Effects of isoflurane and enflurane on intracellular Ca2+ mobilization in isolated cardiac myocytes.
BACKGROUND
Enflurane and isoflurane may reduce cardiac contractility by altering mobilization and clearance of intracellular Ca2+ (Ca2+i). It was hypothesized that the negative inotropic actions of these agents involve limiting both membrane Ca2+ entry and altering intracellular Ca2+ release.


METHODS
The Ca2+i transients in rat ventricular myocytes loaded with fura-2 were recorded from a fluorescence microscope. Transients stimulated by membrane depolarization (suction electrode or elevated [K+]o) or 15 mM caffeine to release Ca2+ from the sarcoplasmic reticulum (SR) were analyzed for net amplitude, maximal rate of rise (VR), average rate of decline (VR) in [Ca2+]i, and duration.


RESULTS
Enflurane and isoflurane reduced electrically stimulated Ca2+i transients in a dose-dependent manner. Enflurane depressed the Ca2+i transient amplitude more than isoflurane. Enflurane was more effective than isoflurane in reducing VR and VF in a concentration-dependent manner. At similar concentrations, both enflurane and isoflurane reduced the steady state elevation of [Ca2+]i by 50 mM K+o. Similarly, enflurane and isoflurane depressed caffeine-sensitive release of Ca2+ from the SR. The reduction in the Ca2+i transient because of SR Ca2+ release was greater in enflurane than in equal concentrations of isoflurane. Rates of elevation and decline in [Ca2+]i were also reduced in enflurane and isoflurane.


CONCLUSIONS
The negative inotropic actions of enflurane and isoflurane involve a depression of Ca2+ influx during membrane excitation, as well as a reduction in SR Ca2+ release. Slowed rates of elevation in [Ca2+]i indicate that the latter mechanism may, in part, be caused by alterations in the kinetics of SR Ca2+ release.
Wilde
D W
DW
Department of Anesthesiology, University of Michigan Medical Center, Ann Arbor 48109-0572.
Davidson
B A
BA
Smith
M D
MD
Knight
P R
PR
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002478:Cells, Cultured; D004347:Drug Interactions; D004558:Electric Stimulation; D004737:Enflurane / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D007530:Isoflurane / Q000494:pharmacology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D013268:Stimulation, Chemical
D015220:Calcium Channels; D002110:Caffeine; D004737:Enflurane; D007530:Isoflurane; D011188:Potassium; D002118:Calcium