Cyclophilin D Modulates the Cardiac Mitochondrial Target of Isoflurane, Sevoflurane, and Desflurane.
BACKGROUND
Volatile anesthetics are known to limit myocardial ischemia-reperfusion injuries. Mitochondria were shown to be major contributors to cardioprotection. Cyclophilin D (CypD) is one of the main regulators of mitochondria-induced cell death. We compared the effect of isoflurane, sevoflurane, and desflurane in the presence or absence of CypD, to clarify its role in the mechanism of cardioprotection induced by these anesthetics.


METHODS
Oxidative phosphorylation, mitochondrial membrane potential, and H2O2 production were measured in isolated mitochondria from wild-type (WT) or CypD knockout mice in basal conditions and after hypoxia-reoxygenation in the presence or absence of volatile anesthetics.


RESULTS
All volatile anesthetics inhibited mitochondrial state 3 of complex I, decreased membrane potential, and increased adenosine diphosphate consumption duration in both WT and CypD knockout mice. However, they differently modified H2O2 production after stimulation by succinate: CypD ablation reduced H2O2 production, isoflurane decreased H2O2 level in WT but not in CypD knockout mice, sevoflurane affected both lines whereas desflurane increased H2O2 production in CypD knockout and had no effect on WT mice.


CONCLUSIONS
This study showed different effects of isoflurane, sevoflurane, and desflurane on mitochondrial functions and highlighted the implication of CypD in the regulation of adenosine diphosphate consumption and complex I-induced radical oxygen species production.
*INSERM UMR 1060, CarMeN Laboratory, Univ Lyon1, IHU OPERA, Hôpital Louis Pradel, Hospices Civils de Lyon, Lyon, France; †Service d'Anesthésie Réanimation, Hôpital Louis Pradel, Hospices Civils de Lyon, Lyon, France; and ‡Service d'Explorations Fonctionnelles Cardiovasculaires & CIC de Lyon, Hôpital Louis Pradel, Hospices Civils de Lyon, Lyon, France.
Rania
R
Harisseh
Pascal
P
Chiari
Camille
C
Villedieu
Pauline
P
Sueur
Maryline
M
Abrial
Jean-Luc
JL
Fellahi
Michel
M
Ovize
Abdallah
A
Gharib
D000255:Adenosine Triphosphate / Q000378:metabolism; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D019610:Cytoprotection; D000077335:Desflurane; D004734:Energy Metabolism / Q000187:drug effects*; D005838:Genotype; D006861:Hydrogen Peroxide / Q000378:metabolism; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008738:Methyl Ethers / Q000494:pharmacology*; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010641:Phenotype; D020011:Protective Agents / Q000494:pharmacology*; D000077149:Sevoflurane; D013997:Time Factors
D018685:Anesthetics, Inhalation; D000081406:Peptidyl-Prolyl Isomerase F; D008738:Methyl Ethers; C000631446:PPIF protein, mouse; D020011:Protective Agents; D000077149:Sevoflurane; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D000077335:Desflurane; D007530:Isoflurane; D021983:Cyclophilins