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The effect of 100% oxygen on intestinal preservation and recovery following ischemia-reperfusion injury in rats*

Sukhotnik, Igor MD; Brod, Vera PhD; Lurie, Michael MD; Rahat, Michal A. PhD; Shnizer, Sergei PhD; Lahat, Nitza PhD; Mogilner, Jorge G. MD; Bitterman, Haim MD

doi: 10.1097/CCM.0b013e31819d0f5c
Laboratory Investigations
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Objective: Inhalation of oxygen improves the hemodynamic status and attenuates the inflammatory response after intestinal ischemia-reperfusion (IR). Yet, the use of hyperoxia is hindered by concerns that it could exacerbate reperfusion injury by increasing free radical formation. We examined the effect of hyperoxia on enterocyte turnover and intestinal preservation and rehabilitation following IR injury in rats.

Design: Animal study.

Setting: Research laboratory.

Subjects: Male Sprague-Dawley rats.

Interventions: Animals were assigned to four experimental groups: 1) Sham rats underwent laparotomy without vascular occlusion and breathed air, 2) Sham-oxygen rats underwent laparotomy without vascular occlusion and breathed 100% oxygen, 3) IR rats underwent occlusion of the superior mesenteric artery and portal vein for 30 minutes and breathed air, and 4) IR group treated with oxygen (IR-O2)rats underwent IR and breathed 100% oxygen starting 10 minutes before and continued for the first 6 hours after reperfusion. Intestinal structural changes, enterocyte proliferation, and enterocyte apoptosis were determined 24 hours after IR.

Measurements and Main Results: In IR rats, breathing 100% oxygen resulted in a significant decrease in Park's injury score in the ileum (p < 0.05 from untreated IR rats). Rats treated with oxygen also demonstrated a significant increase in mucosal weight (p < 0.05) and mucosal DNA (p < 0.05) in the jejunum and ileum, and an increase in villus height (p < 0.01), and crypt depth (p < 0.05) in the ileum. Enterocyte proliferation (assessed by bromodeoxyuridine uptake) was significantly decreased in the jejunum and ileum in untreated IR rats. Oxygen therapy increased enterocyte proliferation in the ileum, and diminished both the apoptosis index and Bax gene expression in the jejunum and ileum (p < 0.05). Plasma thermochemiluminescence oxidizability assay revealed significantly higher thermochemiluminescence ratios in IR group treated with oxygen than in untreated IR rats (p < 0.05) at 6 hours postreperfusion suggesting a significantly lower prior in vivo molecular oxidation.

Conclusions: Hyperoxia reduces small bowel injury, accelerates enterocyte turnover, and improves intestinal rehabilitation after IR.

From the Departments of Pediatric Surgery (IS, JGM) and Pathology (ML), Bnai Zion Medical Center, Haifa, Israel; The Ischemia-shock (VB, HB) and Immunology (MAR, NL) Research Laboratories, Carmel Medical Center. Haifa, Israel; Technion–Israel Institute of Technology, Haifa, Israel; and Lumitest Ltd (SS), Nesher, Israel.

The authors have not disclosed any potential conflicts of interest.

For information regarding this article, E-mail: igor-dr@internet-zahav.net.

© 2009 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins