Differential depression of myocardial contractility by volatile anesthetics in vitro: comparison with uncouplers of excitation-contraction coupling.
Depression of rested state contractions (RSCs) and 0.1-0.25 Hz contractions by equianesthetic concentrations of isoflurane (2.5%), halothane (1.5%), and enflurane (3.5%) was studied in guinea pig papillary muscles in which tension development was enhanced by 0.1 microM isoproterenol. In a second series of experiments, an RSC was elicited, followed by a second contraction elicited with stimulus intervals of 300-600 ms. In both types of experiments, the results were similar. Halothane and enflurane depressed rapid initial tension development more than isoflurane. This initial tension development was also selectively depressed by 0.1 microM ryanodine, which specifically decreases Ca2+ release from the sarcoplasmic reticulum (SR). Isoflurane and also enflurane depressed a delayed and late peaking component of tension development, which was very prominent after rest and was depressed by 200 microM procaine or 500 microM benzocaine. Although isoflurane and enflurane were similar to the local anesthetics in depressing late tension, unlike the local anesthetics they prolonged the late phase of tension development as well. The late tension of the RSC is associated with Ca2+, which enters the rested myocyte on depolarization and may be transiently sequestered in the SR before release. Both early initial and late tension development are depressed to a similar degree by application of 10-20 nM nifedipine. These results emphasize the multiple differing actions of the volatile anesthetics on myocardial contractions, with halothane and isoflurane possessing distinct depressant characteristics.
Lynch
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Department of Anesthesiology, University of Virginia Health Sciences Center, Charlottesville 22908.
D000818:Animals; D004558:Electric Stimulation; D004737:Enflurane / Q000494:pharmacology*; D006168:Guinea Pigs; D006221:Halothane / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D012433:Ryanodine / Q000378:metabolism; D014475:Uncoupling Agents / Q000494:pharmacology*
D014475:Uncoupling Agents; D012433:Ryanodine; D004737:Enflurane; D007530:Isoflurane; D007545:Isoproterenol; D006221:Halothane