Effects of insulin on experimental catecholamine cardiomyopathy

We have recently shown that insulin attenuates norepinephrine (NE) dose-response curves in both isolated cardiac muscle and intact heart preparations. Accordingly, an intact rabbit model was used to determine if insulin would reduce the extent of myocardial damage following a standard NE infusion. Each animal was given pentobarbital, 30 mg/kg, and heart rate, arterial pressure, glucose, blood gases, and pH were measured. NE (2 microgram/min/kg) was given intravenously for 90 minutes. After 48 hours the rabbits were killed and the hearts were examined microscopically and assigned a histologic score. Florid lesions were present in 17 of 24 sections (71%) from 12 animals. They were characterized by myofiber necrosis and an intense cellular reaction. However, only 5 of 40 sections (12.5%) from 20 rabbits given insulin (10 units/kg) 30 minutes before the NE infusion showed advanced lesions (P less than 0.001). The mean histologic score was reduced from 1.7 to 1.0 (P less than 0.001). The frequency of advanced lesions increased to 86% in animals given a higher dose of NE (3 microgram/kg/min) and was reduced to 53% by pretreatment with insulin. A dosage of 5 units/kg was as effective as 10 units/kg, but rabbits given 1 unit/kg manifested cardiomyopathic changes identical to those in rabbits not pretreated with insulin. No differences in heart rate, arterial pressure, PO2, or pH were evident between the groups. It is concluded that large doses of insulin reduce myocardial damage produced by NE in this model. This may be linked with the phenomenon of insulin inhibition of the inotropic action of NE.