On the nature of protection by propranolol against myocardial necrosis after temporary coronary occlusion in dogs.

Propranolol has been shown to reduce the extent of necrosis that develops after temporary coronary occlusion in dogs. To determine whether this protective action was related to beta adrenergic blockade or to direct effects, necrosis was quantitated in the posterior papillary muscle 2 to 4 days after 40 minute periods of coronary occlusion in anesthetized open chest dogs. Groups of dogs either were untreated or were pretreated with doses of d,l-propranolol, 0.005 to 5 mg/kg body weight, or doses of d-propranolol 2.5 or 5 mg/kg. Necrosis was greatly reduced in dogs treated with 5 mg/kg of d, l-propranolol. This protective effect was significant but quantitatively less with 0.5 and 0.05 mg/kg of d, l-propranolol. A dose of 0.005 mg/kg d, l-propranolol and d-propranolol failed to alter myocardial necrosis significantly. The dose-related reduction of necrosis with d, l-propranolol correlated with a similar dose relation for beta adrenergic blockade and suggested that a protective effect was related to beta blockade. The reduction of necrosis with 0.05 and 0.5 mg/kg of d, l-propranolol (a level at which direct "membrane stabilizing" effects are insignificant) suggested that direct effects were not essential for protection. The negative results with d-propranolol further support our conclusion that propranolol reduces myocardial ischemic injury through beta adrenergic blockade rather than through direct myocardial actions.