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.