Myocardial salvage efficacy of a thromboxane receptor antagonist, SQ, 30,741, in relation to inhibition ex vivo of platelet function in the ferret.

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.

• Authors: A W Gomoll, M L Ogletree
• Journal: Prostaglandins (Prostaglandins) Vol. 46 Issue 3 Pg. 233-42 (Sep 1993) ISSN: 0090-6980 [Print] United States
• PMID: 8234831 (Publication Type: Journal Article)

Chemical References

• Prostaglandin Endoperoxides, Synthetic
• Receptors, Thromboxane
• Vasoconstrictor Agents
• SQ 30741
• Thromboxane A2
• 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid

Topics

• 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
• Analysis of Variance
• Animals
• Blood Platelets (drug effects, physiology)
• Blood Pressure (drug effects)
• Ferrets
• Heart (drug effects)
• Heart Rate (drug effects)
• In Vitro Techniques
• Male
• Myocardial Infarction (blood, pathology)
• Myocardial Ischemia (blood, pathology)
• Myocardium (pathology)
• Orchiectomy
• Prostaglandin Endoperoxides, Synthetic (pharmacology)
• Receptors, Thromboxane (antagonists & inhibitors)
• Reperfusion
• Thromboxane A2 (analogs & derivatives, antagonists & inhibitors, pharmacology)
• Vasoconstrictor Agents (pharmacology)