Desflurane-induced preconditioning against myocardial infarction is mediated by nitric oxide.
BACKGROUND
Volatile anesthetics induce myocardial preconditioning through a signal transduction pathway that is remarkably similar to that observed during ischemic preconditioning. Nitric oxide-dependent signaling plays an important role in anesthetic and ischemic preconditioning. Therefore, the authors tested the hypothesis that desflurane-induced preconditioning is mediated by nitric oxide.


METHODS
Barbiturate-anesthetized rabbits were instrumented for measurement of hemodynamics. All rabbits were subjected to 30-min coronary artery occlusion followed by 3 h of reperfusion. Myocardial infarct size was assessed with triphenyltetrazolium chloride staining. Myocardial nitric oxide synthase activity was assessed with a [H]L-arginine-conversion assay. Rabbits were randomized to five separate experimental groups. They received 0.0 or 1.0 minimum alveolar concentration desflurane for 30 min, which was discontinued 30 min before ischemia in the absence or presence of the nitric oxide synthase inhibitor N-nitro-L-arginine (L-NA). L-NA was given either 20 min before or 10 min after desflurane administration, respectively. Data are mean +/- SEM.


RESULTS
Infarct size was 56 +/- 8% in control experiments. Desflurane significantly (P < 0.05) reduced infarct size to 35 +/- 4%. Preconditioning by desflurane was totally blocked by administration of L-NA either during or after desflurane inhalation (58 +/- 4 and 59 +/- 9%, respectively). L-NA alone had no effect on infarct size (56 +/- 7%). Nitric oxide synthase activity was significantly (P < 0.05) increased by desflurane.


CONCLUSIONS
The results demonstrate that desflurane-induced preconditioning markedly reduced myocardial infarct size. This beneficial effect was blocked by the nitric oxide synthase inhibitor L-NA either during or after desflurane-administration. These data suggest that early desflurane-induced preconditioning is mediated by nitric oxide.
Smul
Thorsten M
TM
Department of Anesthesiology, Bayerische Julius-Maximilians-Universität, Oberdürrbacher Strasse 6, 97080 Würzburg, Germany.
Lange
Markus
M
Redel
Andreas
A
Burkhard
Natalie
N
Roewer
Norbert
N
Kehl
Franz
F
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D000077335:Desflurane; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D019157:Ischemic Preconditioning, Myocardial; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D011817:Rabbits
D018685:Anesthetics, Inhalation; D004791:Enzyme Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D000077335:Desflurane; D007530:Isoflurane; D019001:Nitric Oxide Synthase