Influence of propranolol withdrawal on the induction of sudden death in chronically infarcted rats by isoproterenol challenge

The infarcted rats induced by ligation of left coronary artery were divided into the untreated, sc propranolol 25 mg/ kg×9 d, withdrawal for 2 d after sc propranolol 25 mg/kg×7 d and the normal control group. ECG, NE, E, cAMP and CPK were measured among the normal and 3 chronically infarcted groups following iv isoproterenol 100μg/kg. The increments in heart rate after isoproterenol were the same in various groups, however, cardiac arrhythmias occurred more frequent in both the withdrawal and the untreated groups than the others and the incidence of severe arrhythmia in the former two groups was more than 50%. In spite of the same sensitivity ofβ-receptor in the sinoatrial node, automaticity of ectopic foci in the low segment of cardiac conducting system was markedly increased in response to isoproterenol challenge. The decrease in NE in the right ventricle (noninfarcted area) was observed in rats with left anterior infarction, but E level remained intact. The malignant arrhythmia was accompanied by a depletion of NE in myocardium, an elevation of cAMP in myocardium and plasma, and an increased CPK in serum. The reduction of NE level in myocardium may be an important factor facilitating the occurrence of life-threatening arrhythmias resulting in sudden coronary death.