Intestinal Ischemic Preconditioning Protects the Intestine and Reduces Bacterial Translocation

Abstract

Ischemic preconditioning (IPC) was first demonstrated in the heart, but this protective effect has been also recently described in the intestine. The aim of this study was to determine the effects of intestinal ischemic preconditioning on the morphology of intestine and bacterial translocation. Twenty-four male Wistar rats weighting 250 to 300 g were randomized into three groups. A control group of rats (n = 8) were subjected laparotomy. In an ischemic group (n = 8), laparotomy was performed and the superior mesenteric artery was occluded by an atraumatic clamp for 30 min. In the preconditioned group (n = 8), before the ischemia-reperfusion (I/R) period (as in ischemic group), rats were subjected to an initial 10 min of intestinal ischemia and 10 min of reperfusion. Twenty-four hours later, to evaluate whether the I/R induced intestinal injury and bacterial translocation (BT), tissue and blood samples were collected, and liver, spleen, and mesenteric lymph node specimens were obtained under sterile conditions for microbiological analysis. Samples of ileum were removed for both biochemical and histopathological evaluation. In the I/R group, the incidence of bacteria-isolated mesenteric lymph nodes, spleen, liver, and blood was significantly higher than other groups (P < 0.05). IPC prevented I/R-induced BT and it significantly reduced the I/R-induced intestinal injury (P < 0.05). Increased inducible nitric oxide (NO) synthase (iNOS) expression observed on the ileal specimens of the I/R group was found to be prevented by IPC. Our data suggest IPC as a key factor that reduces BT and iNOS activation in intestinal I/R. This is the first study showing that intestinal IPC blocks the cascade of events that causes BT and intestinal injury that may lead to sepsis.

Pré-condicionamento isquêmico em diferentes tempos e seu efeito na translocação bacteriana induzida por isquemia e reperfusão intestinal em ratos

“…Aksoyek et al performed intestinal preconditioning for ten minutes and observed a reduction of BT for bloodstream, liver, spleen and mesenteric lymph nodes, corroborating our results 10 . As differential, the model used by us, characterized by a time scale of preconditioning of two, five, ten and 15 minutes, showed that the greatest reduction of serum cytokines and BT occurred at 15 minutes.…”

“…Based on the fact that ischemic preconditioning attenuates the tissue injury caused by ischemia-reperfusion, Aksoyek et al 10 demonstrated in an experimental model, in which rats were subjected to ischemic preconditioning ten minutes prior to sustained ischemia, that BT was lower than in those animals that had not undergone preconditioning. Although most reports in the literature using the time of ten minutes in ischemic preconditioning of the small intestine of rats, the optimal protocol of intestinal preconditioning in these animals, including the short ischemia time, is not yet well established 5,11 .…”

Reply to Oltean and Olausson

“…Second, previous studies by other groups [7,8] also showed that 60 min ischemia followed by 60 min reperfusion in the same rat model as used in our study could cause severe intestinal injury, which was evidenced by significant morphological changes and mucosal cell apoptosis. Also, in our study, a preconditioning strategy of 10 min ischemia and 10 min reperfusion could significantly alleviate intestinal injury, which was in accordance with the previous report [9,10].…”

Clinical Importance of Ischemic Preconditioning

“…İskemik önkoşullamanın mukozal permeabiliteyi azalttığı, en önemlisi intestinal epitelyal apoptozisi önlediği, mezenterik venöz kanda CO 2 birikimini ve bakteriyel translokasyonu azalttığı gösterilmiştir (26)(27)(28)(29)(30) . İntestinal sistem önkoşulla-masının mekanizmasında nitrik oksit (NO), adenozin A1 reseptörleri, PKC, serbest radikaller ve opioidler önemli rol oynarlar (30)(31)(32) . Önkoşullama iskelet kasında da koruyucu etkiye sahiptir ve bu koruyucu etkisini iskelet kasındaki mitokondriyal KATP kanalları aracılığıyla gösterir (33) .…”