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  • 1.
    Abrahamsson, Pernilla
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Åberg, Anna-Maja
    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.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Haney, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Detection of myocardial ischaemia using surface microdialysis on the beating heart2011In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 31, no 3, p. 175-181Article in journal (Refereed)
    Abstract [en]

    Microdialysis (MD) can be used to study metabolism of the beating heart. We investigated whether microdialysis results obtained from epicardial (surface) sampling reflect acute changes in the same way as myocardial sampling from within the substance of the ventricular wall. In anaesthetized open-thorax pigs a coronary snare was placed. One microdialysis probe was placed with the sampling membrane intramyocardially (myocardial), and a second probe was placed with the sampling membrane epicardially (surface), both in the area which was made ischaemic. Ten minutes collection intervals were used for microdialysis samples. Samples from 19 pigs were analysed for lactate, glucose, pyruvate and glycerol during equilibration, baseline, ischaemia and reperfusion periods. For both probes (surface and myocardial), a total of 475 paired simultaneous samples were analysed. Results from analyses showed no differences in relative changes for glucose, lactate and glycerol during baseline, ischaemia and reperfusion. Surface microdialysis sampling is a new application of the microdialysis technique that shows promise and should be further studied.

  • 2.
    Ahlström, Katarina
    et al.
    Anesthesia and Intensive Care Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Biber, Björn
    Anesthesia and Intensive Care Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Åberg, Anna-Maja
    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.
    Ronquist, Gunnar
    Department of Medical Chemistry, Uppsala University, Uppsala, Sweden.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Haney, Michael F.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Exogenous carbon monoxide does not affect cell membrane energy availability assessed by sarcolemmal calcium fluxes during myocardial ischaemia-reperfusion in the pig2011In: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 28, no 5, p. 356-362Article in journal (Refereed)
    Abstract [en]

    Carbon monoxide is thought to be cytoprotective and may hold therapeutic promise for mitigating ischaemic injury. The purpose of this study was to test low-dose carbon monoxide for protective effects in a porcine model of acute myocardial ischaemia and reperfusion.In acute open-thorax experiments in anaesthetised pigs, pretreatment with low-dose carbon monoxide (5% increase in carboxyhaemoglobin) was conducted for 120 min before localised ischaemia (45 min) and reperfusion (60 min) was performed using a coronary snare. Metabolic and injury markers were collected by microdialysis sampling in the ventricular wall. Recovery of radio-marked calcium delivered locally by microperfusate was measured to assess carbon monoxide treatment effects during ischaemia/reperfusion on the intracellular calcium pool.Coronary occlusion and ischaemia/reperfusion were analysed for 16 animals (eight in each group). Changes in glucose, lactate and pyruvate from the ischaemic area were observed during ischaemia and reperfusion interventions, though there was no difference between carbon monoxide-treated and control groups during ischaemia or reperfusion. Similar results were observed for glycerol and microdialysate Ca recovery.These findings show that a relatively low and clinically relevant dose of carbon monoxide did not seem to provide acute protection as indicated by metabolic, energy-related and injury markers in a porcine myocardial ischaemia/reperfusion experimental model. We conclude that protective effects of carbon monoxide related to ischaemia/reperfusion either require higher doses of carbon monoxide or occur later after reperfusion than the immediate time frame studied here. More study is needed to characterise the mechanism and time frame of carbon monoxide-related cytoprotection.

  • 3.
    Ahlström, Katarina
    et al.
    Anestesi, Sahlgrenska akademin, Göteborgs universitet.
    Biber, Björn
    Anestesi, Sahlgrenska akademin, Göteborgs universitet.
    Åberg, Annamaja
    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
    Abrahamsson, Pernilla
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Strandén, Per
    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.
    Metabolic responses in ischemic myocardium after inhalation of carbon monoxide2009In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 53, no 8, p. 1036-1042Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: To clarify the mechanisms of carbon monoxide (CO) tissue-protective effects, we studied energy metabolism in an animal model of acute coronary occlusion and pre-treatment with CO. METHODS: In anesthetized pigs, a coronary snare and microdialysis probes were placed. CO (carboxyhemoglobin 5%) was inhaled for 200 min in test animals, followed by 40 min of coronary occlusion. Microdialysate was analyzed for lactate and glucose, and myocardial tissue samples were analyzed for adenosine tri-phosphate, adenosine di-phosphate, and adenosine mono-phosphate. RESULTS: Lactate during coronary occlusion was approximately half as high in CO pre-treated animals and glucose levels decreased to a much lesser degree during ischemia. Energy charge was no different between groups. CONCLUSIONS: CO in the low-doses tested in this model results in a more favorable energy metabolic condition in that glycolysis is decreased in spite of maintained energy charge. Further work is warranted to clarify the possible mechanistic role of energy metabolism for CO protection.

  • 4.
    Andersen, Grethe Neumann
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Caidahl, Kenneth
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Kazzam, Elsadig
    Petersson, Ann-Sofi
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mincheva-Nilsson, Lucia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Correlation between increased nitric oxide production and markers of endothelial activation in systemic sclerosis: findings with the soluble adhesion molecules E-selectin, intercellular adhesion molecule 1, and vascular adhesion molecule 12000In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 43, no 5, p. 1085-1093Article in journal (Refereed)
    Abstract [en]

    Objective To determine the relationship between vascular function and the inflammatory response in systemic sclerosis (SSc), and to investigate whether production of endothelial-derived nitric oxide (NO) is disturbed in this disease.

    Methods We measured plasma nitrate, urinary excretion of both nitrate and cGMP, and soluble adhesion molecules of endothelial origin in patients with SSc and in age- and sex-matched controls and compared these levels between groups. Additionally, we performed correlation analysis to determine how these variables were related to one another. Plasma nitrate and 24-hour-urinary excretion of nitrate in patients and controls were measured after a 72-hour nitrate-free-diet, using a gas chromatography/mass spectrometric method. Soluble adhesion molecules intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1 (sVCAM-1), and E-selectin and cytokines were measured by enzyme-linked immunosorbent assay. The expression of E-selectin was further investigated in skin biopsy specimens by immunoperoxidase staining, and the presence of inducible NO synthase by immunoblotting.

    Results Plasma nitrate and 24-hour-urinary-excretion of cGMP were significantly elevated in patients compared with controls, while 24-hour-urinary-excretion of nitrate tended to be elevated in SSc patients. Levels of sICAM-1, sVCAM-1, and sE-selectin were significantly elevated in the patients. Levels of plasma nitrate in the patients correlated significantly with levels of sVCAM-1 (P = 0.020) and sE-selectin (P = 0.018) and approached a significant correlation with sICAM-1 (P = 0.055), suggesting that activated endothelial cells may produce plasma nitrate.

    Conclusion NO synthesis is elevated in SSc patients, and the activated endothelial cell is a likely site of its production.

  • 5.
    Andersen, Grethe Neumann
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Mincheva-Nilsson, Lucia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Kazzam, Elsadig
    Mälar Hospital, Eskilstuna, Sweden.
    Nyberg, Gunnar
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Klintland, Natalia
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Petersson, Ann-Sofi
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Caidahl, Kenneth
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Assessment of vascular function in systemic sclerosis: indications of the development of nitrate tolerance as a result of enhanced endothelial nitric oxide production2002In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 46, no 5, p. 1324-1332Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the relationship between endothelium-dependent and endothelium-independent functions and the stiffness of conduit arteries as well as levels of endothelial activation markers in patients with systemic sclerosis (SSc).

    METHODS: Endothelium-dependent (i.e., flow-mediated) and endothelium-independent (i.e., nitroglycerin-induced) dilation of the brachial artery was measured as the percentage of change from baseline (FMD% and NTG%, respectively) in 24 SSc patients and 24 age- and sex-matched healthy controls by high-resolution ultrasound imaging. The maximum increase in systolic pressure per unit of time (dP/dt(max)), as a measure of arterial wall stiffness, was assessed in the radial artery by pulse applanation tonometry. Plasma nitrate, the most important metabolite of nitric oxide, and 24-hour urinary excretion of nitrate were measured by gas chromatography mass spectrometry. Soluble E-selectin and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured by enzyme-linked immunosorbent assay.

    RESULTS: Brachial artery FMD% and NTG% did not differ between SSc patients and controls. Radial artery dP/dt(max) was significantly increased in the patients and correlated significantly with elevated levels of plasma nitrate and sVCAM-1. Twenty-four-hour urinary nitrate excretion tended to be elevated. Brachial artery NTG% was significantly inversely correlated with levels of plasma nitrate and soluble endothelial adhesion molecules.

