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-inhibi tor properties on intestinal and hepatic perfusion, O-2 exchange, and metab olism 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 en dotoxemia, hepatic arterial and portal venous blood flow, ileal mucosal-art erial PCO2 gap, portal and hepatic venous lactate/pyruvate ratio, free glut athione (GSH), and 8-isoprostanes were measured. Expired NO and plasma nitr ate levels were assessed as well. MEG blunted the endotoxin-induced increas e in expired NO and prevented the progressive fall in blood pressure withou t 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 b eneficially affect variables of oxidative stress.