EFFECTS OF SELECTIVE iNOS INHIBITION ON GUT AND LIVER O2-EXCHANGE AND ENERGY METABOLISM DURING HYPERDYNAMIC PORCINE ENDOTOXEMIA

Effect of combining nicotinamide as a PARS-inhibitor with selective iNOS blockade during porcine endotoxemia

“…It is remarkable all the more that the LPS-induced progressive increase of the ileo-arterial PCO 2 gap, indicating intramucosal acidosis, was not attenuated to the same extent. To which extent NAD was a disrupting element in our experiment remains speculative, but intramucosal acidosis had largely been attenuated by therapy with 1400 W alone [17].…”

“…The experiments described were simultaneously carried out with the investigation of selective iNOS inhibition and PARS blockade, respectively, alone. Therefore, the control-group receiving only LPS was the same as reported elsewhere [16,17] in order to minimize the number of animals needed as required by the German regulations for animal protection. The mean weight of the pigs [Deutsches Landschwein) (CON: 51 (47-53) kg; 1400W+NAD: 52 (49-56 kg)] and sex distribution (CON: 7 m and 1 f; 1400W+NAD: 7 m and 1 f) were comparable in both groups.…”

“…The mean weight of the pigs [Deutsches Landschwein) (CON: 51 (47-53) kg; 1400W+NAD: 52 (49-56 kg)] and sex distribution (CON: 7 m and 1 f; 1400W+NAD: 7 m and 1 f) were comparable in both groups. The preparation of the animals-including anesthesia, central venous, arterial, and balloon-tipped thermodilution pulmonary artery catheter, hepatic vein catheter (placed by ultrasound guidance, correct position confirmed by inspection post-mortem), midline laparotomy, placement of ultrasound transit time flow probes around portal vein and common hepatic artery, performing a double-lumen ileostomy, placement of a fiberoptic gas tension and pH sensor, and insertion of a cystostomy catheter-were performed under sterile condition without any adjunctive antibiotic therapy, as described previously in detail [16,17]. Body temperature was kept within 0.5°C of the baseline value using a heating mattress or external cooling as necessary.…”

“…To calculate the portal venous lactate/pyruvate ratios, both the lactate and the pyruvate concentrations were spectrophotometrically determined in duplicate as described previously [7,8,16,17]. The variation coefficients for the lactate and pyruvate measurements were 1.8% and 9.2%, respectively.…”

l-Lysine Decreases Nitric Oxide Production and Increases Vascular Resistance in Lungs Isolated from Lipopolysaccharide-Treated Neonatal Pigs

“…Gundersen et al (24) found that LPS decreased MAP and that the effect could be inhibited using a selective iNOS inhibitor in intact pigs. Matejovic et al (18) found that in intact pigs, the infusion of LPS increased expired NO and plasma nitrite levels and decreased MAP and furthermore that the increase in expired NO and plasma nitrite and the decrease in MAP could be prevented using a selective iNOS inhibitor. Taken together, these studies are consistent with the premise that LPS treatment in pigs increased NO production most likely via an increase in iNOS expression and that this increased NO production resulted in a decrease in systemic blood pressure.…”