Remifentanil preconditioning protects the small intestine against ischemia/reperfusion injury via intestinal δ- and µ-opioid receptors.

BACKGROUND: Intestinal ischemia/reperfusion (I/R) injury can cause a high rate of mortality in the perioperative period. Remifentanil has been reported to provide protection for organs against I/R injury. We hypothesized that remifentanil preconditioning would attenuate the small intestinal injury induced by intestinal I/R. METHODS: We used both an in vivo rat model of intestinal I/R injury and a cell culture model using IEC-6 cells (the rat intestinal epithelial cell line) subjected to oxygen and glucose deprivation (OGD). Remifentanil was administered before ischemia or OGD, and 3 specific opioid receptors antagonists, naltrindole (a δ-OR selective antagonist), nor-binaltorphimine (nor-BNI, a κ-OR selective antagonist), and CTOP (a µ-OR selective antagonist), were administered before preconditioning to determine the role of opioid receptors in the intestinal protection mediated by remifentanil. RESULTS: In the in vivo rat model, intestinal I/R induced obvious intestinal injury as evidenced by increases in the Chiu score, serum diamine oxidase activity, the apoptosis index, and the level of cleaved caspase-3 protein expression, whereas remifentanil preconditioning significantly improved these changes in vivo. In the in vitro cell culture exposed to OGD, cell viability (MTT, ie, (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay and flow cytometric analysis showed that remifentanil preconditioning enhanced IEC-6 cell viability and decreased apoptosis. In both in vitro and in vivo models, the aforementioned protective effects of remifentanil preconditioning were abolished completely by previous administration of the δ- or µ-opioid markedly attentuated but not the κ-opioid receptor antagonist. CONCLUSION: Remifentanil preconditioning appears to act via δ- and µ-opioid receptors to protect the small intestine from intestinal I/R injury by attenuating apoptosis of the intestinal mucosal epithelial cells.

Clinical benefits of aortic cross-clamping versus limb remote ischemic preconditioning in coronary artery bypass grafting with cardiopulmonary bypass: a meta-analysis of randomized controlled trials.

BACKGROUND: We assessed whether aortic cross-clamping or limb remote ischemic preconditioning improved postoperative outcomes, reduced myocardial injury and incidences of postoperative complications in patients undergoing on-pump coronary artery bypass grafting (CABG). MATERIALS AND METHODS: PubMed, EMBASE, the Cochrane Library, and ClinicalTrials databases were searched for studies comparing the effects of ischemic preconditioning with no preconditioning in adult patients undergoing on-pump CABG. The primary end points were mechanical ventilation time, the length of stay in intensive care unit and hospital, whereas the secondary end points were peak values of myocardial biomarkers and postoperative complications. Mean differences were estimated for the primary end points, as well as standard mean differences and odds ratios for the secondary end points. RESULTS: A total of 29 randomized controlled trials with 1791 patients were included. Compared with control group, aortic cross-clamping preconditioning reduced mechanical ventilation time (mean difference [95% confidence interval {CI}]) (-5.59 h [-9.21 to -1.96]), whereas limb remote ischemic preconditioning was not associated with improvement of postoperative outcomes. For myocardial biomarkers, both aortic cross-clamping and limb remote ischemic preconditioning reduced peak values of myocardial biomarkers (standard mean difference [95% CI]) (-0.48 [-0.81 to -0.14]; -0.19 [-0.36 to -0.02], respectively). Subgroup analysis showed that aortic cross-clamping preconditioning protocols with ischemia episodes <5 min did reduce the release of biomarkers (-0.69 [-1.04 to -0.34]) but those with 5 min ischemia episodes elevated them (0.40 [0.04-0.75]). Cardiovascular, cerebrovascular, renal, and intestinal complications were reported, and aortic cross-clamping preconditioning seemed to reduce the incidences of cardiac arrhythmia (odds ratio [95% CI]) (0.46 [0.27-0.80], P = 0.006). CONCLUSIONS: Cardiac surgeons could consider aortic cross-clamping or limb remote ischemic preconditioning to reduce myocardial injury during CABG. Moreover, aortic cross-clamping preconditioning is associated with a decreased risk of postoperative respiratory failure and cardiac arrhythmia.