    CONCLUSION: The ability of the brachial arteries to dilate in response to hyperemia and nitroglycerin challenge is preserved in SSc. Stiffness of the radial artery is increased, however. Endothelial activation seems to determine the extent of the brachial artery NTG% and the radial artery dP/dt(max). The data are compatible with the hypothesis that nitrate tolerance is present in the vascular smooth muscle cells of the brachial artery wall in SSc.

  • 6.
    Andersen, Grethe Neumann
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Nilsson, Kenneth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Hackett, Tillie-Louise
    Kazzam, Elsadig
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Warner, Jane
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Mincheva-Nilsson, Lucia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Sandström, Thomas
    Bronchoalveolar matrix metalloproteinase 9 relates to restrictive lung function impairment in systemic sclerosis.2007In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 101, no 10, p. 2199-2206Article in journal (Refereed)
    Abstract [en]

    Systemic sclerosis (SSc) is frequently associated with interstitial lung disease (ILD) often leading to lung fibrosis. In this study we investigated whether matrix metalloproteinase 9 (MMP-9) and its natural inhibitor; the tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), would be associated with remodelling in ILD in SSc. Levels of total MMP-9, pro-MMP-9 and TIMP-1 were measured in bronchoalveolar lavage (BAL) fluid from nine SSc patients with ILD, seven SSc patients without ILD and 16 age- and sex-matched healthy controls. Total MMP-9 and pro-MMP-9 levels were significantly elevated in SSc patients with ILD, compared to levels in SSc patients without ILD and healthy controls. In SSc patients with ILD calculated active MMP-9 levels were significantly higher than in SSc patients without ILD and tended to be higher than in healthy controls. TIMP-1 levels were elevated in both patient groups compared to healthy controls. Total-, pro- and active MMP-9 levels as well as pro-MMP-TIMP-1 and active MMP-9/TIMP-1 ratios were inversely associated with total lung capacity. The present study suggests that MMP-9 plays a pathophysiological role in the remodelling in ILD and lung fibrosis associated with SSc, and may represent a new therapeutic target in this condition.

  • 7.
    Bailey, Leslie
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Engström, Patrik
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Nordström, Anna
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Rehabilitation Medicine. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Bergström, Sven
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nordström, Peter
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Chlamydia pneumoniae infection results in generalized bone loss in mice2008In: Microbes and infection, ISSN 1286-4579, E-ISSN 1769-714X, Vol. 10, no 10-11, p. 1175-1181Article in journal (Refereed)
  • 8.
    Bailey, Leslie
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Gylfe, Åsa
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Sundin, Charlotta
    Muschiol, Sandra
    Elofsson, Mikael
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Nordström, Peter
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Henriques-Normark, Birgitta
    Lugert, Raimond
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wolf-Watz, Hans
    Bergström, Sven
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Small molecule inhibitors of type III secretion in Yersinia block the Chlamydia pneumoniae infection cycle2007In: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 581, no 4, p. 587-595Article in journal (Refereed)
    Abstract [en]

    Intracellular parasitism by Chlamydiales is a complex process involving transmission of metabolically inactive particles that differentiate, replicate, and re-differentiate within the host cell. A type three secretion system (T3SS) has been implicated in this process. We have here identified small molecules of a chemical class of acylated hydrazones of salicylaldehydes that specifically blocks the T3SS of Chlamydia. These compounds also affect the developmental cycle showing that the T3SS has a pivotal role in the pathogenesis of Chlamydia. Our results suggest a previously unexplored avenue for development of novel anti-chlamydial drugs.

  • 9.
    Bergenheim, A Tommy
    et al.
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurosurgery.
    Roslin, Michael
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurosurgery.
    Ungerstedt, Urban
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Ronquist, Gunnar
    Metabolic manipulation of glioblastoma in vivo by retrograde microdialysis of L-2, 4 diaminobutyric acid (DAB).2006In: J Neurooncol, ISSN 0167-594X, Vol. 80, no 3, p. 285-293Article in journal (Refereed)
  • 10. Bergström, G
    et al.
    Berglund, G
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Brandberg, J
    Engström, G
    Engvall, J
    Eriksson, M
    de Faire, U
    Flinck, A
    Hansson, M G
    Hedblad, B
    Hjelmgren, O
    Janson, C
    Jernberg, T
    Johnsson, Å
    Johansson, L
    Lind, L
    Löfdahl, C-G
    Melander, O
    Östgren, C J
    Persson, A
    Persson, M
    Sandström, Anette
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Schmidt, C
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Sundström, J
    Toren, K
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Thoracic Center, Umeå University Hospital.
    Wedel, H
    Vikgren, J
    Fagerberg, B
    Rosengren, A
    The Swedish CArdioPulmonary BioImage Study: objectives and design.2015In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 278, no 6, p. 645-659Article in journal (Refereed)
    Abstract [en]

    Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.

  • 11. Biber, Björn
    et al.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    [New data on hypothermia. Now we have to keep cool!]2004In: Läkartidningen, ISSN 0023-7205, Vol. 101, no 6, p. 438-9Article in journal (Other academic)
  • 12. Boman, J
    et al.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Forsberg, J
    Birgander, L S
    Allard, A
    Persson, K
    Jidell, E
    Kumlin, U
    Juto, P
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Wadell, G
    High prevalence of Chlamydia pneumoniae DNA in peripheral blood mononuclear cells in patients with cardiovascular disease and in middle-aged blood donors.1998In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 178, no 1Article in journal (Refereed)
    Abstract [en]

    Nested polymerase chain reaction (nPCR) demonstrated the presence of Chlamydia pneumoniae-specific DNA in peripheral blood mononuclear cells (PBMC). PBMC samples were obtained from 103 consecutive patients (62 male, 41 female) aged 22-85 years (mean, 64) admitted for coronary angiography because of suspected coronary heart disease and from 52 blood donors (43 male, 9 female) aged 40-64 years (mean, 49). Of the 101 evaluable patients, 60 (59%) were identified by nPCR assay as C. pneumoniae DNA carriers; C. pneumoniae-specific microimmunofluorescence (MIF) serology confirmed exposure to the bacterium in 57 (95%) of the 60 nPCR-positive patients. Among the 52 blood donors, the nPCR assay identified 24 (46%) C. pneumoniae DNA carriers, all of whom were positive by C. pneumoniae-specific serology. Thirty-two patients (32%) and 23 blood donors (44%) were MIF antibody-positive but repeatedly nPCR-negative; Bartonella henselae- or Bartonella quintana-specific antibodies were not detected among any of these subjects. In this study, C. pneumoniae DNA was common in PBMC of patients with coronary heart disease and in middle-aged blood donors.

  • 13.
    Bukachi, Frederich
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Mörner, Stellan
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Henein, M Y
    Kazzam, Elsadig
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Pulmonary venous flow reversal and its relationship to atrial mechanical function in normal subjects--Umeå General Population Heart Study.2005In: European Journal of Echocardiography, ISSN 1525-2167, E-ISSN 1532-2114, Vol. 6, no 2, p. 107-116Article in journal (Refereed)
    Abstract [en]

    AIMS: Although pulmonary venous flow reversal (Ar) is useful in the evaluation of left ventricular (LV) diastolic function, it is often difficult to study with transthoracic echocardiography (TTE). We determined the relationship between Ar and left atrial (LA) mechanical function and sought to define surrogate measurements for Ar. METHODS AND RESULTS: A total of 130 healthy subjects, mean age 54.3+/-18.3 years, 62 women, were studied and classified into three groups: [young (Y), 25-44 years; n=44], [middle-age (M), 45-64 years; n=43] and [elderly (E), > or =65 years; n=43]. Pulmonary venous flow and LV inflow studies were performed by TTE and LV basal free-wall motion was studied by Doppler tissue imaging (DTI). All images were acquired with a superimposed electrocardiogram. RR interval was similar in all groups while LA dimension and PR interval were increased in Group E vs. Y (P<0.001). LA contraction (A(m)) on DTI, transmitral A-wave (A) and Ar were simultaneous and started 84ms after onset of P wave and this interval increased with age (P=0.02). Similarly, the time intervals from the same landmark to peak A(m), A, and Ar were prolonged with age (all, P<0.001). Despite this prolongation, peak A(m) coincided with peak Ar in every age group (r=0.97, P<0.001) and Ar acceleration and deceleration times were consistently equal. CONCLUSION: The timing of A(m) obtained by DTI can be used to accurately estimate corresponding measurements of Ar recorded by TTE in subjects without cardiac disease.

