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Am J Physiol Heart Circ Physiol (September 23, 2004). doi:10.1152/ajpheart.00494.2004
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Submitted on May 25, 2004
Accepted on September 7, 2004

DELAYED CARDIOPROTECTION WITH ISOFLURANE: ROLE OF REACTIVE OXYGEN AND NITROGEN

Yang Shi1, William C. Hutchins1, Jidong Su1, Daniel Siker1, Neil Hogg1, Kirkwood A. Pritchard, Jr.1, Agnes Keszler1, James S. Tweddell1, and John E. Baker1*

1 Division of Pediatric Surgery, Medical College of Wisconsin, Milwaukee, WI, USA

* To whom correspondence should be addressed. E-mail: jbaker{at}mcw.edu.

We determined whether isoflurane can confer delayed cardioprotection in the adult rat by triggering increased production of reactive oxygen (ROS) and nitrogen species (RNS). Our objectives were to determine (1) the concentration of isoflurane that confers delayed cardioprotection in the adult rat, (2) the role of ROS and RNS in the induction of delayed cardioprotection, and (3) the cellular sources of ROS and RNS responsible for induction of delayed cardioprotection by isoflurane. Male Sprague Dawley rats at 8-week of age (n = 8/group) were exposed to 0.5%, 0.8%, 1% and 2% isoflurane (v/v)-100% oxygen for 2 hours. Isoflurane conferred delayed cardioprotection 24 hours later at a concentration of 0.8% (v/v). Administration of MnTBAP, a superoxide scavenger, (15mg/kg i.p.) or L-NAME, a general nitric oxide synthase inhibitor, (15 mg/kg i.p.) 15 minutes prior to isoflurane treatment abolished the delayed cardioprotective effects of isoflurane. MnTBAP and L-NAME had no effect on delayed cardioprotection in untreated hearts. Perfusion of isolated hearts with hydroethidine, a fluorescent probe for superoxide following isoflurane treatment, resulted in a 2-fold increase in ethidine staining of isoflurane-treated hearts compared with untreated controls which was attenuated by myxothiazol, an inhibitor of the mitochondrial electron transport chain, (0.2 mg/kg i.p.) and L-NAME (15 mg/kg i.p.). Nitrite and nitrate content in isoflurane-treated hearts was 1.5-fold higher than in untreated hearts, while myocardial reduced glutathione levels were decreased by 13% in 0.8% but not in 1.0% isoflurane-treated hearts. We conclude isoflurane confers delayed cardioprotection in adult rat, triggered by ROS and RNS.




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