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  • 1.
    Broomé, Michael
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Åneman, Anders
    Lehtipalo, Stefan
    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.
    Biber, Björn
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Splanchnic vasoconstriction by angiotensin II is arterial pressure dependent2002In: Acta Anaesthesiol Scand, Vol. 46, no 1, p. 57-63Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Our hypothesis was that splanchnic vasoconstriction by exogenous angiotensin II (Ang II) is significantly potentiated by local mechanisms increasing vasomotor tone and that splanchnic tissue oxygenation during administration of Ang II is perfusion pressure dependent. The aim was to study local splanchnic circulatory effects and tissue oxygenation during intravenous infusion of Ang II at different levels of regional arterial driving pressure in a whole-body large animal model. METHODS: Ang II was infused in incremental doses (0-200 microg x h-1) in anaesthetised instrumented pigs (n=8). Mean superior mesenteric arterial pressure (PSMA) was adjusted by a local variable perivascular occluder. Perivascular ultrasound and laser-Doppler flowmetry were used for measurements of mesenteric venous blood flow and superficial intestinal blood flow, respectively. Intestinal oxygenation was evaluated by oxygen tissue tension (PtiO2) and lactate fluxes. RESULTS: Ang II produced prominent and dose-dependent increases in mesenteric vascular resistance (RSMA) when the intestine was exposed to systemic arterial pressure, but Ang II increased RSMA only minimally when PSMA was artificially kept constant at a lower level (50 mmHg) by the occluder. Although Ang II decreased PtiO2 at a PSMA of 50 mmHg, splanchnic lactate production was not observed. CONCLUSION: We demonstrate that splanchnic vasoconstriction by exogenous Ang II is dependent on arterial driving pressure, suggesting significant potentiation through autoregulatory increases in vasomotor tone. Intestinal hypoxaemia does not seem to occur during short-term infusion of Ang II in doses that significantly increases systemic arterial pressure.

  • 2.
    Claesson, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Anestesiologi och intensivvård.
    Lehtipalo, Stefan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Anestesiologi och intensivvård.
    Bergstrand, Ulf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Anestesiologi och intensivvård.
    Arnerlöv, Conny
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Kirurgi.
    Rocksen, David
    Hultin, Magnus
    Winsö, Ola
    Intestinal circulation, oxygenation and metabolism is not affected by oleic acid lung injury.2005In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 25, no 6, p. 357-363Article in journal (Refereed)
    Abstract [en]

    This study was performed to establish a platform for further studies on effects of ventilatory treatment modalities on the intestines during mechanical ventilation of acute lung injury (ALI). We tested the hypotheses that oleic acid (OA) infusion causes changes in intestinal circulation, oxygenation and metabolism, and that OA is distributed to tissues outside the lung. This was performed as an experimental, prospective and controlled study in an university animal research laboratory. Thirteen juvenile anaesthetized pigs were used in the main study, where seven were given an intravenous infusion of 0.1 ml kg(-1) OA and six served as control (surgery only). In a separate study, four animals were given an intravenous infusion of 0.1 ml kg(-1) (3)H-labelled OA. We measured systemic and mesenteric (portal venous blood flow, jejunal mucosal perfusion) haemodynamic parameters, mesenteric oxygenation (jejunal tissue oxygen tension) and systemic cytokines (tumour necrosis factor-alpha and interleukin-6). We calculated mesenteric lactate flux and mesenteric oxygen delivery, uptake and extraction ratio. In the animals given 3H-OA, we measured 3H-OA in different tissues (lungs, heart, liver, kidney, stomach, jejunum, colon and arterial blood). We found that OA given intravenously is distributed in small amounts to the intestines. This intestinal exposure to OA does not cause intestinal injury when evaluating mesenteric blood flow, metabolism or oxygenation. OA infusion induced a moderate increase in mean pulmonary arterial pressure and a decrease in PaO2/Fraction inspired O2 (P/F) ratio, giving evidence of severe lung injury. Consequently, the OA lung injury model is suitable for studies on intestinal effects of ventilatory treatment modalities during mechanical ventilation of ALI.

