Differential depression of myocardial contractility by halothane and isoflurane in vitro.
Depressant effects of halothane and isoflurane on isolated right ventricular guinea pig papillary muscle bathed in Tyrode's solution at 37 degrees C were examined. Contractions were elicited by stimulation through external field electrodes while tension was recorded continuously and the intracellular cardiac action potential (AP) was monitored simultaneously by microelectrodes. The time differential of tension (dT/dt) and of membrane potential (V) was determined electronically and recorded also. Contractions after rest and at stimulation rates of 0.1, 0.25, 0.5, 1, 2, and 3 Hz were studied. With normal APs, isoflurane (1.3 and 2.5%) depressed peak tension significantly less at high frequencies than did equivalent doses of halothane (0.75 or 1.5%). Isoflurane depressed dT/dt max less than halothane at all frequencies. At 0.3 Hz stimulation, isoflurane (1-4%) significantly increased the normal AP duration by 7-11%. Slow calcium-dependent APs and accompanying contractions were studied in partially depolarized muscles (-40 to -45 mV resting potential in 26 mM K+ Tyrode's solution) stimulated with 0.1 microM isoproterenol. Following rest and at 0.1, 0.25, 0.5, 1, 2, and 3 Hz, both isoflurane (1.3% or 2.5%) and enflurane (1.7% or 3.5%) markedly depressed the late-peaking slow AP contraction observed with low-frequency stimulation. Halothane (0.75% or 1.5%) caused a similar contractile depression (40-60%) at all frequencies. In contrast, isoflurane depressed early peaking tension and the dT/dt max at frequencies greater than 1 Hz significantly less than did halothane or enflurane. At 0.3 Hz, 2% and 4% isoflurane caused 9% and 17% depression of slow AP maximum rate of depolarization (Vmax), but significantly prolonged the AP duration. Isoflurane altered the pattern of tension development in a different manner than halothane, suggesting differing mechanisms of myocardial depression by these anesthetics.
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D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003864:Depression, Chemical; D004558:Electric Stimulation; D004737:Enflurane / Q000494:pharmacology; D006168:Guinea Pigs; D006221:Halothane / Q000494:pharmacology*; D066298:In Vitro Techniques; D007473:Ion Channels; D007530:Isoflurane / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D007552:Isotonic Solutions; D008564:Membrane Potentials / Q000187:drug effects; D008738:Methyl Ethers / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D013997:Time Factors
D007473:Ion Channels; D007552:Isotonic Solutions; D008738:Methyl Ethers; C037692:Tyrode's solution; D004737:Enflurane; D007530:Isoflurane; D007545:Isoproterenol; D002118:Calcium; D006221:Halothane