Basic Research
Copyright ©2007 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 7, 2007; 13(25): 3487-3492
Published online Jul 7, 2007. doi: 10.3748/wjg.v13.i25.3487
Effect of atrial natriuretic peptide on ischemia-reperfusion injury in a porcine total hepatic vascular exclusion model
Katsumi Kobayashi, Kiyohiro Oshima, Masato Muraoka, Takahiko Akao, Osamu Totsuka, Hisashi Shimizu, Hiroaki Sato, Kazumi Tanaka, Kenjiro Konno, Koshi Matsumoto, Izumi Takeyoshi
Katsumi Kobayashi, Masato Muraoka, Takahiko Akao, Osamu Totsuka, Hisashi Shimizu, Hiroaki Sato, Kazumi Tanaka, Izumi Takeyoshi, Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, 3-39-15 Showa-Machi, Maebashi, Gunma 371-8511, Japan
Kiyohiro Oshima, Intensive Care Unit, Gunma University Hospital, 3-39-15 Showa-Machi, Maebashi, Gunma 371-8511, Japan
Kenjiro Konno, Animal Resource Project, Center for Molecular Medicine, Jichi Medical University Institute, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan
Koshi Matsumoto, Department of Pathology, Nippon Medical School Musashi-Kosugi Hospital, 1-396 Kosugi-chou, Nakaharaku, Kawasaki, Kanagawa 211-8533, Japan
Author contributions: All authors contributed equally to the work.
Correspondence to: Izumi Takeyoshi, MD, Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, 3-39-15 Showa-Machi, Maebashi, Gunma 371-8511, Japan. takeyosi@showa.gunma-u.ac.jp
Telephone: +81-27-2208240 Fax: +81-27-2208250
Received: March 30, 2007
Revised: March 31, 2007
Accepted: April 18, 2007
Published online: July 7, 2007
Abstract

AIM: To evaluate the effect of ANP on warm I/R injury in a porcine THVE model.

METHODS: Miniature pigs (mini-pigs) weighing 16-24 kg were observed for 120 min after reperfusion following 120 min of THVE. The animals were divided into two groups. ANP (0.1 μg/kg per min) was administered to the ANP group (n = 7), and vehicle was administered to the control group (n = 7). Either vehicle or ANP was intravenously administered from 30 min before the THVE to the end of the experiment. Arterial blood was collected to measure AST, LDH, and TNF-α. Hepatic tissue blood flow (HTBF) was also measured. Liver specimens were harvested for p38 MAPK analysis and histological study. Those results were compared between the two groups.

RESULTS: The AST and LDH levels were lower in the ANP group than in the control group; the AST levels were significantly different between the two groups (60 min: 568.7 ± 113.3 vs 321.6 ± 60.1, P = 0.038 < 0.05, 120 min: 673.6 ± 148.2 vs 281.1 ± 44.8, P = 0.004 < 0.01). No significant difference was observed in the TNF-α levels between the two groups. HTBF was higher in the ANP group, but the difference was not significant. A significantly higher level of phosphorylated p38 MAPK was observed in the ANP group compared to the control group (0 min: 2.92 ± 1.1 vs 6.38 ± 1.1, P = 0.011 < 0.05). Histological tissue damage was milder in the ANP group than in the control group.

CONCLUSION: Our results show that ANP has a protective role in I/R injury with p38 MAPK activation in a porcine THVE model.

Keywords: Atrial natriuretic peptide, p38 MAPK, Ischemia-reperfusion injury, Porcine liver, Total hepatic vascular exclusion