Antithrombotic effects of BMY21190, an inhibitor of cAMP phosphodiesterase, in a canine model of coronary artery thrombosis.
BMY21190, an inhibitor of cyclic AMP phosphodiesterase, has a coronary vasodilating effect. BMY21190 was evaluated for its ability to modify the development of experimental thrombosis resulting from anodal current injury (100 microA for 6 h) of the intimal surface of the left circumflex coronary artery (LCX) in anesthetized dogs. Two groups of dogs were studied. One group received BMY21190 (1 mg/kg) and the other group received an equal volume of vehicle infused into the left jugular vein. After a 30 min administration of BMY21190, heart rate and mean coronary blood flow were increased significantly and mean arterial pressure was decreased. However, the myocardial tension of the left anterior descending coronary artery (LAD) and LCX areas did not increase significantly after BMY21190 infusion. During LCX stimulation, the first LCX occlusion and hyperemic reaction of the control group both occurred significantly earlier than those of the BMY21190 group. BMY21190 treatment reduced the development of the LCX thrombus mass, as compared to that in the controls. In ex vivo studies, platelet aggregation in response to arachidonic acid, ADP or collagen was inhibited by BMY21190. These results suggest that BMY21190 possesses anti-thrombotic and coronary vasodilating effects which may be mediated through the inhibition of cyclic AMP phosphodiesterase.
Minami
M
M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Higashi-Nippon-Gakuen University, Hokkaido, Japan.
Driscoll
E M
EM
Lucchesi
B R
BR
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003328:Coronary Thrombosis / Q000188:drug therapy*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D066298:In Vitro Techniques; D008297:Male; D010100:Oxygen / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000627:therapeutic use*
D007093:Imidazoles; D010975:Platelet Aggregation Inhibitors; D011804:Quinolines; D014665:Vasodilator Agents; C083876:BMY 21190; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D010100:Oxygen