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  • Title: Myocardial salvage efficacy of a thromboxane receptor antagonist, SQ, 30,741, in relation to inhibition ex vivo of platelet function in the ferret.
    Author: Gomoll AW, Ogletree ML.
    Journal: Prostaglandins; 1993 Sep; 46(3):233-42. PubMed ID: 8234831.
    Abstract:
    The myocardial salvage efficacy of a thromboxane A2/prostaglandin endoperoxide (TP) receptor antagonist has not been previously determined in a ferret model of ischemia and reperfusion. Assessments of the reproducibility of infarct size resulting from a 90 min period of occlusion followed by 5 hr of reperfusion of the left anterior descending coronary artery in saline-treated control ferrets revealed a consistent mean level of tissue damage representing 23.1 +/- 1.4% of the left ventricle. In subsequent studies, ferrets were given the thromboxane receptor antagonist SQ 30,741 (1 mg/kg bolus and 1 mg/kg/hr infusion, i.v.) or vehicle. At this dose, SQ 30,741 significantly reduced infarct size from that measured in control ferrets by 44%. Concurrently, the drug produced a 97% inhibition of platelet TP receptors as measured by inhibition of the ex vivo platelet shape change response to U-46,619. Drug administration was not associated with measurable alterations in mean blood pressure, heart rate or the rate-pressure-product. The importance of this finding to clinical utility and the mechanism of the observed cardioprotective action, however, remain unclear. These data indicate that the ferret represents a useful model for the assessment of the myocardial salvage efficacy of TP receptor antagonists and are consistent with attenuation of ischemic myocardial damage by doses of these agents which produce > 96% TP receptor blockade.
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