Exploration of anatomical distribution of brain metastasis from breast cancer at first diagnosis assisted by artificial intelligence.

Objectives: This study aimed to explore the spatial distribution of brain metastases (BMs) from breast cancer (BC) and to identify the high-risk sub-structures in BMs that are involved at first diagnosis. Methods: Magnetic resonance imaging (MRI) scans were retrospectively reviewed at our centre. The brain was divided into eight regions according to its anatomy and function, and the volume of each region was calculated. The identification and volume calculation of metastatic brain lesions were accomplished using an automatically segmented 3D BUC-Net model. The observed and expected rates of BMs were compared using 2-tailed proportional hypothesis testing. Results: A total of 250 patients with BC who presented with 1694 BMs were retrospectively identified. The overall observed incidences of the substructures were as follows: cerebellum, 42.1 %; frontal lobe, 20.1 %; occipital lobe, 9.7 %; temporal lobe, 8.0 %; parietal lobe, 13.1 %; thalamus, 4.7 %; brainstem, 0.9 %; and hippocampus, 1.3 %. Compared with the expected rate based on the volume of different brain regions, the cerebellum, occipital lobe, and thalamus were identified as higher risk regions for BMs (P value ≤ 5.6*10-3). Sub-group analysis according to the type of BC indicated that patients with triple-negative BC had a high risk of involvement of the hippocampus and brainstem. Conclusions: Among patients with BC, the cerebellum, occipital lobe and thalamus were identified as higher-risk regions than expected for BMs. The brainstem and hippocampus were high-risk areas of the BMs in triple negative breast cancer. However, further validation of this conclusion requires a larger sample size.

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.

The follow-up surgical results of coarctation of the aorta procedures in a cohort of Chinese children from a single institution.

OBJECTIVES: The aim of this study was to evaluate the results following surgeries for the treatment of coarctation of the aorta in Chinese paediatric patients and to compare the surgery outcomes between simple and complex coarctation procedures. METHODS: Between January 2006 and December 2011, 107 consecutive paediatric patients with coarctation of the aorta underwent surgery. Forty-four patients (41.12%) were classified as having simple coarctations (group A), and 54 patients (50.47%) were classified as having complex coarctations (group B). Echocardiography and the resting systolic blood pressure were evaluated prior to the operation, at one month following the operation, and then once annually. RESULTS: Follow-up was 93.5% complete (100 patients), without significant differences between the two groups. Arch hypoplasias and bicuspid aortic valves were initially present in 10 (9.35%) and 11 (10.28%) of 107 patients, respectively. There were no deaths among the group A patients and three (5.56%) early deaths among the group B patients. There was a significant difference in the restenosis incidence rate between the two groups during the most recent follow-up consultations (p<0.05). Additionally, only 10 of 43 group A and 10 of 51 group B patients had persistently abnormal blood pressures during the annual follow-up consultations. CONCLUSIONS: The postoperative restenosis ratio was increased in the complex coarctation group compared with the simple coarctation group. Additionally, the complex coarctation patients who did not have restenosis at follow-up had a lower proportion of hypertension.

Stented elephant trunk technique for retrograde type A aortic dissection after endovascular stent graft repair.

BACKGROUND: Retrograde type A aortic dissection is a rare but deadly complication after thoracic endovascular aortic repair of type B aortic dissection. Total arch replacement combined with a modified stented elephant trunk technique (SET), was performed for these complicated dissections. We reviewed our results of the procedure for this serious complication, aiming to evaluate the feasibility of the technique. METHODS: Between April 2005 and September 2012, 24 patients with retrograde type A aortic dissection after thoracic endovascular aortic repair underwent the SET procedure in our center. The mean age at operation was 44.1±8.8 years old. Postoperative mortality and morbidity were analyzed to evaluate the immediate and mid-term results. RESULTS: Death at 30 days was 4.2% (1 of 24 patients). No patient suffered paraplegia or stroke after operation. Follow-up was completed with 23 survivors. The mean follow-up period was 32.2±13.1 months (range, 12 to 49 months). No late deaths occurred during follow-up. One patient underwent reoperation for replacement of the thoracoabdominal aorta and enjoyed an uneventful survival. CONCLUSIONS: The stented elephant trunk technique could be an alternative for treatment of retrograde type A aortic dissection with acceptable surgical risks and satisfactory results.

The effects of neuromuscular blockade on operating conditions during general anesthesia for spinal surgery.

