Selective β1-Blockade Improves Cardiac Bioenergetics and Function and Decreases Neuroendocrine Activation in Rats during Early Postinfarct Remodeling

Ömerovic, Elmir; Bollano, Entela; Mobini, Reza; Madhu, B; Kujacic, V.; Soussi, B.; Hjalmarson, Åke; Waagstein, Finn

doi:10.1006/bbrc.2001.4336

Cited by 21 publications

(18 citation statements)

References 34 publications

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“…Such alterations in cardiac function are most likely due to cardiac remodelling as various parameters including increased LVIDd, LVIDs, LVPWs and LVPWd, as well as decreased IVSs were evident in 20 weeks infarcted animals. These observations are consistent with other reports showing cardiac remodelling in heart failure due to MI of different durations . In view of the role of the prolonged activation of SNS in the development of heart failure , the elevated levels of plasma, NE, EPI and dopamine can be seen to produce cardiac dysfunction and cause cardiac hypertrophy, as well as cardiac dilatation in the infarcted animals.…”

Section: Discussionsupporting

confidence: 93%

Reversal of subcellular remodelling by losartan in heart failure due to myocardial infarction

Babick

Chapman

Zieroth

et al. 2012

J Cellular Molecular Medi

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This study tested the reversal of subcellular remodelling in heart failure due to myocardial infarction (MI) upon treatment with losartan, an angiotensin II receptor antagonist. Twelve weeks after inducing MI, rats were treated with or without losartan (20 mg/kg; daily) for 8 weeks and assessed for cardiac function, cardiac remodelling, subcellular alterations and plasma catecholamines. Cardiac hypertrophy and lung congestion in 20 weeks MI-induced heart failure were associated with increases in plasma catecholamine levels. Haemodynamic examination revealed depressed cardiac function, whereas echocardiographic analysis showed impaired cardiac performance and marked increases in left ventricle wall thickness and chamber dilatation at 20 weeks of inducing MI. These changes in cardiac function, cardiac remodelling and plasma dopamine levels in heart failure were partially or fully reversed by losartan. Sarcoplasmic reticular (SR) Ca 2+ -pump activity and protein expression, protein and gene expression for phospholamban, as well as myofibrillar (MF) Ca 2+ -stimulated ATPase activity and a-myosin heavy chain mRNA levels were depressed, whereas b-myosin heavy chain expression was increased in failing hearts; these alterations were partially reversed by losartan. Although SR Ca 2+ -release activity and mRNA levels for SR Ca 2+ -pump were decreased in failing heart, these changes were not reversed upon losartan treatment; no changes in mRNA levels for SR Ca 2+ -release channels were observed in untreated or treated heart failure. These results suggest that the partial improvement of cardiac performance in heart failure due to MI by losartan treatment is associated with partial reversal of cardiac remodelling as well as partial recovery of SR and MF functions.

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Section: Discussionsupporting

confidence: 93%

Reversal of subcellular remodelling by losartan in heart failure due to myocardial infarction

Babick

Chapman

Zieroth

et al. 2012

J Cellular Molecular Medi

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“…β‐blockers may also improve microcirculation by reducing release of vasoconstricting substances, by increasing nitric oxide production or by some other rheological effect [33,34]. Metoprolol also increases the energy supply/demand ratio and improves energy utilization [35–37] Recently, metoprolol was shown to down‐regulate G i proteins in patients with CHF due to IHD and DCM [38]. This effect improves the compromised receptor‐effect coupling and may improve LV function in both IHD and DCM.…”

Section: Discussionmentioning

confidence: 99%

Increased exercise ejection fraction and reversed remodeling after long‐term treatment with metoprolol in congestive heart failure: a randomized, stratified, double‐blind, placebo‐controlled trial in mild to moderate heart failure due to ischemic or idiopathic dilated cardiomyopathy

