| 1. |
- Gizurarson, Sigfus, et al.
(författare)
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358 Effects of complete heart block on myocardial function; morphology and energy metabolism in rat model
- 2007
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Ingår i: European Journal of Heart Failure Supplements. ; 6:Supplement 1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Severe sustained bradycardia may cause acute and possibly even chronic congestive heart failure (CHF). The aims of this study were: a) to set up a small-animal model of complete heart block (CHB) in rats, and b) to investigate acute and chronic effects of CHB on cardiac function, morphology and energy metabolism Methods: CHB was induced in 6 male Sprague-Dawley rats (∼ 250 g) by means of electrocautery applied to the region of AV node and were compared to controls (n=15). The rats were investigated 1, 3 and 12 weeks after induction of CHB with transthoracic ultrasound. After 12 weeks the animals were anesthetized and intubated. The chest was opened and right respectively left ventricular pressure curves were obtained. After the sacrifice, the hearts were freeze-clamped for analysis of myocardial creatine, adenine nucleotides, catecholamines and intracellular lipids. Results: The efficacy of operative procedure was 100%. The perioperative mortality rate was 20%. While heart rate was decreased by ∼ 50% (p < 0.01), stroke volume doubled (p < 0.01) in the CHB rats. Cardiac index remained unchanged. The rats with CHB grew normally and were in no apparent distress. Filling pressures in left and right ventricle were normal. The CHB rats developed cardiomegaly with biventricular dilatation and hypertrophy with markedly increased left ventricular mass (LV) (p < 0.01). There was no change in the myocardial content of creatine and adenine nucleotides. Conclusions: Rats with CHB are compensating for reduction in heart rate with dramatically increased stroke volume without hemodynamical signs of heart failure even after prolonged period of time. Markedly increased LV mass is probably due to volume overload but is not associated with metabolical derangement as seen in other forms of pathologic LV hypertrophy. This model may be useful to study the effects of severe bradycardia on myocardial structure, function, electrophysiology and metabolism as well as for different aspects of LV hypertrophy. Similarly, the model may be useful for studies of cell therapy for reparation of AV node.
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| 2. |
- Gizurarson, Sigfus, et al.
(författare)
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Effects of complete heart block on myocardial function, morphology, and energy metabolism in the rat.
- 2007
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Ingår i: Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology. - : Oxford University Press (OUP). - 1099-5129. ; 9:6, s. 411-6
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Tidskriftsartikel (refereegranskat)abstract
- Severe sustained bradycardia may cause acute and possibly chronic congestive heart failure (CHF). The aim of this study was to investigate acute and chronic effects of complete heart block (CHB) on cardiac function, morphology, and creatine (Cr) metabolism.
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| 3. |
- Lorentzon, Malin, 1976, et al.
(författare)
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In vivo effects of myocardial creatine depletion on left ventricular function, morphology, and energy metabolism--consequences in acute myocardial infarction
- 2007
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Ingår i: Journal of cardiac failure. - 1532-8414. ; 13:3, s. 230-7
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 4. |
- Omerovic, Elmir, 1968, et al.
(författare)
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Aqueous fish extract increases survival in the mouse model of cytostatic toxicity
- 2008
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Ingår i: Journal of Experimental & Clinical Cancer Research. - : Springer Science and Business Media LLC. - 1756-9966 .- 0392-9078. ; 4:27
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Tidskriftsartikel (refereegranskat)abstract
- Background: Treatment of cancer patients with anthracycline antibiotic doxorubicin (DOX) may be complicated by development of acute and chronic congestive heart failure (CHF), malignant arrhythmias and death. The aim of this study was to test whether an aqueous low molecular weight (LMW) extract from cod muscle decreases acute mortality in the mouse model of acute CHF caused by DOX. Methods: A LMW fraction (< 500 Da) of the aqueous phase of cod light muscle (AOX) was used for treatment of male BALB/c mice (similar to 25 g, n = 70). The animals were divided into four groups, DOX + AOX (n = 20), DOX + saline (NaCl) (n = 30), NaCl + AOX (n = 10) and NaCl only (n = 10). Echocardiography was performed in the separate subgroups (DOX treated n = 6 and controls n = 6) to verify the presence and the grade of acute CHF. The cod extract was delivered by subcutaneously implanted osmotic minipumps over the period of 2 weeks. High-dose injection of DOX was administered to randomly selected animals. The animals received single intraperitoneal injection of DOX (25 mg/kg) and were followed over two weeks for mortality. Results: Mortality rate was 68% lower (p < 0.05) in the mice treated with the extract. The analyses of cod extract have shown strong antioxidative effect in vitro. Conclusion: The aqueous LMW cod muscles extract decreases mortality in the mouse model of DOX induced acute CHF. This effect may be mediated by cardioprotection through antioxidative mechanisms.
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| 5. |
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| 6. |
- Omerovic, Elmir, 1968, et al.
(författare)
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Silent myocardial infarction in women with type II diabetes mellitus and microalbuminuria.
