Attenuation of lipopolysaccharide-mediated left ventricular dysfunction by glutamine preconditioning.
OBJECTIVE
Myocardial dysfunction is often seen during the inflammatory response to major surgery at 4 to 6h postoperatively. The aim of this study was to investigate the effect of glutamine pretreatment, as a means of preconditioning, on lipopolysaccharide-induced myocardial dysfunction.


METHODS
C57BL/6 mice were randomized into four groups: Control; lipopolysaccharide; glutamine plus lipopolysaccharide; and Quercetin, an inhibitor of heat shock protein synthesis plus glutamine and lipopolysaccharide. Left ventricular function was assessed at 6h following lipopolysaccharide (LPS) insult by invasive hemodynamics. Heat shock protein (HSP)72 in heart tissue was determined by Western immunoblot at 12h after glutamine administration.


RESULTS
Administration of lipopolysaccharide resulted in significant decrease in left ventricular end systolic pressure (LVESP) (69.1 +/- 2.52 mm Hg versus 106.3 +/- 3.36 mm Hg in controls), reduced dP/dtmax (4704.1 +/- 425.31 mm Hg/s versus 9389.8 +/- 999.4 mm Hg/s in controls), and the increase in left ventricular end diastolic pressure (LVEDP) (5.10 +/- 0.28 mm Hg versus 2.16 +/- 0.27 mm Hg in controls) (P < 0.05). Peritoneal injection of 25 g/kg of glutamine 12 h prior to lipopolysaccharide exposure induced HSP72 expression in heart tissues and attenuated lipopolysaccharide-induced left ventricular dysfunction: LVESP 85.94 +/- 3.8 mm Hg (P < 0.05), dP/dtmax 8331 +/- 425 mm Hg (P < 0.05), LVEDP 2.32 +/- 0.23 mm Hg (P < 0.01). Quercetin partially attenuated glutamine induced HSP72 expression and blocked the protective response of glutamine.


CONCLUSIONS
These data demonstrate that cardioprotection with glutamine is associated with induction of HSP72 and may be an approach to activating the preconditioning response in the heart in clinical practise.
Chen
Gang
G
Department of Surgery, Royal College of Surgeons in Ireland, Education and Research CentreBeaumont Hospital, Dublin 9, Ireland. gchen@rcsi.ie
Neilan
Tom G
TG
Chen
Hong
H
Condron
Claire
C
Kelly
Cathal
C
Hill
Arnold D K
AD
Bouchier-Hayes
David J
DJ
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D005973:Glutamine / Q000494:pharmacology*; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D011794:Quercetin / Q000494:pharmacology; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced* / Q000188:drug therapy*
D000975:Antioxidants; D050884:HSP72 Heat-Shock Proteins; D008070:Lipopolysaccharides; D005973:Glutamine; D011794:Quercetin