Zusammenfassung
Objectives: 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. Design: Randomized, prospective, blinded laboratory investigation. Setting: Experimental laboratory. Participants: Mice. Interventions: ...
Zusammenfassung
Objectives: 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. Design: Randomized, prospective, blinded laboratory investigation. Setting: Experimental laboratory. Participants: Mice. Interventions: 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 GAO. In eNOS(-/-) and iNOS(-/-) mice, desflurane was given 30 minutes and 48 hours before GAO. In the control groups, no desflurane was administered. Myocardial infarct size (IS) was determined after staining with Evans blue and triphenyltetrazolium chloride. Measurements and Main 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 GAO in eNOS(-/-) mice, and 30 minutes (13 +/- 6%) before GAO 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. (C) 2013 Elsevier Inc. All rights reserved.
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