  • 14.
    Bukachi, Frederick
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Clague, Jonathan
    Waldenstrom, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Kazzam, Elsadig
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Clinical outcome of coronary angioplasty in patients with ischaemic cardiomyopathy2003In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 88, no 2-3, p. 167-174Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To assess the clinical outcome of successful percutaneous transluminal coronary angioplasty (PTCA) in patients with poor ventricular function. METHODS: Analysis of angiographic, echocardiographic and clinical records of patients with severe LV dysfunction who underwent PTCA from January 1, 1995 to December 31, 1997 was undertaken. Forty-one patients aged 63+/-10 years, 36 men, all with significant coronary artery disease and impaired LV function (fractional shortening, FS<or=20%) were identified. Patients' data before and after angioplasty were analyzed. RESULTS: Post PTCA: angiographic success was 95.2%. Major complications occurred in 19.5% and hospital mortality was 2.7%. At 6 months after PTCA:LV fractional shortening (FS) increased from 15.9+/-3.4% to 19.6+/-6.6%, P=0.02 and consequently cardiac output from 4.28+/-0.98 to 5.34+/-1.77 l/min, P<0.01. Change in at least one class of angina and cardiac functional status was observed in 46% of patients, P<0.001, and this was maintained to the end of the year. After 12 months follow-up: restenosis occurred in 10.8%; mortality was 5.4%; event-free and actuarial survivals were 62.3% and 91.9%, respectively. CONCLUSIONS: In patients with severe LV dysfunction, continued symptomatic improvement can be achieved with successful coronary angioplasty. This is associated with significant recovery of LV systolic function and cardiac output. In order to minimize procedure-related complications, careful patient selection should be considered.

  • 15.
    Bukachi, Frederick
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mörner, Stellan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Kazzam, Elsadig
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Age dependency in the timing of mitral annular motion in relation to ventricular filling in healthy subjects: Umea General Population Heart Study2008In: European Journal of Echocardiography, ISSN 1525-2167, E-ISSN 1532-2114, Vol. 9, no 4, p. 522-529Article in journal (Refereed)
    Abstract [en]

    AIMS: Peak left ventricular (LV) relaxation normally precedes peak filling (E), which supports the hypothesis that LV suction contributes to early-diastolic filling. The significance of similar temporal discordance in late diastole has previously not been studied. We describe the time relationships between mitral annular motion and LV filling in early and late diastole and examine the effect of normal ageing on these time intervals. METHODS AND RESULTS: A total of 128 healthy subjects aged 25-88 years were studied. Transmitral and pulmonary venous flow reversals (Ar) were recorded by Doppler echocardiography. Mitral annular diastolic displacement-early (E(m)) and late (A(m))-were recorded by Doppler tissue imaging. With reference to electrocardiographic R and P-waves, the following measurements were made: R to peak E-wave (R-E) and E(m) (R-E(m)); onset P to peak A-wave (P-pA), A(m) (P-pA(m)), and Ar (P-pAr). The differences between [(R-E) and (R-E(m))] for early-diastolic temporal discordance (EDTD) and [(P-A) and (P-A(m))] for late-diastolic temporal discordance (LDTD) were calculated. Isovolumic relaxation time (IVRT) was also measured. Early-diastolic temporal discordance was approximately 26 ms in all age groups. Late-diastolic temporal discordance, however, was inversely related to age (r = -0.35, P < 0.001) and IVRT (r = -0.34, P < 0.001) and therefore decreased in the elderly vs. young (13 +/- 10 vs. 23 +/- 10 ms; P < 0.001). In multivariate analysis, age failed to predict LDTD in the presence of IVRT. A, A(m), and Ar were simultaneous at onset, and peak A(m) coincided with peak Ar in all age groups (r = 0.97, P < 0.001). No significant differences were noted in the RR intervals. CONCLUSIONS: Sequential prolongation of IVRT with ageing reduces LDTD, thus converging the peaks of A(m), A, and Ar (atrial mechanical alignment)-a potential novel method to identify subjects at increased dependency on atrial contraction for late-diastolic filling.

  • 16. Dahlström, Ulf
    et al.
    Håkansson, Jan
    Swedberg, Karl
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Adequacy of diagnosis and treatment of chronic heart failure in primary health care in Sweden2009In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 11, no 1, p. 92-98Article in journal (Refereed)
    Abstract [en]

    AIMS: We performed an observational multicentre study to obtain information of the diagnostic tools and treatments currently used in patients with chronic heart failure (CHF) in primary health care (PHC) in Sweden. Data were collected from 2093 patients in 158 randomly selected PHC centres. METHODS AND RESULTS: The mean age was 79 years. The dominating aetiology of HF was hypertension and/or ischaemic heart disease. Diagnosis was based on symptoms and/or ECG and/or chest X-ray in 69% of the patients. Treatment with a renin-angiotensin system (RAS) blocker was ongoing in 74% of the patients, but only 37% had > or = 50% of the recommended target dose. In 68%, treatment with a beta-blocker (BB) was present, but only 31% had > or = 50% of the recommended target dose. Only 42% of the patients were on treatment with an RAS blocker and a BB and only 20% had > or = 50% of the recommended target dose. CONCLUSION: The diagnostic criteria for CHF according to the European Society of Cardiology were fulfilled in only approximately 30% of the patients. In addition, evidenced-based treatments to reduce morbidity and mortality were markedly underused, particularly regarding dosing. Our findings may reflect the patients' high age and the presence of important co-morbidities.

  • 17. Friedrich, Felix W
    et al.
    Bausero, Pedro
    Sun, Yuli
    Treszl, Andras
    Krämer, Elisabeth
    Juhr, Denise
    Richard, Pascale
    Wegscheider, Karl
    Schwartz, Ketty
    Brito, Dulce
    Arbustini, Eloisa
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Isnard, Richard
    Komajda, Michel
    Eschenhagen, Thomas
    Carrier, Lucie
    A new polymorphism in human calmodulin III gene promoter is a potential modifier gene for familial hypertrophic cardiomyopathy.2009In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 30, no 13, p. 1648-1655Article in journal (Refereed)
    Abstract [en]

    AIMS: Familial hypertrophic cardiomyopathy (FHC) is caused by mutations in genes encoding sarcomeric proteins. Incomplete penetrance suggests the existence of modifier genes. Calmodulin (CaM) could be of importance given the key role of Ca(2+) for cardiac contractile function and growth. Any variant that affects CaM expression and/or function may impact on FHC clinical expression. METHODS AND RESULTS: We screened the promoter region of human calmodulin III gene (CALM3) and identified a new -34T>A polymorphism with a T-allele frequency of 0.70. The distribution of CALM3 genotypes differed in 180 unrelated FHC patients carrying a known FHC mutation compared with 134 controls, with higher TT-genotype frequency (0.73 vs. 0.51) and lower frequencies of AT- (0.24 vs. 0.37) and AA genotypes (0.03 vs. 0.11; P = 0.0005). To study whether the -34T>A polymorphism could play a modifier role, patients' relatives including both affected and healthy carriers were added. Affected carriers had a 0.56 times higher odds of carrying a T allele than healthy carriers (P = 0.053). We then investigated whether the -34T>A polymorphism affects the promoter activity using luciferase reporter vectors containing either CALM3-T or CALM3-A promoters. The activity of CALM3-T was lower than CALM3-A in HEK293 cells (1.00 +/- 0.19 vs. 2.31 +/- 0.13, P = 0.00001) and in cardiomyocytes (0.96 +/- 0.10 vs. 1.33 +/- 0.08, P = 0.00727). CONCLUSION: These data suggest that the -34T>A CALM3 polymorphism is a modifier gene for FHC, potentially by affecting expression level of CALM3 and therefore Ca(2+)-handling and development of hypertrophy.

