Coronary vasoconstriction and catecholamine cardiomyopathy

Abstract

Norepinephrine (NE) causes extensive myocardial injury in the rabbit. To investigate a potential mechanism we measured coronary blood flow with radioactive microspheres. Coronary resistance and oxygen demand (heart rate-blood pressure double product) were calculated. Severity of injury was determined by semiquantitative histologic evaluation. Changes resulting from NE infusion were determined in animals with or without alpha-receptor blockade with phentolamine (10 mg). In all animals oxygen demand remained constant. Coronary blood flow (ml/gm/min) was 2.66 at the beginning of the experiment, rose to 3.46 after 3 minutes of NE infusion (p less than 0.05), then declined to baseline values (2.33) after 10 minutes. However, coronary blood flow was sharply lower than baseline (1.51; p less than 0.05) after 40 minutes of infusion. Coronary resistance rose progressively from baseline values of 40.9 (units) to 74.8 at 40 minutes (p less than 0.05). Animals given phentolamine manifested none of these changes. Control subjects infused with saline solution showed no significant changes in coronary blood flow or coronary resistance. Animals pretreated with phentolamine had minimal histologic damage at 48 hours compared with NE alone (p less than 0.01). We conclude that NE induces sustained coronary vasoconstriction in the rabbit and that reduced coronary blood flow may contribute to the pathogenesis of NE cardiomyopathy in this species.