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 AG (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 microgram/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; Pa(O(2)) decreased, AaPO(2) 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, Pa(O(2)) rose, and AaPO(2) 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.
Department of Anesthesiology, Institute of Clinical Medicine, University of Tromso, Tromso, Norway.
O V
OV
Evgenov
O
O
Hevroy
K E
KE
Bremnes
L J
LJ
Bjertnaes
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D019446:Endotoxemia / Q000503:physiopathology; D004731:Endotoxins / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015633:Extravascular Lung Water / Q000187:drug effects*; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D011897:Random Allocation; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects
D004731:Endotoxins; D004791:Enzyme Inhibitors; D006146:Guanidines; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C004479:pimagedine