Halothane and isoflurane decrease calcium sensitivity and maximal force in human skinned cardiac fibers.
BACKGROUND
Reports of the direct effects of volatile anesthetics on cardiac myofibrils, studied in various mammalian species but not in humans, have conflicted. To determine whether volatile anesthetics directly affect cardiac contractile proteins in humans, we examined the effects of various equianesthetic doses of halothane (0.46, 0.83, and 1.23 mM, equivalent to 0.75, 1.50, and 2.25%, respectively) and isoflurane (0.63, 1.22, and 1.93 mM, equivalent to 1.15, 2.30, and 3.50%, respectively) on the Ca2+ sensitivity and maximal force in human skinned cardiac fibers.


METHODS
Left ventricular muscle strips were obtained from seven patients undergoing cardiac surgery. Sarcolemma was disrupted with EGTA (ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid), and sarcoplasmic reticulum was destroyed with EGTA plus BRIJ 58 detergent. Ca2+ sensitivity was studied by observing the isometric tension developed by skinned fiber bundles challenged with solutions of increasing Ca2+ concentrations expressed in pCa (where pCa = -log10[Ca2+]). Maximal force was measured with a pCa 4.8 solution.


RESULTS
Both anesthetics shifted the pCa-tension curves toward higher Ca2+ concentrations and decreased pCa for half-maximal activation in a dose-dependent and reversible fashion (from 5.71 for control to 5.56 and 5.55 for 1 MAC halothane and isoflurane, respectively) without changing the slope of this relationship (Hill coefficient). No differences between agents were observed at equianesthetic concentrations. The two agents also decreased the maximal activated tension in a dose-dependent fashion (-27 and -28% vs. control for 2 MAC halothane and isoflurane, respectively).


CONCLUSIONS
The current study indicates that halothane and isoflurane decrease Ca2+ sensitivity and maximal force in human skinned cardiac fibers at 20 degrees C. If these effects extend to higher temperatures, they may contribute to the negative inotropic effect of these agents.
Tavernier
B M
BM
Département d'Anesthésie-Réanimation Chirurgicale I, Hôpital B, Centre Hospitalier Régional Universitaire, Lille, France.
Adnet
P J
PJ
Imbenotte
M
M
Etchrivi
T S
TS
Reyford
H
H
Haudecoeur
G
G
Scherpereel
P
P
Krivosic-Horber
R M
RM
D000368:Aged; D002118:Calcium / Q000494:pharmacology* / Q000502:physiology; D002592:Cetomacrogol / Q000494:pharmacology; D003864:Depression, Chemical; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D006221:Halothane / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000187:drug effects* / Q000502:physiology*; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000737:chemistry; D012680:Sensitivity and Specificity
D009124:Muscle Proteins; D004533:Egtazic Acid; D002592:Cetomacrogol; D007530:Isoflurane; D002118:Calcium; D006221:Halothane