A summary of second systemic pulmonary shunt for congenital heart disease with pulmonary hypoxemia.

BACKGROUND: There has been an increasing number of children with congenital heart disease that undergo primary or second systemic-pulmonary shunt, while there are few reports on the second systemic-pulmonary shunt. Therefore, this study summarizes the experience of second systemic-pulmonary shunt for congenital heart disease in our hospital. METHODS AND RESULTS: Sixty-five children with congenital heart disease who underwent systemic-pulmonary shunt for the second time in our hospital were analyzed. At the early stage after the operation, cyanosis improved and SpO2 significantly increased. One patient died in hospital (1.54%) and the causes of death were aggravated atrioventricular regurgitation, low cardiac output syndrome, and liver failure. Early complications occurred in 18 patients (27.7%). All the children were rechecked in our hospital every 3-6 months and the McGoon index significantly increased. CONCLUSION: Systemic-pulmonary artery shunt can promote pulmonary vascular development, improve cyanosis symptoms, and increase the chance of radical treatment in children with pulmonary vascular dysplasia.

Serum UCH-L1 as a Novel Biomarker to Predict Neuronal Apoptosis Following Deep Hypothermic Circulatory Arrest.

BACKGROUND: Deep hypothermic circulatory arrest (DHCA) has been used in cardiac surgery involving infant complex congenital heart disease and aortic dissection. DHCA carries a risk of neuronal apoptotic death in brain. Serum ubiquitin C-terminal hydrolase L1 (UCH-L1) level is elevated in a number of neurological diseases involving neuron injury and death. We studied the hypothesis that UCH-L1 may be a potential biomarker for DHCA-induced ischemic neuronal apoptosis. METHODS: Anesthetized piglets were used to perform cardiopulmonary bypass (CPB). DHCA was induced for 1 hour followed by CPB rewarming. Blood samples were collected and serum UCH-L1 levels were measured. Neuron apoptosis and Bax and Bcl-2 proteins in hippocampus were examined. The relationship between neuron apoptosis and UCH-L1 level was determined by receiver operating characteristics (ROC) curves and correlation analysis. RESULTS: DHCA resulted in marked neuronal apoptosis, significant increase in Bax:Bcl-2 ratio in hippocampus and UCH-L1 level elevations in serum (all P<0.05). Positive correlation was obtained between serum UCH-L1 level and the severity of neuron apoptosis (r= 0.78, P<0.01). By ROC, the area under the curve were 0.88 (95% CI: 0.74-0.99; P<0.01), 0.81 (95% CI: 0.81-0.96; P<0.05), 0.71 (95% CI: 0.47-0.92; P=0.11) for UCH-L1, Bax/Bcl-2 ratio and Bax, respectively. Using a cut-off point of 0.25, the UCH-L1 predicted neuronal apoptosis with a sensitivity of 85% and specificity of 57%. CONCLUSION: Serum UCH-L1, as an easy and quick measurable biomarker, can predict neural apoptosis induced by DHCA. The elevation in UCH-L1 concentration is consistent with the severity of neural apoptosis following DHCA.

Total liquid ventilation reduces oleic acid-induced lung injury in piglets.

BACKGROUND: Pediatric patients are susceptible to lung injury that does not respond to traditional therapies. Total liquid ventilation has been developed as an alternative ventilatory strategy for severe lung injury. The aim of this study is to investigate the effect of total liquid ventilation on oleic acid (OA)-induced lung injury in piglets. METHODS: Twelve Chinese immature piglets were induced acute lung injury by OA. Twelve piglets were randomly treated with conventional gas ventilation (control group) or total liquid ventilation (study group) for 240 minutes. Samples for blood gas analysis were collected before, and at 60-minute intervals after OA-induced lung injury. The degree of lung injury was quantified by histologic examination. The inflammatory cells and the levels of IL-1ß, IL-6, IL-10 and TNF-α in plasma, tissue and bronchoalveolar lavage were analyzed. RESULTS: Neutrophil and macrophage counts in bronchoalveolar lavage were significantly decreased in the study group (P < 0.05). The total lung injury score was also reduced in the study group (P < 0.05). The concentrations of IL-1ß, IL-6, IL-10 and TNF-α in plasma, tissue and bronchoalveolar lavage were significantly reduced in the study group (P < 0.05). CONCLUSIONS: Total liquid ventilation reduces biochemical and histologic OA-induced lung injury in piglets.

