Selective beta(1)-blockade improves cardiac bioenergetics and function and decreases neuroendocrine activation in rats during early postinfarct remodeling.

In spite of the solid evidence that beta-blockade reduces mortality and morbidity in congestive heart failure (CHF) this therapy continues to be underused in clinical praxis. The reason for this may lie in scarcity of knowledge about the mechanisms of beta-blockade action. The major aim of this study was to investigate in vivo whether selective beta(1)-blockade may improve cardiac energy metabolism in rats with myocardial infarction in early postinfarct remodeling phase. Myocardial infarction (MI) was induced in male Sprague-Dawley rats by ligation of the left coronary artery. Two different groups of rats were studied, rats with MI treated with metoprolol (5 mg/kg/h; n = 9) and rats with MI saline treated (n = 9). The treatment with metoprolol was given by subcutaneously implanted minipumps and was initiated at 3 days postinfarct and during the period of 4 weeks. All rats were investigated with noninvasive methods (31)P magnetic resonance spectroscopy (MRS) and transthoracic echocardiography 3 days after induction of MI and 4 weeks later. Phosphocreatine/ATP ratio was normalized after the treatment with metoprolol while it was 50% lower in the saline group (p < 0.001). In the metoprolol group stroke volume and ejection fraction increased while deceleration time of mitral early filling was longer (all p < 0.05). Left ventricular weight as well as volumes and dimensions were similar between the groups. Plasma levels of noradrenaline (p = 0.058), adrenaline (p < 0.01) and brain natriuretic peptide (p = 0.09) were lower in the metoprolol group. Selective beta(1)-blockade with high dose of metoprolol initiated in the early postinfarct phase improves myocardial energy metabolism and function and prevents overactivation of sympathetic system. The beneficial effect on myocardial bioenergetics may be an important mode of action of beta-blockers which contributes to the clinical benefits of the therapy in CHF.

Reduced heart rate variability in ischemic heart disease is only partially caused by ischemia. An HRV study before and after PTCA.

BACKGROUND: Reduced heart rate variability (HRV) after acute myocardial infarction (AMI) indicates poor prognosis. HRV in patients with uncomplicated coronary artery disease is reduced, and an association with poor prognosis has been suggested. The mechanism of the HRV reduction is not known, but ischemia is a possibility. AIM: To evaluate, in angina patients with no prior AMI, no other disease and drug-free, if complete revascularization and thus important reduction of ischemia by means of PTCA influences HRV. PATIENTS AND METHODS: Twenty-four-hour Holter recordings were performed at baseline prior to PTCA in 48 patients with angina and in 41 age-matched healthy control subjects. The recording was repeated 1 and 6 months after complete revascularization. In addition, HRV was registered during controlled respiration in the supine and standing positions and during cold pressure test at baseline in all angina patients and controls and in 17 consecutive angina patients 6 months after PTCA. RESULTS: Compared to controls, angina patients had a significantly reduced mean RR interval (p = 0.02), SD (p = 0.003), rMSSD (p = 0.03), pNN50 (p = 0.03), total power (p = 0.003), low- (p = 0.004) and high-frequency peak (p = 0.04), but normal SDNN, SDANN and LF/HF. One and 6 months after PTCA, 42/46 and 32/40 follow-up patients, respectively, were free of angina. Six months after PTCA, there was a significant recovery of vagal modulation seen in the frequency domain during controlled respiration, but only nonsignificant trends in HRV parameters analyzed over 24 h. CONCLUSION: Patients with uncomplicated angina had reduced HRV, mainly affecting vagal activity, but normal low frequency variability associated with mortality. Complete revascularization caused a partial normalization of vagal modulation indicating that ischemia may be one of but not the only mechanism of the HRV reduction in uncomplicated chronic coronary artery disease.