nitroarginine and Systemic-Inflammatory-Response-Syndrome

Mesenteric ischemia and acidosis leading to intestinal ischemia has been observed during cardiopulmonary bypass (CPB) despite normal flow in the mesenteric vessels. The aim of this study was to assess mesenteric endothelium-dependent reactivity and vasoconstrictor responses of small mesenteric arteries in a rat model of CPB without aortic cross-clamping.. After femoral cannulation a partial 90 minutes CPB was performed with hemodynamics and blood gas parameters monitoring. Blood samples and segments of small mesenteric arteries were obtained in rats sacrificed 2.5 hours (CPBH2.5) or 6 hours (CPBH6) after femoral cannulation. Sham surgery (sham H2.5, sham H6) was performed with femoral cannulation only. Segments of small mesenteric arteries were placed in a myograph in order to assess the contractile response to phenylephrine (with or without NO synthase inhibitor) or the endothelium-dependent relaxation to acetylcholine. Systemic inflammation was evaluated by measuring plasma concentrations of TNFalpha. Pulmonary and intestinal infiltration of activated leukocytes was assessed by immunohistochemistry.. CPB induced increased contractile response to phenylephrine which persisted after blockade of NO synthesis as well as transient impairment of endothelium-dependent relaxations. CPB also led to early and marked release of TNFalpha.. CPB was responsible for mesenteric endothelial dysfunction and direct increase in the contractile response to alpha1-adrenergic agonist with increased systemic inflammatory response. This phenomenon might contribute to an increase in the risk of mesenteric ischemic events during cardiac surgery especially when vasopressor agents are used.

Topics: Acetylcholine; Animals; Arterioles; Cardiopulmonary Bypass; Ileum; In Vitro Techniques; Male; Mesenteric Arteries; Mesenteric Vascular Occlusion; Nitroarginine; Nitroprusside; Phenylephrine; Rats; Rats, Wistar; Splanchnic Circulation; Systemic Inflammatory Response Syndrome; Tumor Necrosis Factor-alpha; Vasoconstriction; Vasoconstrictor Agents; Vasodilation

We investigated the effects of aminoguanidine, a relatively selective inhibitor of inducible nitric oxide (NO) synthase, on the systemic inflammatory response syndrome induced by platelet activating factor (PAF) and by lipopolysaccharide in rats, with emphasis on NO production in vivo. Aminoguanidine treatment improved survival rates after lipopolysaccharide challenge, whereas it aggravated the lethality caused by PAF. Lipopolysaccharide induced a marked increase in the concentrations of nitrate and nitrite in plasma compared with vehicle administration, and the increase was prevented by aminoguanidine. In contrast, PAF challenge with or without aminoguanidine did not affect the concentrations of nitrate and nitrite in plasma compared with vehicle administration. These results suggest that NO derived from inducible NO synthase is not a major participant in the systemic inflammatory response syndrome induced by PAF. Aminoguanidine is not likely to provide beneficial effects in conditions where PAF is produced and the concentrations of nitrate and nitrite in plasma are not significantly increased.

Topics: Animals; Disease Models, Animal; Enzyme Induction; Enzyme Inhibitors; Guanidines; Injections, Intravenous; Lipopolysaccharides; Male; Nitrates; Nitric Oxide Synthase; Nitrites; Nitroarginine; Platelet Activating Factor; Rats; Systemic Inflammatory Response Syndrome