Comparative analysis of early and middle outcomes of the arterial switch operation in children with complete transposition of the great arteries with ventricular septal defect and severe pulmonary artery hypertension.

BACKGROUND: The best age for the arterial switch operation (ASO) in complete transposition of great arteries with ventricular septal defect is usually considered to be within six months. This is because of severe pulmonary arterial hypertension and pulmonary arterial obstructive pathological changes. There are few reports on ASO surgery in children older than three years old. METHODS: We studied 41 children, including 24 males and 17 females, from January 2010 to December 2011. They were divided into three groups by operation age; 15 patients were < 1 year old, 13 were 1 - 3 years old, and 13 were > 3 years old. Associated cardiac abnormalities included patent ductus arteriosus in six cases, atrial septal defect in five cases, and mitral regurgitation in two cases. All the patients had echocardiography before the operation. Seventeen patients underwent a coronary computed tomography examination and five patients underwent right heart catheterization. All ASO surgeries were performed under inhalation anesthesia and hypothermic cardiopulmonary bypass. RESULTS: Three operative deaths occurred. Two were in the < 1 year old group, who died from severe postoperative low cardiac output. The other was two years old and died of postoperative multiple organ failure. There was no significant difference in postoperative mortality and the recent mid-term survival rate among the three groups. Thirty-eight cases were followed up for an average of 11.2 months, ranging 6 - 20 months. One seven years old patient died of acute diarrhea and electrolyte disturbance arrhythmia caused by food poisoning. Three patients more than three years old still had residual pulmonary arterial hypertension. CONCLUSION: Children older than three years old can still undergo the ASO procedure, but residual pulmonary hypertension is present.

Clinical results of combined palliative procedures for cyanotic congenital heart defects with intractable hypoplasia of pulmonary arteries.

BACKGROUND: Congenital heart defects with intractable hypoplasia of the pulmonary arteries without intercourse or with intercourse stenosis is unsuitable for surgical correction or regular palliative procedures. We reported our experience with combined palliative procedures for congenital heart defects with intractable hypoplasia pulmonary arteries. METHODS: From 2001 to 2012, a total of 41 patients with cyanotic congenital heart defects and intractable hypoplasia of the pulmonary arteries underwent surgical procedures. From among them, 31 patients had pulmonary atresia with ventricular septal defect (VSD) and the other 10 cases had complicated congenital heart defects with pulmonary stenosis. Different kinds of palliative procedures were performed according to the morphology of the right and left pulmonary arteries in every patient. If the pulmonary artery was well developed, a Glenn procedure was performed. A modified Blalock-Taussig shunt or modified Waterston shunt was performed if pulmonary arteries were hypoplastic. If the pulmonary arteries were severely hypoplastic, a Melbourne shunt was performed. Systemic pulmonary artery shunts were performed bilaterally in 25 cases. A systemic-pulmonary shunt was performed on one side and a Glenn procedure was performed contralaterally in 16 cases. Major aortopulmonary collateral arteries were unifocalized in six cases, ligated in two cases and interventionally embolized in two cases. There was one early death because of cardiac arrest and the hospital mortality was 2.4%. RESULTS: Five patients suffered from postoperative low cardiac output syndrome, three had perfusion of the lungs, and two pulmonary infections. Systemic pulmonary shunts were repeated after the original operation in three cases due to the occlusion of conduits. The mean follow-up time was 25 months. The pre- and the post-operation left pulmonary indices were (8.13 ± 3.68) vs. (14.9 ± 6.21) mm(2)/m(2). The pre- and post-operation right pulmonary indices were (12.7 ± 8.13) vs. (17.7 ± 7.78) mm(2)/m(2). The pre- and post-operational pulmonary indices were (20.87 ± 9.43) vs. (32.6 ± 11.7) mm(2)/m(2). They were all significantly increased (P < 0.001). The diameter of the pulmonary artery increased after the modified Blalock-Taussig shunt ((5.51 ± 0.94) mm(2)/m(2) pre-operation vs. (7.01 ± 1.97) mm(2)/m(2) post-operation), the modified Waterston shunt ((5.70 ± 3.96) mm(2)/m(2) pre-operation vs. (9.17 ± 3.62) mm(2)/m(2) post-operation) and the Melbourne shunt ((2.17 ± 0.41) mm(2)/m(2) pre-operation vs. (7.35 ± 2.49) mm(2)/m(2) post-operation) (all P < 0.05). Bilateral pulmonary arteries developed well as compared to their pre-operation development. Hemoglobin decreased from (194 ± 27) to (174 ± 24) g/L (P < 0.05) and peripheral oxygen saturation increased from (65 ± 11)% to (84 ± 6)% (P < 0.001). During the follow-up of 27 to 49 months, ultimate complete repair was performed in four cases and one patient underwent a Glenn procedure. CONCLUSIONS: The procedures should be considered on a case to case basis in patients having hypoplasia of the pulmonary arteries with cyanotic congenital heart defects. Combined palliative operations could be an adequate strategic treatment.

