title: Preoperative glutamine administration induces heat-shock protein 70 expression and attenuates cardiopulmonary bypass-induced inflammatory response by regulating nitric oxide synthase activity.
abstract: 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.
  
  
  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 degrees 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.
authors.affiliation: Department of Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. hayashi@surg1.med.osaka-u.ac.jp
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sawa
authors.forename: Naoto
authors.initials: N
authors.lastname: Fukuyama
authors.forename: Hiroe
authors.initials: H
authors.lastname: Nakazawa
authors.forename: Hikaru
authors.initials: H
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D002448:Cell Adhesion; D016207:Cytokines / Q000097:blood; D005973:Glutamine / Q000494:pharmacology* / Q000627:therapeutic use; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D006321:Heart / Q000503:physiopathology; D006439:Hemodynamics; D007249:Inflammation / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D009206:Myocardium / Q000473:pathology; D009504:Neutrophils / Q000276:immunology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D017672:Nitrogen Compounds / Q000097:blood; D011300:Preoperative Care; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins; D017672:Nitrogen Compounds; D005973:Glutamine; C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat