Systemic and regional hemodynamic, antiarrhythmic and antiischemic effects of bevantolol in anesthetized pigs

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In doses of 0.5 to 3.0 mg/kg bevantolol caused dose-dependent decreases in cardiac output (10% to 35%), primarily due to negative chronotropic actions, as heart rate decreased by 10% to 25%. Stroke volume decreased after the highest dose (15%), due to a negative inotropic action (maximum left ventricular dP/dt decreased by 40%) and a mild vasoconstriction in systemic vascular beds. Decreases in perfusion of the heart, kidneys, liver, spleen, stomach, muscles and adrenals were similar to those in cardiac output. However, blood flow to the brain and small intestine was not significantly affected. Bevantolol (0.5 or 1.5 mg/kg IV) gave full protection against ventricular fibrillation during the first period (10 minutes) of proximal left anterior descending (LAD) coronary artery occlusion in the highest dose. After the third and last reperfusion period, 70% of these animals survived, while only 8% of the untreated and 15% of the animals treated with the lower dose survived. After permanent ligation of the LAD coronary artery at midpoint, bevantolol prevented ventricular fibrillation during the first phase of early ventricular arrhythmias but was unable to prevent it during the second phase of early arrhythmias. Administration of bevantolol (1.5 mg/kg) to animals in which the LAD coronary artery blood flow was reduced to 35% of baseline did not improve transmural myocardial blood flow to the ischemic zone. However, the drug caused a redistribution in favor of the endocardial layers. The changes in flow were accompanied by a narrowing of the arterial-coronary venous differences in pH and pCO 2. We conclude that bevantolol protects against the first phase of early cardiac arrhythmias and alleviates myocardial ischemia. The antiischemic effects seem related to a decrease in myocardial oxygen consumption, but an enhancement of diastolic perfusion time (17%) may also be of major importance.