Endothelial nitric oxide synthase mediates the first and inducible nitric oxide synthase mediates the second window of desflurane-induced preconditioning.
OBJECTIVE
Nitric oxide synthases (NOSs) mediate the first window of anesthetic-induced preconditioning (APC). The authors tested the hypothesis that endothelial NOS (eNOS) mediates the first window and inducible NOS (iNOS) mediates the second window of APC.


METHODS
Randomized, prospective, blinded laboratory investigation.


METHODS
Experimental laboratory.


METHODS
Mice.


METHODS
Mice were subjected to a 45-minute coronary artery occlusion (CAO) and a 180-minute reperfusion. C57BL/6 mice received desflurane, 1.0 minimum alveolar concentration, for 30 minutes or 12, 24, 48, or 96 hours before CAO. In eNOS(-/-) and iNOS(-/-) mice, desflurane was given 30 minutes and 48 hours before CAO. In the control groups, no desflurane was administered. Myocardial infarct size (IS) was determined after staining with Evans blue and triphenyltetrazolium chloride.


RESULTS
The second window of APC was detectable at 48 hours but not at 12, 24, and 96 hours after preconditioning. In the control groups, IS was not different among the wild-type (50 ± 10%), eNOS(-/-) (52 ± 14%), and iNOS(-/-) (46 ± 10%) mice. The IS decreased significantly (p < 0.05) when desflurane was administered 30 minutes (10 ± 6%) or 48 hours (16 ± 7%) before CAO in wild-type mice, 48 hours (21 ± 13%) before CAO in eNOS(-/-) mice, and 30 minutes (13 ± 6%) before CAO in iNOS(-/-) mice. Desflurane given 30 minutes before CAO in eNOS(-/-) mice (60 ± 10%) and 48 hours before CAO in iNOS(-/-) mice (48 ± 21%) did not decrease the IS significantly compared with controls.


CONCLUSIONS
Endothelial NOS and iNOS work independently to mediate the first and second windows of APC, respectively. Endothelial NOS is not necessary to trigger the second window of APC.
Department of Anesthesia and Critical Care, University of Würzburg, Würzburg, Germany. andreas.redel@ukr.de
Andreas
A
Redel
Jan
J
Stumpner
Thorsten M
TM
Smul
Markus
M
Lange
Virginija
V
Jazbutyte
Douglas G
DG
Ridyard
Norbert
N
Roewer
Franz
F
Kehl
D018685:Anesthetics, Inhalation / Q000627:therapeutic use*; D000818:Animals; D062186:Arterial Pressure / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D003331:Coronary Vessels / Q000502:physiology; D000077335:Desflurane; D006339:Heart Rate / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000502:physiology*
D018685:Anesthetics, Inhalation; D000077335:Desflurane; D007530:Isoflurane; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III