BACKGROUND: Muscle relaxants are prescribed routinely for patients undergoing general anesthesia, but the requirement for paralysis in spinal surgery is unclear. This study compared the operating conditions of general anesthesia with and without a muscle relaxant on spinal surgery patients. METHODS: Eighty-six adults who underwent elective spinal surgery were randomly assigned to a relaxant group (group R) or a no-relaxant group (group NR). All patients were induced with intravenous midazolam (0.05 mg/kg), fentanyl (4 µg/kg), propofol (1.0 mg/kg), and succinylcholine (2 mg/kg) and then atracurium was used in group R but not in group NR. The operating conditions, including muscle tone, body movements, airway pressure, anesthetics consumption, eye-opening time, extubation time, and the Observer's Assessment of the Alertness/Sedation (OAA/S) score 20 minutes after the extubation were compared between the 2 groups. RESULTS: The operating conditions including muscle tone scales, body movements, and airway pressure did not differ between the 2 groups. Eye-opening time (9.35±2.34 vs. 11.02±2.50 min; P=0.002) and extubation time (13.95±3.41 vs. 16.72±3.67 min; P=0.001) were shorter in group NR than in group R. The BIS score at extubation (87.2±5.0 vs. 83.3±5.7; P=0.001) and the OAA/S score 20 minutes after extubation (5 [3 to 5] vs. 4 [3 to 5]; P=0.005) were significantly higher in group NR than in group R. Propofol consumption was higher in group NR than in group R (4206.10±415.80 vs. 3900.60±365.40 µg/kg, respectively; P=0.001). CONCLUSIONS: General anesthesia without muscle relaxant provides similar working conditions to those observed with muscle relaxant, and it is associated with earlier eye opening and extubation and higher level of consciousness on emergence from spinal surgery.

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.

Progression of aortic regurgitation in Asian patients with congenital sinus of valsalva aneurysm.

BACKGROUND: We reviewed the experience of An Zhen and Fu Wai Hospital for congenital sinus of Valsalva aneurysm (SVA) to determine risk factors for aortic valve replacement (AVR) and postoperative progression of aortic regurgitation (AR). METHODS: Over a 7-year period, 255 patients underwent surgical repair of an SVA. Aneurysms originated from the right sinus and the noncoronary sinus in 212 patients (83.1%) and 38 patients (14.9%), respectively, and protruded into the right ventricle and right atrium in 171 patients (67.1%) and 80 patients (31.4%), respectively. AR presented in 142 patients (55.7%), 60 patients underwent AVR, and 13 patients underwent aortic valvuloplasty (3 patients eventually received AVR for valvuloplasty failure). RESULTS: All patients survived the operation. Late death occurred in 2 patients (0.8%), and 2 patients (0.8%) experienced anticoagulation-related complications. Logistic regression analysis revealed that infective endocarditis, the cardiothoracic ratio, and a nonruptured SVA were risk factors for AVR. Late follow-up of 150 patients by echocardiographic assessment revealed that AR improved in 17 patients and worsened in 20 patients. Cox regression analysis revealed AR at discharge to be an independent risk factor for AR aggravation at late follow-up. CONCLUSIONS: SVA can be repaired with low mortality and excellent long-term results. AR at discharge is an important factor in determining AR aggravation at late follow-up after the operation. We recommend early diagnosis and aggressive treatment for SVA.

Effect of oleic acid-induced acute lung injury and conventional mechanical ventilation on renal function in piglets.

BACKGROUND: Animal models that demonstrate changes of renal function in response to acute lung injury (ALI) and mechanical ventilation (MV) are few. The present study was performed to examine the effect of ALI induced by oleic acid (OA) in combination with conventional MV strategy on renal function in piglets. METHODS: Twelve Chinese mini-piglets were randomly divided into two groups: the OA group (n = 6), animals were ventilated with a conventional MV strategy of 12 ml/kg and suffered an ALI induced by administration of OA, and the control group (n = 6), animals were ventilated with a protective MV strategy of 6 ml/kg and received the same amount of sterile saline. RESULTS: Six hours after OA injection a severe lung injury and a mild-moderate degree of renal histopathological injury were seen, while no apparent histological abnormalities were observed in the control group. Although we observed an increase in the plasma concentrations of creatinine and urea after ALI, there was no significant difference compared with the control group. Plasma concentrations of neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C increased (5.6 ± 1.3) and (7.4 ± 1.5) times in the OA group compared to baseline values, and were significantly higher than the values in the control group. OA injection in combination with conventional MV strategy resulted in a dramatic aggravation of hemodynamic and blood gas exchange parameters, while these parameters remained stable during the experiment in the control group. The plasma expression of TNF-α and IL-6 in the OA group were significantly higher than that in the control group. Compared with high expression in the lung and renal tissue in the OA group, TNF-α and IL-6 were too low to be detected in the lung and renal tissue in the control group. CONCLUSIONS: OA injection in combination with conventional MV strategy not only resulted in a severe lung injury but also an apparent renal injury. The potential mechanisms involved a cytokine response of TNF-α and IL-6 in plasma, lung and renal tissues.

