HMGB1 signaling-regulated endoplasmic reticulum stress mediates intestinal ischemia/reperfusion-induced acute renal damage.

BACKGROUND: Ischemia/reperfusion of the intestine often leads to distant organ injury, but the mechanism of intestinal ischemia/reperfusion-induced renal dysfunction is still not clear. The present study aimed to investigate the mechanisms of acute renal damage after intestinal ischemia/reperfusion challenge and explore the role of released high-mobility group box-1 in this process. METHODS: Intestinal ischemia/reperfusion was induced in male Sprague-Dawley rats by clamping the superior mesenteric artery for 1.5 hours. At different reperfusion time points, anti-high-mobility group box-1 neutralizing antibodies or ethyl pyruvate were administered to neutralize or inhibit circulating high-mobility group box-1, respectively. RESULTS: Significant kidney injury was observed after 6 hours of intestinal reperfusion, as indicated by increased serum levels of urea nitrogen and creatinine, increased expression of neutrophil gelatinase-associated lipocalin, interleukin-6, and MIP-2, and enhanced cell apoptosis, as indicated by cleaved caspase 3 levels in renal tissues. The levels of phosphorylated eIF2ɑ, activating transcription factor 4, and C/EBP-homologous protein (CHOP) were markedly elevated, indicating the activation of endoplasmic reticulum stress in the impaired kidney. High-mobility group box-1 translocated to cytoplasm in the intestine and serum concentrations of high-mobility group box-1 increased notably during the reperfusion phase. Both anti-high-mobility group box-1 antibodies and ethyl pyruvate treatment significantly reduced serum high-mobility group box-1 concentrations, attenuated endoplasmic reticulum stress in renal tissue and inhibited the development of renal damage. Moreover, the elevated expression of receptor for advanced glycation end products in the kidneys after intestinal ischemia/reperfusion was abrogated after high-mobility group box-1 inhibition. CONCLUSION: These results suggested that high-mobility group box-1 signaling regulated endoplasmic reticulum stress and promoted intestinal ischemia/reperfusion-induced acute kidney injury. High-mobility group box-1 neutralization/inhibition might serve as a pharmacological intervention strategy for these pathophysiological processes.

Percutaneous US-guided Cholecystocholangiography with Microbubbles for Assessment of Infants with US Findings Equivocal for Biliary Atresia and Gallbladder Longer than 1.5 cm: A Pilot Study.

Purpose To evaluate the feasibility of ultrasonographically (US) guided percutaneous cholecystocholangiography (PCC) for early exclusion of biliary atresia (BA) in infants suspected of having BA with equivocal US findings or indeterminate type of BA and a gallbladder longer than 1.5 cm at US. Materials and Methods This study was approved by the ethics committee; written informed parental consent was obtained. From February 2016 to December 2016, nine infants (four boys, five girls; mean age, 60.2 days; median age, 57 days; age range, 23-117 days) with conjugated hyperbilirubinemia and gallbladder longer than 1.5 cm at US were referred for US-guided PCC after US findings were equivocal for BA (n = 7) or the type of BA was unclear (n = 2). PCC was performed with a US machine with incorporated contrast pulse sequencing, contrast-specific software, and a linear transducer by injecting diluted contrast material via an 18-gauge needle. Images from US and US-guided PCC were evaluated in consensus by two radiologists. US criteria for BA were fibrotic cord sign (>2 mm) and gallbladder length-to-width ratio greater than 5.2. BA was excluded at PCC when contrast material was visualized in the gallbladder, common hepatic ducts, and common bile duct and during passage to the duodenum. Patients in whom BA was diagnosed after PCC underwent surgery or liver biopsy as the reference standard. Nonparametric and Fisher exact tests were used. Results US-guided PCC was successful in all patients. There were no procedural-related complications. BA was excluded in five of the nine patients. The median serum direct bilirubin level in these patients slightly decreased 1 week after PCC, from 91.1 µmol/L (interquartile range [IQR], 81.6-113.8 µmol/L) to 65.3 µmol/L (IQR, 57.8-74.7 µmol/L); however, this difference was not statistically significant (P = .062). BA was diagnosed in four patients, with the diagnosis confirmed at surgery (n = 2) or liver biopsy (n = 2). BA in two patients with unclear type of BA was defined as type III without patency of the common bile duct in one patient and as type III with patency of the common bile duct in the other. Conclusion In this highly selected group of infants with indeterminate type of BA or inconclusive US findings, US-guided PCC enabled the diagnosis of BA in four infants and the exclusion of BA in five. US-guided PCC may be a safe and effective tool to exclude BA early in infants with equivocal US findings. © RSNA, 2017.

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.