Influence of thromboxane inhibition on the severity of myocardial ischemia in cats.
The effects of thromboxane (Tx) inhibition or arachidonic acid (AA) infusion were studied in anesthetized cats during acute myocardial ischemia (MI). AA (7.2 mg kg-1 h-1) or imidazole (25 mg kg-1 h-1) infusions were initiated 30 min after occlusion of the left anterior descending coronary artery. Assessment of the degree of protection of the ischemic myocardium was made by measurement of S-T segment elevation, plasma and myocardial creatine phosphokinase (CPK) activities, and myocardial amino-nitrogen content. Assessment of Tx inhibition was performed by radioimmunoassay. Administration of imidazole inhibited the sevenfold increase in plasma thromboxane B2 (TxB2) levels occurring in MI (p less than 0.001 at 2-5 h), markedly decreased S-T segment elevations at 2-k h (p less than 0.025), significantly prevented the elevation  in plasma CPK (p less than 0.05, at 4 and 5 h), the increase in TxB2 post-MI, significantly decreased (p less than 0.025) S-T segment evaluations at 2-5 h, caused a decrease in plasmaCPK levels (p less than 0.05 at 5 h), but did not prevent loss of myocardial CPK or amino-nitrogen. In summary, the administration of imidazole resulted in significant protection of the myocardium in all indices of ischemic damage measured, while AA infusion resulted in only a partial protection. The mechanism of the imidazole protection of ischemic myocardial tissue appears to be via inhibition of Tx synthesis althoug we cannot exclude a hemodynamic or cytoprotective mechanism. These results suggest that specific inhibition of Tx formation is beneficial during acute MI.
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D002415:Cats; D003327:Coronary Disease / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D003402:Creatine Kinase / Q000097:blood; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects; D008247:Lysosomes / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors*; D013929:Thromboxane B2 / Q000097:blood; D013931:Thromboxanes / Q000037:antagonists & inhibitors*
D001095:Arachidonic Acids; D007093:Imidazoles; D013931:Thromboxanes; D013929:Thromboxane B2; D013928:Thromboxane A2; D003402:Creatine Kinase