SIMULTANEOUS ASSESSMENT OF EFFECTS OF CORONARY VASODILATORS ON THE CORONARY BLOOD FLOW AND THE MYOCARDIAL CONTRACTILITY BY USING THE BLOOD-PERFUSED CANINE PAPILLARY MUSCLE

Abstract

The effects of 6 coronary vasodilators on the coronary blood flow and the contractile force of the ventricular muscle were examined simultaneously by injecting them into the arterially blood-perfused canine papillary muscle preparation. All compounds produced a dose-dependent increase in blood flow rate, and relative potencies determined on the basis of doses producing a 100% increase in blood flow rate, ED100 [100% effective dose], were in the descending order: nifedipine > verapamil > diltiazem > dilazep > dipyridamole > carbocromen, and approximately 1:1/12:1/26:1/100:1/300:1/500. All drugs except for dipyridamole caused a dose-dependent decrease in the developed tension of the papillary muscle, although nifedipine and diltiazem in low doses produced a slight increase. Relative potencies determined on the basis of doses producing a 50% decrease in developed tension, ID50 [median inhibitory dose], were as follows: nifedipine (1), verapamil (1/13), diltiazem (1/40), dilazep (1/100) and carbocromen (1/270). Ratios of the ID50 to ED100 were as follows: diltiazem (5.2), nifedipine (3.5), verapamil (3.5), dilazep (2.5), and carbocromen (1.8). The higher the value the more predominant on the coronary vascular bed or the less depressant were their actions on the myocardial contractility.