Methylene blue reduces lung fluid filtration during the early phase of endotoxemia in awake sheep

Objective: To determine whether methylene blue (MB), an inhibitor of soluble guanylate cyclase and nitric oxide synthase, alters lung hemodynamics and fluid filtration after endotoxin in sheep, Design: Prospective, randomized, controlled experimental study with repeated measurements. Setting: University animal laboratory. Subjects: Eight yearling, awake sheep. Interventions: Sheep were instrumented for a chronic study with vascular and lung lymph catheters, In two experiments, separated by 1 wk of recovery, the animals received intravenously either an injection of MB 10 mg/kg or a corresponding volume of 0.9% sodium chloride as pretreatment. Thirty minutes later, sheep received a bolus injection of Escherichia coli endotoxin 1 mug/kg, followed by either an infusion of MB 2.5 mg/kg/hr or a corresponding volume of 0.9% sodium chloride for 5 hrs, Measurements and Main Results: MB decreased the early phase endotoxin-induced rises in pulmonary capillary pressure and pulmonary vascular resistance. MB also reduced the increments in lung lymph flow ((Q) over dot (L)) and protein clearance (C-L) as well as the rightward shift of the permeability-surface area product (PS), In addition, MB diminished the decrease in cardiac output, stabilized mean arterial pressure, and precluded the rise in plasma and lung lymph cyclic guanosine 3 ' -5 ' monophosphate, However, during the late phase, MB-treated sheep presented with a faster rise in (Q) over dot(L) with no difference in C-L and PS from the endotoxemic controls. Conclusions: During the early phase of endotoxemia in sheep, MB attenuates lung injury by decreasing the enhanced lung fluid filtration as a result of reduced pulmonary capillary pressure and permeability. However, MB does not counteract the late phase increase in lung fluid filtration.