Neuroprotective effects of ginsenosides on neural progenitor cells against oxidative injury.

Ginsenosides exhibit various neuroprotective effects against oxidative stress. However, which ginsenoside provides optimal effects for the treatment of neurological disorders as a potent antioxidant remains to be elucidated. Therefore, the present study investigated and compared the neuroprotective effects of the Rb1, Rd, Rg1 and Re ginsenosides on neural progenitor cells (NPCs) following tert-Butylhydroperoxide (t-BHP)-induced oxidative injury. Primary rat embryonic cortical NPCs were prepared from E14.5 embryos of Sprague-Dawley rats. The oxidative injury model was established with t­BHP. A lactate dehydrogenase assay and terminal deoxynucleotidyl transferase dUTP nick­end labeling staining were used to measure the viability of the NPCs pre­treated with ginsenosides under oxidative stress. Reverse transcription­quantitative polymerase chain reaction analysis was used to determine the activation of intracellular signaling pathways triggered by the pretreatment of ginsenosides. Among the four ginsenosides, only Rb1 attenuated t­BHP toxicity in the NPCs, and the nuclear factor (erythroizd­derived 2)­like 2/heme oxygenase­1 pathway was found to be key in the intracellular defense against oxidative stress. The present study demonstrated the anti-oxidative effects of ginsenoside Rb1 on NPCs, and suggested that Rb1 may offer potential as a potent antioxidant for the treatment of neurological disorders.

Protection against Oxygen-Glucose Deprivation/Reperfusion Injury in Cortical Neurons by Combining Omega-3 Polyunsaturated Acid with Lyciumbarbarum Polysaccharide.

Ischemic stroke, characterized by the disturbance of the blood supply to the brain, is a severe worldwide health threat with high mortality and morbidity. However, there is no effective pharmacotherapy for ischemic injury. Currently, combined treatment is highly recommended for this devastating injury. In the present study, we investigated neuroprotective effects of the combination of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) and Lyciumbarbarum polysaccharide (LBP) on cortical neurons using an in vitro ischemic model. Our study demonstrated that treatment with docosahexaenoic acid (DHA), a major component of the ω-3 PUFAs family, significantly inhibited the increase of intracellular Ca(2+) in cultured wild type (WT) cortical neurons subjected to oxygen-glucose deprivation/reperfusion (OGD/R) injury and promoted their survival compared with the vehicle-treated control. The protective effects were further confirmed in cultured neurons with high endogenous ω-3 PUFAs that were isolated from fat-1 mice, in that a higher survival rate was found in fat-1 neurons compared with wild-type neurons after OGD/R injury. Our study also found that treatment with LBP (50 mg/L) activated Trk-B signaling in cortical neurons and significantly attenuated OGD/R-induced cell apoptosis compared with the control. Notably, both combining LBP treatment with ω-3 PUFAs administration to WT neurons and adding LBP to fat-1 neurons showed enhanced effects on protecting cortical neurons against OGD/R injury via concurrently regulating the intracellular calcium overload and neurotrophic pathway. The results of the study suggest that ω-3 PUFAs and LBP are promising candidates for combined pharmacotherapy for ischemic stroke.

Retrograde Cerebral Perfusion Results in Better Perfusion to the Striatum Than the Cerebral Cortex During Deep Hypothermic Circulatory Arrest: A Microdialysis Study.

It remains controversial whether contemporary cerebral perfusion techniques, utilized during deep hypothermic circulatory arrest (DHCA), establish adequate perfusion to deep structures in the brain. This study aimed to investigate whether selective antegrade cerebral perfusion (SACP) or retrograde cerebral perfusion (RCP) can provide perfusion equally to various anatomical positions in the brain using metabolic evidence obtained from microdialysis. Eighteen piglets were randomly assigned to 40 min of circulatory arrest (CA) at 18°C without cerebral perfusion (DHCA group, n = 6) or with SACP (SACP group, n = 6) or RCP (RCP group, n = 6). Microdialysis parameters (glucose, lactate, pyruvate, and glutamate) were measured every 30 min in cortex and striatum. After 3 h of reperfusion, brain tissue was harvested for Western blot measurement of α-spectrin. After 40 min of CA, the DHCA group showed marked elevations of lactate and glycerol and a reduction in glucose in the microdialysis perfusate (all P < 0.05). The changes in glucose, lactate, and glycerol in the perfusate and α-spectrin expression in brain tissue were similar between cortex and striatum in the SACP group (all P > 0.05). In the RCP group, the cortex exhibited lower glucose, higher lactate, and higher glycerol in the perfusate and higher α-spectrin expression in brain tissue compared with the striatum (all P < 0.05). Glutamate showed no difference between cortex and striatum in all groups (all P > 0.05). In summary, SACP provided uniform and continuous cerebral perfusion to most anatomical sites in the brain, whereas RCP resulted in less sufficient perfusion to the cortex but better perfusion to the striatum.

