Gu H, Gaugl J F, Barron B A, Caffrey J L
Department of Physiology, Texas College of Osteopathic Medicine, Fort Worth 76107.
Circ Shock. 1990 Dec;32(4):257-71.
Naloxone potentiates the inotropic effect of selected beta-agonists in the canine isolated heart. This could be accomplished by elevating circulating catecholamines through a reduction in their disposal or by the facilitation of events at or subsequent to the cardiac beta-receptor. To evaluate the first hypothesis, epinephrine was infused intravenously into a blood-perfused isolated heart-lung preparation. Catecholamines were determined and myocardial and pulmonary epinephrine uptakes were calculated. Naloxone enhanced the inotropic effect (peak +dP/dt) during epinephrine infusion. Coronary blood flow and coronary venous epinephrine concentrations were also elevated after naloxone. Calculated myocardial and pulmonary uptake of epinephrine were, however, unaltered by naloxone. The increased coronary sinus epinephrine after naloxone was evaluated further in experiments redesigned to eliminate the influence of changing coronary blood flow. Epinephrine was infused into the left common coronary and coronary blood flow as maintained constant, 100% above the resting flow rate. Naloxone enhanced the contractile response to epinephrine without altering coronary artery or coronary sinus epinephrine concentrations or myocardial epinephrine uptake. By comparison, corticosterone, an extra-neuronal uptake inhibitor, also potentiated the inotropic effect of infused epinephrine under identical conditions. However, corticosterone was accompanied by a significant increase in coronary sinus epinephrine concentration and a decrease in myocardial epinephrine uptake. We therefore concluded that the ability of naloxone to enhance the inotropic effect of epinephrine is not mediate through an increase in plasma epinephrine concentration secondary to a decrease in the disposal of circulating catecholamines.
纳洛酮可增强犬离体心脏中某些β-激动剂的正性肌力作用。这可以通过减少儿茶酚胺的清除以提高循环中的儿茶酚胺水平来实现，或者通过促进心脏β受体处或之后的事件来实现。为了评估第一个假设，将肾上腺素静脉注入血液灌注的离体心肺制备物中。测定了儿茶酚胺，并计算了心肌和肺对肾上腺素的摄取。纳洛酮增强了肾上腺素输注期间的正性肌力作用（峰值 +dP/dt）。纳洛酮给药后，冠状动脉血流量和冠状静脉肾上腺素浓度也升高。然而，计算得出的心肌和肺对肾上腺素的摄取并未因纳洛酮而改变。在重新设计的实验中进一步评估了纳洛酮给药后冠状窦肾上腺素增加的情况，以消除冠状动脉血流量变化的影响。将肾上腺素注入左冠状动脉主干，冠状动脉血流量保持恒定，比静息流量高100%。纳洛酮增强了对肾上腺素的收缩反应，而不改变冠状动脉或冠状窦肾上腺素浓度或心肌对肾上腺素的摄取。相比之下，皮质酮是一种非神经元摄取抑制剂，在相同条件下也增强了输注肾上腺素的正性肌力作用。然而，皮质酮伴随着冠状窦肾上腺素浓度的显著增加和心肌对肾上腺素摄取的减少。因此，我们得出结论，纳洛酮增强肾上腺素正性肌力作用的能力不是通过循环儿茶酚胺清除减少继发血浆肾上腺素浓度增加来介导的。
