Combined depressant effects of diltiazem and volatile anesthetics on contractility in isolated ventricular myocardium.
Because the volatile anesthetics depress the entry of calcium (Ca) into myocardial cells and also alter release of intracellular Ca stores, additional pharmacologic blockade of Ca entry could potentially enhance anesthetic-induced depression. The depressant effects of the calcium entry blocker diltiazem combined with the volatile anesthetics halothane, enflurane, or isoflurane were investigated in isolated guinea pig papillary muscle. Muscle contractions were studied in normal Tyrode solution after rest and at stimulation rates of 0.1, 0.25, 0.5, 1, 2, and 3 Hz. Anesthetics were studied in the presence of 0.1 and 1 microM diltiazem, which depressed tension to approximately 85 and 55% of control at 2-3 Hz, respectively; depression at the higher concentration was frequency-dependent. Depressant effects of enflurane were determined as previously done for equianesthetic concentrations (approximately 1 and 2 MAC) of halothane and isoflurane. At all stimulation rates, 1.7 and 3.5% enflurane depressed peak tension and dT/dt-max to approximately 73 and 50% of the mean control-recovery value, respectively. After control measurements of contractile characteristics, effects of 0.1 microM diltiazem were determined alone and then with the addition of halothane (0.75 or 1.5%), isoflurane (1.3 or 2.5%), or enflurane (1.7 or 3.5%), respectively. Recovery from anesthetic was then determined in the continued presence of diltiazem. After rest and at rates less than or equal to 0.5 Hz, equianesthetic concentrations of these volatile agents caused similar depression in the presence of diltiazem. At 3 Hz stimulation rate, 1.3% isoflurane caused significantly less contractile depression than did 1.7% enflurane or than 0.75% halothane. At 2-MAC concentrations, differences among the anesthetics were more apparent: 2.5% isoflurane depressed peak tension and dT/dt-max less than did halothane at 1-3 Hz stimulation rates, and depressed dT/dt-max less than 3.5% enflurane at 2-3 Hz. Similar frequency-dependent differences in depression by approximately 2 MAC anesthetics were observed in the presence of 1 microM diltiazem. The patterns of depressant action by the volatile anesthetics were similar to those previously observed in the absence of diltiazem. Furthermore, when the volatile anesthetic depression of contractions was combined with the depression due to diltiazem-induced blockade of Ca entry, the resulting contractile depression did not differ significantly from a prediction that assumed simply additive effects.
Lynch
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Department of Anesthesiology, University of Virginia Medical Center, Charlottesville 22908.
D000818:Animals; D004110:Diltiazem / Q000494:pharmacology*; D004347:Drug Interactions; D004558:Electric Stimulation; D004737:Enflurane / Q000494:pharmacology*; D006168:Guinea Pigs; D006221:Halothane / Q000494:pharmacology*; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*
D004737:Enflurane; D007530:Isoflurane; D004110:Diltiazem; D006221:Halothane