Published Online
on September 30, 2002

A more recent version of this article appeared on November 12, 2002

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Submitted on June 26, 2002
Revised on August 19, 2002
Accepted on August 19, 2002

Preoperative Glutamine Administration Induces Heat-Shock Protein 70 Expression and Attenuates Cardiopulmonary Bypass-Induced Inflammatory Response by Regulating Nitric Oxide Synthase Activity

Yoshitaka Hayashi MD, PhD^*, Yoshiki Sawa MD, Naoto Fukuyama MD, Hiroe Nakazawa MD, and Hikaru Matsuda MD

From the Department of Surgery (Y.H., Y.S., H.M.), Course of Interventional Medicine (E1), Osaka University Graduate School of Medicine, Osaka; and the Second Department of Physiology (N.F., H.N.), Tokai University School of Medicine, Isehara, Kanagawa, Japan.

^* To whom correspondence should be addressed. E-mail: hayashi{at}surg1.med.osaka-u.ac.jp.

Background—Heat-shock protein 70 (HSP70) plays a major role in the pathophysiology of inflammation, and the induction of HSP70 before the onset of inflammation can reduce organ damage through a self-protective system. Glutamine is known to be an inducer of HSP70, and its preoperative administration seems useful in attenuating cardiopulmonary bypass (CPB)-induced inflammatory response.

Methods and Results—Adult male Sprague-Dawley rats (group G, received 100 mg/kg of glutamine via the right jugular vein 3 times per day for 1 week and just before the initiation of CPB; group C served as control) underwent CPB (60 minutes, 100 mL/kg per minute, 34°C) and were killed 3 hours after the termination of CPB. Group G showed significantly lower plasma concentrations of interleukin-6 and interleukin-8 after CPB termination. Myocardial and respiratory damages were significantly attenuated in group G, as evidenced by Langendorff perfusion, respiratory index, and neutrophil adherence. HSP70 expressions in the heart, lung, and liver were detected only in group G before CPB and were markedly stronger in group G 3 hours after CPB termination. Although plasma nitrate+nitrite concentrations were not significantly different between the groups, endothelial-constitutive nitric oxide synthase (NOS) activity was markedly preserved and inducible NOS activity was markedly attenuated in the tissues of group G.

Conclusions—These results suggest that preoperative glutamine administration induces HSP70 expression before CPB and attenuates CPB-induced inflammation by regulating NOS activity, which may be a prospective management for conferring tolerance to CPB-induced inflammatory response through a self-protective mechanism.

Key words: cardiopulmonary bypass • inflammation • nitric oxide synthase • interleukins • proteins

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