Atrial natriuretic peptide attenuates inflammatory responses on oleic acid-induced acute lung injury model in rats.

BACKGROUND: An inflammatory response leading to organ dysfunction and failure continues to be a major problem after injury in many clinical conditions such as sepsis, severe burns, and trauma. It is increasingly recognized that atrial natriuretic peptide (ANP) possesses a broad range of biological activities, including effects on endothelial function and inflammation. A recent study has revealed that ANP exerts anti-inflammatory effects. In this study we tested the effects of human ANP (hANP) on lung injury in a model of oleic acid (OA)-induced acute lung injury (ALI) in rats. METHODS: Rats were randomly assigned to three groups (n = 6 in each group). Rats in the control group received a 0.9% solution of NaCl (1 ml × kg(-1) × h(-1)) by continuous intravenous infusion, after 30 minutes a 0.9% solution of NaCl (1 ml/kg) was injected intravenously, and then the 0.9% NaCl infusion was restarted. Rats in the ALI group received a 0.9% NaCl solution (1 ml × kg(-1) × h(-1)) intravenous infusion, after 30 minutes OA was injected intravenously (0.1 ml/kg), and then the 0.9% NaCl infusion was restarted. Rats in the hANP-treated ALI group received a hANP (0.1 µg × kg(-1) × min(-1)) infusion, after 30 minutes OA was injected intravenously (0.1 ml/kg), and then the hANP infusion was restarted. The anti-inflammation effects of hANP were evaluated by histological examination and determination of serum cytokine levels. RESULTS: Serum interleukin (IL)-1ß, IL-6, IL-10 and tumor necrosis factor (TNF) α were increased in the ALI group at six hours. The levels of all factors were significantly lower in the hANP treated rats (P < 0.005). Similarly, levels of IL-1ß, IL-6, IL-10 and TNF-α were higher in the lung tissue in the ALI group at six hours. hANP treatment significantly reduced the levels of these factors in the lungs (P < 0.005). Histological examination revealed marked reduction in interstitial congestion, edema, and inflammation. CONCLUSION: hANP can attenuate inflammation in an OA-induced lung injury in rat model.

A novel and feasible way to cultivate and purify endothelial progenitor cells from bone marrow of children with congenital heart diseases.

BACKGROUND: Endothelial progenitor cells (EPCs) are used in vascular tissue engineering and clinic therapy. Some investigators get EPCs from the peripheral blood for clinic treatment, but the number of EPCs is seldom enough. We have developed the cultivation and purification of EPCs from the bone marrow of children with congenital heart disease, to provide enough seed cells for a small calibre vascular tissue engineering study. METHODS: The 0.5-ml of bone marrow was separated from the sternum bone, and 5-ml of peripheral blood was collected from children with congenital heart diseases who had undergone open thoracic surgery. CD34+ and CD34+/VEGFR+ cells in the bone marrow and peripheral blood were quantified by flow cytometry. CD34+/VEGFR+ cells were defined as EPCs. Mononuclear cells in the bone marrow were isolated by Ficoll(®) density gradient centrifugation and cultured by the EndoCult Liquid Medium Kit(™). Colony forming endothelial cells was detected. Immunohistochemistry staining for Dil-ac-LDL and FITC-UEA-1 confirmed the endothelial lineage of these cells. RESULTS: CD34+ and CD34+/VEGFR+ cells in peripheral blood were (0.07 ± 0.05)% and (0.05 ± 0.02)%, respectively. The number of CD34+ and CD34+/VEGFR+ cells in bone marrow were significantly higher than in blood, (4.41 ± 1.47)% and (0.98 ± 0.65)%, respectively (P < 0.0001). Many colony forming units formed in the culture. These cells also expressed high levels of Dil-ac-LDL and FITC-UEA-1. CONCLUSION: This is a novel and feasible approach that can cultivate and purify EPCs from the bone marrow of children with congenital heart disease, and provide seed cells for small calibre vascular tissue engineering.

