Pyrrolidine dithiocarbamate protects small bowel from warm ischemia/reperfusion injury of the intestine: the role of heme oxygenase

Ismail H Mallick , Marc C Winslet , Alexander M Seifalian (1)

1 Academic Division of Surgical & Interventional Sciences

Ischemia reperfusion (IR) injury of the intestine occurs commonly during abdominal surgery. We have previously shown that pyrrolidine dithiocarbamate (PDTC), a heme oxygenase-1 (HO-1) donor improves intestinal microvascular perfusion. In this study we investigate the effects of PDTC on the intestinal microcirculation following ischemia reperfusion (IR) injury of the intestine. 72 Male Sprague-Dawley rats were randomly assigned to four groups (n=18/group): 1) sham group underwent laparotomy without induction of IR of the intestine, 2) IR group, subjected to superior mesenteric artery occlusion consisting of 30 minutes and 2 hours of reperfusion, 3) PDTC+IR group, received PDTC prior to IR and 4) Zn-PP group, received HO-1 inhibitor Zinc Protoporrphyrin (ZnPP) followed by procedures as in group C. The ileum was evaluated for changes in tissue cytochrome oxidase redox status, red blood cell (RBC) dynamics and leukocyte-endothelial interactions. The expression of HO-1 in the ileal tissue was examined at the end of the reperfusion. PDTC significantly improved the intestinal tissue oxygenation, mucosal perfusion index and RBC velocity as compared to IR and ZnPP groups. PDTC also decreased the leukocyte-endothelial interactions (p<0.05 vs. IR and ZnPP). PDTC induced the expression of HO-1 whereas ZnPP abolished this effect.

Mots clés: Medicine

Ismail H Mallick, Marc C Winslet, Alexander M Seifalian. Pyrrolidine dithiocarbamate protects small bowel from warm ischemia/reperfusion injury of the intestine: the role of heme oxygenase. Clinical Science, 2006, 111 (6), pp.373-380. ⟨10.1042/CS20060119⟩. ⟨hal-00479326⟩