Effects of L-arginine infusion during ischemia on gut blood perfusion, oxygen tension, and circulating myeloid cell activation in a murine gut ischemia/reperfusion model.
BACKGROUND
Gut hypoperfusion is considered to be a mechanism for early multiple-organ failure after severe surgical insults. L-Arginine (ARG) may preserve gut microcirculation as a substrate of nitric oxide synthase, but simultaneously may enhance immune cell response. It remains unknown if ARG infusion during gut ischemia improves the outcome after gut ischemia-reperfusion (I/R).


METHODS
Male Institute of Cancer Research mice were randomized to control and ARG groups. After i.v. cannulation, mice underwent 90 (Exp. 1) or 60 (Exp. 2 and 3) minutes of gut I/R. Control mice received normal saline infusion at 1 mL/h for 60 minutes during ischemia, whereas the ARG group was given 1% ARG hydrochloride solution. In Exp. 1, survival was observed for 72 hours (n = 35). In Exp. 2, blood perfusion and oxygen tension of the small intestine were measured (n = 9). In Exp. 3, peripheral blood was obtained at 2 or 4 hours after reperfusion (n = 22). Reactive oxygen intermediate (ROI) production by myeloid cells with or without phorbol myristate acetate (PMA) stimulation and expression of CD11a and CD11b on myeloid cells were examined using flow cytometry.


RESULTS
Exp. 1: There was no significant difference in survival times (log rank test, p = .2). However, survival rates at 12 hours were 72% (13/18) for the control group and 35% (6/17) for the ARG group (p < .05 Fisher). Exp. 2: ARG infusion significantly improved gut blood perfusion ratio during ischemia but had no effect on oxygen tension. Exp. 3: In the ARG group, ROI production with PMA and CD11b expression at 4 hours were higher than those at 2 hours, whereas there were no significant changes in the control mice.


CONCLUSIONS
ARG infusion improves intestinal blood perfusion during ischemia but primes and activates circulating myeloid cells excessively. Consequently, i.v. infusion of ARG during ischemia reduces survival rate.
Fukatsu
Kazuhiko
K
Division of Basic Traumatology, National Defense Medical College Research Institute, Saitama, Japan. kazfukatsu@yahoo.co.jp
Ueno
Chikara
C
Maeshima
Yoshinori
Y
Hara
Etsuko
E
Nagayoshi
Hidetoshi
H
Omata
Jiro
J
Mochizuki
Hidetaka
H
Hiraide
Hoshio
H
D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007262:Infusions, Intravenous; D007421:Intestine, Small / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008641:Mesenteric Vascular Occlusion; D051379:Mice; D008813:Mice, Inbred ICR; D010100:Oxygen / Q000378:metabolism*; D010289:Parenteral Nutrition, Total; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism*; D016019:Survival Analysis
D017382:Reactive Oxygen Species; D001120:Arginine; D010100:Oxygen