Comparative myocardial depression of sevoflurane, isoflurane, and halothane in cultured neonatal rat ventricular myocytes.
In this study, we compared the direct myocardial depressant effects of sevoflurane, isoflurane, and halothane and determined whether an L-type Ca2+ channel agonist, Bay K 8644, could attenuate the myocardial depression induced by these anesthetics in cultured neonatal rat ventricular myocytes. Ventricular myocytes were obtained from neonatal rats by enzymatic digestion with collagenase and then cultured for 6-7 days. The myocytes were stabilized in serum-free medium, and the spontaneous beating rate and contractile amplitude were measured by using a fiberoptic sensor. Each anesthetic decreased the beating rate and amplitude in a concentration-dependent manner (1%-4% vol/vol) (P < 0.001), with halothane decreasing the beating rate and amplitude the most (P < 0.01). Isoflurane caused larger decreases in the beating rate than sevoflurane at 3% and 4% (P < 0.05). Potency for suppression of contractile amplitude was in the order of halothane > > isoflurane > sevoflurane. However, the myocardial depressant effects of the anesthetics were not different when their concentrations were corrected for minimum alveolar anesthetic concentration values. Bay K 8644 significantly prevented the anesthetic-depressed amplitude (P < 0.05). We conclude that sevoflurane, isoflurane, and halothane have direct myocardial depressant effects on cultured neonatal rat ventricular myocytes and that the reduction of sarcolemmal L-type Ca2+ channel current levels mediates the myocardial depression observed in these immature hearts.


CONCLUSIONS
Sevoflurane, isoflurane, and halothane have a direct cardiodepressant effect on cardiac excitation-contraction coupling in the immature heart, which is mediated by an interaction with the L-type Ca2+ channel.
Kanaya
N
N
Department of Anesthesiology, Sapporo Medical University, School of Medicine, Japan.
Kawana
S
S
Tsuchida
H
H
Miyamoto
A
A
Ohshika
H
H
Namiki
A
A
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002478:Cells, Cultured; D006221:Halothane / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007530:Isoflurane / Q000494:pharmacology*; D008738:Methyl Ethers / Q000494:pharmacology*; D009206:Myocardium / Q000166:cytology*; D051381:Rats; D017208:Rats, Wistar; D000077149:Sevoflurane
D018685:Anesthetics, Inhalation; D002120:Calcium Channel Agonists; D008738:Methyl Ethers; D000077149:Sevoflurane; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D007530:Isoflurane; D006221:Halothane