MicroRNA profiling of the intestine during hypothermic circulatory arrest in swine.

AIM: To perform a profiling analysis of changes in intestinal microRNA (miRNA) expression during hypothermic circulatory arrest (HCA). METHODS: A total of eight piglets were randomly divided into HCA and sham operation (SO) groups. Under general anesthesia, swine in the HCA group were subjected to hypothermic cardiopulmonary bypass at 24 °C followed by 80 min of circulatory arrest, and the reperfusion lasted for 180 min after cross-clamp removal. The counterparts in the SO group were only subjected to median sternotomy. Histopathological analysis was used to detect mucosal injury, and Pick-and-Mix custom miRNA real-time polymerase chain reaction (PCR) panels containing 306 unique primer sets were utilized to assay unpooled intestinal samples harvested from the two groups. RESULTS: The intestinal mucosa of the animals that were subjected to 24 °C HCA exhibited representative ischemic reperfusion injury of grade 2 or 3 according to the Chiu score. Such intestinal mucosal injuries, with the subepithelial space and epithelial layer lifting away from the lamina propria, were accompanied by shortened and irregular villi. On the contrary, the intestinal mucosa remained normal in the sham-operated animals. In total, twenty-five miRNAs were differentially expressed between the two groups (15 upregulated and 10 downregulated in the HCA group). Among these, eight miRNAs (miR-122, miR-221-5p, miR-31, miR-421-5p, miR-4333, miR-499-3p, miR-542 and let-7d-3p) were significantly dysregulated (four higher and four lower). The expression of miR-122 was significantly (5.37-fold) increased in the HCA group vs the SO group, indicating that it may play a key role in HCA-induced mucosal injury. CONCLUSION: Exposure to HCA caused intestinal miRNA dysregulation and barrier dysfunction in swine. These altered miRNAs might be related to the protection or destruction of the intestinal barrier.

DACT1 is involved in human placenta development by promoting Wnt signaling.

OBJECTIVE: The aim of this study was to evaluate the expression of DACT1 in human placenta tissue and the relationship between DACT1 and target genes of the Wnt signaling pathway. METHOD: Real-time PCR and western blotting were used to detect the expression of DACT1 and the target genes of Wnt signaling pathway in human placenta tissue. And the relationship between them was analyzed using SPSS 19. RESULTS: Real-time PCR results showed that DACT1 expression was significantly higher in 49- to 71-day placenta tissues (mean value = 0.020) than that in 39- to 48-day (the mean value = 0.009). The mRNA expressions of the Wnt signaling pathway target genes, CCND1, CCND2, FOSL1, DAB2 and JUN, were also increased expressed in human placenta tissues. Significant positive associations between DACT1 and CCND1, CCND2, FOSL1, DAB2 and JUN were observed. Western blotting analysis showed that the protein expression of DACT1, CCND1, CCND2, FOSL1, DAB2 and JUN displayed the increasing trend in 43-, 49- and 71-day placenta samples. CONCLUSION: DACT1 might play an important role in human placenta development via promoting Wnt signaling.

Ellagic acid prevents monocrotaline-induced pulmonary artery hypertension via inhibiting NLRP3 inflammasome activation in rats.

