Prevention of extension of ischaemic damage following acute myocardial ischaemia by dazoxiben, a new thromboxane synthetase inhibitor.

Abstract 1 Dazoxiben, a new thromboxane synthetase inhibitor, at an infusion rate of 5 mg/kg/h inhibited the ischaemia-induced increase in circulating thromboxane B2 in cats. 2 Dazoxiben also restored the S-T segment of the electrocardiogram toward normal values after the onset of ischaemia, and prevented the rise in plasma creatine kinase activity usually observed during myocardial ischaemia. 3 Associated with the above changes were reduced loss of myocardial creatine kinase activity and aminonitrogen concentration in the ischaemic region of those cats treated with dazoxiben. 4 No significant effects of dazoxiben were observed on heart rate, mean arterial blood pressure or the product of the two, the pressure-rate index. Therefore, dazoxiben does not protect by reducing myocardial oxygen demand. 5 The mechanism of the protective action of dazoxiben in acute myocardial ischaemia seems to be either due to prevention of the constrictor and cytolytic actions of thromboxane A2 or to metabolic and cellular actions of dazoxiben unrelated to thromboxane synthetase inhibition.