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In vivo effects of ...
In vivo effects of myocardial creatine depletion on left ventricular function, morphology, and energy metabolism--consequences in acute myocardial infarction
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- Lorentzon, Malin, 1976 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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- Råmunddal, Truls, 1973 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberg Laboratory,Institute of Medicine, Department of Molecular and Clinical Medicine
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- Bollano, Entela, 1970 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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- Soussi, Bassam, 1957 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences
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- Waagstein, Finn, 1938 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Omerovic, Elmir, 1968 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberg Laboratory,Institute of Medicine, Department of Molecular and Clinical Medicine
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(creator_code:org_t)
- 2007
- 2007
- English.
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In: Journal of cardiac failure. - 1532-8414. ; 13:3, s. 230-7
- Related links:
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https://gup.ub.gu.se...
Abstract
Subject headings
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- BACKGROUND: The failing heart is characterized by disturbed myocardial energy metabolism and creatine (Cr) depletion. The aims of this study were to in vivo evaluate the effects of Cr depletion on: a) left ventricular (LV) function and morphology during rest and stress, b) LV energy metabolism, c) catecholamine in LV and plasma content, and d) incidence of malignant ventricular arrhythmias (MVA) during acute myocardial infarction (MI). METHODS AND RESULTS: Male rats weighing approximately 200 g were used. Two groups were studied: the rats treated with Cr analogue beta-guanidinopropionic acid (BGP) (n = 25) and controls (n = 23). BGP (1 M) was administered by subcutaneously implanted osmotic minipumps over 4 weeks. The rats (BGP n = 9, control n = 12) were than examined with transthoracic echocardiography at basal and at stress conditions induced by transesophageal pacing. In vivo (31)P magnetic resonance spectroscopy (MRS) was used for evaluation of myocardial energy status (BGP n = 7, control n = 12). (31)P MRS, echocardiography and high-performance liquid chromatography analysis of myocardial Cr, total adenine nucleotides and catecholamines in myocardium and plasma were performed on noninfarcted hearts. Myocardial infarction was induced in a subgroup of animals (BGP n = 15, control n = 15) by ligation of the left coronary artery resulting in a large ( approximately 50%) anterolateral MI and acute HF. A computerized electrocardiogram tracing was obtained continuously before induction of MI and up to 60 minutes postinfarction. Qualitative and quantitative variables of ventricular arrhythmias were analyzed using arrhythmia score. Body weight (BW) was lower (P < .01), whereas LV/BW was higher (P < .01) in the BGP group. Total myocardial Cr pool was decreased for at least 50% (P < .01) compared with the controls. There was no difference in total nucleotide pool. Phosphocreatine/adenosine-3-phosphate ratio was lower in the BGP group (P < .01). LV systolic function was disturbed during rest and stress (P < .05). Similarly, LV dimensions were increased in the BGP group (P < .05). Induction of acute MI resulted in markedly increased incidence of MVA and higher mortality in the BGP group (P < .01). CONCLUSIONS: Myocardial Cr depletion results in functional and structural LV alterations associated with lower myocardial energy reserve. Intact myocardial Cr metabolism is important for normal LV function during basal and stress conditions. Acute MI in the setting of myocardial Cr depletion leads to excessive mortality from ventricular arrhythmias and progressive heart failure.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Keyword
- Animals
- Arrhythmia/diagnosis/etiology/metabolism
- Biological Markers/metabolism
- Catecholamines/metabolism
- Creatine/*metabolism
- Disease Models
- Animal
- Electrocardiography
- Energy Metabolism
- Magnetic Resonance Spectroscopy
- Male
- Myocardial Infarction/complications/diagnosis/*metabolism
- Myocardium/metabolism
- Rats
- Rats
- Sprague-Dawley
- Reference Values
- Ventricular Dysfunction
- Left/etiology/*metabolism/ultrasonography
Publication and Content Type
- ref (subject category)
- art (subject category)
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Lorentzon, Malin ...
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Råmunddal, Truls ...
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Bollano, Entela, ...
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Soussi, Bassam, ...
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Waagstein, Finn, ...
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Omerovic, Elmir, ...
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University of Gothenburg