PURPOSE OF REVIEW: Vascular endothelial cells control vascular smooth muscle tone via the release of nitric oxide. Following adverse circulatory conditions, namely trauma and hemorrhage, endothelial cell dysfunction occurs, leading to a decrease in the release of endothelium-derived nitric oxide, which contributes to further alterations in tissue perfusion and organ function. RECENT FINDINGS: Early administration of L-arginine (the precursor of nitric oxide) and the substrate for nitric oxide synthase in vascular endothelial cells has been found to restore the depressed organ blood flow and to reduce tissue injury following shock. This improvement in cardiovascular function was associated with restoration of the depressed cell-mediated immune responses and attenuation of the massive inflammatory response encountered under such conditions. Furthermore, the excessive infiltration of the liver with neutrophils following trauma-hemorrhage was decreased by L-arginine administration, thereby reducing hepatic injury. In addition, L-arginine treatment decreased the inflammatory response at the site of trauma and the improved wound-healing process following blood loss. SUMMARY: Despite those promising results in animal models at present, none of the published clinical trials has demonstrated efficacy of L-arginine at doses above standard dietary practices on the outcome in critically ill surgical patients, besides the reduction in infectious complications.
PURPOSE OF REVIEW: Vascular endothelial cells control vascular smooth muscle tone via the release of nitric oxide. Following adverse circulatory conditions, namely trauma and hemorrhage, endothelial cell dysfunction occurs, leading to a decrease in the release of endothelium-derived nitric oxide, which contributes to further alterations in tissue perfusion and organ function. RECENT FINDINGS: Early administration of L-arginine (the precursor of nitric oxide) and the substrate for nitric oxide synthase in vascular endothelial cells has been found to restore the depressed organ blood flow and to reduce tissue injury following shock. This improvement in cardiovascular function was associated with restoration of the depressed cell-mediated immune responses and attenuation of the massive inflammatory response encountered under such conditions. Furthermore, the excessive infiltration of the liver with neutrophils following trauma-hemorrhage was decreased by L-arginine administration, thereby reducing hepatic injury. In addition, L-arginine treatment decreased the inflammatory response at the site of trauma and the improved wound-healing process following blood loss. SUMMARY: Despite those promising results in animal models at present, none of the published clinical trials has demonstrated efficacy of L-arginine at doses above standard dietary practices on the outcome in critically ill surgical patients, besides the reduction in infectious complications.
Authors: Tsin W Yeo; Daniel A Lampah; Retno Gitawati; Emiliana Tjitra; Enny Kenangalem; Yvette R McNeil; Christabelle J Darcy; Donald L Granger; J Brice Weinberg; Bert K Lopansri; Ric N Price; Stephen B Duffull; David S Celermajer; Nicholas M Anstey Journal: J Infect Dis Date: 2008-08-15 Impact factor: 5.226