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  • 3.
    Claesson, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Anestesiologi och intensivvård.
    Lehtipalo, Stefan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Anestesiologi och intensivvård.
    Bergstrand, Ulf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Anestesiologi och intensivvård.
    Arnerlöv, Conny
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Kirurgi.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Anestesiologi och intensivvård.
    Negative mesenteric effects of lung recruitment maneuvers in oleic acid lung injury are transient and short lasting.2007In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 35, no 1, p. 230-238Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To test the hypothesis that repeated recruitment maneuvers (RMs) have sustained negative effects on mesenteric circulation, metabolism, and oxygenation 60 mins after RMs in pigs with oleic acid lung injury. Further, we aimed to test the hypothesis that an infusion of prostacyclin (PC) at 33 ng.kg.min would attenuate such possible negative mesenteric effects. DESIGN: Randomized, experimental, controlled study. SETTING: University hospital animal laboratory. SUBJECTS: A total of 31 anesthetized, fluid-resuscitated pigs with oleic acid lung injury. INTERVENTIONS: Animals were randomized to one of the following four groups: a control group (n = 7) that received no intervention, recruitment group (n = 8) that underwent the RM sequence, a prostacyclin group (n = 8) that received an infusion of PC, and a recruitment-prostacyclin group (n = 8) that received an infusion of PC and concomitant RM sequence. MEASUREMENTS AND MAIN RESULTS: We measured systemic and mesenteric hemodynamic variables, jejunal mucosal perfusion, mesenteric lactate flux, jejunal tissue oxygen tension, and mesenteric oxygen delivery, uptake, and extraction ratio. Five minutes after RMs, mesenteric oxygen extraction ratio and mesenteric lactate flux were more prominently increased in the recruitment group, giving evidence of worsened mesenteric conditions after RMs. These signs of worsened conditions were further supported by more decreased jejunal tissue oxygen tension and portal vein oxygen saturation in the recruitment group. PC preserved mesenteric oxygenation, as indicated by less of a decrease in portal vein oxygen saturation at the time corresponding to 5 mins after RM and less of a decrease in mesenteric oxygen delivery at the time corresponding to 15 mins after RM. PC preserved mesenteric oxygenation as indicated by less of a decrease in portal vein oxygen saturation at 5 mins after RM and an attenuated increase in mesenteric oxygen extraction ratio at 5 mins after RM. There was a trend toward worsened jejunal mucosal perfusion, although not significant. CONCLUSIONS: In an oleic acid lung injury model, three repeated RMs did not improve systemic oxygenation or lung mechanics. Negative effects on mesenteric oxygenation and metabolism were transient and short lasting. The intestinal effects of PC during RMs were minor and opposing, showing preserved oxygenation but a trend toward worsened mucosal perfusion.

  • 4.
    Claesson, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Anestesiologi och intensivvård.
    Lehtipalo, Stefan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Anestesiologi och intensivvård.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Anestesiologi och intensivvård.
    Abrahamsson, Pernilla
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Anestesiologi och intensivvård.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    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. Anestesiologi och intensivvård.
    Evaluation of intestinal preconditioning in a porcine model using classic ischemic preconditioning or lung recruitment maneuvers.2008In: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 21, no 1, p. 98-103Article in journal (Refereed)
    Abstract [en]

    To test the hypotheses that repeated brief intestinal ischemic insults would elicit an intestinal preconditioning response to a subsequent intestinal I/R injury and that a similar response would be elicited by repeated lung recruitment maneuvers (RMs). Randomized experimental controlled animal study. University hospital animal laboratory. Eighteen anesthetized pigs. Animals were randomized to one of three groups, with six animals in each group. Control group 75-min superior mesenteric artery (SMA) occlusion followed by 60-min reperfusion. Ischemic preconditioning group, three 5-min-long SMA occlusions preceding 75-min SMA occlusion and 60-min reperfusion. Recruitment maneuver (RM) group, three 2-min-long RMs preceding 75-min SMA occlusion and 60-min reperfusion. We measured systemic and mesenteric hemodynamic parameters, jejunal mucosal perfusion, net mesenteric lactate flux, jejunal tissue oxygen tension, and mesenteric oxygenation. Every 15 min, jejunal microdialysate samples were collected and analyzed for glucose, lactate, and glycerol. Jejunal tissue samples were collected postmortem. After occlusion of SMA, regional parameters in all groups indicated abolished perfusion and gradually increasing intraluminal microdialysate lactate and glycerol levels. At reperfusion, regional parameters indicated mesenteric hyperperfusion, whereas microdialysis markers of mucosal anaerobic metabolism and cell injury decreased, although not reaching baseline. Histological examination revealed severe mucosal injury in all groups. There were no significant differences between groups in the observed parameters. No protective preconditioning response could be observed when performing repeated brief intestinal ischemic insults or repeated lung RMs before an intestinal I/R injury.

