Pi 8/9981 Alternative mechanisms of nitric oxide mediated vasodilation: Experimental evidence

Background: The mechanisms for the beneficial effects of beta-blockade in heart failure are incompletely understood. The aim of this study was to investigate the effects of betal-blockade on cardiac bioenergetics and function in rats during early postinfarct remodeling phase. Methods: Large myocardial infarction (MI) was induced in male Sprague-Dawley rats. Two different groups were studied: rats with MI treated with metoprolol (5 mg!kg/b; n = 9) during 4 weeks and rats with MI placebo treated (n = 9). All rats were investigated with 31P MRS and transthoracic echocardiography (ECHO) 3 days after induction of MI and 4 weeks later. Volume-selective 31P MRS was performed on 2.35 T Bruker Biospec magnet. Results: Trentrnent with metoprolol increased myocardial PCr/ATP ratio indicating improved myocardial energy reserve which was associated with improvement in systolic and diastolic function. PCXATP EF% DT ms HR ba&min Mctoprolol 1.2 f 0.09* 3.4 f Ia* 17 f03’ -168* PlaCebo 0.04 k 0.056 -9.66 i 1.8 3 * 03 -36 The values represent the means f SBM of the difference before and after the treatment, * = p < 0.05 v. placebo. PCdAm = phosphocreatine/adenosine-3-phosphate ratio, EF = ejection fraction, DT = deceleration time of mitral E-wave, HR = heart rate