Sobel B E, Fields L E, Robison A K, Fox K A, Sarnoff S J
Proc Natl Acad Sci U S A. 1985 Jun;82(12):4258-62. doi: 10.1073/pnas.82.12.4258.
Conventional activators of the fibrinolytic system used for coronary thrombolysis entail unavoidable delay, risk of bleeding, or both in contrast to tissue-type plasminogen activator (t-PA). Because the potential benefit of coronary thrombolysis is inversely related to the duration of antecedent ischemia, this study was performed to develop an approach for facilitated absorption of intramuscularly injected t-PA potentially adaptable for prompt, self-medication. In rabbits, absorption was markedly potentiated by hydroxylamine hydrochloride and electrical stimulation at the injection site. Intramuscular administration of t-PA in doses of 1 mg/kg of body weight, comparable to amounts given intravenously to patients (0.5-0.75 mg/kg), elicited peak blood levels of 431 +/- 52 (SEM) ng/ml 5 min after injection, well within the therapeutic range. In dogs, absorption facilitated by hydroxylamine promptly elicited angiographically documented coronary thrombolysis as well. The approach developed should ultimately permit prompt coronary thrombolysis and enhanced salvage of jeopardized ischemic myocardium in patients with life-threatening coronary thrombi.
与组织型纤溶酶原激活剂（t-PA）相比，用于冠状动脉溶栓的传统纤溶系统激活剂不可避免地会导致延迟、出血风险或两者兼有。由于冠状动脉溶栓的潜在益处与先前缺血的持续时间成反比，因此进行本研究以开发一种促进肌肉注射t-PA吸收的方法，该方法可能适用于快速的自我给药。在兔子中，注射部位的盐酸羟胺和电刺激可显著增强吸收。以1mg/kg体重的剂量肌肉注射t-PA，与静脉注射给患者的量（0.5-0.75mg/kg）相当，注射后5分钟血药峰值水平为431±52（SEM）ng/ml，完全在治疗范围内。在狗中，羟胺促进的吸收也能迅速引发血管造影记录的冠状动脉溶栓。所开发的方法最终应能使患有危及生命的冠状动脉血栓的患者迅速进行冠状动脉溶栓，并增强对濒危缺血心肌的挽救。
