title: L-Arginine restores splenocyte functions after trauma and hemorrhage potentially by improving splenic blood flow.
abstract: Several studies indicate that immune responses are markedly depressed early after onset of hemorrhage. Decreased organ blood flow has been implicated in the pathophysiology of altered immune responses after trauma-hemorrhage. In this regard, administration of L-arginine has been shown to restore depressed intestinal and hepatic blood flow after trauma-hemorrhage, probably due to provision of substrate for constitutive nitric oxide synthase (cNOS). It remains unknown, however, whether administration of L-arginine also ameliorates depressed splenic blood flow and whether this agent has any salutary effects on depressed splenocyte functions after trauma-hemorrhage. Male rats underwent sham operation or laparotomy and were bled to and maintained at a mean arterial blood pressure of 40 mmHg until 40% of maximum shed blood volume (MBV) was returned as Ringer lactate (RL). Hemorrhaged rats were then resuscitated with RL (4 times MBV over 1 h). During resuscitation, rats received 300 mg/kg L-arginine or saline (vehicle) intravenously; 4 h later, splenic blood flow, splenocyte proliferation, and splenocyte interleukin (IL)-2 and IL-3 were determined. Administration of L-arginine improved depressed splenic blood flow and restored depressed splenocyte functions after trauma-hemorrhage. Therefore, provision of L-arginine during resuscitation after trauma-hemorrhage should be considered a novel and safe approach for improving splenic organ blood flow and depressed splenocyte functions under such conditions.
authors.affiliation: Center for Surgical Research and Department of Surgery, Brown University School of Medicine and Rhode Island Hospital, Providence, Rhode Island 02903, USA.
authors.forename: M K
authors.initials: MK
authors.lastname: Angele
authors.forename: N
authors.initials: N
authors.lastname: Smail
authors.forename: M W
authors.initials: MW
authors.lastname: Knöferl
authors.forename: A
authors.initials: A
authors.lastname: Ayala
authors.forename: W G
authors.initials: WG
authors.lastname: Cioffi
authors.forename: I H
authors.initials: IH
authors.lastname: Chaudry
mesh_terms: D000818:Animals; D001120:Arginine / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005938:Glucocorticoids / Q000097:blood; D006146:Guanidines / Q000494:pharmacology; D006470:Hemorrhage / Q000188:drug therapy* / Q000503:physiopathology; D007376:Interleukin-2 / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation / Q000187:drug effects* / Q000502:physiology; D013154:Spleen / Q000098:blood supply / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D014947:Wounds and Injuries / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D006146:Guanidines; D007376:Interleukin-2; D001120:Arginine; C004479:pimagedine