  • 18.
    Gennebäck, Nina
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hellman, Urban
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Malm, Linus
    Institutionen för skoglig genetik och växtfysiologi, Sveriges lantbruks universitet.
    Larsson, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Rongquist, Gunnar
    Institutionen för medicinska vetenskaper, Klinisk kemi.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mörner, Stellan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Characterisation of exosomes derived from cultured cardiomyocytes treated with different growth factorsArticle in journal (Refereed)
  • 19.
    Gennebäck, Nina
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Hellman, Urban
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Malm, Linus
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Larsson, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Ronquist, Gunnar
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Mörner, Stellan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Growth factor stimulation of cardiomyocytes induces changes in the transcriptional contents of secreted exosomes2013In: Journal of Extracellular Vesicles, ISSN 2001-3078, E-ISSN 2001-3078, Vol. 2Article in journal (Refereed)
    Abstract [en]

    Exosomes are nano-sized extracellular vesicles, released from various cells, which can stimulate or repress responses in targets cells. We recently reported that cultured cardiomyocytes are able to release exosomes and that they, in turn, are involved in facilitating events in target cells by alteration of gene expression. We investigated whether external stimuli of the cardiomyocyte might influence the transcriptional content of the released exosomes. Exosomes were isolated from media collected from cultured cardiomyocytes (HL-1) with or without growth factor treatment (TGF-β2 and PDGF-BB), with a series of differential centrifugations, including preparative ultracentrifugation and separation with a sucrose gradient. The exosomes were characterized with dynamic light scattering (DLS), electron microscopy (EM) and Western blot and analyzed with Illumina whole genome microarray gene expression. The exosomes were rounded in shape and had an average size of 50-90 nm in diameter with no difference between treatment groups. Analysis of the mRNA content in repeated experiments conclusively revealed 505 transcripts in the control group, 562 in the TGF-β2-treated group and 300 in the PDGF-BB-treated group. Common transcripts (217) were found in all 3 groups. We show that the mode of stimulation of parental cells affects the characteristics of exosomes released. Hence, there is a difference in mRNA content between exosomes derived from cultured cardiomyocytes stimulated, or not stimulated, with growth factors. We also conclude that all exosomes contain a basic package consisting of ribosomal transcripts and mRNAs coding for proteins with functions within the energy supply system.

  • 20.
    Gennebäck, Nina
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Malm, Linus
    Institutionen för skoglig genetik och växtfysiologi, Sveriges lantbruks universitet.
    Hellman, Urban
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mörner, Stellan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    OPLS-DA of myocardial gene expression in the progression of cardiac hypertrophy in aorta ligated ratArticle in journal (Refereed)
  • 21.
    Gennebäck, Nina
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Malm, Linus
    Hellman, Urban
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Mörner, Stellan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Using OPLS-DA to find new hypotheses in vast amounts of gene expression data - Studying the progression of cardiac hypertrophy in the heart of aorta ligated rat2013In: Gene, ISSN 0378-1119, E-ISSN 1879-0038, Vol. 522, no 1, p. 27-36Article in journal (Refereed)
    Abstract [en]

    One of the great problems facing science today lies in data mining of the vast amount of data. In this study we explore a new way of using orthogonal partial least squares-discrimination analysis (OPLS-DA) to analyze multidimensional data. Myocardial tissues from aorta ligated and control rats (sacrificed at the acute, the adaptive and the stable phases of hypertrophy) were analyzed with whole genome microarray and OPLS-DA. Five functional gene transcript groups were found to show interesting clusters associated with the aorta ligated or the control animals. Clustering of "ECM and adhesion molecules" confirmed previous results found with traditional statistics. The clustering of "Fatty acid metabolism", "Glucose metabolism", "Mitochondria" and "Atherosclerosis" which are new results is hard to interpret, thereby being possible subject to new hypothesis formation. We propose that OPLS-DA is very useful in finding new results not found with traditional statistics, thereby presenting an easy way of creating new hypotheses.

  • 22.
    Gennebäck, Nina
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Wikström, Gerhard
    Institutionen för Medicinska Vetenskaper, Kardiologi, Uppsala univerisitet.
    Hellman, Urban
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Samuel, Jane-Lise
    INSERM U 942, Hôpital Lariboisière, Paris, France.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Mörner, Stellam
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Transcriptional regulation of cardiac genes balance pro and anti hypertrophic mechanisms in hypertrophic cardiomyopathy2012In: Cardiogenetics, ISSN 2035-8148, Vol. 2, no 1Article in journal (Refereed)
    Abstract [en]

    Background: Hypertrophic cardiomyopathy (HCM) is characterised by unexplained left ventricular hypertrophy. HCM is often hereditary, but the knowledge about the mechanisms leading from mutation to phenotype is incomplete. The transcriptional expression patterns in the myocardium of HCM patients may contribute to the understanding of the mechanisms that drive and stabilize the hypertrophy.

    Design and Methods: Cardiac myectomies/biopsies from 8 patients with hypertrophic obstructive cardiomyopathy (HOCM) and 5 controls were studied with whole genome Illumina microarray gene expression (detecting 18 189 mRNA).

    Results: When comparing HOCM myocardium to controls, there was significant transcriptional down-regulation of the MYH6, EGR1, APOB and FOS genes, and significant transcriptional up-regulation of the ACE2, JAK2, NPPA (ANP), APOA1 and HDAC5genes. 

    Conclusion: The transcriptional regulation revealed both pro and anti hypertrophic mechanisms. The pro hypertrophic response was explained by the transcriptional down-regulation of MYH6, indicating that the switch to the fetal gene program is maintained, and the transcriptional up-regulation of JAK2 in JAK-STAT pathway. The anti hypertrophic response was seen as a transcriptional down-regulation of the immediate early genes (IEGs), FOS and EGR1, and a transcriptional up-regulation of ACE2 and HDAC5. This can be interpreted as a transcriptional endogenous protection system in the heart of the HOCM patients, neither growing nor suppressing the already hypertrophic myocardium.

  • 23. Glader, C A
    et al.
    Birgander, L S
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Ildgruben, H P
    Saikku, P
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Dahlén, G H
    Lipoprotein(a), Chlamydia pneumoniae, leptin and tissue plasminogen activator as risk markers for valvular aortic stenosis.2003In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 24, no 2, p. 198-208Article in journal (Refereed)
    Abstract [en]

    AIMS: The aim of the present study was to identify risk markers for the development of valvular aortic stenosis (AS). Lipoprotein(a) (Lp(a)) and Chlamydia pneumoniae IgG antibody titres in plasma and in circulating immune complexes as well as leptin and tissue plasminogen activator (t-PA) in plasma were studied.

    METHODS AND RESULTS: One hundred and one patients (41 women and 60 men, mean age 71+/-8 years) with significant AS and 101 age- and sex-matched controls were included in this study. All patients underwent aortic valve replacement at the University Hospital in Umeå, Sweden. The controls had no symptoms of cardiovascular disease and they were examined echocardiographically. An Lp(a) level >or=480 mg x l(-1), a C. pneumoniae-specific IgG titre >or=1/128, a high leptin level and a high t-PA mass concentration in plasma were identified as risk markers for AS. A strong synergism between Lp(a) and C. pneumoniae IgG antibodies in circulating immune complexes was found.

    CONCLUSION: Our data indicate that a chronic C. pneumoniae infection and a high plasma Lp(a) level might influence and aggravate aortic heart valve sclerosis via the formation of circulating immune complexes. The present study also strongly suggests an association between high plasma leptin, t-PA mass concentration and AS.

  • 24. Gustafsson, Ida
    et al.
    Malmberg, Klas
    Rydén, Lars
    Wedel, Hans
    Birkeland, Kåre
    Bootsma, Aart
    Dickstein, Kenneth
    Efendic, Suad
    Fisher, Miles
    Hamsten, Anders
    Herlitz, Johan
    Hildebrandt, Per Rossen
    MacLeod, Kenneth
    Laakso, Markku
    Torp-Pedersen, Christian T
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    [Metabolic control by means of insulin in patients with type 2 diabetes and acute myocardial infarction (DIGAMI 2): effects on mortality and morbidity--secondary publication]2006In: Ugeskr Laeger, ISSN 1603-6824, Vol. 168, no 6, p. 581-584Article in journal (Refereed)
  • 25.
    Gustafsson, Ulf
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Larsson, M
    School of Technology and Health, Royal Institute of Technology, Stockholm, Sweden.
    Bjällmark, A
    School of Technology and Health, Royal Institute of Technology, Stockholm, Sweden.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Aroch, Roman
    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.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    The effect of acute myocardial ischemia on the rotation axis of the left ventricleManuscript (preprint) (Other academic)
    Abstract [en]

    Introduction: We have developed a method to assess the axis around which the left ventricle (LV) rotates. The aim was to assess the effect of acute regional ischemia on the otation axis.

