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Am. J. Respir. Crit. Care Med., Volume 162, Number 2, August 2000, 465-470

Effect of Aminoguanidine on Lung Fluid Filtration after Endotoxin in Awake Sheep

OLEG V. EVGENOV, OLAV HEVR ØY, KATJA E. BREMNES, and LARS J. BJERTNAES

Department of Anesthesiology, Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway

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 AG (10 mg/kg + 1 mg/kg/h), or NaCl 0.9% intravenously for 4 h, beginning 2 h after injection of Esch-erichia coli endotoxin (1 µg/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 L) and protein clearance (CL). Extravascular lung water (EVLW) doubled, as assessed with the thermal dye dilution technique; PaO2 decreased, AaPO2 and venous admixture (Q S/Q T) increased. After AG, Q 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, PaO2 rose, and AaPO2 and Q S/Q T decreased. We conclude that in endotoxemic sheep, AG improves gas exchange and increases Q L and CL, whereas EVLW remains unchanged in spite of enhanced Pc. Apparently, increased lymphatic drainage prevents EVLW from rising after AG.




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