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 (
L) and protein clearance (CL). Extravascular lung water
(EVLW) doubled, as assessed with the thermal dye dilution
technique; PaO2 decreased, AaPO2 and venous admixture (
S/
T)
increased. After AG,
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
S/
T decreased.
We conclude that in endotoxemic sheep, AG improves gas exchange
and increases
L and CL, whereas EVLW remains unchanged in
spite of enhanced Pc. Apparently, increased lymphatic drainage
prevents EVLW from rising after AG.