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Open AccessArticle

A Dual Protective Effect of Intestinal Remote Ischemic Conditioning in a Rat Model of Total Hepatic Ischemia

1
Department of Surgery and Transplantation, University Hospital RWTH Aachen, 52074 Aachen, Germany
2
Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan
3
Organ Transplantation Department, Tongji Hospital, Wuhan 430030, China
4
Institutes of Molecular Medicine and Experimental Immunology (IMMEI), University of Bonn, 53127 Bonn, Germany
5
Department of Gastroenterological Surgery, Akita University Graduate School of Medicine, Akita 010-8543, Japan
6
Institute for Laboratory Animal Science and Experimental Surgery, RWTH-Aachen University, 52074 Aachen, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
J. Clin. Med. 2019, 8(10), 1546; https://doi.org/10.3390/jcm8101546
Received: 10 August 2019 / Revised: 10 September 2019 / Accepted: 17 September 2019 / Published: 26 September 2019
The present study aimed to investigate the effects of intestinal remote ischemic preconditioning (iRIC) on ischemia-reperfusion injury (IRI) and gut barrier integrity in a rat model of total hepatic ischemia (THI). Male Wistar rats (n = 50; 250–300 g) were randomly allocated into two experimental groups: RIC/Control. Thirty minutes of THI was induced by clamping the hepatoduodenal ligament. iRIC was applied as 4-min of ischemia followed by 11-min of reperfusion by clamping the superior mesenteric artery. Animals were sacrificed at 1, 2, 6, 24 h post-reperfusion (n = 5/group/timepoint). RIC of the gut significantly improved microcirculation of the ileum and the liver. Tissue ATP-levels were higher following iRIC (Liver: 1.34 ± 0.12 vs. 0.97 ± 0.20 μmol/g, p = 0.04) and hepatocellular injury was reduced significantly (ALT: 2409 ± 447 vs. 6613 ± 1117 IU/L, p = 0.003). Systemic- and portal venous IL-6 and TNF-alpha levels were markedly lower following iRIC, demonstrating a reduced inflammatory response. iRIC led to a structural and functional preservation of the intestinal barrier. These results suggest that iRIC might confer a potent protection against the detrimental effects of THI in rats via reducing IRI and systemic inflammatory responses and at the same time by mitigating the dramatic consequences of severe intestinal congestion and bacterial translocation. View Full-Text
Keywords: liver ischemia; total hepatic ischemia; ischemia; reperfusion; remote conditioning; ischemic conditioning; intestinal conditioning liver ischemia; total hepatic ischemia; ischemia; reperfusion; remote conditioning; ischemic conditioning; intestinal conditioning
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Czigany, Z.; Hata, K.; Lai, W.; Schwandt, T.; Yamamoto, Y.; Uemoto, S.; Tolba, R.H. A Dual Protective Effect of Intestinal Remote Ischemic Conditioning in a Rat Model of Total Hepatic Ischemia. J. Clin. Med. 2019, 8, 1546.

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