Inhibition of thromboxane A2 synthetase failed to limit myocardial infarct size in a rabbit ischemia-reperfusion model.
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.
Tsuchida
A
A
Second Department of Internal Medicine, Sapporo Medical College, Japan.
Miura
T
T
Ogawa
T
T
Iwamoto
T
T
Shimamoto
K
K
Iimura
O
O
D000818:Animals; D003250:Constriction; D003331:Coronary Vessels; D004195:Disease Models, Animal; D006493:Heparin / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000473:pathology; D009336:Necrosis; D011817:Rabbits; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000502:physiology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D007093:Imidazoles; D013764:Tetrahydronaphthalenes; D013928:Thromboxane A2; D006493:Heparin; C056295:nafagrel; D013930:Thromboxane-A Synthase