Inhibition of coronary circulatory failure and thromboxane A2 release during coronary occlusion and reperfusion by 2-phenylaminoadenosine (CV-1808) in anesthetized dogs.
The effects of potent coronary vasodilator, 2- phenylaminoadenosine (CV-1808), on coronary circulatory failure and thromboxane (TX) A2 release were studied during coronary occlusion (for 60 min) and subsequent reperfusion (for 60 min) in anesthetized dogs. During coronary reperfusion, reactive hyperemic response was attenuated, and coronary conductance decreased gradually with time, suggesting coronary circulatory failure. TXA2 release was markedly increased, as demonstrated by contraction of rabbit aortic strips perfused with coronary venous blood draining the ischemic myocardium, and by increased release of radioimmunologically assayable TXB2. CV-1808 (0.25 microgram/kg/min i.v. infusion throughout the experimental period, starting 10 min before coronary occlusion) inhibited coronary circulatory failure and TXA2 release. TXA2 synthetase of horse platelet microsomes was not significantly inhibited (-11.6 +/- 2.1%) by 10(-4) M CV-1808. The compound (10(-5) and 10(-4) M) inhibited collagen-induced TXB2 formation in a dose-dependent manner (-23.0 +/- 9.0 and -74.0 +/- 15.0%, respectively), but not arachidonic acid-induced TXB2 formation by dog platelets, suggesting that CV-1808 inhibited phospholipases. Myocardial infarct size determined 60 min after reperfusion was significantly reduced by CV-1808. Thus, CV-1808 appeared to be effective for salvaging ischemic myocardium. The effect might be related to improvement of coronary circulation and inhibition of release of vasoactive substances, including TXA2, from the ischemic myocardium.
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000097:blood / Q000503:physiopathology*; D003331:Coronary Vessels / Q000503:physiopathology; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D010477:Perfusion; D011817:Rabbits; D013928:Thromboxane A2 / Q000097:blood*; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D013931:Thromboxanes / Q000097:blood*; D014665:Vasodilator Agents / Q000494:pharmacology*
D001095:Arachidonic Acids; D013931:Thromboxanes; D014665:Vasodilator Agents; D016718:Arachidonic Acid; D013929:Thromboxane B2; D013928:Thromboxane A2; D013930:Thromboxane-A Synthase; C026708:2-phenylaminoadenosine; D000241:Adenosine