- 2008
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Ingår i: Therapeutics and clinical risk management. - 1178-203X. ; 4:4, s. 705-712
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The aim of this study was to investigate whether asymptomatic women with diabetes mellitus (DM) without previous history of ischemic heart disease (IHD) and normal electrocardiogram (ECG) have suffered silent myocardial infarction (MI). METHODS: The study population consisted of 64-years old women with DM and albuminuria (n = 15) and aged- and body mass index-matched controls (n = 16). The patients were selected after screening of 240 women with previously known or unknown DM. The individuals with previous history of IHD and ECG suggesting the presence of IHD were excluded. All subjects were investigated with magnetic resonance imaging (MRI). RESULTS: MRI investigation has revealed the presence of subendocardial MI in the two DM women (13%). No MI was detected in the control group. MR coronary angiography detected the presence of significant stenosis in the proximal segment of left anterior descending (LAD) coronary artery in one DM woman. This patient developed unstable angina 1 week after the MRI investigation. The conventional angiography has confirmed the presence of significant stenosis in LAD demanding invasive revascularization by percutaneous coronary angioplasty. No difference was found in indices of left ventricular (LV) systolic function while diastolic function was disturbed in the DM group. There was a tendency for increased LV mass in the DM group. No difference was found in the LV volumes. CONCLUSION: Clinically significant proportion of the women with DM and albuminuria without previous history of IHD have had silent MI. MRI screening of these high risk female patient is valuable diagnostic tool which may increase diagnostic accuracy and improve prognosis in DM patients with IHD.
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| 7. |
- Råmunddal, Truls, 1973, et al.
(författare)
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Antiarrhythmic effects of growth hormone--in vivo evidence from small-animal models of acute myocardial infarction and invasive electrophysiology.
- 2008
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Ingår i: Journal of electrocardiology. - : Elsevier BV. - 1532-8430 .- 0022-0736. ; 41:2, s. 144-51
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Tidskriftsartikel (refereegranskat)abstract
- A growing body of evidence suggests a possible role for growth hormone (GH) in the treatment of congestive heart failure (CHF) and myocardial infarction (MI). The aim of this study was to investigate in vivo the effects of GH treatment on incidence and severity of ventricular arrhythmias normal and MI rats.Male Sprague-Dawley rats weighing approximately 350 g were randomized into 3 groups. Growth hormone-treated rats (n = 6) received 6 mg/kg of human GH. The placebo group (n = 10) received 1 mL of saline. Amiodarone-treated rats (n = 10) were injected with 25 mg/kg and served as positive controls. All animals received a single intraperitoneal injection 6 hours before induction of MI. Myocardial infarction was induced by ligation of the left coronary artery, resulting in a large (approximately 40%) anterolateral MI. A computerized electrocardiographic tracing was obtained continuously before induction of MI and up to 1 hour postinfarction. Invasive hemodynamics including intraventricular and arterial pressure were registered for 60 minutes post-MI. Qualitative as well as quantitative variables of ventricular arrhythmias were analyzed. Invasive electrophysiology with pacing in right atrium and ventricle was performed in normal rats (control, n = 13; GH, n = 6; amiodarone, n = 6) to asses inducibility of supraventricular and ventricular arrhythmias.Growth hormone- and amiodarone-treated rats had lower resting heart rate at baseline before induction of MI. The arrhythmia scores in the GH- (3.8 +/- 1) and amiodarone-treated (3.9 +/- 0.5) animals were significant lower than in the placebo group (5.9 +/- 0.5, P < .05). There was no significant difference in arrhythmia score between the GH and amiodarone groups. The incident of inducible ventricular arrhythmias was lower in the GH (2/6, 33%) and amiodarone (2/6, 33%) groups compared with controls (13/16, 81%; P = .05). There was no difference in inducibility of atrial fibrillation between the GH (5/6, 83%) and control (13/14, 93%) groups, whereas the inducibility of atrial fibrillation was significantly lower in the amiodarone group (2/6, 33%; P < .05).Pretreatment with GH reduces the burden of ventricular arrhythmias in rats with postinfarction CHF due to acute MI. Growth hormone may be useful in the treatment of CHF and acute MI.
