Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dazoxiben, a selective TXA2 synthetase inhibitor, was studied in the incubating sections of porcine basilar arteries with arachidonic acid (AA) 50 mumols/L and calcimycin (calcium inophore A-23187) 50 mumol/L. TXB2 and 6-keto-PGF1 alpha were determined by radioimmunoassay. Leukotrienes (LT) were extracted and purified with SEP-PAK column, identified by HPLC and determined by bioassay with ileum of guinea pig. The results showed that the production of TXB2 was unaltered whether or not the incubation of arteries were induced by AA or calcimycin. Dazoxiben and indomethacin 0.05-50 mumols/L had no effects on the production of TXB2. However, dazoxiben 0.5, 5 and 50 mumols/L increased the production of 6-keto-PGF1 alpha by 16.3%, 19.0% and 30.7%, respectively. Indomethacin 0.5, 5 and 50 mumols/L decreased the production of 6-keto-PGF1 alpha by 22.3%, 24.9% and 24.0%, respectively. Meanwhile dazoxiben 1, 10 and 100 mumols/L decreased the production of LT by 33.4%, 45.6% and 66.4%, respectively. These results suggest that the protective effect of dazoxiben on the damages which resulted from brain ischemia may be related to the change of TAX2/PGI2 balance in the brain tissue as well as the inhibition of production of LT.
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PMID:[Effect of dazoxiben on the metabolism of arachidonic acid in isolated porcine basilar arteries]. 212 32

This study investigated whether dazoxiben, a thromboxane synthesis inhibitor, could reverse regional contractile dysfunction and protect against adenine nucleotide loss in the "stunned myocardium". Hearts from anesthetized dogs were "stunned" by 15 min of left anterior descending coronary artery occlusion followed by 3 hr of reperfusion. Left ventricular segment shortening (%SS) and regional myocardial blood flow (RMBF) were measured by sonomicrometry and the radioactive microsphere technique, respectively. Local coronary venous blood was withdrawn and thromboxane A2 and prostacyclin measured by radioimmunoassay. Transmural biopsies from the reperfused and nonischemic areas were taken at 3 hr following reperfusion for tissue metabolite analysis. During ischemia, %SS, RMBF and area at risk were decreased to similar levels in both control and dazoxiben-treated hearts indicating equivalent degrees of flow deprivation. During reperfusion, %SS recovered only partially and was not significantly improved by dazoxiben. Dazoxiben augmented peak prostacyclin production (123 +/- 31% vs. 292 +/- 49% of preocclusion values) following reperfusion, while it completely blocked thromboxane A2 production. Dazoxiben attenuated the decline in endocardial ATP (69 +/- 5% vs. 92 +/- 9% normalized to the nonischemic zone) and total adenine nucleotides. The results indicate that dazoxiben may elicit a cardioprotective effect on energy metabolism in the reperfused heart, but this is dissociated from any improvement in regional contractile function.
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PMID:Metabolic protection of the reperfused canine endocardium by the thromboxane synthetase inhibitor, dazoxiben. 305 35