Inhibition of thromboxane A2 synthetase failed to limit myocardial infarct size in a rabbit ischemia-reperfusion model.

Abstract

The role of thromboxane A2 (TXA2) in myocardial necrosis during coronary occlusion and reperfusion was investigated by using a new long-acting TXA2 synthetase inhibitor, DP1904. A rabbit coronary branch was occluded for 30 min and then reperfused for 72h. Infarct size and area at risk were determined histologically and by fluorescent particles, respectively, for 4 groups; a saline receiving control group (C group), a DP1904 treated group (DP group), a heparin treated group (H group), and a DP1904 plus heparin treated group (DP-H group). The H group and DP-H group were included to examine the influence of heparinization on the effect of DP1904. In the DP and DP-H groups, 10 mg/kg of DP1904 was injected i.v. 2h before coronary occlusion, as well as 24 and 48h after reperfusion. This dose of DP1904 (10 mg/kg i.v.) was able to inhibit serum thromboxane B2 formation ex vivo to 1.1% of the control level 2h after its administration, and to 39.5% at 24h, in the rabbit (n = 5). The H and DP-H groups received 1000 units of heparin i.v. 3 min prior to coronary occlusion. The size of the area at risk, heart rate, blood pressure, and rate-pressure products were comparable between the 4 groups. Mortality was not significantly different in any group. Myocardial infarct size as the percentage of area at risk was 43.6 +/- 3.9% in C group (n = 10), 41.1 +/- 4.4% in DP group (n = 9), 47.8 +/- 3.0% in H group (n = 13), and 44.7 +/- 4.0% in DP-H group (n = 10), which were not significantly different. These findings suggest that TXA2 does not contribute directly to myocardial necrosis during coronary occlusion and reperfusion in the rabbit.

• Authors: A Tsuchida, T Miura, T Ogawa, T Iwamoto, K Shimamoto, O Iimura
• Journal: Japanese circulation journal (Jpn Circ J) Vol. 55 Issue 2 Pg. 174-83 (Feb 1991) ISSN: 0047-1828 [Print] Japan
• PMID: 2020088 (Publication Type: Journal Article)

Chemical References

• Imidazoles
• Tetrahydronaphthalenes
• Thromboxane A2
• Heparin
• nafagrel
• Thromboxane-A Synthase

Topics

• Animals
• Constriction
• Coronary Vessels
• Disease Models, Animal
• Heparin (pharmacology)
• Imidazoles (pharmacology)
• Male
• Myocardial Infarction (metabolism, pathology)
• Myocardial Reperfusion
• Myocardium (pathology)
• Necrosis
• Rabbits
• Tetrahydronaphthalenes (pharmacology)
• Thromboxane A2 (physiology)
• Thromboxane-A Synthase (antagonists & inhibitors)