L-arginine restores the depressed cardiac output and regional perfusion after trauma-hemorrhage.
BACKGROUND
Previous studies indicate that vascular endothelial cell dysfunction occurs early after trauma-hemorrhage and may contribute to further alteration in tissue perfusion and cellular function. Because endothelial cell dysfunction is characterized by the reduced release of nitric oxide (NO) by endothelial constitutive NO synthase (cNOS), we tested the hypothesis that administration of L-arginine (ie, the substrate for cNOS) after trauma and hemorrhage should have beneficial effects on depressed cardiac output and organ blood flow under those conditions.


METHODS
Rats underwent a laparotomy (ie, trauma induced) and were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of maximal shed blood volume was returned in the form of Ringer's lactate solution. The animals were than resuscitated with 4 times the volume of the shed blood in the form of Ringer's lactate solution over 1 hour. L-arginine (300 mg/kg body wt) or saline solution was infused intravenously during the first 15 minutes of resuscitation. Cardiac output and organ blood flow were determined by 85Sr-microspheres at 1.5 and 4 hours after the completion of resuscitation. Plasma interleukin-6 (IL-6) was determined by bioassay at 4 hours after resuscitation.


RESULTS
Cardiac output and blood flow in the kidneys, small intestine, and lungs decreased significantly after hemorrhage and resuscitation. In addition, portal blood flow and total hepatic perfusion were also significantly reduced. Administration of L-arginine at the onset of fluid resuscitation, however, restored the depressed cardiac output and tissue perfusion. Moreover, the up-regulated plasma levels of IL-6 were also attenuated by L-arginine administration.


CONCLUSIONS
Because the adjuvant use of L-arginine restored the depressed cardiac output and organ blood flow and decreased plasma levels of IL-6, administration of this essential amino acid should be considered as a useful adjunct to fluid resuscitation for improving cardiovascular function in trauma victims.
Department of Surgery, Brown University School of Medicine, Providence, RI, USA.
M K
MK
Angele
N
N
Smail
P
P
Wang
W G
WG
Cioffi
K I
KI
Bland
I H
IH
Chaudry
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects*; D004064:Digestive System / Q000098:blood supply; D006470:Hemorrhage / Q000188:drug therapy / Q000503:physiopathology*; D015850:Interleukin-6 / Q000097:blood; D007668:Kidney / Q000098:blood supply; D007813:Laparotomy; D008099:Liver / Q000098:blood supply; D008168:Lung / Q000098:blood supply; D008297:Male; D008643:Mesentery / Q000098:blood supply; D018482:Muscle, Skeletal / Q000098:blood supply; D010179:Pancreas / Q000098:blood supply; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012151:Resuscitation; D012867:Skin / Q000098:blood supply; D017695:Soft Tissue Injuries / Q000188:drug therapy / Q000503:physiopathology*; D014655:Vascular Resistance / Q000187:drug effects
D015850:Interleukin-6; D001120:Arginine