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.

Two cases of a rare association: double aortic arch with tetralogy of Fallot.

Two cases of asymptomatic double aortic arch with tetralogy of Fallot are reported. One presented with a non-dominant left arch and left-sided descending thoracic aorta and the other with a non-dominant left arch, a right-sided descending thoracic aorta and a patent ductus arteriosus. One-stage operation was performed and both patients were discharged free of symptoms and signs related to the double aortic arch and tetralogy of Fallot after the operation. A preoperative recognition of DAA is important, especially in echocardiographic investigation.

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.

[Early prediction of acute kidney injury in infants and young children after cardiopulmonary bypass surgery].

OBJECTIVE: To understand the incidence of acute kidney injury (AKI) in infants and toddlers and evaluate the possibility of predicting AKI with urine neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), N-acetyl-beta-D-glucosaminidase (NAG), microalbumin (MA) and α1-microglobulin (α1-MG) after surgeries for congenital heart diseases with cardiopulmonary bypass (CPB). METHOD: Fifty-eight children (ages ≤ 3 years) who had undergone surgery for congenital heart diseases with CPB were enrolled. Urinary samples were collected before and 4 h, 6 h, 12 h, 24 h post CPB to detect the concentration of NGAL, IL-18, NAG, MA and α1-MG. RESULT: The AKI group had 29 cases, none AKI group also had 29 cases. Urinary concentration of NGAL 4, 6, and 12 h post CPB were significantly higher in AKI group (2820 µg/g, 905.7 µg/g, 76.1 µg/g separately) than in none AKI group (27.6 µg/g, 19.5 µg/g, 16.0 µg/g separately, P < 0.01). Urinary concentration of IL-18 4, 6, 12 and 24 h post CPB were significantly higher in AKI group than in none AKI group (P < 0.05). Urinary concentration of NAG 4 h and 6 h post CPB were significantly higher in AKI group than in none AKI group (P < 0.01). Urinary concentration of MA/UCr post CPB 4 h, 6 h and 12 h were significantly higher in AKI group than in none AKI group (P < 0.05). Urinary concentration of α1-MG/UCr post CPB 4 h, 6 h and 12 h were significantly higher in AKI group than in none AKI group (P < 0.01). All the five biomarkers had predictive abilities at 4-hour after surgery. CONCLUSION: Urine biomarkers NGAL, IL-18, NAG, MA and α1-MG were valuable early predictors of AKI after CPB surgery.

[Diagnosis and surgery of anomalous origin of the left coronary artery from the pulmonary artery in children].

OBJECTIVE: To explore the clinical features, diagnosis and management of anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) in children. METHODS: The clinical manifestations, examinations, diagnostic modalities and treatments of children identified as ALCAPA at Beijing Anzhen Hospital from September 1993 to September 2011 were retrospectively reviewed. RESULTS: A total of 27 children were recruited. There were 16 males and 11 females with an age range of 1 month to 13 years. Among them, 19 patients had an onset age of ≤ 1 years. The initial symptoms were acute heart failure (n = 15), pneumonia (n = 7) and cardiac dilation with murmur (n = 5). The pre-admission misdiagnoses included endocardial fibroelastosis (EFE) (n = 13), dilated cardiomyopathy (DCM) (n = 4) and mitral severe regurgitation (n = 2). The definite diagnosis was established on the basis of electrocardiography (ECG), echocardiography and 64-slice computed tomography or angiography. Twenty-six cases underwent immediate surgery after an accurate diagnosis, including left coronary artery (LCA) ligation (n = 1), LCA ligation plus coronary artery bypass grafting (n = 1), Takeuchi operation (n = 7) and LCA reimplantation (n = 17). Six died postoperatively. And 20 cases were routinely followed up with symptoms, signs, ECG and echocardiography for 3-192 months. The outpatient visits were at Months 3, 6 and 12 post-operation and then annual check-ups by returning to hospital, telephone, letters and other forms. The cohort had no overt symptoms and left ventricular ejection fraction returned to normal range. No complications occurred after LCA reimplantation. CONCLUSIONS: As a rare congenital heart anomaly, ALCAPA may be definitely diagnosed with clinical features and serial diagnostic methods. It can be treated with several types of cardiac surgery. Coronary reimplantation is the technique of choice for surgical correction of ALCAPA due to its excellent prognosis.

