Mechanism of the negative inotropic effect of propofol in isolated ferret ventricular myocardium

Anesthesiology. 1994 Apr;80(4):859-71. doi: 10.1097/00000542-199404000-00020.

Abstract

Background: The aim of this study was to investigate propofol's effect on myocardial contractility and relaxation and examine its underlying mechanism of action in isolated ferret ventricular myocardium.

Methods: The effects of propofol on variables of contractility and relaxation and on the free intracellular Ca++ transient detected with the Ca(++)-regulated photoprotein aequorin were analyzed. Propofol's effects were evaluated in a preparation in which the sarcoplasmic reticulum function was impaired by ryanodine. The effects of propofol's solvent, intralipid, on myocardial contractility, relaxation, and the intracellular Ca++ transient also were examined.

Results: Propofol, at concentrations of 10 microM or greater, decreased contractility and, at concentrations of 30 of microns or greater, decreased the amplitude of the intracellular Ca++ transient. At equal peak force, control peak aequorin luminescence in [Ca++]o = 2.25 mM and peak aequorin luminescence in 300 microM [Ca++]o = 2.25 mM and peak aequorin luminescence in 300 microM propofol in [Ca++]o > 2.25 mM did not differ, which suggests that propofol does not alter myofibrillar Ca++ sensitivity. After inactivation of sarcoplasmic reticulum Ca++ release with 1 microM ryanodine, a condition in which myofibrillar activation depends almost exclusively on transsarcolemmal Ca++ influx, propofol caused a decrease in contractility and in the amplitude of the intracellular Ca++ transient. Under these conditions, propofol's relative negative inotropic effect did not differ from that in control muscles not exposed to ryanodine. Propofol's solvent, 10% intralipid, exerted a modest positive inotropic effect in this preparation. The intracellular Ca++ transient was unchanged by intralipid. Neither propofol nor intralipid altered the load sensitivity of relaxation.

Conclusions: These findings suggest that the negative inotropic effect of propofol results from a decrease in intracellular Ca++ availability with no changes in myofibrillar Ca++ sensitivity. At least part of propofol's action is attributable to inhibition of transsarcolemmal Ca++ influx.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium / metabolism
  • Depression, Chemical
  • Ferrets
  • Heart / drug effects*
  • Heart / physiology
  • Heart Ventricles / drug effects
  • In Vitro Techniques
  • Intracellular Fluid / metabolism
  • Male
  • Myocardial Contraction / drug effects*
  • Myocardium / metabolism
  • Papillary Muscles / drug effects
  • Papillary Muscles / metabolism
  • Papillary Muscles / physiology
  • Propofol / pharmacology*
  • Ryanodine / pharmacology
  • Ventricular Function

Substances

  • Ryanodine
  • Calcium
  • Propofol