Propranolol Antagonizes the Anti-Inflammatory Effect of Alcohol and Improves Survival of Infected Intoxicated Rabbits

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Abstract
We studied the effects of alcohol and propranolol on the course of peritonitis in rabbits. Induction of sterile peritonitis with normal saline led to a 50% augmentation of granulocyte adherence in normal rabbits, and a mean cumulative granulocyte count of 27,000/mm3 in peritoneal exudate by 8 h. Rabbits intoxicated with alcohol at the time of peritonitis induction maintained a granulocyte adherence below pretreatment values, and only delivered a cumulative mean of 12,000 granulocytes/mm3 into the peritoneal fluid. When intoxicated rabbits received propranolol intravenously at the time of intoxication, adherence increased above preperitonitis levels, and stayed significantly above values for animals given alcohol alone. In addition, the defect in granulocyte delivery was prevented by propranolol, resulting in a mean cumulative granulocyte count in peritoneal fluid of 24,000/mm3. When peritonitis was induced with live pneumococci instead of a sterile inflammatory stimulus, 14/18 normal animals survived the infection and were culture-negative when sacrificed at 2 wk. In contrast, 17/18 intoxicated animals died of the infection, in a mean of 2.8 days. 9 of 18 intoxicated animals who also received propranolol survived, and those who died lived a mean of 7.5 days. The survival rates and the time-to-death among the nonsurvivors given propranolol were both significantly greater than in the animals intoxicated without propranolol. Thus, propranolol prevents the granulocyte adherence and delivery defects induced by alcohol intoxication, and significantly improves survival from infection.