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Protective role of nitric oxide in ischemia and reperfusion injury of the liver

Shimamura, T and Zhu, Y and Zhang, S and Jin, MB and Ishizaki, N and Urakami, A and Totsuka, E and Kishida, A and Lee, R and Subbotin, V and Furukawa, H and Starzl, TE and Todo, S (1999) Protective role of nitric oxide in ischemia and reperfusion injury of the liver. Journal of the American College of Surgeons, 188 (1). 43 - 52. ISSN 1072-7515

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Background: The suppressed production of nitric oxide (NO), associated with endothelial dysfunction, is thought to be a cause of ischemia and reperfusion injury of the liver. But findings of the salutary effects of NO enhancement on such injury have been conflicting. In this study, we tested our hypothesis that NO enhancement would attenuate ischemic liver injury. For this purpose, an NO precursor, L-arginine, and a novel NO donor, FK409, were applied to a 2-hour total hepatic vascular exclusion model in dogs. Study Design: L-arginine was administered IV at a dose of 100 mg/kg twice (n = 5), while 300 mg/kg twice of FK409 was infused continuously into the portal vein (n = 5). The drugs were given to the animals for 30 and 60 minutes before and after ischemia, respectively. Nontreated animals were used as the control (n = 10). Two-week survival, systemic and hepatic hemodynamics indices, liver function tests, energy metabolism, and histopathology were analyzed. Results: Both treatments comparably augmented hepatic tissue blood flow, decreased liver enzyme release, and increased high-energy phosphate restoration during the reperfusion period, all of which contributed to rescuing all of the treated animals from the 2-hour total hepatic ischemia. In contrast, ischemia caused 70% mortality in the control group. Histologically, structural abnormality and neutrophil infiltration were markedly attenuated by the treatments. Systemic hypotension was observed in the animals treated with FK409, however. Conclusions: Our data demonstrate that NO enhancement alleviates the liver injury caused by ischemia and reperfusion. The supplementation of L-arginine, rather than FK409, is considered more applicable to clinical use because of the absence of systemic adverse effects.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Shimamura, T
Zhu, Y
Zhang, S
Jin, MB
Ishizaki, N
Urakami, A
Totsuka, E
Kishida, A
Lee, R
Subbotin, V
Furukawa, H
Starzl, TEtes11@pitt.eduTES11
Todo, S
Centers: Other Centers, Institutes, Offices, or Units > Thomas E. Starzl Transplantation Institute
Date: 1 January 1999
Date Type: Publication
Journal or Publication Title: Journal of the American College of Surgeons
Volume: 188
Number: 1
Page Range: 43 - 52
DOI or Unique Handle: 10.1016/s1072-7515(98)00259-2
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 1072-7515
Other ID: uls-drl:31735062127869, Starzl CV No. 2065
Date Deposited: 08 Apr 2010 17:35
Last Modified: 04 Feb 2019 22:55


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