Effects of isoflurane and sevoflurane on intracellular calcium and contractility in pressure-overload hypertrophy.
BACKGROUND
Depression of myocardial contractility as a result of isoflurane appears to be greater in myocardial hypertrophy, and the cellular basis for this difference in susceptibility is not clear. In this study we examined the effects of isoflurane and sevoflurane on contractility and intracellular calcium in an animal model of pressure-overload hypertrophy.


METHODS
Pressure-overload hypertrophy was established in young male ferrets by banding the main pulmonary artery for 1 month and the effects of isoflurane and sevoflurane on contractility and intracellular calcium ([Ca]i) were examined in isolated right ventricular papillary muscles, trabeculae, and myocytes. Intracellular calcium was measured with the bioluminescent photoprotein aequorin in isolated papillary muscles, and also with the fluorescent indicator fluo-3 in isolated ventricular myocytes. In addition, Ca sensitivity was assessed in isolated trabeculae after disruption of the surface membrane with a nonionic detergent (skinned fibers).


RESULTS
In the presence of isoflurane and sevoflurane, papillary muscles from banded animals exhibited a greater depression of contractility and isolated ventricular myocytes showed a greater decrease in peak [Ca]i. Furthermore, baseline calcium sensitivity was decreased and the slope of the relationship between [Ca] and force was increased in skinned trabeculae from banded animals. Isoflurane decreased calcium sensitivity in trabeculae from both normal and banded animals.


CONCLUSIONS
These results suggest that changes in [Ca]i and altered calcium sensitivity are both responsible for the exaggerated effects of some volatile anesthetics on contractility in pressure-overload hypertrophy.
Department of Anesthesiology, Mayo Foundation, Rochester, Minnesota 55905, USA. hannon.james@mayo.edu
James D
JD
Hannon
Mark J
MJ
Cody
David X
DX
Sun
Philippe R
PR
Housmans
D000331:Aequorin / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D004558:Electric Stimulation; D004591:Electrophoresis, Polyacrylamide Gel; D005289:Ferrets; D006973:Hypertension / Q000503:physiopathology; D017380:Hypertrophy, Right Ventricular / Q000503:physiopathology*; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology*; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology; D011651:Pulmonary Artery / Q000502:physiology; D000077149:Sevoflurane
D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane; D000331:Aequorin; D007530:Isoflurane; D002118:Calcium