[Role of nitric oxide in hemodynamic and extravascular lung water in a dog endotoxin shock model]

To verify the effects of nitric oxide pathway modification on hemodynamics and extravascular lung water during sepsis.

Experiments were conducted in three groups of anesthetized dogs with sodium pentobarbital. In group 1 (n = 8), lipopolysaccharide was injected intravenously to produce endotoxin shock. Group 2 (n = 8) received both lipopolysaccharide and L-arginine, a precursor of nitric oxide synthesis, intravenously. Group 3 (n = 8) received both lipopolysaccharide and N-nitro-L-arginine (L-NNA), a competitive inhibitor of nitric oxide generation, intravenously. Hemodynamic data included MAP, CVP, PAP, PAWP, CI, SI, SVRI, PVRI, LVSWI and RVSWI were measured or calculated. Oxygenational data included DO2, O2ER, and VO2 were calculated. Extravascular lung water (EVLW) was measured.

L-arginine increased CI (2.2 +/- 0.7 to 2.7 +/- 0.7 L.min-1)/m2 and SI (15 +/- 3 to 19 +/- 5 ml/m2, P < 0.05) and decreased PVRI (320 +/- 86 to 211 +/- 87 dyne. sec/cm5-m2, P < 0.05) without significant changes in O2ER, DO2 and VO2. All of the untoward hemodynamic effects of endotoxin were exacerbated by the addition of L-NNA (CI-56 +/- 2%, SI -58 +/- 5%, P < 0.05, SVRI + 170 +/- 10%, PVRI + 129 +/-15%, P < 0.01). As DO2, was significantly decreased by L-NNA (534 +/- 104 to 300 +/- 90 ml.min-1/m2, P < 0.01), therefore, O2ER was also increased (insufficiently), and VO2 was still decreased significantly (146 +/- 58) to 115 +/- 38 ml.min-1/m2, P < 0.05. EVLW was markedly increased by L-NNA (5.4 +/- 1.0 to 6.2 +/- 0.7 g/kg, P < 0.01).

The inhibition of nitric oxide synthesis has serious adverse hemodynamic and oxygenational consequences in our endotoxin shock model. We speculate that nitric oxide inhibition has no foreseeable therapeutic role in early stage of septic shock.