Inhibition of inducible nitric oxide synthase ameliorates lung injury in rats after gut ischemia-reperfusion.
BACKGROUND
Gut hypoperfusion is considered to be a critical event for organ failure during severe surgical insults. The mechanism of remote organ injury after intestinal ischemia-reperfusion (I/R) may involve the excessive nitric oxide (NO) production; however, its role has been controversial. We sought to determine whether a selective inducible NO synthase inhibitor, aminoguanidine (AG), ameliorates pulmonary microvascular injury after superior mesenteric artery occlusion.


METHODS
Anesthetized rats underwent superior mesenteric artery occlusion for 30 minutes and reperfusion for 6 hours (I/R) or sham operation (control). Another set of animals undergoing I/R received an AG at the end of the ischemia. Pulmonary vascular permeability was assessed by measuring tissue retention of Evans Blue dye that binds albumin. The plasma was harvested and NO2/NO3 (end products of NO) was measured. The bacterial cultures of the mesenteric lymph node of animals were performed to estimate the gut bacterial translocation after injury.


RESULTS
The concentration of NO2/NO3 of plasma in the I/R group was higher than that of the control (p < 0.05). The lung-to-plasma Evans Blue dye ratio in the I/R group was also higher than that of the control (p < 0.01). Treatment with the AG prevented this lung injury induced by the gut I/R. The incidences of gut translocation were not significantly different between the I/R and AG groups.


CONCLUSIONS
Increased lung vascular permeability elicited by gut I/R was significantly attenuated with inhibition of an inducible NO release by AG. Control of bacterial translocation was not needed to prevent lung injury in this model.
Uchida
Kotaro
K
Department of Emergency and Critical Care Medicine, Tokyo Medical University, Tokyo, Japan.
Mishima
Shiro
S
Ohta
Sho-Ichi
S
Yukioka
Tetsuo
T
D000704:Analysis of Variance; D000818:Animals; D018988:Bacterial Translocation; D016009:Chi-Square Distribution; D006146:Guanidines / Q000494:pharmacology*; D007422:Intestines / Q000098:blood supply*; D007511:Ischemia / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D017538:Mesenteric Artery, Superior; D008641:Mesenteric Vascular Occlusion / Q000503:physiopathology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000502:physiology; D015427:Reperfusion Injury / Q000503:physiopathology*
D006146:Guanidines; D019001:Nitric Oxide Synthase; C004479:pimagedine