Lazaroids--not nitric oxide synthetase inhibitors--improve hemodynamics after thermal injury in anesthetized guinea pigs.

Our objective was to study the effects of a lipid peroxidation inhibitor (U74389G) and nitric oxide synthetase inhibitor (NG-methyl-L-arginine) on hemodynamic stability in burn shock. The design was a prospective, placebo control, randomized, and masked multigroup study in a research laboratory of a university hospital. We used 24 guinea pigs (N = 24), and induced burn shock by a scalding thermal injury (75 degrees C) to 35% of their body surface area. Hemodynamics and gas exchange were observed for 90 minutes after the burn injury in the four groups: no burn, burn-control, burn-U74 (10 mg/kg U74389G), and burn-LNMA (20 mg/Kg NG-methyl-L-arginine). The percentage of mean arterial pressure, normalized for the initial value at 30 minutes after the burn injury, decreased in all groups over time but was not significantly different in any group. The normalized percentage of flow also decreased over time in all groups with the slope of the linear regression significantly less in the burn-U74 group (-0.32 95% CI, -0.05, -0.15) and the no burn group (-0.37 95% CI, -0.48, -0.26), compared with the burn-control group (-0.66 95% CI, -0.77, -0.56) and the burn-LNMA group (-0.66 95% CI, -0.77, -0.56). The slope of the linear regression for the normalized percentage of systemic vascular resistance was significantly more marked in the burn-control group (2.45 95% CI, 1.35, 3.54) and the burn-LNMA group (1.22 95% CI, 0.89, 1.55) compared with the no burn group (0.16 95% CI, 0.11, 0.44) or the burn-U74 group (0.34 95% CI, 0.06, 0.74). The burn shock resulted in hemodynamic instability as measured with increased systemic vascular resistance, decreased cardiac output, and mean arterial pressure. Use of a lazaroid (U74389G), not a nitric oxide synthetase inhibitor (NG-methyl-L-arginine), altered the clinical course after thermal injury. These data suggest the importance of lipid peroxidation and free radicals as secondary mediators in the evolution of burn shock.