The Protective Role and Mechanism of Mild Therapeutic Hypothermia Protection on Brain Cells.

Background: Moderate therapeutic hypothermia is protective against several cellular stressors. However, the mechanisms behind this protection are not entirely known. In the current investigation, we investigated that therapeutic hypothermia at 33°C administered following peroxide-induced oxidative stress might protect human oligodendroglioma cells using an in vitro model. Methods and Results: Tert-butyl peroxide treatment for one hour significantly increased cell apoptosis and suppressed cell viability. In the range of 50-1000 M tert-butyl peroxide, this cell death was dose-dependent. MTT assay and cell apoptosis assay were applied to analyze cell viability/death at 24 hours after peroxide-induced stress. Therapeutic hypothermia at 33°C delivered for two hours after peroxide exposure significantly increased cell viability and suppressed cell death. Even 15 minutes after peroxide washout when delayed hypothermia was used, this protection was still apparent. Three FDA-approved antioxidants (Tempol, EUK134, and Edaravone at 100 M) were added immediately after tert-butyl peroxide, followed by hypothermia treatment. These three antioxidants greatly increased cell viability and cell apoptosis. RT-qPCR was applied to determine the effects of hypothermia treatment on the expression of caspase-3 and -8 as well as tumor necrosis factor-alpha (TNF-α). Therapeutic hypothermia significantly downregulated these three factors. Conclusion: Overall, these findings confirmed that hypothermia and antioxidants quenching reactive oxygen species may lower mitochondrial oxidative stress and/or apoptotic pathways. Further investigation are needed to investigate the role of hypothermia in other cell models.

Coagulation after paediatric miniaturised versus conventional cardiopulmonary bypass: Retrospective cohort study.

BACKGROUND: Cardiopulmonary bypass (CPB) causes coagulation disorders after surgery. This study aimed to compare the coagulation parameters after congenital cardiac surgery with miniaturised CPB (MCPB) versus conventional CPB (CCPB). METHODS: We gathered information about children who underwent cardiac surgery between 1/1/2016 and 12/31/2019. Using propensity score-matched data, we compared the coagulation parameters and postoperative outcomes of the MCPB and CCPB groups. RESULTS: A total of 496 patients (327 with MCPB, 169 withCCPB) underwent congenital cardiac surgery, and 160 matched pairs in each group were enrolled in the analysis. Compared with CCPB children, MCPB children had a lowermean prothrombin time (14.9 ± 2.0 vs 16.4 ± 4.1; p < 0.001)and international normalised ratio (1.3 ± 0.2 vs. 1.4 ± 0.3; p < 0.001), but higher thrombin time (23.4 ± 20.4 vs 18.2 ± 4.4; p = 0.002). The CCPB group had greaterperioperative changes inprothrombin time, international normalised ratio, fibrinogen, and antithrombin III activity (all p < 0.01) but lower perioperative changesin thrombin time (p = 0.001) thanthe MCPB group. Ultra-fasttrack extubation and blood transfusionrates, postoperative blood loss, and intensive care unitlength of stay were considerably decreased in the MCPB group. There were no considerable intergroup differences in the activated partial thromboplastin time or platelet count. CONCLUSIONS: Compared with CCPB, MCPB was associated with lower coagulation changes and better early outcomes, including shorter intensive care unit stay and less postoperative blood loss.

Inhibition of Microglial Activation by Delayed Mild Hypothermia Reduced Preoligodendrocyte Injury in a Neonatal Rat Brain Slice Model.

Periventricular leukomalacia (PVL), characterized by distinctive form of white matter injury, often arises after neonatal cardiac surgery. Proven therapies for PVL are absent. In this study, we designed to quest therapeutic effects of delayed mild hypothermia on PVL and its mechanism in a neonatal rat brain slice model. With the increase of delayed mild hypothermia-treating time, the reduced expression of myelin basic protein and loss of preoligodendrocytes were significantly attenuated after oxygen-glucose deprivation. In addition, the proportion of ionized calcium binding adapter molecule 1 (Iba-1)-positive cells and the expression of Iba-1 were apparently reduced with the increased duration of mild hypothermia treatment. Furthermore, the levels of tumor necrosis factor alpha and interleukin-6 reduced after the mild hypothermia treatment relative to the control. Inhibition of microglial activation with prolonged mild hypothermia may be a potential strategy for white matter protection during cardiopulmonary bypass and hypothermic circulatory arrest.