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  • 5.
    Claesson, Jonas
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences.
    Lehtipalo, Stefan
    Winsö, Ola
    Do lung recruitment maneuvers decrease gastric mucosal perfusion?2003In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 29, no 8, p. 1314-1321Article in journal (Refereed)
  • 6.
    Fröjse, Rolf
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Surgery.
    Lehtipalo, Stefan
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Bergstrand, Ulf
    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.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Johansson, Göran
    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.
    Local metabolic effects of dopexamine on the intestine during mesenteric hypoperfusion.2004In: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 21, no 3, p. 241-247Article in journal (Refereed)
    Abstract [en]

    This self-controlled experimental study was designed to test the hypothesis that dopexamine, a synthetic catecholamine that activates dopaminergic (DA-1) and beta2-adrenergic receptors, improves oxygenation in the jejunal mucosa during intestinal hypotension. In six normoventilated barbiturate-anesthetized pigs, controlled reductions in superior mesenteric arterial pressure (PSMA) was obtained by an adjustable clamp around the artery. Dopexamine infusions (0.5 and 1.0 microg.kg(-1).min(-1)) were administered at a freely variable PSMA (i.e., with the perivascular clamp fully open) and at a PSMA of 50 mmHg and 30 mmHg. We continuously measured superior mesenteric venous blood flow (QMES; transit-time ultrasonic flowmetry), jejunal mucosal perfusion (laser Doppler flowmetry), and tissue oxygen tension (PO2TISSUE; microoximetry). Jejunal luminal microdialysate of lactate, pyruvate, and glucose were measured every 5 min. Measurements of mucosal PCO2 (air tonometry), together with blood sampling and end-tidal PCO2 measurements, enabled calculations of pHi and PCO2 gap. Dopexamine reduced mesenteric vascular resistance and increased QMES at a PSMA of 50 mmHg and 30 mmHg. At a PSMA of 30 mmHg, dopexamine increased mesenteric oxygen delivery but did not influence mesenteric oxygen uptake or extraction. In this situation, dopexamine had no beneficial effect on jejunal mucosal blood flow. On the contrary, dopexamine increased mesenteric net lactate production and PCO2 gap, whereas PO2TISSUE and pHi decreased. Jejunal luminal microdialysate data demonstrated an increased lactate concentration and a pattern of decreased glucose concentration and increased luminal lactate-pyruvate ratio. These negative metabolic effects of dopexamine should be taken into account in situations of low perfusion pressures.

  • 7.
    Fröjse, Rolf
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Surgery.
    Lehtipalo, Stefan
    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.
    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.
    Arnerlöv, Conny
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Surgery.
    Assessment of graded intestinal hypoperfusion and reperfusion using continuous saline tonometry in a porcine model.2004In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 28, no 1, p. 79-88Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate effects of graded intestinal hypoperfusion and reperfusion on intestinal metabolic parameters as assessed by a modified continuous saline tonometry technique. MATERIALS: Twelve barbiturate-anaesthetized female pigs. METHODS: Measurements were performed prior to and during three predefined levels of superior mesenteric mean arterial blood pressure (P(SMA) 70, 50 and 30 mmHg, respectively, each 80 min long), obtained by an adjustable clamp around the origin of the superior mesenteric artery, and during reperfusion. We continuously measured jejunal mucosal perfusion (laser Doppler flowmetry), jejunal tissue oxygen tension (PO(2TISSUE); microoximetry) and intramucosal PCO(2) (continuous saline tonometry) and calculated net intestinal lactate production, mesenteric oxygenation, PCO(2) gap (jejunal mucosal PCO(2)-arterial PCO(2)) and pHi. RESULTS: At P(SMA) 70 and 50 mmHg mesenteric oxygen uptake and net lactate production remained unaltered, in spite of decreased oxygen delivery. At these P(SMA) levels PCO(2) gap increased, while pHi and PO(2TISSUE) decreased. At P(SMA) 30 mmHg pronounced increases in PCO(2) gap and mesenteric net lactate production as well as marked decreases in PO(2TISSUE) and pHi were demonstrated. Data indicate absence of anaerobic conditions at an intestinal perfusion pressure (IPP)> or =41 mmHg, a pHi> or =7.22 or PCO(2) gap< or =15.8 mmHg. CONCLUSIONS: Continuous saline tonometry detected intestinal ischemia as induced by graded reductions in IPP. A threshold could be defined above which intestinal ischemia does not occur.

