Abstract
Ischemic preconditioning (IPC) has been considered to be a potential therapy to reduce ischemia-reperfusion injury (IRI) since the 1980s. Our previous study indicated that sevoflurane preconditioning (SPC) also reduced intestinal IRI in rats. However, whether the protective effect of SPC is similar to IPC and the mechanisms of SPC are unclear. Thus, we compared the efficacy of SPC and IPC against intestinal IRI and the role of protein kinase C (PKC) and mitochondrial ATP-sensitive potassium channel (mKATP) in SPC. A rat model of intestinal IRI was used in this study. The superior mesenteric artery (SMA) was clamped for 60 min followed by 120 min of reperfusion. Rats with IPC underwent three cycles of SMA occlusion for 5 min and reperfusion for 5 min before intestinal ischemia. Rats with SPC inhaled sevoflurane at 0.5 minimum alveolar concentration (MAC) for 30 min before the intestinal ischemic insult. Additionally, the PKC inhibitor Chelerythrine (CHE) or mKATP inhibitor 5-Hydroxydecanoic (5-HD) was injected intraperitoneally before sevoflurane inhalation. Both SPC and IPC ameliorated intestinal IRI-induced histopathological changes, decreased Chiu’s scores, reduced terminal deoxyribonucleotide transferase-mediated dUTP nick end labeling (TUNEL) positive cells in the epithelium, and inhibited the expression of malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α). These protective effects of SPC were similar to those of IPC. Pretreatment with PKC or mKATP inhibitor abolished SPC—induced protective effects by increasing Chiu’s scores, down-regulated the expression of Bcl-2 and activated caspase-3. Our results suggest that pretreatment with 0.5 MAC sevoflurane is as effective as IPC against intestinal IRI. The activation of PKC and mKATP may be involved in the protective mechanisms of SPC.
Highlights
Intestinal ischemia-reperfusion injury (IRI) is a potentially severe consequence of several surgical procedures, including abdominal aortic aneurysm surgery, cardiopulmonary bypass, intestine transplantation and strangulated hernias [1, 2]
The morphology in the intestinal mucosa was normal in rats of the sham and sevoflurane preconditioning (SPC)-sham groups (Fig 2A and 2B), whereas mildly injured villi and glands were observed in the IPCsham group (Fig 2C)
The present study demonstrated that 0.5 minimum alveolar concentration (MAC) SPC provides similar protective effects as ischemic preconditioning (IPC) by preventing intestinal IR-induced histopathological changes, intestinal mucosa apoptosis, MDA activation and expression of tumor necrosis factor-α (TNF-α)
Summary
Intestinal ischemia-reperfusion injury (IRI) is a potentially severe consequence of several surgical procedures, including abdominal aortic aneurysm surgery, cardiopulmonary bypass, intestine transplantation and strangulated hernias [1, 2]. Considering the disastrous outcomes of intestinal IRI, more efforts are needed to develop effective and safe therapeutic methods. Intestinal IPC has been identified as an effective measure to reduce intestinal IRI [3,4,5,6,7,8]. IPC has limited application in the clinic due to its invasive nature and the unpredictability of when intestinal ischemia will occur. Our recent finding suggested that sevoflurane, a widely used volatile anesthetic, reduces IR—induced intestinal injury at clinical related concentrations when given before, during or after ischemia. Sevoflurane preconditioning (SPC) at 0.5 minimum alveolar concentration (MAC) is the most effective method among all the strategies [9]. Whether the protective effect of SPC is similar to IPC is still unclear. A comparison between these two interventions will help to choose a more appropriate therapeutic method if intestinal IRI is inevitable
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