Clinical analysis of extralobar pulmonary sequestration with torsion in children: report of 6 cases.

BACKGROUND: Extralobar pulmonary sequestration is an uncommon congenital pulmonary malformation. Clinically, pedicle torsion of extralobar pulmonary sequestration is extremely rare. Due to inadequate awareness of its atypical presentation and imaging characteristics, clinical diagnosis is very difficult, and it is extremely easy to misdiagnose. CASE PRESENTATION: There were 6 children (3 males and 3 females), aged 3-12 years old. The main clinical symptoms of the children were abdominal and chest pain (3 cases), abdominal pain (1 case), chest pain (1 case), and vomiting and abdominal distension (1 case). Two cases were accompanied by fever. Preoperative ultrasound revealed a well-bordered mass with soft-tissue density, accompanied by pleural effusion. On contrast-enhanced computed tomography scans, the mass showed no obvious enhancement. A blood supply was only present in 1 case, and there was no feeding artery shown in the other 5 cases. Extralobar pulmonary sequestration with haemorrhagic infarction was pathologically confirmed. On postoperative days 2-6, the children were discharged uneventfully. There were no complications during the median follow-up of 4 months. CONCLUSIONS: Torsed extralobar pulmonary sequestration usually occurs in childhood or adolescence, with abdominal and/or chest pain as the primary symptoms. Imaging examination shows a well-defined soft-tissue mass without enhancement. The feeding vessel is not clearly displayed in the mass, and extralobar pulmonary sequestration is accompanied by varying amounts of pleural effusion. Video-assisted thoracoscopic surgical resection is associated with excellent prognosis.

The Experience of Early Extubation After Paediatric Congenital Heart Surgery in a Chinese Hospital.

BACKGROUND: Early extubation has become widely adopted in cardiac surgery practices. This study aimed to present experience of early extubation after congenital heart surgery and to explore the factors that affect successful immediate postoperative extubation and early extubation. METHODS: A retrospective analysis was performed of all patients who underwent congenital heart surgery with cardiopulmonary bypass (CPB) at Shenzhen Children's Hospital between 01 May 2015 and 30 September 2019. The demographic and cardiac surgery information were derived from the medical records. Multivariable logistic regression models were used to explore the influence factors for successful immediate postoperative extubation and early extubation. RESULTS: This study consisted of 2,060 patients, 65.0% of whom were extubated in the operating room and 16.1% of whom were extubated early (within 6 hours) in the Intensive Care Unit. The overall rates of reintubation and nasal continuous positive airway pressure were 2.0% and 6.4%, respectively. Preoperative weight (OR, 1.24; 95% CI, 1.20-1.29), preoperative pneumonia (OR, 0.60; 95% CI, 0.44-0.80), CPB type (OR, 1.23; 95% CI, 1.06-1.43), CPB time (OR, 0.98; 95% CI, 0.98-0.99), deep hypothermic circulatory arrest (OR, 0.42; 95% CI, 0.25-0.70), and Society of Thoracic Surgeons-European Association for Cardiothoracic Surgery Congenital Heart Surgery (STAT) categories (OR, 0.54; 95% CI, 0.45-0.65) were included in the immediate postoperative extubation model. In addition to the above six variables, ultrafiltration (OR, 0.63; 95% CI, 0.44-0.89) was also included in the early extubation model. Similar results were found in the immediate postoperative extubation model for non-newborns. The influencing factors for early extubation in the non-newborn population included preoperative weight, preoperative pneumonia, ultrafiltration, CPB time, and STAT categories. CONCLUSIONS: Early extubation for children with congenital heart surgery was successful in this hospital. Patients with early extubation had a lower reintubation rate and nasal continuous positive airway pressure rate, and a shorter length of stay in the ICU and hospital. Early extubation was influenced by age, weight at surgery, preoperative pneumonia, CPB type, CPB time, deep hypothermic circulatory arrest, ultrafiltration, and STAT categories.

[A preliminary investigation of relationship between serum apelin level and pulmonary artery pressure in children with congenital heart disease].

