EFFECTS OF A HYDRAZINE MONOAMINE OXIDASE INHIBITOR (PHENELZINE) ON ISOPROTERENOL-INDUCED MYOCARDIOPATHIES IN THE RAT

Phenetzine partially prevented grossly detectable cardiac necrosis and cardiomegaly induced in the rat by large, multiple doses of isoproterenol (ISO). Protection was also afforded by iproniazid but not by isoniazid. ISO (80 mg/kg s.c.) simultaneously increased heart rate and decreased mean arterial blood pressure in unanesthetized rats with chronically indwelling aortic catheters. The onset of ISO-induced tachycardia was delayed in animals pretreated with phenelzine. ISO treatment increased cardiac Na+, water and Cl- but decreased K+. These changes were partially prevented by phenelzine pretreatment. ISO increased cardiac ribonucleic acid but did not alter deoxyribonucleic acid or protein when these were expressed as milligrams per gram of wet tissue. Cardiac mitochondrial respiratory control, but not the P/O ratio, was significantly reduced in ISO-treated rats. Myocardial hypoxia resulting from the hemodynamic actions of ISO may be the major initiating event in the development of cardiac necrosis. Edema contributes significantly to the cardiomegaly, but new protein synthesis seems to occur with repeated ISO administration.