Mild endotoxaemia during low arginine plasma levels reduces blood flow to the small intestine

Abstract

Abstract Background Arginine is the sole precursor in the generation of the vasodilating agent nitric oxide. Plasma levels of arginine are low in situations associated with endotoxaemia such as major trauma, sepsis and experimental obstructive jaundice. The aim of the study was to evaluate haemodynamics at low arginine plasma levels during low-grade endotoxaemia. Methods Rats were assigned randomly to receive (at t = 0 min) an intravenous infusion of 1·5 ml sodium chloride 0·9 per cent (SAL, n = 12) or 1·5 ml arginase solution (3200 units) (ASE, n = 17) over 20 min. After the SAL or ASE infusion, rats were randomly assigned to receive an intravenous endotoxin (lipopolysaccharide; LPS; 150 μg kg−1 in 1·0 ml 0·9 per cent sodium chloride) challenge (ASE-LPS, n = 10 and SAL-LPS, n = 6) or a control infusion of 1·0 ml 0·9 per cent sodium chloride (ASE-SAL, n = 7 and SAL-SAL, n = 6) at t = 30 min. Organ blood flow was measured at t = 270 min, using radiolabelled microspheres. Results At 270 min arginine plasma levels were lower in the ASE-treated rats (ASE-SAL versus SAL-SAL and ASE-LPS versus SAL-LPS, both P < 0·005). Cardiac output, mean arterial pressure and therefore total peripheral resistance were similar for all groups. In the LPS-treated animals (SAL-LPS and ASE-LPS) cardiac output was maintained by a higher heart rate compensating for the lower stroke volume. Organ blood flow to the small intestine and splanchnic blood flow were lower in the ASE-LPS-treated rats (both P < 0·05 compared with other groups). Total liver blood flow was similar for all groups; the lower splanchnic blood flow was compensated for by a higher hepatic arterial blood flow. Conclusion This study shows that low plasma levels of arginine do not influence organ blood flow while, during low-grade endotoxaemia, low arginine plasma levels result in reduced blood flow to the small intestine.