Waagstein

Strömblad

Andersson

et al. 2003

European J of Heart Fail

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Background: the effects of long-term administration of b-blockers on left ventricular (LV) function during exercise in patients with ischemic heart disease (IHD) and idiopathic dilated cardiomyopathy (DCM) are controversial. Patients and methods: patients with stable congestive heart failure (CHF) (New York heart association wNYHAx class II and III) and ejection fraction (EF) F0.40 were randomized to metoprolol, 50 mg t.i.d. or placebo for 6 months. Patients were divided into two groups: ischemic heart disease (IHD) and idiopathic dilated cardiomyopathy (DCM). The mean EF was 0.29 in both groups and 92% were taking angiotensin-converting enzyme (ACE) inhibitors. In the IHD group, 84% had suffered a myocardial infarction (MI) and 64% had undergone revascularization at least 6 months before the study. LV volumes were measured by equilibrium radionuclide angiography. Mitral regurgitation was assessed by Doppler echocardiography. All values are changes for metoprolol subtracted by changes for placebo. Results: metoprolol improved LV function markedly both at rest and during sub-maximal exercise in both groups. The mean increase in EF was 0.069 at rest (P-0.001) and 0.078 during submaximal exercise (P-0.001). LV enddiastolic volume decreased by 22 ml at rest (Ps0.006) and by 15 ml during exercise (Ps0.006). LV end-systolic volume decreased by 23 ml both at rest (Ps0.001) and during exercise (Ps0.004). Exercise time increased by 39 s (Ps0.08). In the metoprolol group, mitral regurgitation decreased (Ps0.0026) and only one patient developed atrial fibrillation vs. eight in the placebo group (Ps0.01). Conclusion: metoprolol improves EF both at rest and during submaximal exercise and prevents LV dilatation in mild to moderate CHF due to IHD or DCM.

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“…On the other hand, both carvedilol and propranolol were reported to decrease cardiac norepinephrine spillover by affecting the sympathetic nerve activity in patients with CHF [18,19]. Although cardiac norepinephrine spillover, an index of norepinephrine release from the heart, was either unaffected or increased upon treatment of patients with CHF with metoprolol [18,19], this selective b 1 -AR antagonist decreased plasma levels of both norepinephrine and epinephrine in infarcted rats [20]. These observations suggest that both selective and non-selective b-AR antagonists may depress the increased activity of the sympathetic nervous system in CHF and may attenuate cardiac dysfunction.…”

Section: Introductionmentioning

confidence: 94%

Amelioration of Cardiac Remodeling in Congestive Heart Failure by β-Adrenoceptor Blockade is Associated with Depression in Sympathetic Activity

et al. 2009

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This study investigated whether improvement in cardiac function and attenuation of cardiac remodeling by some beta-adrenoceptor (beta-AR) antagonists were associated with a depression in sympathetic activity in congestive heart failure (CHF) due to myocardial infarction (MI). Although cardiac dysfunction, hypertrophy and dilatation as well as increased plasma level of catecholamines are known to occur in CHF, the relationship between these parameters is poorly understood. Three weeks after occlusion of the coronary artery, rats were treated daily with 20 and 75 mg/kg of either atenolol or propranolol for 5 weeks. Sham-operated rats served as controls. Both atenolol and propranolol at 20 and 75 mg/kg doses attenuated the MI-induced cardiac hypertrophy, increases in left ventricular (LV) end-diastolic pressure, LV end-systolic volume and LV end-diastolic volume as well as depressions in LV systolic pressure, LV fractional shortening and cardiac output. PR interval was decreased and QT( c ) interval was increased in CHF; these alterations were ameliorated by both atenolol and propranolol. The increased level of plasma epinephrine in CHF was also depressed by both low and high doses of atenolol and propranolol whereas the increased level of plasma norepinephrine was reduced by high but not low doses of these drugs. The results indicate that the beneficial effects of beta-AR antagonists on cardiac remodeling and heart dysfunction in CHF may be due to the blockade of beta-ARs in the myocardium and a depression in the sympathetic activity.

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Selective β1-Blockade Improves Cardiac Bioenergetics and Function and Decreases Neuroendocrine Activation in Rats during Early Postinfarct Remodeling

Cited by 21 publications

References 34 publications

Reversal of subcellular remodelling by losartan in heart failure due to myocardial infarction

Reversal of subcellular remodelling by losartan in heart failure due to myocardial infarction

Increased exercise ejection fraction and reversed remodeling after long‐term treatment with metoprolol in congestive heart failure: a randomized, stratified, double‐blind, placebo‐controlled trial in mild to moderate heart failure due to ischemic or idiopathic dilated cardiomyopathy

Amelioration of Cardiac Remodeling in Congestive Heart Failure by β-Adrenoceptor Blockade is Associated with Depression in Sympathetic Activity

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