Sevoflurane- and desflurane-induced human myocardial post-conditioning through Phosphatidylinositol-3-kinase/Akt signalling.
BACKGROUND
The role of phosphatidylinositol-3-kinase (PI3K) in sevoflurane- and desflurane-induced myocardial post-conditioning remains unknown.


METHODS
We recorded isometric contraction of isolated human right atrial trabeculae (oxygenated Tyrode's at 34 degrees C, stimulation frequency 1 Hz). In all groups, a 30-min hypoxic period was followed by a 60-min reoxygenation period. At the onset of reoxygenation, muscles were exposed to 5 min of sevoflurane 1%, 2%, and 3%, and desflurane 3%, 6%, and 9%. In separate groups, sevoflurane 2% and desflurane 6% were administered in the presence of 100 nM wortmannin, a PI3K inhibitor. Recovery of force after the 60-min reoxygenation period was compared between groups (mean +/- SD).


RESULTS
As compared with the Control group (49 +/- 7% of baseline) PostC by sevoflurane 1%, 2%, and 3% (78 +/- 4%, 79 +/- 5%, and 85 +/- 4% of baseline, respectively) and desflurane 3%, 6%, and 9% (74 +/- 5%, 84 +/- 4%, and 86 +/- 11% of baseline, respectively) enhanced the recovery of force. This effect was abolished in the presence of wortmannin (56 +/- 5% of baseline for sevoflurane 2%+wortmannin; 56 +/- 3% of baseline for desflurane 6%+wortmannin). Wortmannin alone had no effect on the recovery of force (57 +/- 7% of baseline).


CONCLUSIONS
In vitro, sevoflurane and desflurane post-conditioned human myocardium against hypoxia through activation of phosphatidylinositol-3-kinase.
Zhu
L
L
Laboratoire d'Anesthesiologie et de Physiologie Cellulaire, Centre Hospitalier Régional, Caen, France.
Lemoine
S
S
Babatasi
G
G
Lepage
O
O
Massetti
M
M
Gérard
J-L
JL
Hanouz
J-L
JL
D000368:Aged; D000730:Androstadienes / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000077335:Desflurane; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D006325:Heart Atria; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D008875:Middle Aged; D009206:Myocardium / Q000201:enzymology*; D051058:Oncogene Protein v-akt / Q000378:metabolism / Q000502:physiology*; D009929:Organ Size / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011229:Preanesthetic Medication; D000077149:Sevoflurane; D015398:Signal Transduction / Q000187:drug effects*; D000077191:Wortmannin
D000730:Androstadienes; D018685:Anesthetics, Inhalation; D000077335:Desflurane; D004791:Enzyme Inhibitors; D007530:Isoflurane; D008738:Methyl Ethers; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000077149:Sevoflurane; D000077191:Wortmannin