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

Mallick, Ismail H.; Winslet, Marc C.; Seifalian, Alexander M.

doi:10.1016/j.amjsurg.2009.01.011

« Previous Next »The American Journal of Surgery
Volume 199, Issue 2 , Pages 223-231, February 2010

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

Ismail H. Mallick, M.B.B.S., M.R.C.S., M.Sc., D.I.C., Ph.D.
- Gastrointestinal and Hepatobiliary Research Unit, UCL Division of Surgery and Interventional Science, Royal Free and University College Medical School, University College London, UK
- Department of Surgery, Royal Free Hospital, Hampstead NHS Trust, London, UK
Marc C. Winslet, M.D., F.R.C.S.
- Gastrointestinal and Hepatobiliary Research Unit, UCL Division of Surgery and Interventional Science, Royal Free and University College Medical School, University College London, UK
- Department of Surgery, Royal Free Hospital, Hampstead NHS Trust, London, UK
Alexander M. Seifalian, Ph.D., FIoN
- Gastrointestinal and Hepatobiliary Research Unit, UCL Division of Surgery and Interventional Science, Royal Free and University College Medical School, University College London, UK
- Department of Surgery, Royal Free Hospital, Hampstead NHS Trust, London, UK
- Corresponding author. Tel.: +44 20 7830 2901; fax: +44 20 7472 6444

Received 11 October 2008; received in revised form 28 December 2008 published online 13 April 2009.

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.

Keywords: Intestine, Ischemia, Reperfusion, Transplantation, Preconditioning, Heme oxygenase