The Local Anesthetic Effect of Meperidine on the Direct Myocardial Depression in Isolated Ventricular Myocardium

Park, Wyun Kon; Kim, Jong Hoon; Kim, Seoung Jun; Kim, Jung Sub

Abstract

BACKGROUND
The effects of various concentration (20, 50, 100 micrometer) of meperidine were studied in isolated guinea pig and rat ventricular papillary muscles.
METHODS
Isometric force of guinea pig ventricular papillary muscle was examined in normal and 26 mM K+ Tyrode's solution. Experiments using rat and guinea pig papillary muscle under normal and low Na+ (40 mM), respectively, were performed to evaluate the effect on Ca2+ release from the sarcoplasmic reticulum (SR). Normal and slow action potentials (APs) were evaluated by using conventional microelectrode technique. Rapid cooling contractures were performed.
RESULTS
Meperidine caused dose-dependent depression of peak force from rested-state (RS) to 3 Hz stimulation rates in guinea pig papillary muscles. Conduction block was frequently noted at high stimulation rates (2 and 3 Hz) at 150 micrometer meperidine. ~40% depression of peak force was shown at RS contraction under low Na+ Tyrode's solution, although contractile depression was not shown at RS and low stimulation rates in rat papillary muscles. 100 micrometer naloxone did not reverse the contractile depression caused by 100 micrometer meperidine. Either depression of dV/dt-max from 0.1 to 3 Hz stimulation rates or rate-dependent depression among 1, 2 and 3 Hz could be observed at 150 micrometer meperidine. In 26 mM K+ Tyrode's solution, 50 and 100 micrometer meperidine caused dose-dependent depression of early and late force development. In slow APs, changes of dV/dt-max were not shown at 100 micrometer meperidine. ~40% depression of contracture induced by rapid cooling following 2 Hz stimulation rates was shown at 100 micrometer meperidine.
CONCLUSION
The direct myocardial depressant effect of meperidine seems likely to be caused by local anesthetic properties of meperidine, not by the opioid action. Inhibition of SR Ca2+ release, and decreased intracellular Ca2+ secondary to Na+ channel blocking action of meperidine may at least in part be related to direct myocardial depression.