  • 8.
    Larsson, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Claesson Lingehall, Helena
    Umeå University, Faculty of Medicine, Department of Nursing.
    Al Zaidi, Nefar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Claesson, Jonas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Jensen-Waern, Marianne
    Lehtipalo, Stefan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Percutaneously inserted long-term central venous catheters in pigs of different sizes2015In: Laboratory Animals. Journal of the Laboratory Animal Science Association, ISSN 0023-6772, E-ISSN 1758-1117, Vol. 49, no 3, p. 215-219Article in journal (Refereed)
    Abstract [en]

    Pigs are used for long-term biomedical experiments requiring repeated injections, infusions and collections of blood samples. Thus, it is necessary for vascular catheters to be indwelling to avoid undue stress to the animals and the use of restraints. We propose a refined model of percutaneous insertion of long-term central venous catheters to minimize the surgical trauma and postoperative complications associated with catheter insertion. Different sizes of needles (18 Ga versus 21 Ga) for initial puncture of the veins were compared. In conventional pigs weighing less than 30 kg, catheter insertion may be facilitated by using a microintroducer set with a 21 Ga needle. In pigs weighing 50 kg, a standard 18 Ga needle may be preferable.

  • 9.
    Larsson, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Gouveia-Figueira, Sandra
    Umeå University.
    Claesson, Jonas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Lehtipalo, Stefan
    Umeå University.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Tyden, Jonas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Joakim
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Pinto, Rui
    Umeå University.
    Nording, M. L.
    Umeå University.
    Oxylipin Profiling In The Acute Respiratory Distress Syndrome2016In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 193, article id A4419Article in journal (Refereed)
  • 10.
    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.

  • 11.
    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.

  • 12.
    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.

  • 13.
    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.

  • 14.
    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 Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 44, no 8, p. 946-952Article 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.

  • 15.
    Lindgren, Lenita
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Lehtipalo, Stefan
    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.
    Karlsson, Marcus
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Brulin, Christine
    Umeå University, Faculty of Medicine, Department of Nursing.
    Touch massage: a pilot study of a complex intervention2013In: Nursing in Critical Care, ISSN 1362-1017, E-ISSN 1478-5153, Vol. 18, no 6, p. 269-277Article in journal (Refereed)
    Abstract [en]

    Objectives: To report and evaluate a complex touch massage intervention according to the British Medical Research Council framework. This study aimed to evaluate the effects of touch massage on levels of anxiety and physiological stress in patients scheduled for elective aortic surgery.

    Background: The use of touch massage has increased during the past decade but no systematic studies have been implemented to investigate the effectiveness of such treatment. It is important to conduct multidisciplinary investigations into the effects of complex interventions such as touch massage. For this, the British Medical Research Council has provided a useful framework to guide the development, piloting, evaluation and reporting of complex intervention studies.

    Method: A pilot study with a randomized controlled design including 20 patients (10 + 10) scheduled for elective aortic surgery. Selected outcome parameters included; self-reported anxiety, measured by the State-Trait Anxiety Inventory Form Y instrument, and physiological stress, measured by heart rate variability, blood pressure, respiratory frequency, oxygen saturation and concentrations of cortisol, insulin and glucose in serum.

    Results: There were significant differences in self-reported anxiety levels before and after touch massage (p = 0·007), this was not observed in the control group (p = 0·833). There was a significant difference in self-reported anxiety levels between the touch massage group and the control group after touch massage and rest (p = 0·001). There were no significant differences in physiological stress-related outcome parameters between patients who received touch massage and controls.

    Conclusion: In our study, touch massage decreased anxiety levels in patients scheduled for elective aortic surgery, and the British Medical Research Council framework was a useful guideline for the development, evaluation and reporting of a touch massage intervention.

    Relevance to clinical practice: Touch massage can reduce patients' anxiety levels and is thus an important nursing intervention in intensive and post-operative care.

  • 16.
    Lindgren, Lenita
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Rundgren, S
    Umeå University, Faculty of Medicine, Department of Nursing.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Lehtipalo, Stefan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Karlsson, Markus
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Jacobsson, Catrine
    Umeå University, Faculty of Medicine, Department of Nursing.
    Brulin, Christine
    Umeå University, Faculty of Medicine, Department of Nursing.
    Physiological responses to touch massage in healthy volunteers2010In: Autonomic Neuroscience: Basic & Clinical, ISSN 1566-0702, E-ISSN 1872-7484, Vol. 158, no 1-2, p. 105-110Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To evaluate effects of touch massage (TM) on stress responses in healthy volunteers.

    METHODS: A crossover design including twenty-two (mean age=28.2) healthy volunteers (11 male and 11 female) cardiac autonomic tone was measured by heart rate (HR) and heart rate variability (HRV). Stress hormone levels (cortisol) were followed in saliva. We also measured blood glucose and serum insulin. Extracellular (ECV) levels of glucose, lactate, pyruvate and glycerol were followed using the microdialysis technique (MD). TM was performed on hands and feet for 80min, during control, participants rested in the same setting. Data were collected before, during, and after TM and at rest. Saliva cortisol, serum glucose, and serum insulin were collected before, immediately following, and 1h after intervention or control, respectively.

