Abstract：
Although morphine has been used for treatment-resistant dyspnea in end-stage heart failure patients, information on its cardiovascular safety profile remains limited. Morphine was intravenously administered to halothane-anesthetized dogs (n=4) in doses of 0.1, 1 and 10 mg/kg/10 min with 20 min of observation period. The low and middle doses attained therapeutic (0.13 µg/mL) and supratherapeutic (0.97 µg/mL) plasma concentrations, respectively. The low dose hardly altered any of the cardiovascular variables except that the QT interval was prolonged for 10-15 min after its start of infusion. The middle dose reduced the preload and afterload to the left ventricle for 5-15 min, then decreased the left ventricular contractility and mean blood pressure for 10-30 min, and finally suppressed the heart rate for 15-30 min. Moreover, the middle dose gradually but progressively prolonged the atrioventricular conduction time, QT interval/QTcV, ventricular late repolarization period and ventricular effective refractory period without altering the intraventricular conduction time, ventricular early repolarization period or terminal repolarization period. A reverse-frequency-dependent delay of ventricular repolarization was confirmed. The high dose induced cardiohemodynamic collapse mainly due to vasodilation in the initial 2 animals by 1.9 and 3.3 min after its start of infusion, respectively, which needed circulatory support to treat. The high dose was not tested further in the remaining 2 animals. Thus, intravenously administered morphine exerts a rapidly appearing vasodilator action followed by slowly developing cardiosuppressive effects. Morphine can delay the ventricular repolarization possibly through IKr inhibition in vivo, but its potential to develop torsade de pointes will be small.
摘要：
尽管吗啡已用于治疗终末期心力衰竭患者的难治性呼吸困难，关于其心血管安全性的信息仍然有限.将吗啡以0.1、1和10mg/kg/10分钟的剂量静脉内给予氟烷麻醉的狗（n=4），观察期20分钟。低剂量和中等剂量达到治疗（0.13µg/mL）和超治疗（0.97µg/mL）血浆浓度，分别。低剂量几乎不改变任何心血管变量，除了QT间隔在开始输注后延长10-15分钟。中剂量减少左心室的前负荷和后负荷5-15分钟，然后降低左心室收缩力和平均血压10-30分钟，最后抑制心率15-30分钟。此外，中剂量逐渐但逐渐延长房室传导时间，QT间期/QTcV,心室复极期和心室有效不应期不改变心室内传导时间，心室早期复极期或终末复极期。证实了心室复极的反向频率依赖性延迟。大剂量诱导的心血流动力学崩溃主要是由于最初的2只动物在开始输注后1.9和3.3分钟的血管舒张。分别,需要循环支持来治疗。在其余2只动物中不进一步测试高剂量。因此，静脉注射吗啡会产生迅速出现的血管舒张作用，随后缓慢产生心脏抑制作用。吗啡可能通过体内抑制IKr延迟心室复极，但是它发展尖端扭转的潜力将很小。