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| 8. |
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| 9. |
- Råmunddal, Truls, 1973
(författare)
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Myocardial metabolism in experimental infarction and heart failure
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Abstract The heart is an organ heavily dependent on exogenous lipids for the oxidative production of adenosine-triphosphate (ATP) and therefore maintenance of normal cellular energy homeostasis. However, high energy flux organs such as the heart must closely match lipid import and utilization or otherwise lipids will accumulate in the cardiomyocytes. Intracellular lipid accumulation has detrimental effects on cardiomyocyte function and viability and results in development of lipotoxic cardiomyopathy. Different pathophysiological states such as congestive heart failure (CHF), myocardial ischemia and hypertrophy are associated with myocardial lipid accumulation. The heart, however, produces and secretes apolipoprotein B containing lipoproteins (apoB), which enables the cardiomyocyte to export lipids. It has been proposed that apoB may be involved in cardioprotection by means of elimination of toxic intracellular lipids. An important part of the patologic cardiac remodelling in CHF is disturbed myocardial energy metabolism. The failing myocardium contains low levels of creatine (Cr), phosphocreatine (PCr), and ATP. Cr depletion in the heart may result in disturbed energy production, transfer and utilisation of chemical energy and therefore compromised left ventricular function. Growth hormone (GH) has been shown to exert numerous positive effects on the failing and remodelled heart suggesting that GH may be an additional agent in the treatment of CHF and myocardial infarction (MI). The aims of this thesis were: I. To investigate in vivo the effects of Cr depletion in mice on left ventricular function and morphology, energy metabolism and myocardial lipids. II. To investigate importance of endogenous lipoproteins in the heart for cardiac function, morphology and survival in the settings of acute and chronic myocardial infarction and doxorubicine induced acute heart failure. III. To investigate the effects of Growth hormone on arrhythmogenesis IV. To evaluate the predictive value of native cardiac reserve on outcome after myocardial infarction in mice Using a mouse model of chemically-induced Cr depletion we show in vivo that myocardial Cr depletion leads to disturbed energy metabolism, left ventricular dysfunction, pathologic remodeling and accumulation of intracellular triglycerides. These alterations are reversible upon the normalization of the creatine levels suggesting that creatine metabolism may be an important target for pharmacological interventions. Using transgenic animals we show that myocardial apoB may be a cardioprotective system which is activated during ischemia, pathologic remodeling and heart failure and may be important for survival in myocardial infarction and heart failure. We show that GH possess novel antiarrhythmic properties in the setting of acute MI which adds further evidence to the concept of GH as an additional pharmacological agent in the treatment of CHF and MI. We demonstrate that native cardiac reserve is a predictor of post-MI survival.
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| 10. |
- Råmunddal, Truls, 1973, et al.
(författare)
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Overexpression of apolipoprotein-B improves cardiac function and increases survival in mice with myocardial infarction.
- 2009
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Ingår i: Biochemical and biophysical research communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 385:3, s. 336-40
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The heart produces apolipoprotein-B containing lipoproteins (apoB) whose function is not well understood. The aim of this study was to evaluate importance of myocardial apoB for cardiac function, structure and survival in myocardial infarction (MI) and heart failure (HF). METHODS AND RESULTS: MI was induced in mice (n=137) and myocardial apoB content was measured at 30 min, 3, 6, 24, 48, 120 h and 8 weeks post-MI. Transgenic mice overexpressing apoB (n=27) and genetically matched controls (n=27) were used to study the effects of myocardial apoB on cardiac function, remodeling, arrhythmias and survival after MI. Echocardiography was performed at rest and stress conditions at baseline, 2, 4 and 6 week post-MI and cumulative survival rate was registered. The myocardial apoB content increased both in the injured and the remote myocardium (p<0.05) in response to ischemic injury. ApoB mice had 2-fold higher survival rate (p<0.05) and better systolic function (p<0.05) post-MI. CONCLUSION: Overexpression of apoB in the heart increases survival and improves cardiac function after acute MI. Myocardial apoB may be an important cardioprotective system in settings such as myocardial ischemia and HF.
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| 11. |
- Scharin Täng, Margareta, 1962, et al.
(författare)
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Native cardiac reserve predicts survival in acute post infarction heart failure in mice.
- 2007
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Ingår i: Cardiovascular Ultrasound. - : Springer Science and Business Media LLC. - 1476-7120. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: Cardiac reserve can be used to predict survival and outcome in patients with heart failure. The aim of this study was to investigate if native cardiac reserve could predict survival after myocardial infarction (MI) in mice. METHOD: We investigated 27 healthy C57Bl6 mice (male, 10-12 weeks old) with echocardiography using a high-frequency 15-MHz linear transducer. Investigations were performed both at rest and after pharmacological stress induced by dobutamine (1 ug/g body weight i.p.). The day after the echocardiography examination, a large MI was induced by ligation of the left anterior descending (LAD) coronary artery for evaluation of mortality rate. Result: Two weeks after induction of MI, 7 mice were alive (26%). Evaluation of the difference between the surviving and deceased animals showed that the survivors had a better native ability to increase systolic performance (DeltaLVESd -1.86 vs -1.28mm p=0.02) upon dobutamine challenge, resulting in a better cardiac reserve (DeltaFS 37 vs 25% p=0.02 and DeltaCO 0.27 vs -0.10 ml/min p=0.02) and a better chronotropic reserve (DeltaR-R interval -68 vs -19 ms p< 0.01). A positive relationship was found between ability to survive and both cardiac (p<0.05) and chronotropic reserve (p<0.05) when the mice were divided into three groups: survivors, surviving <7 days, and surviving <1 day. CONCLUSION: We conclude that before MI induction the surviving animals had a better cardiac function compared with the deceased. This indicates that native cardiac and chronotropic reserve may be an important determinant and predictor of survival in the setting of large MI and post-infarction heart failure.
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