Effects of sevoflurane on the intracellular Ca2+ transient in ferret cardiac muscle.
BACKGROUND
Sevoflurane depresses myocardial contractility by decreasing transsarcolemmal Ca2+ influx. In skinned muscle fibers, sevoflurane affects actin-myosin cross-bridge cycling, which might contribute to the negative inotropic effect. It is uncertain to what extent decreases in Ca2+ sensitivity of the contractile proteins play a role in the negative inotropic effect of sevoflurane in intact cardiac muscle tissue. The aim of this study was to assess whether sevoflurane decreases myofibrillar Ca2+ sensitivity in intact living cardiac fibers and to quantify the relative importance of changes in myofibrillar Ca2+ sensitivity versus changes in myoplasmic Ca2+ availability by sevoflurane.


METHODS
The effects of sevoflurane 0-4.05% vol/vol (0-1.5 minimum alveolar concentration [MAC]) on isometric and isotonic variables of contractility and on the intracellular calcium transient were assessed in isolated ferret right ventricular papillary muscles microinjected with the Ca2+-regulated photoprotein aequorin. The intracellular calcium transient was analyzed in the context of a multicompartment model of intracellular Ca2+ buffers in mammalian ventricular myocardium.


RESULTS
Sevoflurane decreased contractility, time to peak force, time to half isometric relaxation, and the [Ca2+]i transient in a reversible, concentration-dependent manner. Increasing [Ca2+]o in the presence of sevoflurane to produce peak force equal to control increased intracellular Ca2+ transient higher than control.


CONCLUSIONS
Sevoflurane decreases myoplasmic Ca2+ availability and myofibrillar Ca2+ sensitivity in equal proportions except at 4.05% vol/vol (1.5 MAC), where Ca2+ availability is decreased more. These changes are at the basis of the negative inotropic effect of sevoflurane in mammalian ventricular myocardium.
Bartunek
A E
AE
Department of Anesthesiology, Mayo Foundation, Rochester, Minnesota, USA.
Housmans
P R
PR
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005289:Ferrets; D008738:Methyl Ethers / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D010210:Papillary Muscles / Q000187:drug effects; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000502:physiology; D000077149:Sevoflurane
D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane; D002118:Calcium