Beta Blockers in Experimental Myocardial Infarction

Widespread interest has developed in the possibility of using beta-adrenoceptor antagonists to protect the myocardium against the deleterious consequences of an impaired coronary blood flow. The consequences include loss of active tension generating capacity, impaired mitochondrial function, destruction of tissue ultrastructure and loss of ionic homeostasis. The ionic imbalance includes loss of tissue K+ and gain in Na+ and Ca2+. Under conditions of low flow, or when coronary flow is absent, a loss of K+ from the cell must result in a localized increase in extracellular K+. This, in turn, may be sufficient to trigger arrhythmias. Theoretically beta-adrenoceptor antagonists should protect against such an ischaemic induced increase in extracellular K+. To test this hypothesis isolated Sprague-Dawley rat hearts have been pretreated with either timolol (25 micrograms/1) or propranolol (100 micrograms/l). The hearts have then been made ischaemic at 37 degrees C for 60 minutes and then reperfused. Coronary effluent collected during the first 5 minutes reperfusion showed a significant (p less than 0.001) increase in K+. This increase in coronary K+ was attenuated by prior beta-blockade. Adding the beta blockers during the phase of reperfusion had no effect on the rate of K+ loss. The significance of these results will be discussed with reference to the use of beta-adrenoceptor antagonists for the protection of ischaemic heart muscle.