Myocardial salvage by a novel thromboxane A2 synthetase inhibitor in a canine coronary occlusion-reperfusion model.

Abstract

The effects of the new thromboxane A2 (TXA2) synthetase inhibitor sodium 6-(2-[1-(1H)-imidazolyl]methyl-4,5-dihydrobenzo[b]thiophene)carboxylate (RS-5186), 10 mg/kg i.v., on infarct size, polymorphonuclear leukocytes (PMNs) infiltration, gross myocardial hemorrhage and ventricular arrhythmias were studied using a canine coronary occlusion (2 h)-reperfusion (5 h) model. Infarct size (IS) and risk area (RA) were determined by a dual staining technique. 60 min before coronary occlusion dogs were randomly assigned to either the RS-5186 treated group (n = 11) or the control group (n = 15). RS-5186 reduced infarct size (RS-5186: 26.3 +/- 2.4% of RA (mean +/- SEM) vs control: 50.7 +/- 5.9%, p less than 0.01), and also reduced the area of gross myocardial hemorrhage (RS-5186: 3.9 +/- 2.6% of IS vs control: 22.4 +/- 4.0%, p less than 0.01). The drug also decreased the intensity of PMNs infiltration into the infarcted area (p less than 0.05). However, RS-5186 had no significant influence on the incidence of ventricular arrhythmias. These results suggest that the new thromboxane A2 synthetase inhibitor RS-5186 might be useful in salvaging ischemic myocardium.

• Authors: Y Toki, N Hieda, K Okumura, H Hashimoto, T Ito, K Ogawa, T Satake
• Journal: Arzneimittel-Forschung (Arzneimittelforschung) Vol. 38 Issue 2 Pg. 224-7 (Feb 1988) ISSN: 0004-4172 [Print] Germany
• PMID: 3370068 (Publication Type: Journal Article)

Chemical References

• Thiophenes
• RS 5186
• Thromboxane A2
• Thromboxane-A Synthase

Topics

• Animals
• Arrhythmias, Cardiac (physiopathology)
• Coronary Disease (physiopathology, prevention & control)
• Coronary Vessels (drug effects, physiopathology)
• Dogs
• Hemodynamics (drug effects)
• In Vitro Techniques
• Male
• Neutrophils (drug effects)
• Risk Factors
• Thiophenes (pharmacology)
• Thromboxane A2 (metabolism)
• Thromboxane-A Synthase (antagonists & inhibitors)