Cardioprotective actions of the specific thromboxane receptor antagonist (+)-S145Na following coronary occlusion and reperfusion in the rat.
We studied the effects of a novel thromboxane receptor antagonist (+)-S145Na, on the loss of myocardial creatine kinase activity in the rat myocardium after 10 minutes of coronary artery ligation, followed by 24 hours of reperfusion. (+)-S145Na (500 micrograms/kg), or its vehicle, was administered 10 minutes after occlusion (just prior to reperfusion) intravenously. Myocardial creatine kinase activity was significantly reduced in the ischemic areas of hearts obtained from rats receiving vehicle when compared to sham operated control rats. This loss in creatine kinase activity was significantly attenuated in hearts obtained from rats receiving (+)-S145Na. These findings further support the important role of thromboxane A2 in the pathogenesis of reperfusion injury following myocardial ischemia, and that (+)-S145Na may be a useful agent in the treatment of myocardial reperfusion injury.
Tsao
P S
PS
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Lefer
A M
AM
D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D003327:Coronary Disease / Q000503:physiopathology*; D003402:Creatine Kinase / Q000032:analysis; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D011982:Receptors, Prostaglandin / Q000187:drug effects*; D017482:Receptors, Thromboxane; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors*
D001643:Bridged Bicyclo Compounds; D005229:Fatty Acids, Monounsaturated; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; C056566:S 145; D013928:Thromboxane A2; D003402:Creatine Kinase