The effect of mild endotoxemia during low arginine plasma levels on organ blood flow in rats

Objective: Arginine is the sole precursor in the generation of the vasodila ting agent nitric oxide. Arginine plasma levels are low in situations assoc iated with endotoxemia such as major trauma, sepsis, and experimental obstr uctive jaundice. The aim of the study was to evaluate hemodynamics at low a rginine plasma levels during a low-grade endotoxemia. Design: Randomized, placebo-controlled animal laboratory investigation. Subjects: Male Wistar rats (n = 29), anesthetized. Interventions: Rats were randomly assigned to receive (at t = 0 mins) an in travenous infusion of 1.5 mt of 0.9% NaCl (SAL, n = 12) or 1.5 mt of an arg inase (3200 IU) solution (ASE, n = 17) over a 20-min period. After the SAL or ASE infusion, rats were randomly assigned to receive an intravenous endo toxin (lipopolysaccharide [LPS], 150 mu g/kg in 1.0 mt of 0.9% NaCl; ASE/LP S, n = 10 and SAL/LPS, n = 6) challenge or a control infusion (1.0 mL of 0. 9% NaCl; ASE/SAL, n = 7 and SAL/SAL, n = 6) at t = 30 mins. Measurements and Main Results:Organ blood flow was measured at t = 270 mins , using radiolabeled microspheres. At this time point, arginine plasma leve ls were lower in the ASE-treated rats (ASE/SAL vs. SAL/SAL and ASE/LPS vs. SAL/LPS, both p < .005, respectively). Cardiac output, mean arterial pressu re, and therefore total peripheral resistance were similar for all groups. In the LPS-treated animals (SAL/LPS and ASE/LPS), cardiac output was mainta ined by a higher heart rate compensating the lower stroke volume, Organ blo od flow to the small intestine and splanchnic blood flow was lower in the A SE/LPS-treated rats (both p < .05 when compared with of her groups). Total liver blood flow was similar for all groups; the lower splanchnic blood flo w was compensated for by a higher hepatic arterial blood flow. Conclusion: The present study shows that low arginine plasma levels do not influence organ blood flow, whereas, during a low-grade endotoxemia, low ar ginine plasma levels result in reduced blood flow to the small intestine.