Comparison of the inotropic action of morphine and ketamine studied in canine cardiac muscle.

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.