Vatner S F, Marsh J D, Swain J A
J Clin Invest. 1975 Feb;55(2):207-17. doi: 10.1172/JCI107923.
We studied the effects of i.v. 2 mg/kg morphine sulfate (MS) on coronary blood flow and resistance, left ventricular (LV) diameter and pressure (P), rate of change of pressure (dP/dt), and dP/dt/P in conscious dogs. An initial transient reduction in coronary vascular resistance, associated with increases in heart rate, dP/dt, dP/dt/P, and reductions in LV end-diastolic and end-systolic size were observed. This was followed by a prolonged increase in mean coronary vascular resistance, lasting from 5 to 30 min, while heart rate, arterial pressure, and LV end-diastolic diameter returned to control levels and dP/dt/P remained slightly but significantly above control. At 10 min, late diastolic coronary flow had fallen from 44 plus or minus 3 ml/min to a minimum level of 25 plus or minus 3 ml/min, while late diastolic coronary resistance had risen from 1.68 plus or minus 0.10 to 3.04 plus or minus 0.28 mm Hg/ml/min. Morphine also induced substantial coronary vasoconstriction when heart rate was held constant. Neither the MS-induced coronary vasoconstriction nor the positive inotropic response was abolished by bilateral adrenalectomy. The positive inotropic response of MS was reversed after beta blockade, but not the coronary vasoconstriction. Alpha receptor blockade abolished the late coronary vasoconstriction effects of morphine, and only dilatation occurred. In anesthetized dogs MS failed to produce late coronary vasoconstriction. Coronary after a respiratory-depressant dose of morphine, 10 mg/kg i.v. Smaller doses of MS, 0.25 mg/kg every 15 min, produced significant coronary vasoconstriction after a total dose of 0.75 mg/kg in the conscious dogs. The effects of morphine may differ in the normal dog and man and may vary depending upon the presence or absence of coronary artery disease. However, in the normal conscious dog, MS elicits a mild beta adrenergic increase in contractility and an important coronary vasoconstrictor effect, which is mediated through alpha adrenergic receptors.
我们研究了静脉注射2毫克/千克硫酸吗啡（MS）对清醒犬冠状动脉血流和阻力、左心室（LV）直径和压力（P）、压力变化率（dP/dt）以及dP/dt/P的影响。观察到冠状动脉血管阻力最初出现短暂降低，同时心率、dP/dt、dP/dt/P增加，左心室舒张末期和收缩末期大小减小。随后平均冠状动脉血管阻力持续增加5至30分钟，而心率、动脉压和左心室舒张末期直径恢复到对照水平，dP/dt/P仍略高于对照但差异显著。在10分钟时，舒张末期冠状动脉血流从44±3毫升/分钟降至最低水平25±3毫升/分钟，而舒张末期冠状动脉阻力从1.68±0.10升至3.04±0.28毫米汞柱/毫升/分钟。当心率保持恒定时，吗啡也会引起显著的冠状动脉血管收缩。双侧肾上腺切除并未消除MS诱导的冠状动脉血管收缩或正性肌力反应。MS的正性肌力反应在β受体阻断后逆转，但冠状动脉血管收缩未被逆转。α受体阻断消除了吗啡后期的冠状动脉血管收缩作用，仅出现扩张。在麻醉犬中，MS未能产生后期冠状动脉血管收缩。静脉注射10毫克/千克呼吸抑制剂量的吗啡后。较小剂量的MS，每15分钟0.25毫克/千克，在清醒犬中总剂量达到0.75毫克/千克后会产生显著的冠状动脉血管收缩。吗啡的作用在正常犬和人中可能不同，并且可能因是否存在冠状动脉疾病而有所变化。然而，在正常清醒犬中，MS会引起轻度的β肾上腺素能介导的收缩力增加以及重要的冠状动脉血管收缩效应，该效应通过α肾上腺素能受体介导。