Intravenous transplantation of mesenchymal stem cells attenuates oleic acid induced acute lung injury in rats.

BACKGROUND: Acute lung injury (ALI) and end-stage acute respiratory distress syndrome (ARDS) were among the most common causes of death in intensive care units. The activation of an inflammatory response and the damage of pulmonary epithelium and endotheliumwerethe hallmark of ALI/ARDS. Recent studies had demonstrated the importance of mesenchymal stem cells (MSCs) in maintaining the normal pulmonary endothelial and epithelial function as well as participating in modulating the inflammatory response and they are involved in epithelial and endothelial repair after injury. Here, our study demonstrates MSCs therapeutic potential in a rat model of ALI/ARDS. METHODS: Bone marrow derived MSCs were obtained from Sprague-Dawley (SD) rats and their differential potential was verified. ALI was induced in rats byoleic acid (OA), and MSCs were transplanted intravenously. The lung injury and the concentration of cytokines in plasma and lung tissue extracts were assessed at 8 hours, 24 hours and 48 hours after OA-injection. RESULTS: The histological appearance and water content in rat lung tissue were significantly improved at different time points in rats treated with MSCs. The concentration of tumor necrosis factor-a and intercellular adhesion molecular-1 in rats plasma and lung tissue extracts were significantly inhibited after intravenous transplantation of MSCs, whereas interleukin-10 was significantly higher after MSCs transplantation at 8 hours, 24 hours and 48 hours after OA-challenge. CONCLUSIONS: Intravenous transplantation of MSCs could maintain the integrity of the pulmonary alveolar-capillary barrier and modulate the inflammatory response to attenuate the experimental ALI/ARDS. Transplantation of MSCs could be a novel cell-based therapeutic strategy for prevention and treatment of ALI/ARDS.

Angiotensin-converting enzyme 2 activation protects against pulmonary arterial hypertension through improving early endothelial function and mediating cytokines levels.

BACKGROUND: Increasing evidences indicate that an activated renin-angiotensin system (RAS) causes an imbalance between the vasoconstrictive and vasodilator mechanisms involving the pulmonary circulation leading to the development of pulmonary arterial hypertension (PAH). Angiotensin-converting enzyme 2 (ACE2), a primary component of the vasoprotective axis in RAS, is recently identified that it has regulatory actions in lung pathophysiology, but the mechanism in these processes is uncertain yet. METHODS: Severe PAH was induced by monocrotaline injection one week following pneumonectomy in rats. The activation of ACE2 by continuous injection of resorcinolnaphthalein was studied by real time-polymerase chain reaction (RT-PCR), Western blotting and fluorogenic peptide assay. Endothelial functions were evaluated by the response to acetylcholine and cytokines were measured by RT-PCR seven days after monocrotaline injection. The PAH-related hemodynamics and pathological changes were examined at day 21 when severe PAH was completely established. RESULTS: Resorcinolnaphthalein caused significant activation of ACE2 in both normal and diseased rats in 7 days after treatment. The pulmonary arterial pressure (PAP) started to increase at least 7 days after monocrotaline injection, and the rats developed severe PAH in 21 days with high PAP, right ventricular hypertrophy and neointimal formation. Treatment with resorcinolnaphthalein prevented these features. Resorcinolnaphthalein caused an improved endothelia-dependent vasorelaxation and decrease in proinflammatory cytokines (tumor necrosis factor (TNF)-α, monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-6) and increase in anti-inflammatory cytokine IL-10 in the early stage of the pathogenesis. CONCLUSIONS: These results demonstrated that activation of ACE2 by continuous injection of resorcinolnaphthalein prevented the development of PAH through improving early endothelial dysfunction and mediating the level of proinflammatory and anti-inflammatory cytokines.

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.

Effects of low potassium dextran glucose solution on oleic acid-induced acute lung injury in juvenile piglets.

