Effects of combined selective iNOS inhibition and peroxynitrite blockade during endotoxemia in pigs.
We investigated the effect of mercaptoethylguanidine (MEG, 3 mg kg(-1)h(-1)), a combined selective inducible nitric oxide synthase (iNOS) inhibitor, a peroxynitrite and oxygen free radical scavenger with cyclooxygenase-inhibitor properties on intestinal and hepatic perfusion, O2 exchange, and metabolism during long-term hyperdynamic porcine endotoxemia. MEG was started 12 h after onset of endotoxemia. At baseline and after 12, 18, and 24 h of endotoxemia, hepatic arterial and portal venous blood flow, ileal mucosal-arterial PCO2 gap, portal and hepatic venous lactate/pyruvate ratio, free glutathione (GSH), and 8-isoprostanes were measured. Expired NO and plasma nitrate levels were assessed as well. MEG blunted the endotoxin-induced increase in expired NO and prevented the progressive fall in blood pressure without affecting cardiac output. It attenuated both systemic and regional venous acidosis without influencing the impairment of hepatosplanchnic metabolism nor counteracting the increase in GSH levels. In our model MEG failed to beneficially affect variables of oxidative stress.
Ploner
F
F
Bezirkskrankenhaus Sterzing, Abteilung Anaesthesie und Reanimation, Sterzing, Italy.
Radermacher
P
P
Theisen
M
M
Tugtekin
I F
IF
Matejovic
M
M
Stehr
A
A
Szabó
C
C
Southan
G J
GJ
Georgieff
M
M
Bruckner
U B
UB
Träger
K
K
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D002302:Cardiac Output; D019446:Endotoxemia / Q000097:blood / Q000503:physiopathology*; D004926:Escherichia coli; D005260:Female; D005978:Glutathione / Q000097:blood; D006439:Hemodynamics / Q000502:physiology*; D006454:Hemoglobins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D009569:Nitric Oxide / Q000032:analysis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D010101:Oxygen Consumption; D030421:Peroxynitrous Acid / Q000037:antagonists & inhibitors*; D015656:Respiratory Mechanics; D013552:Swine; D013929:Thromboxane B2 / Q000097:blood; D014655:Vascular Resistance
D006454:Hemoglobins; D008070:Lipopolysaccharides; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D005978:Glutathione