Desflurane-induced preconditioning alters calcium-induced mitochondrial permeability transition.
BACKGROUND
Recent investigations have focused on the pivotal role of the mitochondria in the underlying mechanisms volatile anesthetic-induced myocardial preconditioning. This study aimed at examining the effect of anesthetic preconditioning on mitochondrial permeability transition (MPT) pore opening.


METHODS
Anesthetized open chest rabbits were randomized to one of four groups and underwent 10 min of ischemia, except for the sham 1 group (n = 12). Before this, they underwent a treatment period consisting of (1) no intervention (ischemic group; n = 12), (2) 30 min of desflurane inhalation (8.9% end-tidal concentration) followed by a 15-min washout period (desflurane group; n = 12), or (3) ischemic preconditioning (IPC group; n = 12). A second set of experiments was performed to evaluate the effect of a putative mitochondrial adenosine triphosphate-sensitive potassium channel antagonist, 5-hydroxydecanoate (5-HD). The animals underwent the same protocol as previously, plus pretreatment with 5 mg/kg 5-HD. They were randomized to one of five groups: the sham 2 group, receiving no 5-HD (n = 12); the sham 5-HD group (n = 12); the ischemic 5-HD group (n = 12), the desflurane 5-HD group (n = 12), and the IPC 5-HD group (n = 12). At the end of the protocol, the hearts were excised, and mitochondria were isolated. MPT pore opening was assessed by measuring the amount of calcium required to trigger a massive calcium release indicative of MPT pore opening.


RESULTS
Desflurane and IPC group mitochondria needed a higher calcium load than ischemic group mitochondria (362 +/- 84, 372 +/- 74, and 268 +/- 110 microM calcium, respectively; P < 0.05) to induce MPT pore opening. The sham 1 and sham 2 groups needed a similar amount of calcium to trigger mitochondrial calcium release (472 +/- 70 and 458 +/- 90 microM calcium, respectively). 5-HD preadministration had no effect on sham animals (458 +/- 90 and 440 +/- 128 microM calcium without and with 5-HD, respectively) and ischemic group animals (268 +/- 110 and 292 +/- 102 microM calcium without and with 5-HD, respectively) but abolished the effects of desflurane on calcium-induced MPT pore opening (362 +/- 84 microM calcium without 5-HD vs. 238 +/- 96 microM calcium with 5-HD; P < 0.05) and IPC (372 +/- 74 microM calcium without 5-HD vs. 270 +/- 104 microM calcium with 5-HD; P < 0.05).


CONCLUSIONS
Like ischemic preconditioning, desflurane improved the resistance of the transition pore to calcium-induced opening. This effect was inhibited by 5-HD, suggesting a link between mitochondrial adenosine triphosphate-sensitive potassium and MPT.
Piriou
Vincent
V
Département d'Anesthésie Réanimation, Centre Hospitalier Lyon Sud, Pierre Bénite, France. piriou@univ-lyon1.fr
Chiari
Pascal
P
Gateau-Roesch
Odile
O
Argaud
Laurent
L
Muntean
Danina
D
Salles
Delphine
D
Loufouat
Joseph
J
Gueugniaud
Pierre-Yves
PY
Lehot
Jean-Jacques
JJ
Ovize
Michel
M
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D016572:Cyclosporine / Q000494:pharmacology; D003652:Decanoic Acids / Q000494:pharmacology; D000077335:Desflurane; D006439:Hemodynamics / Q000187:drug effects; D006880:Hydroxy Acids / Q000494:pharmacology; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000819:agonists / Q000187:drug effects; D008854:Microscopy, Electron; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000648:ultrastructure; D017202:Myocardial Ischemia / Q000473:pathology / Q000517:prevention & control; D010539:Permeability / Q000187:drug effects; D015221:Potassium Channels; D011817:Rabbits
D018685:Anesthetics, Inhalation; D003652:Decanoic Acids; D006880:Hydroxy Acids; D008565:Membrane Proteins; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; C052853:5-hydroxydecanoic acid; D016572:Cyclosporine; D000077335:Desflurane; D007530:Isoflurane; D002118:Calcium