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.


METHODS
Prospective, randomized, controlled experimental study with repeated measurements.


METHODS
University animal laboratory.


METHODS
Eight yearling, awake sheep.


METHODS
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 microg/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.


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 (QL) and protein clearance (CL) 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 QL with no difference in CL 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.
Department of Anesthesiology, Faculty of Medicine, University of Tromsø, Tromsø, Norway.
O V
OV
Evgenov
G
G
Sager
L J
LJ
Bjertnaes
D000818:Animals; D001831:Body Temperature; D002199:Capillary Permeability / Q000187:drug effects; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D019446:Endotoxemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D004927:Escherichia coli Infections / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors*; D006439:Hemodynamics / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011446:Prospective Studies; D011652:Pulmonary Circulation / Q000187:drug effects*; D011897:Random Allocation; D012128:Respiratory Distress Syndrome / Q000382:microbiology*; D012756:Sheep; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects; D014851:Wakefulness
D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D008751:Methylene Blue