    Method: Mid‐LAD occlusion was induced in six anesthetised pigs and echocardiographic images were recorded at baseline and after LAD occlusion. The rotation axis was calculated at three different levels of the LV throughout the cardiac cycle. Results: The direction of the rotation axis was significantly changed (p<0.01) after LAD occlusion, being directed towards the ischemic area. AV‐plane displacement was significantly reduced (p<0.05) during ischemia. No significant difference in twist or otation amplitudes was found.

    Conclusion: This new method of assessing rotational function seems as sensitive as AV‐plane displacement and superior to traditional rotation and twist parameters in detecting dysfunction in acute ischemic myocardium. The rotation axis method has the advantage of potentially identifying areas with dysfunction.

  • 26.
    Gustafsson, Ulf
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Larsson, M
    School of Technology and Health, Royal Institute of Technology, Stockholm, Sweden.
    Bjällmark, A
    School of Technology and Health, Royal Institute of Technology, Stockholm, Sweden.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Brodin, LA
    School of Technology and Health, Royal Institute of Technology, Stockholm, Sweden.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    The rotation axis of the left ventricle: a new concept derived from ultrasound data in healthy individualsManuscript (preprint) (Other academic)
    Abstract [en]

    Introduction: The axis around which the left ventricle (LV) rotates has never previously been described. The aim was to develop a method to calculate the spatial motion of the rotation axis throughout the cardiac cycle.

    Method: By constructing a model of the LV, based on dimensions and rotation values at the basal, mid ventricular and apical levels, a rotation axis could be calculated at each level in 39 healthy subjects. The transition plane, defined as the level without rotation, where basal and apical rotation meet was also calculated.

    Results: The rotation axis was not congruent to the longitudinal axis of the LV at any time point. A significant and specific mean direction for each of the rotation axes for the majority of the tested time points displayed a physiological pattern.

    Conclusion: This new method introduces a new concept in cardiac function and provides further insight into the complexity of LV mechanics.

  • 27.
    Gustafsson, Ulf
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mörner, Stellan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Assessment of regional rotation patterns improves the understanding of the systolic and diastolic left ventricular function: an echocardiographic speckle-tracking study in healthy individuals2009In: European Journal of Echocardiography, ISSN 1525-2167, E-ISSN 1532-2114, no 10, p. 56-61Article in journal (Refereed)
    Abstract [en]

    AIM To elucidate the complexity of left ventricular motion throughout the cardiac cycle, we studied regional rotation in detail. METHODS AND RESULTS: Regional rotation in six subdivisions of the circumference at three levels was studied by using speckle-tracking echocardiography in 40 healthy subjects. At the basal level the inferoseptal segments rotated significantly more clockwise during systole than the opposing anterolateral segments. At the papillary level the inferoseptal segments differed significantly from the anterolateral segments, where the inferoseptal segments rotated clockwise and the anterolateral segments rotated counter-clockwise. The apical level showed significant difference in regional rotation only at aortic valve opening. In early systole, untwist before the main systolic twist was seen at the basal and apical levels; however, the duration of the basal untwist was much longer than that of the apical. The diastolic phases of rotation at the basal and apical levels matched the different filling phases. CONCLUSION: Large regional differences in rotation are present at the basal and papillary levels in healthy subjects. The diastolic untwist matches the phases of both the E-wave and A-wave and seems to be related with intraventricular pressure differences, indicating that untwist plays an important role in the filling of the ventricle.

  • 28.
    Gustafsson, Ulf
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Apical circumferential motion of the right and the left ventricles in healthy subjects described with speckle tracking2008In: Journal of the American Society of Echocardiography, ISSN 0894-7317, E-ISSN 1097-6795, Vol. 21, no 12, p. 1326-1330Article in journal (Refereed)
    Abstract [en]

    Background

    The aim of this study was to determine whether right ventricular (RV) apical rotation could be of importance in RV function and compare this with left ventricular (LV) apical rotation.

    Methods

    Short-axis images at the apical level of both ventricles were simultaneously recorded in 14 healthy subjects (mean age, 62 ± 11 years).

    Results

    There was a significant difference in mean rotation between the two ventricles in the time interval between 50% of ejection and aortic valve closure (P < .05). At aortic valve closure, LV rotation was 10.9 ± 4.8° counterclockwise, and RV rotation was 1.1 ± 5.8° clockwise. The anterior and inferior parts of the right ventricle rotated in opposite directions toward the septum. The septal segments of both ventricles rotated inferiorly, thus likely reducing interventricular stress.

    Conclusion

    This study showed clear differences in apical rotation between the two ventricles. Whereas the left ventricle displayed uniform rotation, the right ventricle showed heterogeneous rotation, resulting overall in almost no rotation but in a “tightening belt” motion.

  • 29. Haas, Jan
    et al.
    Frese, Karen S
    Peil, Barbara
    Kloos, Wanda
    Keller, Andreas
    Nietsch, Rouven
    Feng, Zhu
    Müller, Sabine
    Kayvanpour, Elham
    Vogel, Britta
    Sedaghat-Hamedani, Farbod
    Lim, Wei-Keat
    Zhao, Xiaohong
    Fradkin, Dmitriy
    Köhler, Doreen
    Fischer, Simon
    Franke, Jennifer
    Marquart, Sabine
    Barb, Ioana
    Li, Daniel Tian
    Amr, Ali
    Ehlermann, Philipp
    Mereles, Derliz
    Weis, Tanja
    Hassel, Sarah
    Kremer, Andreas
    King, Vanessa
    Wirsz, Emil
    Isnard, Richard
    Komajda, Michel
    Serio, Alessandra
    Grasso, Maurizia
    Syrris, Petros
    Wicks, Eleanor
    Plagnol, Vincent
    Lopes, Luis
    Gadgaard, Tenna
    Eiskjær, Hans
    Jørgensen, Mads
    Garcia-Giustiniani, Diego
    Ortiz-Genga, Martin
    Crespo-Leiro, Maria G
    Deprez, Rondal H Lekanne Dit
    Christiaans, Imke
    van Rijsingen, Ingrid A
    Wilde, Arthur A.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Bolognesi, Martino
    Bellazzi, Riccardo
    Mörner, Stellan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Bermejo, Justo Lorenzo
    Monserrat, Lorenzo
    Villard, Eric
    Mogensen, Jens
    Pinto, Yigal M
    Charron, Philippe
    Elliott, Perry
    Arbustini, Eloisa
    Katus, Hugo A
    Meder, Benjamin
    Atlas of the clinical genetics of human dilated cardiomyopathy2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no 18, p. 1123-U43Article in journal (Refereed)
    Abstract [en]

    Aim: We were able to show that targeted Next-Generation Sequencing is well suited to be applied in clinical routine diagnostics, substantiating the ongoing paradigm shift from low- to high-throughput genomics in medicine. By means of our atlas of the genetics of human DCM, we aspire to soon be able to apply our findings to the individual patient with cardiomyopathy in daily clinical practice. Numerous genes are known to cause dilated cardiomyopathy (DCM). However, until now technological limitations have hindered elucidation of the contribution of all clinically relevant disease genes to DCM phenotypes in larger cohorts. We now utilized next-generation sequencing to overcome these limitations and screened all DCM disease genes in a large cohort. Methods and results: In this multi-centre, multi-national study, we have enrolled 639 patients with sporadic or familial DCM. To all samples, we applied a standardized protocol for ultra-high coverage next-generation sequencing of 84 genes, leading to 99.1% coverage of the target region with at least 50-fold and a mean read depth of 2415. In this well characterized cohort, we find the highest number of known cardiomyopathy mutations in plakophilin-2, myosin-binding protein C-3, and desmoplakin. When we include yet unknown but predicted disease variants, we find titin, plakophilin-2, myosin-binding protein-C 3, desmoplakin, ryanodine receptor 2, desmocollin-2, desmoglein-2, and SCN5A variants among the most commonly mutated genes. The overlap between DCM, hypertrophic cardiomyopathy (HCM), and channelopathy causing mutations is considerably high. Of note, we find that >38% of patients have compound or combined mutations and 12.8% have three or even more mutations. When comparing patients recruited in the eight participating European countries we find remarkably little differences in mutation frequencies and affected genes. Conclusion: This is to our knowledge, the first study that comprehensively investigated the genetics of DCM in a large-scale cohort and across a broad gene panel of the known DCM genes. Our results underline the high analytical quality and feasibility of Next-Generation Sequencing in clinical genetic diagnostics and provide a sound database of the genetic causes of DCM.