The incidence and risk factors of gastrointestinal complications after hepatectomy: a retrospective observational study of 1329 consecutive patients in a single center.

BACKGROUND: Despite of the importance of gastrointestinal (GI) complications in morbidity and mortality after major and moderate surgeries, it is not yet specifically studied in patients undergoing hepatectomy. This study was aimed to investigate the in-hospital incidence and potential risk factors of GI complications after open hepatectomy in our hospital. SUBJECTS AND METHODS: Prospectively recorded perioperative data from 1329 patients undergoing elective hepatectomy were retrospectively reviewed. The in-hospital incidence of GI complications was investigated, and independent risk factors were analyzed by multiple logistic regression. RESULTS: GI complications occurrence was 46.4%. Univariate analysis showed that preoperative Child-Pugh score, total bilirubin, aspartate transaminase, anesthesia duration, operation duration, intraoperative blood loss, crystalloid and colloid infusion, blood transfusion, urine output, use of Pringle maneuver were statistically different between patients with and without GI complications (P < 0.05). Moreover, patients with GI complications had a more prolonged postoperative parenteral nutrient supporting time, hospital stay and ICU stay, and higher incidence of other complications than those without GI complications (P < 0.05). Multivariate regression indicated that long duration of anesthesia (odds ratio 2.51, P < 0.001) and use of Pringle maneuver (odds ratio 1.37, P = 0.007) were independent risk factors of GI complications after hepatectomy. CONCLUSIONS: The incidence of GI complications after hepatectomy is high, which is related to an increase of other complications and a prolonged hospital stay. Avoidance of routinely use of Pringle maneuver and shortening the duration of anesthesia are important measures to reduce the postoperative GI complications.

Clinical benefits of dexmedetomidine versus propofol in adult intensive care unit patients: a meta-analysis of randomized clinical trials.

BACKGROUND: This meta-analysis was performed to assess the influence of dexmedetomidine and propofol for adult intensive care unit (ICU) sedation, with respect to patient outcomes and adverse events. MATERIALS AND METHODS: A systematic review was conducted of all randomized controlled trials exploring the clinical benefits of dexmedetomidine versus propofol for sedation in adult intensive care patients. The primary outcomes of this study were length of ICU stay, duration of mechanical ventilation, and risk of ICU mortality. Secondary outcomes included risk of delirium, hypotension, bradycardia and hypertension. RESULTS: Ten randomized controlled trials, involving 1202 patients, were included. Dexmedetomidine significantly reduced the length of ICU stay by <1 d (five studies, 655 patients; mean difference, -0.81 d; 95% confidence interval [CI], -1.48 to -0.15) and the incidence of delirium (three studies, 658 patients; relative risk [RR], 0.40; 95% CI, 0.22-0.74) in comparison with propofol, whereas there was no difference in the duration of mechanical ventilation (five studies, 895 patients; mean difference, 0.53 h; 95% CI -2.66 to 3.72) or ICU mortality (five studies, 267 patients; RR, 0.83; 95% CI, 0.32-2.12) between these two drugs. Dexmedetomidine was associated with an increased risk of hypertension (three studies, 846 patients; RR, 1.56; 95% CI, 1.11-2.20) compared with propofol. Other adverse event rates were similar between dexmedetomidine and propofol groups. CONCLUSIONS: For ICU patient sedation, dexmedetomidine may offer advantages over propofol in terms of decrease in the length of ICU stay and the risk of delirium. However, transient hypertension may occur when dexmedetomidine is administered with a loading dose or at high infusion rates.

