Nitric oxide does not mediate lipopolysaccharide-induced myocardial depression in guinea pigs.
OBJECTIVE
To determine the role of nitric oxide as a mediator of lipopolysaccharide-induced myocardial depression.


METHODS
Prospective, controlled study.


METHODS
University research laboratory.


METHODS
Male and female Hartley guinea pigs.


METHODS
Animals (n = 97) received intraperitoneal injections of either saline or Escherichia coli lipopolysaccharide (2 mg/kg). Some (n = 5) animals received two injections of dexamethasone before lipopolysaccharide. Left atria were harvested 6 hrs (n = 20) or 16 hrs (n = 77) later and placed in a tissue bath with Krebs-Henseleit buffer. Contractile tension was measured in the presence or absence of two inhibitors of nitric oxide synthase (NG-nitroarginine [NNA] or aminoguanidine). Atrial and serum nitrite/ nitrate and atrial cyclic guanosine monophosphate (cGMP) concentrations were assayed.


RESULTS
Lipopolysaccharide caused significant atrial contractile depression at 16 hrs but not 6 hrs compared with control animals. Neither NNA nor aminoguanidine reversed the depression in atrial function. In contrast, exposure of control atria to NNA worsened contractile function. There were no significant differences between control and lipopolysaccharide-treated animals in atrial and serum nitrite/nitrate and atrial cGMP concentrations.


CONCLUSIONS
Nitric oxide does not mediate lipopolysaccharide-induced myocardial depression in this animal model. Basal concentrations of nitric oxide may be important since NNA worsened contractile function in control atria.
Toth
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Department of Anesthesiology, University of Massachusetts Medical Center, Worcester, USA.
Heard
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D000818:Animals; D004195:Disease Models, Animal; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000503:physiopathology*; D006325:Heart Atria / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000378:metabolism*; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018805:Sepsis / Q000378:metabolism* / Q000503:physiopathology*
D008070:Lipopolysaccharides; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase