Mechanisms of Benefit in the Ischemic Myocardium due to Heart Rate Reduction

Abstract

The studies reviewed here examine the role of heart rate reduction in the beneficial effect observed following beta-adrenoceptor blockade during exercise-induced ischemia in conscious dogs. To further study the effects of heart rate reduction on regional blood flow in an ischemic bed without collateral circulation, anesthetized swine with controlled coronary perfusion were also studied. Measurements of regional myocardial blood flow (microspheres) and contractile function (sonomicrometers) during steady state exercise in dogs with chronic coronary artery stenosis indicated the existence of severe regional contractile dysfunction and subendocardial ischemia. The administration of beta-adrenoceptor blockade (1.0 mg/kg atenolol) improved regional contractile function when heart rate was reduced from 220 to 165 beats/min. Atrial pacing during exercise to prevent the bradycardia following beta-adrenoceptor blockade eliminated the improved regional function and blood flow. Thus, the beneficial effect of beta-blockade was only apparent when exercise heart rate was reduced. In anesthetized swine with constant inflow coronary perfusion, two levels of coronary hypoperfusion were examined at heart rates of 91 beats/min or 55 beats/min. Bradycardia was produced using the bradycardic agent UL-FS 49 (0.3 mg/kg). Regional contractile function and subendocardial blood flow were markedly improved at the lower heart rate for either level of reduced coronary perfusion, indicating a redistribution of blood flow towards the subendocardium. The improvement in contractile function was larger than predicted on the basis of the improvement in blood flow per min to the subendocardium. Independent relationships between regional contractile function and the subendocardial blood flow per min were observed for each heart rate. Thus, the studies in conscious exercising dogs indicated that heart rate reduction is an essential mechanism for the improvement of ischemic regional myocardial contractile function during exercise by beta-blockade. This is likely the result of the marked improvement in subendocardial blood flow per beat which accompanies the reduced heart rate; regional myocardial blood flow per beat appears to be a predictor of regional contractile function during ischemia both at rest and during exercise.