Ischemic preconditioning of small bowel mitigates the late phase of reperfusion injury: heme oxygenase mediates cytoprotection

• Published in: The American journal of surgery Vol. 199; no. 2; pp. 223 - 231
• Main Authors: Mallick, Ismail H., M.B.B.S., M.R.C.S., M.Sc., D.I.C., Ph.D, Winslet, Marc C., M.D., F.R.C.S, Seifalian, Alexander M., Ph.D., FIoN
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.02.2010; Elsevier; Elsevier Limited
• Subjects: Abdomen; Animals; Antioxidants; Biological and medical sciences; Carbon monoxide; Circulatory system; Endothelium; General aspects; Heme; Heme oxygenase; Heme Oxygenase-1 - metabolism; Ileum; Ileum - blood supply; Ileum - enzymology; Ileum - pathology; Ileum - transplantation; Injuries; Intestinal Mucosa - blood supply; Intestinal Mucosa - enzymology; Intestinal Mucosa - pathology; Intestine; Ischemia; Ischemic Preconditioning; L-Lactate dehydrogenase; Lactate dehydrogenase; Lactic acid; Male; Medical sciences; Microcirculation; Morbidity; Mucosa; Nonsteroidal anti-inflammatory drugs; Oxidative stress; Oxygenase; Perfusion; Preconditioning; Pyrrolidine; Pyrrolidine dithiocarbamate; Random Allocation; Rats; Rats, Sprague-Dawley; Reperfusion; Reperfusion Injury - enzymology; Reperfusion Injury - pathology; Reperfusion Injury - prevention & control; Rodents; Short Bowel Syndrome - surgery; Small intestine transplantation; Surgery; Transplantation; Transplants & implants; Zinc; Transplantation; Reperfusion; Ischemia; Intestine; Preconditioning; Heme oxygenase; Digestive system; Enzyme; Heme oxygenase (decyclizing); Cardiovascular disease; Late-phase; Small intestine; Trauma; Medicine; Treatment; Surgery; Graft; Oxidoreductases; Lesion
• ISSN: 0002-9610; 1879-1883
• DOI: 10.1016/j.amjsurg.2009.01.011

Abstract Background Ischemia and reperfusion (IR) injury of the intestine is a major cause of morbidity and mortality following small bowel transplantation. The current study evaluates the effect of ischemic preconditioning (IPC) on the intestinal microcirculation in the late phase of IR injury of the intestine. Methods Sixty rats were randomly allocated to 5 study groups (n = 12 per group): (1) sham, (2) IR (3) IPC, (4) pyrrolidine dithiocarbamate (PDTC) (HO-1 inducer), and (5) zinc protoporhyrin (ZnPP) (HO-1 inhibitor). Mucosal perfusion and leukocyte–endothelial interactions were measured with the aid of an intravital microscope. At the end of the experiments, blood samples for lactate dehydrogenase (LDH) levels and biopsies of ileum for histologic evaluation were obtained. Results IPC significantly improved the mucosal perfusion and decreased the leukocyte–endothelial interactions. Histologic examination showed that ileal mucosa was significantly less injured in the IPC and PDTC groups as compared with the IR group. Conclusions IPC protects the intestine from late reperfusion injury. HO-1 is involved in this protection. These findings may be of significant importance in clinical small bowel transplantation.