Ischemic postconditioning during reperfusion attenuates oxidative stress and intestinal mucosal apoptosis induced by intestinal ischemia/reperfusion via aldose reductase.

BACKGROUND: We demonstrated previously that ischemic postconditioning (IPo) attenuated intestinal injury induced by intestinal ischemia/reperfusion (I/R), and thereafter employed a proteomic method to identify aldose reductase (AR), a differentially expressed protein in intestinal mucosal tissue, which was downregulated by intestinal I/R and upregulated by IPo. This study aimed to further explore the possible role of AR in intestinal protection conferred by IPo. METHODS: Intestinal ischemia was induced by clamping the superior mesenteric artery (SMA) for 60 minutes in male adult rats. Then rats were allocated into 7 groups based on the random number table. The control group involved only sham operation; the control + AR inhibitor epalrestat group underwent sham operation and epalrestat administration; the I/R with and/or without epalrestat groups had SMA clamped for 60 minutes followed by 120 minutes of reperfusion with and/or without epalrestat given before index ischemia; the IPo group underwent 3 cycles of 30 seconds of reperfusion and 30 seconds of re-occlusion imposed immediately on reperfusion; and the epalrestat or vehicle control dimethylsulfoxide + IPo groups had the drugs administrated 10 minutes before ischemia. RESULTS: IPo resulted in significant intestinal protection evidenced as marked decreases in Chiu's score, reflecting changes intestinal histology, serum diamine oxidase activity, and intestinal mucosal levels of lactic acid, malondialdehyde, and myeloperoxidase, the apoptosis index, and downregulated cleaved caspase-3 protein expression; these changes were accompanied by an increase in superoxide dismutase activity and upregulation of AR protein levels. Epalrestat failed to protect against intestinal I/R insult, but abolished the protective effects of IPo. CONCLUSION: These findings suggest that IPo attenuates intestinal I/R-induced intestinal injury via AR-mediated oxidative defense and apoptosis suppression; AR inhibition reverses the protective effects of IPo. AR seems to be an innate protective factor in this model of intestinal I/R.

Ischemic postconditioning during reperfusion attenuates intestinal injury and mucosal cell apoptosis by inhibiting JAK/STAT signaling activation.

The present study attempts to evaluate the role of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling in intestinal ischemia/reperfusion (I/R)-induced intestinal injury and whether immediate ischemic postconditioning ameliorates intestinal injury via attenuation of intestinal mucosal apoptosis subsequent to inhibiting JAK/STAT signaling activation. Anesthetized adult male Sprague-Dawley rats were subjected to superior mesenteric artery occlusion consisting of 60 min of ischemia and 2 h of reperfusion; sham laparotomy served as controls. Animals received either subcutaneous administration of JAK2 inhibitor (AG490, 8 mg/kg) or STAT inhibitor (rapamycin, 0.4 mg/kg) 30 min before ischemia. Ischemic postconditioning was performed by three cycles of 30-s reperfusion and 30-s ischemia initiated immediately upon reperfusion. It was found that intestinal I/R resulted in conspicuous intestinal injury evidenced by significant increases in Chiu's score, lactic acid, and diamine oxidase activity, accompanied with increases in plasma levels of 15-F2t-isoprostane, endothelin 1, and thromboxane B2, as well as increase in the intestinal tissue myeloperoxidase activity. Meanwhile, the apoptotic index and cleaved caspase 3, phosphorylated JAK2, phosphorylated STAT1, and phosphorylated STAT3 expression were significantly enhanced versus sham control. Both ischemic postconditioning and pretreatment with AG490 or rapamycin significantly attenuated all the above changes. These results indicate that JAK/STAT pathway activation plays a critical role in I/R-induced intestinal injury, which is associated with increased oxidative stress, neutrophil accumulation, intestinal mucosal apoptosis, and microcirculation disturbance. Ischemic postconditioning mediates attenuation of intestinal I/R injury, and cell apoptosis may be attributable to the JAK/STAT signaling inhibition.