Urthaler F, Walker A A, James T N
J Thorac Cardiovasc Surg. 1976 Jul;72(1):142-9.
This study compares the inotropic action of morphine sulfate and ketamine hydrochloride on isolated canine right ventricular trabeculae. The heart was removed from 19 mongrel puppies weighing 5 to 9 kilograms and placed in Krebs-Ringer bicarbonate solution. The bathing solution contained 1.3 mM. of Ca2+ and was bubbled with a gas mixture of 95 per cent oxygen and 5 per cent carbon dioxide. At Lmax (i.e., the peak of isometric force-length curve) morphine even in large concentrations (up to 1 mg. per milliter) produced no significant direct inotropic effect. At the lower concentrations tested there was a minor but not significant increase in contractile performance, whereas at the highest concentration used there was a minor but not significant depression in contractility. In these same muscles lower concentrations of ketamine had a significant positive inotropic action, but a concentration of 200 mug per milliliter, which is approximately equimolecular to 1 mg. per milliliter of morphine sulfate, caused a profound depression in contractile performance. In the presence of a beta-blocking agent and in reserpine-pretreated muscles, low concentrations of ketamine, which had only a positive inotropic action in the normal muscles, now caused depression of contractile performance. The positive inotropic action of ketamine is thus indirect and mediated via adrenergic influences. At each concentration studied the direct inotropic action of ketamine was exclusively negative. Because of this bimodal inotropic action seen when adrenergic mechanisms are intact, we conclude that caution must be exercised when ketamine is given to patients previously treated or still under the influence of drugs having adrenolytic properties. Caution is also necessary when ketamine is used in patients having diminished cardiac adrenergic reserves as in congestive heart failure.
本研究比较了硫酸吗啡和盐酸氯胺酮对离体犬右心室小梁的变力作用。从19只体重5至9千克的杂种幼犬身上取出心脏，置于碳酸氢盐林格氏液中。浴液中含有1.3 mM的Ca2+，并用95%氧气和5%二氧化碳的混合气体鼓泡。在Lmax（即等长力-长度曲线的峰值）时，即使是高浓度（高达每毫升1毫克）的吗啡也不会产生显著的直接变力作用。在测试的较低浓度下，收缩性能有轻微但不显著的增加，而在使用的最高浓度下，收缩力有轻微但不显著的降低。在这些相同的肌肉中，较低浓度的氯胺酮有显著的正性变力作用，但每毫升200微克的浓度（约与每毫升1毫克硫酸吗啡等分子）会导致收缩性能严重降低。在存在β受体阻滞剂和利血平预处理的肌肉中，低浓度的氯胺酮在正常肌肉中仅具有正性变力作用，现在却导致收缩性能降低。因此，氯胺酮的正性变力作用是间接的，通过肾上腺素能影响介导。在研究的每个浓度下，氯胺酮的直接变力作用完全是负性的。由于在肾上腺素能机制完整时观察到这种双峰变力作用，我们得出结论，当给先前接受过具有肾上腺素能阻断特性的药物治疗或仍受其影响的患者使用氯胺酮时，必须谨慎。当氯胺酮用于心脏肾上腺素能储备减少的患者（如充血性心力衰竭患者）时，也有必要谨慎使用。
