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Ischemic preconditioning reduces intestinal apoptosis in rodents

Recent experimental studies have described the protective effect of ischemic preconditioning (IPC) on ischemia-reperfusion (I/R) injury of the intestine [1,2]. In order to reach a new point of view in the effect of IPC on the intestinal barrier function, the relationship between I/R-induced mucosal injury and apoptosis must be clarified. The present study was undertaken to investigate the relation between IPC and Bcl-2 expression immunohistochemically and apoptosis (by using conventional light microscopy, immunohistochemical staining for cytokeratin 18 [M30 cytodeath Ab], DNA agarose gel electrophoresis) in the intestine. Furthermore, we also investigated the effect of intestinal IPC on serum nitrite/nitrate levels.

With approval of the Ethical Committee, 33 male Wistar rats weighing 250-300 g were randomized into three groups. A control group of rats (n = 11) was subjected laparotomy. In an ischemic group (n = 11), laparotomy was performed and the superior mesenteric artery (SMA) was occluded by an atraumatic clamp for 30 min. In the preconditioned group (n = 11), before the ischemia-reperfusion period, rats were subjected to initial 10 min of intestinal ischemia and 10 min of reperfusion. Twenty-four hours later, ileum and blood samples were collected. Nitrite/nitrate levels were measured in the blood samples. Serum nitrate level was found to be increased in the I/R group (16.2 ± 0.9 vs 34.3 ± 4.1) but not in the IPC group (11.3 ± 5.9) (P < 0.05). The numbers of apoptotic cells at 24 hours after I/R were significantly lower in IPC-treated rats. Diminished Bcl-2 expression observed on the ileal specimens of the I/R group was found to be prevented by IPC.

Our results indicate that IPC provides a significant protective effect on ileum against I/R injury and that its effect is evidenced by a significant increase in the expression of Bcl-2 following the insult. This study shows that intestinal IPC may block the cascade of events that cause apoptosis that can lead to multiorgan failure. In the future, the use of agents causing Bcl-2 upregulation against the spontaneous I/R attacks as a preservative measure in criticial patients could be seriously considered.

References

  1. 1.

    McCallion K, Wattanasirichaigoon S, Gardiner KR, Fink MP: Ischemic preconditioning ameliorates ischemia- and reperfusion-induced hyperpermeability in rats. Shock 2000, 14: 429-434.

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    Aksöyek S, Cinel I, Avlan D, Cinel L, Oztürk C, Polat G, Nayci A, Oral U: Intestinal ischemic preconditioning protects the intestine and reduces bacterial translocation. Shock, in press. 2002 June

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Cinel, I., Avlan, D., Cinel, L. et al. Ischemic preconditioning reduces intestinal apoptosis in rodents. Crit Care 6, P76 (2002). https://doi.org/10.1186/cc1779

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Keywords

  • Ischemic Precondition
  • Ischemic Group
  • Significant Protective Effect
  • Intestinal Barrier Function
  • Conventional Light Microscopy