Time course of desflurane-induced preconditioning in rabbits.
OBJECTIVE
The authors tested the hypothesis that volatile anesthetic-induced preconditioning (APC) follows a similar time pattern as that described for ischemic preconditioning and that delayed APC is mediated by nitric oxide.


METHODS
A prospective randomized vehicle-controlled study.


METHODS
A university research laboratory.


METHODS
New Zealand white rabbits (n = 75).


METHODS
Rabbits were instrumented for the measurement of systemic hemodynamics and subjected to a 30-minute coronary artery occlusion (CAO) and 3 hours of reperfusion. Desflurane (1.0 minimum alveolar concentration) was administered for 30 minutes and was discontinued 0.5 hours, 2 hours, 3 hours, 12 hours, 24 hours, 48 hours, 72 hours, and 96 hours before CAO, respectively. In 2 separate experimental groups, the nitric oxide synthase inhibitor N-omega-nitro-L-arginine (L-NA) was administered 72 hours after the administration of 0.0 or 1.0 minimum alveolar concentration of desflurane. The infarct size was determined gravimetrically. Data are mean +/- standard deviation.


RESULTS
Desflurane significantly (p < 0.05) reduced the infarct size compared with the control (63% +/- 12%, n = 7) when administered 0.5 hours (35% +/- 5%, n = 7), 2 hours (35% +/- 9%, n = 7), 24 hours (31% +/- 8%, n = 7), 48 hours (30% +/- 11%, n = 6), and 72 hours (39% +/- 5%, n = 6) before CAO. However, when desflurane was administered 3 hours (53% +/- 9%, n = 7), 12 hours (71% +/- 6%, n = 7), or 96 hours (66% +/- 5%, n = 7) before CAO, the myocardial infarct size was not reduced. The second window (72 hours) of preconditioning was abolished by the NOS inhibitor L-NA (52% +/- 16%, n = 7). L-NA alone had no effect on infarct size (64% +/- 11%, n = 7).


CONCLUSIONS
Desflurane induces a first (0.5-2 hours) and second window of preconditioning (24-72 hours) in the rabbit model of acute myocardial infarction. The second window of APC is mediated by nitric oxide.
Smul
Thorsten M
TM
Department of Anesthesiology, University of Würzburg, Bayerische Julius-Maximilians-Universität, Würzburg 97080, Germany.
Redel
Andreas
A
Stumpner
Jan
J
Lange
Markus
M
Lotz
Christopher
C
Roewer
Norbert
N
Kehl
Franz
F
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D000077335:Desflurane; D004195:Disease Models, Animal; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011817:Rabbits; D011897:Random Allocation; D013997:Time Factors
D018685:Anesthetics, Inhalation; C068309:N(omega)-hydroxyarginine; D001120:Arginine; D000077335:Desflurane; D007530:Isoflurane; D019001:Nitric Oxide Synthase