BACKGROUND: Epithelial dysfunction in lungs plays a key role in the pathogenesis of acute lung injury. The beneficial effects of low potassium dextran glucose solution (LPD) have been reported in lung preservation, and LPD enables injured alveolar pneumocytes to recover. So we hypothesized that systemic administration of LPD may have benefits in treating acute lung injury. We investigated the effects of LPD on arterial blood gas and levels of some cytokines in oleic acid-induced acute lung injury in juvenile piglets. METHODS: Oleic acid (0.1 ml/kg) was intrapulmonarily administered to healthy anesthetized juvenile piglets. Ten animals were randomly assigned to two groups (n = 5 each): oleic acid-induced group (control group) with intravenous infusion of 12.5 ml/kg of lactated Ringer's solution 30 minutes before administration of oleic acid and LPD group with systemic administration of LPD (12.5 ml/kg) 30 minutes before injecting oleic acid. Blood gas variables and concentrations of tumor necrosis factor alpha, endothelin 1 and interleukin 10 were measured before and every 1 hour for 6 hours after initial lung injury. RESULTS: Compared with control group, blood pH, partial pressure of arterial oxygen to fraction of inspired oxygen ratio, partial pressure of arterial carbon dioxide, and mean pulmonary arterial pressure in LPD group were improved (P < 0.05 or 0.01). Six hours after lung injury, concentration of tumor necrosis factor alpha in lung tissue was lower in LPD group than control group (P < 0.05). Plasmic concentration of endothelin 1 showed lower in LPD group while plasmic concentration of interleukin 10 showed higher in LPD group (P < 0.05). CONCLUSIONS: Before lung injury, systemic administration of LPD can improve gas exchange, attenuate pulmonary hypertension, decrease plasmic levels of endothelin 1, increase interleukin 10 and decrease concentration of tumor necrosis factor alpha in lung tissue in oleic acid-induced acute lung injury in juvenile piglets.

Risk factors for preoperative and postoperative progression of aortic regurgitation in congenital ruptured sinus of Valsalva aneurysm.

BACKGROUND: We reviewed our experience with congenital ruptured sinus of Valsalva aneurysms (RSVA) to determine risk factors influencing occurrence and postoperative worsening of aortic regurgitation (AR). METHODS: Over an 11-year period, 210 patients (33 ± 9.7 years old) underwent surgical repair of RSVA. Aneurysm originated from the right noncoronary sinus and other sinuses in 171, 35 and 4 patients, respectively; and ruptured into right ventricle outlet tract in 115 patients, right ventricle in 16, right atrium in 75, and other chambers in 4. Aortic regurgitation (111) and ventricular septal defect (108) were common coexisting anomalies. Patch closure of RSVA was performed in 61 patients, direct sutures in 18 patients, patch closure plus direct sutures in 88 patients, and repair simultaneous with aortic valve replacement in 43 patients. RESULTS: All but one patient survived the operation. In early postoperative periods, AR improved in 26 patients and worsened in 23. In 114 late follow-up patients with echocardiographic assessment, 18 showed deteriorated AR. By logistic regression analysis, RSVA ruptured into the right ventricle outlet tract and secondary changes of the aortic valve were risk factors for preoperative AR, and RSVA repaired with direct sutures had a significantly higher incidence of early worsening of AR. By Cox regression analysis, AR at discharge was an independent risk factor for late follow-up AR worsening. CONCLUSIONS: The RSVA can be repaired with a low mortality and excellent long-term result. An early, aggressive treatment should be recommended to prevent postoperative AR, and a direct-suture closure of RSVA should be avoided to prevent early worsening of AR.

Lung biopsy findings in previously inoperable patients with severe pulmonary hypertension associated with congenital heart disease.

BACKGROUND: Congenital heart disease with near-systemic pulmonary arterial pressures, previously thought to have irreversible pulmonary vascular disease (PVD), has been successfully corrected at our institution recently. Whether the PVD is reversible remains unknown. This study aimed to examine the nature of the pulmonary arterial vessels in these selective patients. METHODS: All patients with congenital heart disease and severe pulmonary hypertension (PH) were selected using Diagnostic-treatment to undergo radical repair (n=49). Lung biopsy specimens were obtained during operation. The nature of PVD was determined by Heath-Edwards classification system. All specimens were quantitatively analyzed by calculating percentage media wall area, percentage media wall thickness and arteriole density. RESULTS: Transcutaneous oxygen saturation of all selected patients increased significantly after Diagnostic-treatment (P<0.001). There were no operative deaths. Mean pulmonary artery pressure and pulmonary vascular resistance regressed significantly postoperatively (P<0.001). The incidence of postoperative PH was 59.2% (29/49). Of 49 selected patients with severe PH, 38 (77.6%) showed grade I change, 5 (10.2%) showed grade II change, 4 (8.2%) showed grade III change and only 2 (4%) showed grade IV change with plexiform lesion. The percentage media wall area, percentage media wall thickness and arteriole density were significantly increased in patients associated with PH than in normal subjects (P<0.001). Follow-up data showed the reversal of PVD in these 2 patients with plexiform lesions. CONCLUSIONS: The PVD in these selective patients with congenital heart disease and severe PH using a Diagnostic-treatment-and-Repair strategy is generally reversible and these patients are operable in current era.