  • 30.
    Hagström, Linn
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Karp, Kjell
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Impact of age and sex on normal left heart structure and function2017In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 37, no 6, p. 759-766Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Accurate age- and sex-related normal reference values of ventricular structure and function are important to determine the level of dysfunction in patients. The aim of this study therefore was to document normal age range sex-related measurements of LV structural and functional measurements to serve such purpose.

    METHODS: We evaluated left ventricular structure and function in 293 healthy subjects between 20 and 90 years with equally distributed gender. Doppler echocardiography was used including measure of both systolic and diastolic functions.

    RESULTS: Due to systolic LV function, only long axis function correlated with age (r = 0·55, P<0·01) and the correlation was stronger in females. Concerning diastolic function, there was a strong age correlation in all parameters used (r = 0·40-0·74, P<0·001). Due to LV structural changes over age, females showed a larger reduction in end-diastolic volumes, but no or trivial difference in wall thickness after the age of 60 years.

    CONCLUSION: Age is associated with significant normal changes in left ventricular structure and function, which should be considered when deciding on normality. These changes are related to systemic arterial changes as well as body stature, thus reflecting overall body ageing process. Furthermore, normal cardiac ageing in females might partly explain the higher prevalence of heart failure with preserved ejection in females.

  • 31.
    Hellman, Urban
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Hellström, Martin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mörner, Stellan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Engström Laurent, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Aberg, Anna-Maja
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Oliviero, Patricia
    Samuel, Jane-Lise
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Parallel up-regulation of FGF-2 and hyaluronan during development of cardiac hypertrophy in rat2008In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 332, no 1, p. 49-56Article in journal (Refereed)
  • 32.
    Hellman, Urban
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Malm, Linus
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Ma, Li-Ping
    Larsson, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Mörner, Stellan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Fu, Michael
    Engström-Laurent, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Growth factor PDGF-BB stimulates cultured cardiomyocytes to synthesize the extracellular matrix component hyaluronan2010In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 5, no 12, p. e14393-Article in journal (Refereed)
    Abstract [en]

    Co-cultivation of cardiomyocytes and fibroblasts (80%/20%) increased HA concentration far more that can be explained by HA synthesis by the two cell types separately, revealing a crosstalk between cardiomyocytes and fibroblasts that induces HA synthesis. We conclude that dynamic changes of the myocardium, such as in cardiac hypertrophy, do not depend on the cardiomyocyte alone, but are achieved when both cardiomyocytes and fibroblasts are present.

  • 33.
    Hellman, Urban
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Malm, Linus
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Ma, Li-Ping
    Larsson, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Mörner, Stellan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Fu, Michael
    Engström-Laurent, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Hyaluronan is both a product and stimulator of cardiomyocytes: a study in cell cultures of cardiomyocytes and fibroblastsArticle in journal (Refereed)
  • 34.
    Hellman, Urban
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mörner, Stellan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Engström-Laurent, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Samuel, Jane-Lise
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Temporal correlation between transcriptional changes and increased synthesis of hyaluronan in experimental cardiac hypertrophy2010In: Genomics, ISSN 0888-7543, E-ISSN 1089-8646, Vol. 96, no 2, p. 73-81Article in journal (Refereed)
    Abstract [en]

    The role of hyaluronan in cardiac growth has become evident, previously shown by increased myocardial levels of hyaluronan in a rat model of cardiac hypertrophy. To further investigate the role of hyaluronan and regulation of its synthesis in cardiac hypertrophy, quantitative measurements of myocardial hyaluronan concentration was correlated to gene transcription in hypertrophic cardiac tissue. Factor analysis was used to study this correlation over time. A subset of differentially expressed genes was identified with a transcriptional regulation correlating to the increased synthesis of hyaluronan, suggesting a common regulatory pathway. Four transcription factors, Myc, Fos, Junb and Egr1, were also up-regulated. Furthermore, the Ace gene was up-regulated, representing increase of angiotensin II, an inducer of these transcription factors and fetal genes in cardiac hypertrophy. This demonstrates a coordinated synthesis of hyaluronan and pro-hypertrophic gene expression, regulated by immediate early genes, with angiotensin II as a possible mediator.

  • 35.
    Hellman, Urban
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ronquist, Gunnar
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Cardiomyocyte microvesicles convey bioinformatic messages to target cellsArticle in journal (Refereed)
  • 36.
    Henein, Mark
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Calcuttea, Avin
    Kaba, Agnes
    Maras, Dejan
    Stanton, Marilyn
    Kelly, Mary
    Kazzam, El-Sadig
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Atrial fibrillation (mechanistic view point)2009In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 134, no 2, p. 270-272Article in journal (Refereed)
  • 37.
    Henein, Mark
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Lam, Yat-Yin
    Waldenstöm, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Atrial interaction in the form of 'cross talk' in patients with ventricular outflow tract obstruction.2011In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 17, no 147(3), p. 388-392Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The Bernheim 'a' wave in the jugular venous pulse of patients with left ventricular hypertrophy has been shown to reflect accentuated right atrial activity. OBJECTIVE: To study possible atrial interaction in patients with right and left ventricular outflow tract obstruction due to significant pulmonary (PS) and aortic valvular stenosis (AS) respectively. METHODS: We studied 41 PS patients (age 36+/-10 year) and 41 AS patients (age 35+/-12 year) and their results were compared with those of 27 controls (age 30+/-7 year). RV and LV filling were recorded by conventional PW Doppler. Biventricular segmental function was studied using the PW tissue Doppler imaging (TDI) and M-mode techniques. RESULTS: The 2 patient groups had similar degree of ventricular outflow tract obstruction. Long axis function was impaired while global systolic function was preserved in the pressure-overloaded ventricle. Patients had higher peak late filling (A wave) and TDI late diastolic (Aa) velocities recorded in the disease-free ventricles despite having similar peak early filling velocities (E wave), E wave deceleration time and E/Ea ratios were not different from controls (p>0.05 for all). Such accentuation of atrial activity (A wave) was moderately correlated with the degree of contralateral ventricular outflow tract obstruction (p<0.001 for both). CONCLUSIONS: Long axis function is more sensitive than global function in revealing myocardial dysfunction in the pressure-overloaded ventricles. The increased contralateral atrial systolic activity suggests an evidence for atrial interaction in the form of 'cross talk'.

  • 38.
    Henein, Michael
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Mörner, Stellan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology. Umeå Heart Center.
    The normal impact of age and gender on right heart structure and function2014In: Echocardiography, ISSN 0742-2822, E-ISSN 1540-8175, Vol. 31, no 1, p. 5-11Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: As the proportion of elderly population increases rapidly, it might be difficult to differentiate physiological changes in cardiac function due to age from the pathophysiological ones. In addition, cardiac function variations with gender are well established. The right ventricular (RV) plays an important role in the overall cardiac function, but reference values varying with age and gender are lacking.

    MATERIAL AND METHODS: We studied 255 healthy individuals from a general population register, mean age of 58 ± 19 (range 22-89) years, 125 were females. We used 2D and M-mode echocardiography to measure RV inflow tract (RVIT) and RV outflow tract (RVOT) dimensions and fractional shortening (fs). Spectral Doppler echocardiography was also used.

    RESULTS: We found a modest decrease in RVIT dimensions (P < 0.05), but increase in RVOT dimensions with advancing age (P < 0.05). A small decrease in RVOT fs with age was also found (P < 0.05). Estimated pulmonary pressures and pulmonary vascular resistance increased (P < 0.001) as did RVOT wall thickness (P < 0.001), but RV diastolic function was not altered (P < 0.001) with age. Despite correction for the BSA, males showed larger RVIT dimensions (P < 0.001 for both), but RVOT end-diastolic dimension was larger in females (P < 0.05). RVIT and RVOT fractional shortening were increased in females (P < 0.01 for both).

    CONCLUSION: In a cohort of normal individuals, age has significant impact on RV structure and function, inlet area falls and outflow tract dimensions increase and fractional shortening also increase in females. In addition, RVOT wall thickness significantly increases and Doppler markers of pulmonary vascular resistance show a consistent rise. The age-related changes should carefully be considered when commenting on normality and when using absolute values.