BACKGROUND: Pulmonary artery hypertension (PAH) is characterized by vascular remodeling, high pulmonary blood pressure, and right ventricular hypertrophy. Oxidative stress, inflammation and pulmonary artery remodeling are important components in PAH. Ellagic acid (EA) is a phenolic compound with anti-oxidative, anti-inflammatory, and anti-proliferative properties. This study aimed to investigate whether EA could prevent the development of monocrotaline (MCT)-induced PAH in rats. METHODS: Male Sprague-Dawley rats received EA (30 and 50mg/kg/day) or vehicle one day after a single-dose of monocrotaline (MCT, 60mg/kg). Hemodynamic changes, right ventricular hypertrophy, and lung morphological features were assessed 4weeks later. Activation of the NLRP3 (NACHT, LRR, and PYD domain-containing protein 3) inflammasome pathway in the lungs was assessed using Western blot analysis. RESULTS: MCT induced PAH, oxidative stress, and NLRP3 inflammasome activation in vehicle-treated rats. EA reduced the right ventricle systolic pressure, the right ventricular hypertrophy and the wall thickness/external diameter ratio of the pulmonary arteries compared with vehicle. EA also inhibited the MCT-induced elevation of oxidative stress, NLRP3, and caspase-1, IL-ß in the lungs and the elevated levels of brain natriuretic peptide (BNP) and inflammatory cytokines in serum. CONCLUSIONS: Ellagic acid ameliorates monocrotaline-induced pulmonary artery hypertension via exerting its anti-oxidative property inhibiting NLRP3 inflammasome signal pathway in rats.

Selective antegrade cerebral perfusion attenuating the TLR4/NF-κB pathway during deep hypothermia circulatory arrest in a pig model.

OBJECTIVES: The alteration of the Toll-like receptor/nuclear factor-kappa B (TLR4/NF-κB) signaling pathway during deep hypothermia circulatory arrest (DHCA) has not yet been defined. The aim of this study was to explore the expression of the TLR4/NF-κB pathway cytokine in cerebral injury resulting from DHCA as well as the effect of selective antegrade cerebral perfusion (SACP) on TLR4/NF-κB pathway expression. METHODS: Twelve pigs were randomly assigned to DHCA alone (n = 6) or DHCA with SACP (n = 6) at 18°C for 80 min. Serum interleukin (IL)-6 was assayed by ELISA. Apoptosis and NF-κB proteins were detected by fluorescence TUNEL and Western blot, respectively. The level of TLR4 mRNA and protein were determined through qRT-PCR and Western blot. RESULTS: The serum IL-6 level of the SACP group was significantly lower than that of the DHCA group at the end of circulation arrest and experimentation. Apoptotic index and NF-κB protein were apparently lower in SACP animals (p < 0.05). Compared to the DHCA group, the levels of TLR4 protein and mRNA in the SACP group were lower with significance (p < 0.05). CONCLUSIONS: The TLR4/NF-κB signaling pathway plays a critical role in the pathogenesis of DHCA cerebral injury. Attenuation of the TLR4/NF-κB inflammatory cytokines probably contributes to the neuroprotective effect of SACP. The TLR4/NF-κB inflammatory signaling pathway may be a novel therapeutic target for developing a new strategy for neuroprotection in DHCA.

Comparative expression profiles of microRNA in left and right atrial appendages from patients with rheumatic mitral valve disease exhibiting sinus rhythm or atrial fibrillation.

BACKGROUND: The atrial fibrillation (AF) associated microRNAs (miRNAs) were found in the right atrium (RA) and left atrium (LA) from patients with rheumatic mitral valve disease (RMVD). However, most studies only focus on the RA; and the potential differences of AF-associated miRNAs between the RA and LA are still unknown. The aim of this study was to perform miRNA expression profiles analysis to compare the potential differences of AF-associated miRNAs in the right atrial appendages (RAA) and left atrial appendages (LAA) from RMVD patients. METHODS: Samples tissues from the RAA and LAA were obtained from 18 RMVD patients (10 with AF) during mitral valve replacement surgery. From these tissues, miRNA expression profiles were created and analyzed using a human miRNA microarray. Then, the results were validated using qRT-PCR analysis for 12 selected miRNAs. Finally, potential targets of 10 validated miRNAs were predicted and their functions and potential pathways were analyzed using the miRFocus database. RESULTS: In RAA, 65 AF-associated miRNAs were found and significantly dysregulated (i.e. 28 miRNAs were up-regulated and 37 were down-regulated). In LAA, 42 AF-associated miRNAs were found and significantly dysregulated (i.e. 22 miRNAs were up-regulated and 20 were down-regulated). Among these AF-associated miRNAs, 23 of them were found in both RAA and LAA, 45 of them were found only in RAA, and 19 of them were found only in LAA. Finally, 10 AF-associated miRNAs validated by qRT-PCR were similarly distributed in RAA and LAA; 3 were found in both RAA and LAA, 5 were found only in RAA, and 2 were found only in LAA. Potential miRNA targets and molecular pathways were identified. CONCLUSIONS: We have found the different distributions of AF-associated miRNAs in the RAA and LAA from RMVD patients. This may reflect different miRNA mechanisms in AF between the RA and LA. These findings may provide new insights into the underlying mechanisms of AF in RMVD patients.

