BLOCKADE OF CARDIAC EFFECTS OF ISOPROTERENOL BY 4-(2-HYDROXY-3-ISOPROPYLAMINOPROPOXY)-ACETANILIDE (ICI 50,172)

¹ Department of Pharmacology, Marquette School of Medicine, Milwaukee, Wisconsin

The beta adrenergic blocking activity of 4-(2-hydroxy-3-isopropyl-aminopropoxy)-acetanilide (ICI 50,172) was investigated in the isolated turtle heart preparation and the blood-perfused supported dog heart preparation (ISHP). The pA₂ value for ICI 50,172 in the turtle heart was found to be 7.0. Intracoronary administration of isoproterenol produced a dose-dependent increase in heart rate, left ventricular contractile force, left ventricular systolic pressure and myocardial oxygen consumption and a decrease in coronary artery perfusion pressure in the ISHP. Pretreatment with 0.25 mg/kg of ICI 50,172 effectively blocked the myocardial effects of isoproterenol in a competitive manner. ICI 50,172 reduced the myocardial oxygen consumption of the ISHP with little or no effect on myocardial contractility or heart rate, suggesting an improved myocardial efficiency.