  • 39.
    Johansson, Bengt
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Mörner, Stellan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Myocardial capillary supply is limited in hypertrophic cardiomyopathy: a morphological analysis2008In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 126, no 2, p. 252-257Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To clarify the morphological basis of the limited coronary reserve in hypertrophic cardiomyopathy (HCM). BACKGROUND: Some of the symptoms in Hypertrophic cardiomyopathy (HCM), such as chest pain, dyspnea and arrhythmia, may be explained by myocardial ischemia. Many patients with HCM are known to exhibit these symptoms in the absence of atherosclerosis in the major coronary vessels. Decreased myocardial perfusion has been demonstrated in HCM, however, little is known about the myocardial capillary morphology in this disease. METHODS: Using immunohistochemistry and morphometry, we analysed capillaries and cardiomyocytes in myectomy specimens from 5 patients with HCM with moderate hypertrophy and left ventricular outflow tract obstruction and in 5 control hearts. RESULTS: The number of capillaries per cardiomyocyte (p<0.009) and number of capillaries per cardiomyocyte area unit, reflecting cardiomyocyte mass (p=0.009), were lower in individuals with HCM, i.e. indicating loss of capillaries. In HCM, the capillary density was 33% lower (p<0.05). CONCLUSIONS: Our morphologic findings show that the capillary supply, and thus the coronary reserve, is impaired in HCM with moderate hypertrophy and left ventricular outflow tract obstruction. These data may partly explain the limitation of myocardial perfusion in HCM, which is associated with worse prognosis. Furthermore, we present evidence of actual loss of myocardial capillaries in HCM and a defective capillary growth.

  • 40.
    Kavianipour, Mohammad
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Wikström, Gerhard
    Ronquist, Gunnar
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Validity of elevated interstitial levels of taurine as a predictor of myocardial ischemic injury.2004In: Amino Acids, ISSN 0939-4451, Vol. 27, no 1, p. 107-11Article in journal (Refereed)
  • 41. Kayvanpour, E.
    et al.
    Haas, J.
    Sedaghat-Hamedani, F.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Monserrat, L.
    Charron, P. H.
    Elliott, P.
    Arbustini, E.
    Meder, B.
    Katus, H. A.
    Genetic cardiomyopathy overlaps can modify phenotypic features in dilated cardiomyopathy patients - a comprehensive next-generation sequencing (NGS) study2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, p. 953-954Article in journal (Other academic)
  • 42.
    Kreiner, Marcelo
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Alvarez, R
    Michelis, V
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Isberg, Annika
    Umeå University, Faculty of Medicine, Department of Odontology.
    Craniofacial pain can be the sole prodromal symptom of an acute myocardial infarction: an interdisciplinary studyManuscript (preprint) (Other academic)
  • 43.
    Kreiner, Marcelo
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Alvarez, R
    Michelis, V
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Muñiz, R
    Isberg, Annika
    Umeå University, Faculty of Medicine, Department of Odontology.
    Craniofacial pain of cardiac origin is associated with inferior wall ischemiaManuscript (preprint) (Other academic)
  • 44.
    Kreiner, Marcelo
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Oral and Maxillofacial Radiology.
    Alvarez, Ramón
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Michelis, Virginia
    Muñiz, Rosana
    Isberg, Annika
    Umeå University, Faculty of Medicine, Department of Odontology, Oral and Maxillofacial Radiology.
    Craniofacial pain of cardiac origin is associated with inferior wall ischemia2014In: Journal of oral & facial pain and headache, ISSN 2333-0384, Vol. 28, no 4, p. 317-321Article in journal (Refereed)
    Abstract [en]

    Aims: To investigate possible associations between the presence of craniofacial pain of cardiac origin and the location of cardiac ischemia and conventional risk factors. Methods: A total of 326 consecutive patients with confirmed myocardial ischemia (192 males, 134 females, mean age 64 years) were studied. Demographic details, health history, risk factors, prodromal symptoms, electrocardiogram (ECG) findings, and pain characteristics during the ischemic episode were assessed. The location of the ischemia according to the ECG findings was categorized as anterior, inferior, or lateral. Univariate chi-square analyses and a multivariate logistic regression model were used for data analysis. Two age subgroups (< 65 and > 65) were established when controlling for covariates. Results: Craniofacial pain of cardiac origin was significantly associated with an inferior localization of cardiac ischemia (P < .001) and was more frequently reported in diabetic patients (P = .014). Thirty-eight patients (12%) did not experience chest pain during the myocardial ischemia. Nine patients (3%) experienced a prodromal angina episode without chest pain. Conclusion: The occurrence of craniofacial pain during myocardial ischemia, with or without an acute myocardial infarction, was associated with ischemia within the inferior wall. This result suggests the involvement of the vagal afferent system in the mechanisms of craniofacial pain of cardiac origin.

  • 45.
    Lindqvist, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Caidahl, Kenneth
    Neuman-Andersen, Grete
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Ozolins, Cecilia
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Kazzam, Elsadig
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Disturbed right ventricular diastolic function in patients with systemic sclerosis: a Doppler tissue imaging study.2005In: Chest, ISSN 0012-3692, E-ISSN 1931-3543, Vol. 128, no 2, p. 755-763Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Cardiopulmonary involvement in patients with systemic sclerosis (SSc) carries a poor prognosis, mainly due to pulmonary hypertension and right-heart failure. To date, right ventricular (RV) involvement has not been studied in detail. We therefore assessed RV function in patients with SSc and related the findings to the clinical features of the disease. METHOD: Twenty-six consecutive patients (21 women) with SSc (mean age, 56 +/- 15 years [+/- SD]) and 25 healthy, age-matched control subjects (21 women) were studied. Doppler echocardiography including Doppler tissue imaging was used to evaluate cardiac function. Pulmonary function was also studied. RESULTS: Compared with control subjects, RV free wall thickness (5.8 +/- 1.7 mm vs 3.7 +/- 1.1 mm, p < 0.001) and right atrial (RA) systolic area (15.9 +/- 3.7 cm2 vs 13.0 +/- 2.3 cm2, p < 0.01) were increased in patients with SSc, while the global early diastolic/atrial component velocity ratio was reduced (1.2 +/- 0.4 vs 1.7 +/- 0.6, p < 0.01). The global isovolumic relaxation time (IVRT) [64 +/- 23 ms vs 39 +/- 13 ms, p < 0.001] and regional IVRT (83 +/- 40 ms vs 46 +/- 24 ms, p < 0.001) were prolonged in patients vs control subjects, whereas the RV global filling time was reduced (454 +/- 122 ms vs 548 +/- 104 ms, p < 0.01). RV systolic function and pulmonary pressures at rest were similar in the two groups, but the pulmonary artery acceleration time was reduced (119 +/- 34 ms vs 141 +/- 29 ms, p < 0.05) in patients compared to control subjects. Left ventricular function did not differ between the two groups. CONCLUSION: Patients with SSc exhibit altered RV diastolic function together with an increase in RV wall thickness and RA area. These findings appear to be early markers of RV disturbance, probably in response to intermittent pulmonary arterial hypertension.

  • 46.
    Lindqvist, Per
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Clinical Physiology.
    Mörner, Stellan
    Karp, Kjell
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Clinical Physiology.
    Waldenström, Anders
    New aspects of septal function by using 1-dimensional strain and strain rate imaging.2006In: Journal of the American Society of Echocardiography, ISSN 0894-7317, E-ISSN 1097-6795, Vol. 19, no 11, p. 1345-1349Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The interventricular septum is a complex structure, both anatomically and functionally, which limits the use of Doppler tissue imaging in the assessment of radial septal function. In this study we investigated whether strain (epsilon) and epsilon rate (SR) imaging can improve the measurement of the septal function. METHODS: Thirty healthy participants (18 women; age 60 +/- 11 years, range 42-72) were randomly selected from the population. Systolic epsilon and SR measurements were made of the radial motion from right endocardial layer (RE), left endocardial layer (LE), and middle layer of septum. Furthermore, we also compared RE and longitudinal right ventricular free wall and left ventricular longitudinal and LE septal motion. RESULTS: In both the endocardial sampling sites, LE and RE, we found negative radial epsilon (myocardial shortening), -20.1 +/- 11.5% for RE and -25.0 +/- 14.1% for LE during systole. However, in the middle layer we found a positive radial epsilon (myocardial lengthening), +11.5 +/- 13.2%, significantly different from the two endocardial layers (P < .001 for both). SR was negative in the two endocardial layers and significantly higher for LE, (-2.9 +/- 1.8 1/s) than for RE (-1.2 +/- 1.8 1/s, P < .001) and positive for the middle layer (+1.1 +/- 1.0 1/s), significantly different in comparison with the two endocardial layers (P < .001). Finally, there was a higher longitudinal epsilon compared with radial endocardial epsilon for right ventricle (-26.5 +/- 11.5 vs -20.1 +/- 11.5, P < .05) whereas there was significantly higher left ventricular radial epsilon and SR compared with the longitudinal epsilon and SR (-25.0 +/- 14.1 vs -16.8 +/- 9.5, P < .05; and -2.9 +/- 1.8 vs -1.1 +/- 0.4, P < .001). CONCLUSION: Systolic epsilon and SR imaging indicate differences in the radial deformation in different layers of the interventricular septum, which might be explained by the complexity of the septal fiber arrays and function. It might also explain why using Doppler tissue imaging technique is limited in assessing radial myocardial septal velocities. Furthermore, these results suggest that longitudinal shortening dominates in the right ventricle whereas the radial shortening dominates in the left ventricle.

