Effect of zomepirac on experimental coronary artery thrombosis and ischemic myocardial injury in the conscious dog.
The nonsteroidal anti-inflammatory agent, zomepirac, was evaluated for its in vivo antithrombotic effects in conscious canines by inducing left circumflex (LCX) coronary artery thrombosis with low-amperage electrical stimulation (50 muA for 24 h) of the intimal surface of the vessel. Zomepirac, 10 mg/kg i.v., given at 0 and 12 h, prevented occlusive coronary artery thrombosis (seven of 10 controls developed occlusive thrombi, compared to one of eight zomepirac-treated animals; p = 0.02). LCX thrombus mass also was reduced by zomepirac (control: 24.0 +/- 4.0 mg; zomepirac: 10.2 +/- 2.4 mg, p less than 0.05; means +/- SEM). Left ventricular infarct mass due to occlusive LCX coronary artery thrombosis was likewise reduced. In a separate series of experiments, zomepirac (10 mg/kg i.v.), given 30 min before occlusion, failed to limit the extent of irreversible myocardial injury after temporary (90 min) LCX coronary artery occlusion in the canine. Infarct size, as a percent of the area at risk of infarction, averaged 47.8 +/- 3.9% in controls, and 40.4 +/- 7.5% in zomepirac-treated animals (means +/- SEM). No difference in the mass of myocardium at risk of infarction was observed between the two groups. In this latter study, zomepirac produced no significant hemodynamic effects. Ex vivo platelet aggregation in response to collagen and arachidonic acid was decreased significantly by zomepirac, but aggregation to ADP was unaffected. These results suggest that zomepirac possesses anti-thrombotic properties, but lacks intrinsic cardioprotective effects. Therefore, zomepirac may be of potential value in the prevention of coronary artery thrombosis owing to its ability to modify platelet reactivity.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001095:Arachidonic Acids / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy*; D004195:Disease Models, Animal; D004285:Dogs; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy; D010974:Platelet Aggregation / Q000187:drug effects; D011758:Pyrroles / Q000627:therapeutic use*; D013928:Thromboxane A2 / Q000096:biosynthesis; D014046:Tolmetin / Q000031:analogs & derivatives / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D005343:Fibrinolytic Agents; D011758:Pyrroles; D013928:Thromboxane A2; C020549:zomepirac; D014046:Tolmetin