Partial liquid ventilation decreases tissue and serum tumor necrosis factor-α concentrations in acute lung injury model of immature piglet induced by oleic acid.

BACKGROUND: Pediatric patients are susceptible to lung injury. Acute lung injury in children often results in high mortality. Partial liquid ventilation (PLV) has been shown to markedly improve oxygenation and reduce histologic evidence of injury in a number of lung injury models. This study was designed to examine the hypothesis that PLV would attenuate the production of local and systemic tumor necrosis factor (TNF)-α in an immature piglet model of acute lung injury induced by oleic acid (OA). METHODS: Twelve Chinese immature piglets were induced acute lung injury by OA. The animals were randomly assigned to two groups of six animals, (1) conventional mechanical ventilation (MV) group and (2) PLV with 10 ml/kg FC-77 group. RESULTS: Compared with MV group, the PLV group had better cardiopulmonary variables (P < 0.05). These variables included heart rate, mean blood pressure, blood pH, partial pressure of arterial oxygen (PaO2), PaO2/inspired O2 fraction (FiO2) and partial pressure of arterial carbon dioxide (PaCO2). PLV reduced TNF-α levels both in plasma and tissue compared with MV group (P < 0.05). CONCLUSION: PLV provides protective effects against TNF-α response in OA-induced acute lung injury in immature piglets.

Effect of partial liquid ventilation on oleic acid-induced inflammatory responses in piglets.

BACKGROUND: Pediatric patients are susceptible to lung injury. Acute lung injury (ALI) in children often results in a high mortality. Partial liquid ventilation (PLV) has been shown to markedly improve oxygenation and reduce histologic evidence of injury in a number of lung injury models. This study aimed to examine the hypothesis that PLV would attenuate the production of local and systemic cytokines in an immature piglet model of ALI induced by oleic acid (OA). METHODS: Twelve Chinese immature piglets were induced to develop ALI by oleic acid. The animals were randomly assigned to two groups (n = 6): (1) conventional mechanical ventilation (MV) group and (2) PLV with FC-77 (10 ml/kg) group. RESULTS: Compared with MV group, PLV group got better cardiopulmonary variables (P < 0.05). These variables included heart rate, mean blood pressure, blood pH, partial pressure of arterial oxygen (PaO2), PaO2/FiO2 and partial pressure of arterial carbon dioxide (PaCO2). Partial liquid ventilation reduced IL-1beta, IL-6, IL-10 and TNF-alpha both in plasma and tissue concentrations compared with MV group (P < 0.05). CONCLUSIONS: Partial liquid ventilation provides protective effects against inflammatory responses in the lungs of oleic acid-induced immature piglets.

Novel strategy for treatment of pulmonary arterial hypertension: enhancement of apoptosis.

Advanced pulmonary arterial hypertension is characterized by extensive vascular remodeling that is usually resistant to vasodilator therapy. As the major component of the vascular media, decreased apoptosis of pulmonary arterial smooth muscle cell (PASMC) plays key roles during pulmonary vascular remodeling. Recent studies showed that enhancement of apoptosis of PASMC can reverse pulmonary vascular remodeling and severe pulmonary arterial hypertension. Enhancement of apoptosis of PASMC is becoming a novel strategy to reverse severe pulmonary arterial hypertension. This review analyzes some potential strategies to reverse pulmonary vascular remodeling.