Effects of carvedilol on left ventricular function and arrhythmias during repeated short-time myocardial ischemia in experimental pigs.

The effects of carvedilol, a new vasodilating beta-blocking drug, were studied in experimental pigs during short-term acute myocardial ischemia. In 21 anesthetized pigs 0.01, 0.03, and 0.1 mg/kg b.w. carvedilol was studied during repeated 2-min distal LAD-occlusions and a 60-min-period of ischemia. Left ventricular volume was continuously measured by the impedance catheter method. Intravenous administration of 0.01 mg/kg carvedilol resulted in a significant decrease of heart rate (-13%), dp/dtmax (-32%), and ejection fraction (-9%), slight changes of systolic pressure (-3%), and an increase of vascular resistance (+24%), indicating a beta-blocker effect without vasodilation-while the first vasodilatory effect was found at a dose of 0.1 mg/kg. During ischemia carvedilol had no influence on the time-course or the extent of systolic bulging of the ischemic myocardium, but the ischemia-induced decrease of left ventricular ejection fraction was diminished. Both during short-term ischemia, as well as during the 60-min-ischemia-period carvedilol significantly reduced ventricular premature beats. During the 60-min-ischemia-period activation delay measured from local DC-electrograms of the ischemic myocardium, as well as the occurrence of activation block were not altered by carvedilol, as was the incidence of ventricular fibrillation (69%). We conclude that at low dosages the beta-blocking effect of carvedilol exceeds the vasodilating properties. This may also hold true in patients with cardiac failure; they are more sensitive to beta-blocking drugs. During ischemia carvedilol slightly reduces the ischemia-dependent decrease of global ventricular function and it has an antiarrhythmic effect. Therefore, it may be protective in patients with acute myocardial infarction.