    RESULTS: After 5min TM, HR decreased significantly, indicating a reduced stress response. Total HRV and all HRV components decreased during intervention. Saliva cortisol and insulin levels decreased significantly after intervention, while serum glucose levels remained stable. A similar, though less prominent, pattern was seen during the control situation. Only minor changes were observed in ECV levels of glucose (a decrease) and lactate (an increase). No significant alterations were observed in glycerol or pyruvate levels throughout the study. There were no significant differences between groups in ECV concentrations of analyzed substances.

    CONCLUSIONS: In healthy volunteers, TM decreased sympathetic nervous activity, leading to decreased overall autonomic activity where parasympathetic nervous activity also decreased, thereby maintaining the autonomic balance.

  • 17.
    Lindgren, Lenita
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Westling, Göran
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Brulin, Christine
    Umeå University, Faculty of Medicine, Department of Nursing.
    Lehtipalo, Stefan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Andersson, Micael
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Pleasant human touch is represented in pregenual anterior cingulate cortex2012In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 59, no 4, p. 3427-3432Article in journal (Refereed)
    Abstract [en]

    Touch massage (TM) is a form of pleasant touch stimulation used as treatment in clinical settings and found to improve well-being and decrease anxiety, stress, and pain. Emotional responses reported during and after TM have been studied, but the underlying mechanisms are still largely unexplored. In this study, we used functional magnetic resonance (fMRI) to test the hypothesis that the combination of human touch (i.e. skin-to-skin contact) with movement is eliciting a specific response in brain areas coding for pleasant sensations. The design included four different touch conditions; human touch with or without movement and rubber glove with or without movement. Force (2.5N) and velocity (1.5cm/s) were held constant across conditions. The pleasantness of the four different touch stimulations was rated on a visual analog scale (VAS-scale) and human touch was rated as most pleasant, particularly in combination with movement. The fMRI results revealed that TM stimulation most strongly activated the pregenual anterior cingulate cortex (pgACC). These results are consistent with findings showing pgACC activation during various rewarding pleasant stimulations. This area is also known to be activated by both opioid analgesia and placebo. Together with these prior results, our finding furthers the understanding of the basis for positive TM treatment effects.

  • 18.
    Tydén, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Anestesiläkaravdelningen, Östersund Hospital, Östersund, Sweden.
    Larsson, Niklas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Lehtipalo, Stefan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Herwald, H
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Walldén, Jakob
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Behndig, Annelie F.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johansson, Joakim
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Heparin-binding protein in ventilator-induced lung injury.2018In: Intensive Care Medicine Experimental, ISSN 1646-2335, E-ISSN 2197-425X, Vol. 6, no 1, article id 33Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Although mechanical ventilation is often lifesaving, it can also cause injury to the lungs. The lung injury is caused by not only high pressure and mechanical forces but also by inflammatory processes that are not fully understood. Heparin-binding protein (HBP), released by activated granulocytes, has been indicated as a possible mediator of increased vascular permeability in the lung injury associated with trauma and sepsis. We investigated if HBP levels were increased in the bronchoalveolar lavage fluid (BALF) or plasma in a pig model of ventilator-induced lung injury (VILI). We also investigated if HBP was present in BALF from healthy volunteers and in intubated patients in the intensive care unit (ICU).

    METHODS: Anaesthetized pigs were randomized to receive ventilation with either tidal volumes of 8 ml/kg (controls, n = 6) or 20 ml/kg (VILI group, n = 6). Plasma and BALF samples were taken at 0, 1, 2, 4, and 6 h. In humans, HBP levels in BALF were sampled from 16 healthy volunteers and from 10 intubated patients being cared for in the ICU.

    RESULTS: Plasma levels of HBP did not differ between pigs in the control and VILI groups. The median HBP levels in BALF were higher in the VILI group after 6 h of ventilation compared to those in the controls (1144 ng/ml (IQR 359-1636 ng/ml) versus 89 ng/ml (IQR 33-191 ng/ml) ng/ml, respectively, p = 0.02). The median HBP level in BALF from healthy volunteers was 0.90 ng/ml (IQR 0.79-1.01 ng/ml) as compared to 1959 ng/ml (IQR 612-3306 ng/ml) from intubated ICU patients (p < 0.001).

    CONCLUSIONS: In a model of VILI in pigs, levels of HBP in BALF increased over time compared to controls, while plasma levels did not differ between the two groups. HBP in BALF was high in intubated ICU patients in spite of the seemingly non-harmful ventilation, suggesting that inflammation from other causes might increase HBP levels.

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