Transient and sustained changes in myofilament sensitivity to Ca2+ contribute to the inotropic effects of sevoflurane in rat ventricle.
BACKGROUND
The volatile anaesthetics isoflurane and sevoflurane induce both negative and positive inotropic effects in ventricular myocytes, the mechanisms of which are not fully understood. Previous data suggest that changes in myofilament Ca(2+) sensitivity contribute to their sustained negative inotropic effects. In this study, the role of changes in myofilament Ca(2+) sensitivity in both positive and negative inotropic effects of these agents was examined in intact ventricular myocytes.


METHODS
Contractility and cytosolic Ca(2+) (fura-2) were recorded optically in ventricular myocytes stimulated electrically (1 Hz) at 30 degrees C. Myofilament Ca(2+) sensitivity was assessed from plots of cell length against fura-2 fluorescence ratio (Fr) from individual twitches at various points before, during and after a 1 or 4 min exposure to 0.6 mM anaesthetic.


RESULTS
Isoflurane reduced mean (sd) myofilament Ca(2+) sensitivity from 10.3 (1.9) to 5.9 (1.6) microm Fr(-1) (P<0.001) throughout a 1 min exposure, which returned to control on removal. In contrast, on initial exposure to sevoflurane, Ca(2+) sensitivity was reduced from 10.8 (1.3) to 4.3 (0.9) microm Fr(-1) (P<0.001) but this recovered partially towards control over 3 min. On removal, sensitivity was increased above control (to 17.7 (2.2) microm Fr(-1); P<0.001) before preanaesthetic levels were restored.


CONCLUSIONS
These data show that both isoflurane and sevoflurane reduce apparent myofilament Ca(2+) sensitivity at steady state. However, sevoflurane (but not isoflurane) induced transient changes in apparent myofilament Ca(2+) sensitivity, which would contribute to its inotropic profile.
Graham
M D
MD
School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UK.
Bru-Mercier
G
G
Hopkins
P M
PM
Harrison
S M
SM
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D007530:Isoflurane / Q000494:pharmacology; D008738:Methyl Ethers / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D000077149:Sevoflurane
D018685:Anesthetics, Inhalation; D002316:Cardiotonic Agents; D008738:Methyl Ethers; D000077149:Sevoflurane; D007530:Isoflurane; D002118:Calcium