Effect of aminoguanidine on lung fluid filtration after endotoxin in awake sheep

It has been suggested that enhanced generation of nitric oxide by inducible nitric oxide synthase (iNOS) may contribute to acute lung injury. We hypothesized that aminoguanidine (AG), a proposed selective inhibitor of iNOS, would alter pulmonary hemodynamics, fluid filtration, and gas exchange after endotoxin in chronically instrumented awake sheep. Eighteen sheep were randomly assigned to receive either AC (10 mg/kg + 1 mg/kg/h), or NaCl 0.9% intravenously for 4 h, beginning 2 h after injection of Escherichia coli endotoxin (1 mu g/kg). After endotoxin, pulmonary artery pressure (Ppa), capillary pressure (Pc), and vascular resistance index (PVRI) rose concomitantly with six-fold increments in lung lymph flow ((Q)over dot L) and protein clearance (CL). Extravascular lung water (EVLW) doubled, as assessed with the thermal dye dilution technique; Pa(o2) decreased, AaP(o2) and venous admixture ((Q)over dotS/(Q) over dot T) increased. After AC, (Q) over dot L and CL increased further by approximately 30%, whereas EVLW remained unchanged, despite an additional increase in Pc. Ppa, PVRI, and systemic vascular resistance index rose, whereas cardiac index and pulmonary blood volume index declined. In addition, Pa(o2) rose, and AaPo(2) and (Q)over dotS/(Q)over dotT decreased. We conclude that in endotoxemic sheep, AC improves gas exchange and increases (Q)over dot L and CL, whereas EVLW remains unchanged in spite of enhanced Pc. Apparently, increased lymphatic drainage prevents EVLW from rising after AG.