Augmented thromboxane A2 generation and efficacy of its blockade in acute myocardial infarction.
Serial changes in thromboxane B2, a stable catabolite of thromboxane A2, were measured by radioimmunoassay in peripheral plasma of 55 patients with acute myocardial infarction. Twenty two of 31 patients who were admitted within 6 hr after the onset of acute myocardial infarction, exhibited high thromboxane B2 levels (greater than 300 pg/ml plasma) during the first 24 hr, whereas thromboxane B2 levels of 9 patients never exceeded 300 pg/ml during that period. The former cases were associated with a higher frequency of transmural myocardial infarction, accompanying higher cumulative creatine kinase release (1173 +/- 134 mIU/ml, mean +/- SEM), as compared with the latter cases (393 +/- 104 mIU/ml, P less than 0.001). To evaluate the efficacy of selective thromboxane A2 blockade on diminution of propagating acute myocardial infarction, another group of patients (24 cases) showing transmural myocardial infarction were subjected to therapeutic examination employing OKY-1581, a potent thromboxane A2 synthetase inhibitor. Eleven randomly selected patients were treated with an infusion of OKY-1581 (initiated within 6 hr after onset, 2-3 micrograms/kg per min) for 48 hr, while 13 patient served as controls. The treated patients exhibited a precipitous decrease in thromboxane B2 levels, as compared with the controls, returning to the normal range within 12 hr. The creatine kinase release in the treated patients was markedly reduced (978 +/- 97 mIU/ml) as compared with that in the control patients (1295 +/- 95 mIU/ml, P less than 0.05). These results indicate that a marked increase in thromboxane B2 levels is seen during the early phase of transmural myocardial infarction, and that OKY-1581-induced reduction of thromboxane B2 levels is effective in diminishing creatine kinase release. We suggest that an excessive generation of thromboxane A2 is associated with the evolution of transmural myocardial infarction.
D000179:Acrylates / Q000627:therapeutic use*; D003402:Creatine Kinase / Q000097:blood; D004562:Electrocardiography; D005260:Female; D006801:Humans; D008297:Male; D008689:Methacrylates / Q000627:therapeutic use*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000201:enzymology; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D011379:Prognosis; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors* / Q000097:blood; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D013931:Thromboxanes / Q000037:antagonists & inhibitors*
D000179:Acrylates; D008689:Methacrylates; D013931:Thromboxanes; D013929:Thromboxane B2; D013928:Thromboxane A2; C031517:2-methyl-3-(4-(3-pyridinylmethyl)phenyl)-2-propenoic acid; D010088:Oxidoreductases; D003402:Creatine Kinase; D013930:Thromboxane-A Synthase