronary thrombosis in this patient group.

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