  • 47.
    Lindqvist, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Olofsson, Bert-Ove
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Backman, Christer
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Pulsed tissue Doppler and strain imaging discloses early signs of infiltrative cardiac disease: a study on patients with familial amyloidotic polyneuropathy.2006In: Eur J Echocardiogr, Vol. 7, no 1, p. 22-30Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Familial amyloidotic polyneuropathy (FAP) is a hereditary systemic amyloidosis with cardiac involvement. As early identification of the cardiac involvement is of major clinical interest we performed this study to test the hypothesis that tissue Doppler imaging (TDI) and strain imaging (SI) might disclose cardiac involvement in patients with early stages of FAP. METHODS: Twenty-two patients with FAP and 36 healthy controls were studied. Standard M-mode and Doppler echocardiography were performed. TDI and SI were used to assess the regional longitudinal left ventricular (LV) lateral and septal and right ventricular (RV) wall functions. All time intervals were corrected for heart rate by dividing with R-R interval and presented as percentage. RESULTS: We found that patients in comparison with controls had increased LV and RV wall thickness and by using TDI a prolonged isovolumic relaxation time (IVRt) at the septal segment (15.0+/-7.0 vs 10.7+/-4.1%, p<0.05) and prolonged isovolumic contraction time (IVCt) at LV lateral (12.8+/-4.3 vs 10.1+/-3.3%, p<0.05), septal (12.5+/-3.5 vs 8.9+/-1.9%, p<0.001) and RV free wall segments (12.0+/-3.6 vs 8.3+/-2.1%, p<0.001). Strain was reduced at LV lateral basal segment (-4.6+/-14.0 vs -20.2+9.1, p<0.001), RV free wall mid segment (-16.2+/-12.8 vs -29.4+/-15.2) as well as both septal segments (-4.1+/-11.7 vs -16.2+/-9.0%, p<0.001, -8.8+/-11.5 vs -19.4+/-8.4%, p<0.001 for septal basal and mid-segment). Even in the absence of septal hypertrophy the septal strain was reduced and the regional IVCt was prolonged. CONCLUSIONS: This is the first clinical study using TDI and strain in patients with FAP showing functional abnormalities before any morphological echocardiographic abnormalities were present. Both the left and right heart functions are involved and the disease should therefore be regarded as biventricular.

  • 48.
    Lindqvist, Per
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    Henein, Michael
    Mörner, Stellan
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    Kazzam, Elsadig
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    Regional and global right ventricular function in healthy individuals aged 20-90 years: a pulsed Doppler tissue imaging study: Umeå General Population Heart Study.2005In: Echocardiography, Vol. 22, no 4, p. 305-314Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to describe regional and global right ventricular (RV) function in a wide age range of healthy subjects of both sexes. We studied 255 (125 females) healthy individuals randomly selected from the Umeå General Population Register, age 58 +/- 19 (range 22-89) years. RV function was studied using myocardial tissue Doppler imaging of the RV free wall. Isovolumic contraction (IVCv), systolic (Sv), early (Ev), and late (Av) diastolic velocities were measured. Furthermore, isovolumic periods and ejection time intervals were also measured. Conventional Doppler was used to study RV global filling properties. While systolic myocardial velocities were conserved over age, there was a decrease in myocardial E/A ratio with increasing age (r =-0.67, P < 0.001, for base) taken from the RV free wall. A similar age relation was found in RV global filling velocities with a reduced tricuspid E/A ratio (r =-0.57, P < 0.001). Furthermore, a significant correlation was found between global and regional E/A ratios at the basal (r = 0.58, P </= 0.001) and mid-segmental levels (r = 0.46, P </= 0.001). Systolic myocardial velocities behaved independent of age whereas regional as well as global E/A ratio were age-related. No relationship was found between regional isovolumic time intervals and age. Knowledge of these age-dependent relationships is fundamental when evaluating RV function in patients.

  • 49.
    Lindqvist, Per
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    Wikström, Gerhard
    Kazzam, Elsadig
    Right ventricular myocardial isovolumic relaxation time and pulmonary pressure.2006In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 26, no 1, p. 1-8Article in journal (Refereed)
    Abstract [en]

    AIMS: Non-invasive assessment of pulmonary artery systolic pressure (PASP) has several limitations. As previously described by Burstin, the right ventricular (RV) isovolumic relaxation time (IVRt) is sensitive to changes in PASP. We therefore compared RV myocardial IVRt, derived by Doppler tissue imaging (DTI), with simultaneously measured invasive PASP. METHODS AND RESULTS: Twenty-six consecutive patients (18 males, mean age 52 +/- 12 years, range 23-75) underwent a simultaneous Doppler echocardiography, including DTI, and cardiac catheterization examination for measurement of PASP and right atrial mean pressures. IVRt was measured using the myocardial velocities by pulsed DTI at both basal and mid cavity segments of the RV free wall. As diastolic time intervals are influenced by heart rate IVRt was corrected for heart rate (IVRt/RR%). A significant correlation was found between PASP and regional IVRt/RR% at both the basal (r = 0.42, P<0.05) and mid cavity segment (r = 0.71, P<0.001). Furthermore, when only patients with normal right atrial pressures (<7 mmHg) were taken into account, the correlation coefficient improved at both basal and mid cavity segments (r = 0.74, P<0.05 and r = 0.83, P<0.01). CONCLUSION: Pulsed Doppler-derived IVRt correlates well with PASP. The use of pulsed DTI for measurement of IVRt is simple, reproducible and easy to obtain. We propose this method as an additional non-invasive tool in the assessment of PASP.

  • 50.
    Lindqvist, Per
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    Wikström, Gerhard
    Kazzam, Elsadig
    The use of isovolumic contraction velocity to determine right ventricular state of contractility and filling pressures A pulsed Doppler tissue imaging study.2005In: European Journal of Echocardiography, ISSN 1525-2167, E-ISSN 1532-2114, Eur J Echocardiogr, Vol. 6, no 4, p. 264-270Article in journal (Refereed)
    Abstract [en]

    AIMS: Echocardiographic techniques have not so far been able to provide a good estimation of myocardial contractility in humans. Myocardial motion during the isovolumic contraction phase, measured by Doppler tissue imaging, has only recently in experimental models been shown to describe myocardial contractility. The aim of the present clinical study was to investigate the relationship between right ventricular isovolumic contraction velocity and right ventricular state of contractility. METHODS AND RESULTS: Doppler tissue imaging and cardiac catheterization were performed simultaneously in 26 consecutive patients with different cardiac diseases (18 males, mean age 52 +/- 12, range 23-75 years). Peak isovolumic contraction velocity was measured using Doppler tissue imaging at 2 levels of the right ventricular free wall. During cardiac catheterization, the first derivative of right ventricular pressure related to the pulmonary artery peak pressure (dP/dt/P(max)) was measured. Furthermore, right ventricular end diastolic pressure, right atrial mean pressure, pulmonary artery systolic pressure, and pulmonary artery resistance, were also measured. A significant relationship was found between isovolumic contraction velocity and dP/dt/P(max) (r = 0.59, p < 0.01). This relationship was strengthened after excluding patients with elevated right atrial pressures (r = 0.77, p < 0.001). Furthermore, a correlation was also found between basal and mid cavity isovolumic contraction velocity and right ventricular end diastolic pressure (r = -0.47, r = -0.49, p < 0.05) as well as right atrial mean pressure (r = -0.63, r = -0.55, p < 0.01). CONCLUSION: Isovolumic contraction velocity is a reproducible and easily obtainable non-invasive parameter which correlates with invasive measurements of right ventricular state of contractility and right ventricular filling pressures.

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