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Am J Physiol Heart Circ Physiol (July 8, 2005). doi:10.1152/ajpheart.00400.2005
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Submitted on April 22, 2005
Accepted on July 6, 2005

Isoflurane Induces Second Window of Preconditioning Through Upregulation of Inducible Nitric Oxide Synthase in Rat Heart

Mayu Wakeno-Takahashi1, Hajime Otani2*, Shinichi Nakao1, Hiroji Imamura2, and Koh Shingu1

1 Anesthesiology, Kansai Medical University, Moriguchi, Japan
2 Cardiovascular Center, Kansai Medical University, Moriguchi, Japan

* To whom correspondence should be addressed. E-mail: otanih{at}takii.kmu.ac.jp.

Second window of preconditioning (SWOP) induced by inhalation of volatile anesthetics has been documented in the rat heart and this is triggered by nitric oxide synthase (NOS) but the involvement of NOS in the mediator phase of isoflurane-induced SWOP has not been demonstrated. We tested the hypothesis that isoflurane-induced SWOP is mediated through upregulation of inducible NOS (iNOS). Rats inhaled 0.75 minimum alveolar concentration (MAC) or 1.5 MAC isoflurane or oxygen for 2 hours. Twenty-four, 48, 72, and 96 hours later the isolated heart was buffer-perfused and subjected to 30 minutes of ischemia followed by 2 hours of reperfusion. Inhalation of 0.75 MAC and 1.5 MAC isoflurane conferred a significant infarct size-limiting effect after ischemia/reperfusion between 24 and 72 hours after the inhalation of isoflurane. The maximum effect was obtained 48 hours after inhalation of 1.5 MAC isoflurane. Post-ischemic LV function was improved only 48 hours after inhalation of 1.5 MAC isoflurane. iNOS expression and activity in the heart were increased between 24 and 72 hours after inhalation of 1.5 MAC isoflurane and less pronouncedly after inhalation of 0.75 MAC isoflurane. A selective iNOS inhibitor, 1400W (10 µM), abolished iNOS activation and cardioprotection induced 48 hours after inhalation of 1.5 MAC isoflurane. These results suggest that isoflurane inhalation induces SWOP after 24 to 72 hours through overexpression and activation of iNOS in the rat heart.




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