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 profile.
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Venneker, E.H.G., Remme, W.J., van Hoogenhuyze, D.C.A. et al. Acute systemic and antiischemic effects of epanolol in patients with coronary artery disease. Cardiovasc Drug Ther 8, 211–219 (1994). https://doi.org/10.1007/BF00877329
- myocardial ischemia