Effects ofL-arginine andN-nitro-L-arginine treatment on hemodynamics, DO2, VO 2, and extravascular lung water in a dog endotoxin shock model.

To verify the effect of nitric oxide pathway modification during sepsis, experiments were conducted in four groups of anesthetized dogs which received lipopolysaccharide (LPS) intravenously (group 1), 300 mg·kg(-1) ofL-arginine plus LPS (group 2), 20 mg·kg(-1) ofN-nitro-L-arginine plus LPS (L-NNA, group 3), and normal saline as the control group. Hemodynamic and oxygenation data as well as extravascular lung water (EVLW) were measured or calculated. The results showed thatL-arginine increases cardiac output index (CI) and decreased the peripheral vascular resistance index (PVRI) without a significant influence on oxygen extraction ratio (O2ER), oxygen delivery (DO2), or oxygen consumption (VO2). All of the untoward hemodynamic effects of LPS were exacerbated by the addition ofL-NNA. Therefore, as DO2 was significantlys decreased byL-NNA, and although O2ER was increased (insufficiently), VO2 was still decreased significantly. EVLW was markedly increased byL-NNA. These results support the hypothesis that inhibition of nitric oxide synthesis may exacerbate hemodynamic and oxygenation consequences in septic shock.