Evans S F, Hinds C J, Varley J G
Br J Pharmacol. 1984 Oct;83(2):443-8. doi: 10.1111/j.1476-5381.1984.tb16505.x.
The specific opiate receptor antagonist, naloxone, can produce haemodynamic improvement and increased survival in experimental shock. The efficacy of naloxone therapy in a canine model of endotoxin shock has been evaluated both with and without intravascular volume replacement. Animals were anaesthetized with alpha-chloralose and allowed to breathe spontaneously. A large bolus dose of endotoxin was followed by a continuous infusion and treatment was instituted one hour after the endotoxin bolus. In the absence of volume replacement, naloxone caused only limited and transient increases in mean arterial pressure (MAP) and left ventricular (LV) dp/dt max, with little effect on cardiac index (CI). Total peripheral resistance index (TPRI) tended to rise in both control and naloxone-treated dogs. In volume-replaced animals, naloxone produced substantial and sustained increases in the MAP and LV dp/dt max with an associated rise in the CI. TPRI rose initially in this series and then fell progressively. Further analysis of the improvements in the CI showed an increase in stroke index with a tendency for heart rate to fall. These findings suggest a myocardial action of naloxone in endotoxin shock, which is augmented by volume replacement. An initial, transient vasoconstrictor effect cannot, however, be excluded. Further work is required to determine the mechanism of the effects described.
特异性阿片受体拮抗剂纳洛酮可改善血流动力学，并提高实验性休克的存活率。在有或没有血管内容量补充的情况下，均已评估了纳洛酮疗法在犬内毒素休克模型中的疗效。动物用α-氯醛糖麻醉，并使其自主呼吸。先给予大剂量内毒素推注，随后持续输注，在内毒素推注1小时后开始治疗。在没有容量补充的情况下，纳洛酮仅使平均动脉压（MAP）和左心室（LV）dp/dt max有有限且短暂的升高，对心脏指数（CI）影响很小。在对照组和纳洛酮治疗组的犬中，总外周阻力指数（TPRI）均有升高趋势。在进行容量补充的动物中，纳洛酮使MAP和LV dp/dt max显著且持续升高，同时CI也升高。在该组中，TPRI最初升高，然后逐渐下降。对CI改善情况的进一步分析显示，每搏量指数增加，心率有下降趋势。这些发现提示纳洛酮在内毒素休克中有心肌作用，容量补充可增强这种作用。然而，不能排除最初短暂的血管收缩作用。需要进一步研究以确定上述作用的机制。
