BackgroundPostoperative hypoxemia is quite common in patients with acute aortic dissection (AAD) and is associated with poor clinical outcomes. However, there is no method to predict this potentially life-threatening complication. The study aimed to develop a regression model in patients with AAD to predict postoperative hypoxemia, and to validate it in an independent dataset.MethodsAll patients diagnosed with AAD from December 2012 to December 2017 were retrospectively screened for potential eligibility. Preoperative and intraoperative variables were included for analysis. Logistic regression model was fit by using purposeful selection procedure. The original dataset was split into training and validating datasets by 4:1 ratio. Discrimination and calibration of the model was assessed in the validating dataset. A nomogram was drawn for clinical utility.ResultsA total of 211 patients, involving 168 in non-hypoxemia and 43 in hypoxemia group, were included during the study period (incidence: 20.4%). Duration of mechanical ventilation (MV) was significantly longer in the hypoxemia than non-hypoxemia group (41(10.5140) vs. 12(3.75,70.25) hours; p = 0.002). There was no difference in the hospital mortality rate between the two groups. The purposeful selection procedure identified 8 variables including hematocrit (odds ratio [OR]: 0.89, 95% confidence interval [CI]: 0.80 to 0.98, p = 0.011), PaO2/FiO2 ratio (OR: 0.99, 95% CI: 0.99 to 1.00, p = 0.011), white blood cell count (OR: 1.21, 95% CI: 1.06 to 1.40, p = 0.008), body mass index (OR: 1.32, 95% CI: 1.15 to 1.54; p = 0.000), Stanford type (OR: 0.22, 95% CI: 0.06 to 0.66; p = 0.011), pH (OR: 0.0002, 95% CI: 2*10− 8 to 0.74; p = 0.048), cardiopulmonary bypass time (OR: 0.99, 95% CI: 0.98 to 1.00; p = 0.031) and age (OR: 1.03, 95% CI: 0.99 to 1.08; p = 0.128) to be included in the model. In an independent dataset, the area under curve (AUC) of the prediction model was 0.869 (95% CI: 0.802 to 0.936). The calibration was good by visual inspection.ConclusionsThe study developed a model for the prediction of postoperative hypoxemia in patients undergoing operation for AAD. The model showed good discrimination and calibration in an independent dataset that was not used for model training.

Background: MicroRNAs (miRNAs) are involved in myocardial ischemia-reperfusion injury. miRNA-421 (miR-421) plays a significant role in the initiation of apoptosis and myocardial infarction. However, the molecular regulation of miR-421 in myocardial ischemia-reperfusion injury requires further elucidation. Methods: An in vitro hypoxia/reoxygenation model was established, and the expression levels of miR-421 and Sirtuin-3 (Sirt3) in H9c2 cells were quantified using quantitative real-time polymerase chain reaction. Flow cytometry was employed to measure the effects of miR-421 on myocardial apoptosis induced by hypoxia/reoxygenation. The activity of lactate dehydrogenase and superoxide dismutase and levels of malondialdehyde were measured. The binding sites of miR-421 on Sirt3 were predicted using TargetScan software. A luciferase reporter assay was used to validate the direct targeting of Sirt3 with miR-421. Protein expression levels of Sirt3 and its downstream proteins were evaluated using Western blot analysis. Results: Exposure of H9c2 cells to hypoxia/reoxygenation led to increased apoptosis, levels of malondialdehyde and lactate dehydrogenase, and decreased levels of superoxide dismutase. miR-421 knockdown resulted in decreased apoptosis, levels of lactate dehydrogenase and malondialdehyde, and increased superoxide dismutase levels in H9c2 cells. Hypoxia/reoxygenation significantly decreased the relative expression levels of Sirt3. Down-regulation of Sirt3 resulted from overexpression of miR-421, which directly targeted Sirt3. Knockdown of miR-421 up-regulated Sirt3 expression, inhibited activation of the Jun N-terminal kinase/activator protein 1 pathway and caspase 9/3-dependent cell death. Conclusion: The miR-421-Sirt3-Jun N-terminal kinase/activator protein 1 axis is a novel molecular mechanism that accommodates hypoxia/reoxygenation-induced oxidative stress and apoptosis and provides a new direction for the study and treatment of hypoxia/reoxygenation.

ObjectivesAortic arch replacement is associated with increased mortality and morbidity especially in acute type-A aortic dissection. Although hypothermic circulatory arrest with selective antegrade cerebral perfusion has been widely used because of its excellent cerebral protection, its optimal perfusion characteristics are unknown. The present study investigates clinical results obtained after perfusion method modification and temperature management during cardiopulmonary bypass (CPB).MethodsBetween July 2010 and August 2012, 16 consecutive adult patients (mean age 50.0 yr ± 14.1 yr, range 25 yr to 73 yr, 12 males, 4 females) who presented with acute Stanford type-A aortic dissection underwent aortic arch replacement (total arch, n = 11; hemiarch, n = 5) under mild hypothermia (31.1°C ± 1.5°C) with right axillary and femoral artery perfusion.ResultsThe mean CPB time was 201 min ± 53 min, and the mean myocardial ischemic time was 140 min ± 42 min. The mean selective cerebral perfusion time was 80 min ± 16 min, and the mean lower-body circulatory arrest time was 20 min ± 13 min. No patient death occurred within 30 post-operative days. The following details were observed: new post-operative permanent neurologic deficit in 1 patient (6.3%), temporary neurologic deficit in 2 patients (12.5%), acute renal dysfunction (creatinine level > 230 umol/L) in 3 patients (18.8%) and mechanical ventilation > 72 h in 5 patients (31.2%).ConclusionsAortic arch replacement for acute type-A aortic dissection under mild hypothermia with right axillary and femoral artery perfusion could be safely performed in the patient cohort.