Jejunal mucosal nitric oxide production and substrate dependency during acute mesenteric hypoperfusion in pigs

Objective: Jejunal nitric oxide (NO) formation is impaired during mucosal h ypoperfusion, This study was undertaken to investigate whether this phenome non could result from a restricted mucosal availability of NO-synthase subs trates, ie, oxygen and/or L-arginine. Design: Controlled study using laboratory animals. Setting: University animal research laboratory. Subjects: Eighteen chloralose-anesthetized, ventilated, juvenile Landrace d omestic pigs. Interventions: Mesenteric hypoperfusion was induced by intrapericardial inf usion of Ringer's solution to achieve decreased cardiac output by creation of cardiac tamponade. Measurements and Main Results:Animals were prepared for jejunal intralumina l perfusion with 150 mM NaCl or 3 mM L-arginine solution in an isolated int estinal segment and then subjected to cardiac tamponade, Jejunal mucosal NO formation was measured with a tonometric technique. Mesenteric blood flow was measured as portal blood flow, and mucosal perfusion was measured by la ser Doppler flowmetry, Regional oxygen consumption and delivery were calcul ated from arterial and portal blood samples. Cardiac tamponade reduced jeju nal NO formation (-52%), mesenteric oxygen delivery (-75%), oxygen consumpt ion (-39%), and mucosal perfusion (-43%). Oxygenation of the jejunal intral uminal perfusate completely restored the intestinal NO levels within 30 min s, whereas presence of L-arginine was without effect. Conclusions: The study indicates that oxygen rather than L-arginine is the rate-limiting factor for mucosal NO production during acute reduced splanch nic perfusion.