Daltroban, a thromboxane receptor antagonist, protects the myocardium against reperfusion injury following myocardial ischemia without protecting the coronary endothelium.
The effects of daltroban, a specific thromboxane receptor antagonist, were investigated in a model of myocardial ischemia consisting of 1.5 h of coronary artery occlusion followed by reperfusion for 4.5 h in anesthetized cats. Daltroban (1 mg/kg) was infused as a bolus 10 min prior to reperfusion of the left anterior descending (LAD) coronary artery. Daltroban infusion resulted in a significantly lower necrotic area expressed as a percentage of the myocardial area-at-risk compared to the MI + vehicle group. However, daltroban failed to retard increases in myeloperoxidase activity in the ischemic myocardium, indicating no reduction in neutrophil accumulation. Moreover, left anterior descending coronary artery ring preparations isolated from daltroban treated MI cats exhibited endothelial dysfunction following ischemia reperfusion. Thus, daltroban significantly protected the myocardium from reperfusion injury without protecting the coronary endothelium or retarding neutrophil accumulation.
Viehman
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GE
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
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Lefer
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D000818:Animals; D002415:Cats; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D009336:Necrosis / Q000517:prevention & control; D009195:Peroxidase / Q000378:metabolism; D010648:Phenylacetates / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D013931:Thromboxanes / Q000037:antagonists & inhibitors*; D014661:Vasoconstriction / Q000187:drug effects
D010648:Phenylacetates; D013449:Sulfonamides; D013931:Thromboxanes; D009195:Peroxidase; C051762:daltroban