I. Toth et So. Heard, NITRIC-OXIDE DOES NOT MEDIATE LIPOPOLYSACCHARIDE-INDUCED MYOCARDIAL DEPRESSION IN GUINEA-PIGS, Critical care medicine, 25(4), 1997, pp. 684-688
Objective: To determine the role of nitric oxide as a mediator of lipo
polysaccharide induced myocardial depression. Design: Prospective, con
trolled study. Setting: University research laboratory. Subjects: Mate
and female Hartley guinea pigs. Interventions: Animals (n = 97) recei
ved intraperitoneal injections of either saline or Escherichia coli li
popolysaccharide (2 mg/kg). Some (n = 5) animals received two injectio
ns of dexamethasone before lipopolysaccharide. Left atria were harvest
ed 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. ni
troarginine [NNA] or aminoguanidine). Atrial and serum nitrite/nitrate
and atrial cyclic guanosine monophosphate (cGMP) concentrations were
assayed. Measurements and Main Results: Lipopolysaccharide caused sign
ificant atrial contractile depression at 16 hrs but not 6 hrs compared
with control animals. Neither NNA nor aminoguanidine reversed the dep
ression in atrial function. In contrast, exposure of control atria to
NNA worsened contractile function. There were no significant differenc
es between control and lipopolysaccharide-treated animals in atrial an
d serum nitrite/nitrate and atrial cGMP concentrations. Conclusions: N
itric oxide does not mediate lipopolysaccharide-induced myocardial dep
ression in this animal model. Basal concentrations of nitric oxide may
be important since NNA worsened contractile function in control atria
.