Document Detail

Inhibition of thromboxane A2 synthetase failed to limit myocardial infarct size in a rabbit ischemia-reperfusion model.
MedLine Citation:
PMID:  2020088     Owner:  NLM     Status:  MEDLINE    
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.
A Tsuchida; T Miura; T Ogawa; T Iwamoto; K Shimamoto; O Iimura
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Japanese circulation journal     Volume:  55     ISSN:  0047-1828     ISO Abbreviation:  Jpn. Circ. J.     Publication Date:  1991 Feb 
Date Detail:
Created Date:  1991-05-30     Completed Date:  1991-05-30     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  7806868     Medline TA:  Jpn Circ J     Country:  JAPAN    
Other Details:
Languages:  eng     Pagination:  174-83     Citation Subset:  IM    
Second Department of Internal Medicine, Sapporo Medical College, Japan.
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MeSH Terms
Coronary Vessels
Disease Models, Animal
Heparin / pharmacology
Imidazoles / pharmacology*
Myocardial Infarction / metabolism,  pathology*
Myocardial Reperfusion
Myocardium / pathology
Tetrahydronaphthalenes / pharmacology*
Thromboxane A2 / physiology*
Thromboxane-A Synthase / antagonists & inhibitors*
Reg. No./Substance:
0/Imidazoles; 0/Tetrahydronaphthalenes; 57576-52-0/Thromboxane A2; 9005-49-6/Heparin; 97901-21-8/nafagrel; EC Synthase

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