Alterations in isoproterenol-induced cardiac metabolic changes by a quaternary analog of propranolol, UM-272

Effect of UM-272, a dimethyl propranolol has been studied in experimental myocardial necrosis induced by isoproterenol (ISP, 85 mg/kg, SC X 2 days) in rats. Administration of ISP caused increased serum creatine phosphokinase (CPK), lactate dehydrogenase (LDH) and decreased myocardial glycogen, adenosine triphosphate (ATP) creatine phosphate (CP) and glycolysis through phosphofructokinase (PFK). Myocardial tissue lactate was markedly increased. All these changes resulted in development of myocardial necrosis as calculated from the CPK depletion from the injured myocardium. Rats given UM-272 (10 mg/kg or 20 mg/kg i.p.) 5 days before and 2 days during ISP administration showed significant improvement in all the parameters studied. Furthermore, UM-272 (20 mg/kg X 7 days) in control rats caused a significant (P less than .001) increase in ATP and CP content of the myocardium while other parameters remained unaltered. It would appear from the present study that the cardioprotective effect in ISP induced injury is not related to beta blockade as UM-272 is devoid of beta-blocking properties.