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Effect of Morphine on Isolated Human Atrial Muscle

The effects of 5, 10, 20, and 30 mg/100 ml morphine on the force of contraction of isolated human atrial muscle were studied. The tissue was suspended in Krebs-Ringer bicarbonate solution containing 20 mM glucose at 37 C and stimulated with supramaximal voltage at a rate of 70 pulses/min. Morphine, 5 and 10 mg/100 ml, which represents a much higher concentration than would be achieved in plasma following a usual anesthetizing dose of 2 mg/kg, had no effect on force of contraction over a 30-minute period. Twenty and 30 mg/100 ml morphine depressed force of contraction 21 and 70 per cent, respectively. Simulated morphine diluent, containing chlorbutanol and sodium bisulfite alone, had negligible effects on the force of contraction. Pyruvate, 15 mM, had a marked positive inotropic effect in control preparations. The response to pyruvate remained unimpaired in the presence of 5 and 10 mg/100 ml morphine, whereas it was markedly inhibited in the presence of 20 and 30 mg/100 ml morphine. In the 30 mg/100 ml morphine series there was complete recovery of pyruvate response after washout. It is concluded that clinical doses of morphine do not cause myocardial depression. As previously demonstrated with pentobarbital, morphine in excessive doses may exert a negative inotropic effect by interfering with energy production or utilization at a step subsequent to glycolytic formation of pyruvate.