Coker S J, Parratt J R
Br J Clin Pharmacol. 1983;15 Suppl 1(Suppl 1):87S-95S. doi: 10.1111/j.1365-2125.1983.tb02115.x.
1 The effects of the thromboxane synthetase inhibitor dazoxiben (UK 37248) on haemodynamics, blood gases, thromboxane and prostacyclin release and on arrhythmias were examined in anaesthetised greyhounds subject to acute coronary artery occlusion and reperfusion. 2 Ten minutes after the administration of UK 37248 2 mg/kg intravenously, the plasma concentration of thromboxane B2 in the coronary sinus was significantly reduced whereas the 6-keto-prostaglandin F1 alpha concentration was increased. 3 UK 37248 did not significantly alter the number of arrhythmias or the incidence of ventricular fibrillation resulting from coronary artery occlusion. There was evidence, however, that in some drug-treated animals there may have been incomplete inhibition of thromboxane synthesis during coronary artery occlusion. 4 A further dose of 1 mg/kg UK 37248 was administered intravenously 5 min before the release of the 40 min coronary artery occlusion. Seven out of eight control dogs died in ventricular fibrillation following reperfusion whereas only one out of eight drug-treated animals fibrillated. 5 This latter result suggests that thromboxane may be an important factor in reperfusion induced ventricular fibrillation and that dazoxiben may be a useful drug in clinically related situations.
在麻醉的灵缇犬身上，研究了血栓素合成酶抑制剂达唑氧苯（UK 37248）对急性冠状动脉闭塞和再灌注时血流动力学、血气、血栓素和前列环素释放以及心律失常的影响。
静脉注射2 mg/kg UK 37248十分钟后，冠状窦中血栓素B2的血浆浓度显著降低，而6-酮-前列腺素F1α浓度升高。
UK 37248并未显著改变冠状动脉闭塞导致的心律失常数量或室颤发生率。然而，有证据表明，在一些接受药物治疗的动物中，冠状动脉闭塞期间血栓素合成可能未被完全抑制。
在40分钟冠状动脉闭塞解除前5分钟，静脉注射1 mg/kg UK 37248。八只对照犬中有七只在再灌注后死于室颤，而八只接受药物治疗的动物中只有一只发生室颤。
后一结果表明，血栓素可能是再灌注诱导室颤的一个重要因素，达唑氧苯可能是临床相关情况下的一种有用药物。
