Antiischemic effects of β1-blocking agents are based on intrinsic negative inotropic and chronotropic properties. Partial β1-agonistic activity, although useful in preserving cardiac function, may counteract such antischemic properties by modulating the intrinsic negative cardiac effects of beta-blockade. To investigate the acute hemodynamic and antiischemic profile of epanolol, a cardioselective β1-antagonist and partial agonist, 20 patients with left coronary artery disease underwent two incremental atrial pacing tests, 45 minutes before (APST I) and 15 minutes after (APST II) 4 mg intravenous epanolol, administered over 5 minutes. Additional measurements were carried out at 1, 3, 5, 10, and 15 minutes after epanolol, at basal and fixed heart rates. Epanolol immediately reduced heart rate with a maximum of 10 at 15 minutes and decreased contractility (Vmax) by 7 (both p<.05), whereas cardiac output fell temporarily by 9 (p<.05). Other hemodynamic parameters did not change, except for a significant 11 reduction in myocardial oxygen demand. Despite comparable pacing conditions, both the double product and contractility decreased significantly less during APST II, resulting in a 17 lower myocardial oxygen consumption (p<.05). Myocardial ischemia was markedly reduced, indicated by normalization of lactate metabolism lactate extraction 16±7 vs. −7±8 (APST I), less ST depression (21), and modulation of LV end-diastolic pressure postpacing (all p<.05 vs. APST I), whereas angina was absent or less in 14 patients. None of the patients reported an adverse effect. Thus, under resting conditions intravenous epanolol induces moderate, short-lasting negative chronotropic and inotropic effects, but does not alter cardiac pump function or vascular resistance, reflecting its additional β1-agonistic properties. Alternatively, during pacing it still reduces ischemia through negative inotropic effects and diminishes myocardial oxygen demand, reflecting its β1-antagonistic
展开▼