OBJECTIVE: To preliminarily investigate the relationship between serum apelin level and pulmonary artery pressure in children with congenital heart disease. METHODS: One hundred and twenty-six children with congenital heart disease undergoing surgical treatment were enrolled as subjects. The serum level of apelin was determined before surgery and at 7 days after surgery. The ratio of pulmonary artery systolic pressure to aortic systolic pressure (Pp/Ps) was calculated before extracorporeal circulation. According to the Pp/Ps value, patients were classified into non-pulmonary arterial hypertension (PAH) group, mild PAH group, moderate PAH group, and severe PAH group. Pulmonary artery mean pressure was estimated by echocardiography at 7 days after surgery. RESULTS: The non-PAH group had the highest serum level of apelin before and after surgery, followed by the mild PAH group, moderate PAH group, and severe PAH group (P<0.05). All groups had significantly increased serum levels of apelin at 7 days after surgery (P<0.05). The serum level of apelin was negatively correlated with pulmonary artery pressure before surgery (r=-0.51, P<0.05) and at 7 days after surgery (r=-0.54, P<0.05). CONCLUSIONS: The decrease in serum apelin level is associated with the development of pulmonary hypertension in children with congenital heart disease. The significance of serum apelin in predicting the development and degree of pulmonary hypertension in children with congenital heart disease deserves further studies.

[Intervention of astragalus injection on the kidney injury after cardiopulmonary bypass of infants with congenital heart disease].

OBJECTIVE: To study the intervention of astragalus injection in the kidney injury of infants with congenital heart disease after cardiopulmonary bypass, thus providing a new method for protection of the kidney injury in them. METHODS: Forty infants undergoing cardiac surgery with cardiopulmonary bypass were randomly assigned to the test group and the control group, twenty in each group. Astragalus Injection (at the dose of 2 mL/kg) was added in the perfusion fluid before giving to infants in the test group before bypass, while the normal saline of the same volume was added in the perfusion fluid before giving to infants in the control group (P < 0.01). The concentrations of serum tumor necrosis factor-alpha (TNF)-alpha, interleukin-6 (IL-6), cystatin C (CysC), and N-acetyl-beta-D-glucosaminidase (NAG) were detected with ELISA at the following time points, i.e., before bypass (T1), by the end of the surgery (T2), 2 h after surgery (T3), 6 h after surgery (T4), and 24 h after surgery (T5). RESULTS: The serum CysC concentrations were not significantly higher after CPB (P > 0.05). The urinary NAG level increased significantly in the control group after surgery (P < 0.05), but no obvious increase of the urinary NAG level was found in the test group after surgery (P > 0.05). It was obviously lower than that of the control group (P < 0.05). After CPB serum TNF-alpha and IL-6 levels increased significantly in the control group (P < 0.05), while they were lower in the test group than in the control group (P < 0.01). CONCLUSIONS: CPB may result in the renal tubular injury in infants with congenital heart disease. The application of Astragalus Injection before the CPB plays a role in protecting renal tubular functions.

[Kidney injury after cardiopulmonary bypass in infants with congenital heart disease].

OBJECTIVE: To study kidney injury in infants with congenital heart disease (CHD) who underwent cardiac surgery with cardiopulmonary bypass (CPB). METHODS: Forty CHD infants undergoing cardiac surgery with CPB from October 2009 to July 2010 were enrolled. The concentrations of serum tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), cystatin C (CysC) and urinary N-acetyl-beta-D-glucosaminidase (NAG) were detected using ELISA before bypass, at the end of surgery, and 2 hrs, 6 hrs and 24 hrs after surgery. Serum concentrations of creatinine (Cr) and urea nitrogen (BUN) were measured with conventional biochemistry technique before and after surgery. RESULTS: The concentrations of serum Cr and BUN were normal before and after surgery. After CPB, the concentrations of serum TNF-α and IL-6 and urinary NAG increased significantly (P<0.05). Serum TNF-α was positively correlated with urinary NAG and serum CysC (r=0.195, 0.190, respectively; both P<0.05). Serum IL-6 was positively correlated with urinary NAG (r=0.278, P<0.01). The positive rate in kidney injury was detected by serum CysC and urinary NAG were significantly higher than by serum Cr or BUN (both P<0.01). CONCLUSIONS: CPB can cause acute kidney injury in infants, which may be correlated with the increase in the concentrations of serum TNF-α and IL-6. Serum CysC and urinary NAG may be used as sensitive markers for reflecting the changes of renal function.