Is selective antegrade cerebral perfusion superior to retrograde cerebral perfusion for brain protection during deep hypothermic circulatory arrest? Metabolic evidence from microdialysis.

OBJECTIVES: This study aimed to investigate whether selective antegrade cerebral perfusion or retrograde cerebral perfusion is a better technique for brain protection in deep hypothermic circulatory arrest by obtaining metabolic evidence from microdialysis. DESIGN: Randomized, animal study. SETTING: Assisted circulation laboratory. SUBJECTS: Eighteen piglets of either sex (9.8 ± 3.1 kg). INTERVENTIONS: Animals were randomly assigned to 40 minutes of circulatory arrest at 18°C without cerebral perfusion (deep hypothermic circulatory arrest group, n = 6) or with selective antegrade cerebral perfusion (selective antegrade cerebral perfusion group, n = 6) or retrograde cerebral perfusion (retrograde cerebral perfusion group, n = 6). Reperfusion was continued for 3 hours. MEASUREMENTS AND MAIN RESULTS: Microdialysis (glucose, lactate, pyruvate, and glycerol) variables in the cortex dialysate were measured every 30 minutes. Intracerebral pressure and serum S-100 levels were also monitored. After 3 hours of reperfusion, cortical tissue was harvested for terminal deoxynucleotidyl transferase dUTP nick-end labeling staining. After 40 minutes of circulatory arrest, the deep hypothermic circulatory arrest group presented marked elevations of intracerebral pressure, and serum S-100 levels were higher in the deep hypothermic circulatory arrest group than in the other two groups (p < 0.001, respectively). The selective antegrade cerebral perfusion group exhibited higher glucose, lower lactate, and lower glycerol levels and a lower lactate-to-pyruvate ratio in comparison to the deep hypothermic circulatory arrest group (p < 0.05, respectively); the retrograde cerebral perfusion group had lower lactate and glycerol levels and a lower lactate-to-pyruvate ratio (p < 0.05, respectively) but similar glucose levels compared to deep hypothermic circulatory arrest alone. Furthermore, selective antegrade cerebral perfusion provided better preservation of energy and cell integrity than retrograde cerebral perfusion with higher glucose and lower glycerol levels (p < 0.05, respectively). After 3 hours of reperfusion, fewer apoptotic neurons were found in selective antegrade cerebral perfusion animals than in the other two groups (p < 0.05, respectively). CONCLUSIONS: Both selective antegrade cerebral perfusion and retrograde cerebral perfusion were superior to deep hypothermic circulatory arrest alone during circulatory arrest. Retrograde cerebral perfusion was a moderate technique that had similar advantages with regard to less cerebral edema, better clearance of metabolic waste, and lower levels of biomarkers of injury than selective antegrade cerebral perfusion, but its capacity for energy preservation, maintenance of cellular integrity, and protection against apoptosis was lower than that of selective antegrade cerebral perfusion.

Atrial fibrillation alters the microRNA expression profiles of the left atria of patients with mitral stenosis.

BACKGROUND: Structural changes of the left and right atria associated with atrial fibrillation (AF) in mitral stenosis (MS) patients are well known, and alterations in microRNA (miRNA) expression profiles of the right atria have also been investigated. However, miRNA changes in the left atria still require delineation. This study evaluated alterations in miRNA expression profiles of left atrial tissues from MS patients with AF relative to those with normal sinus rhythm (NSR). METHODS: Sample tissues from left atrial appendages were obtained from 12 MS patients (6 with AF) during mitral valve replacement surgery. From these tissues, miRNA expression profiles were created and analyzed using a human miRNA microarray. Results were validated via reverse-transcription and quantitative PCR for 5 selected miRNAs. Potential miRNA targets were predicted and their functions and potential pathways analyzed via the miRFocus database. RESULTS: The expression levels of 22 miRNAs differed between the AF and NSR groups. Relative to NSR patients, in those with AF the expression levels of 45% (10/22) of these miRNAs were significantly higher, while those of the balance (55%, 12/22) were significantly lower. Potential miRNA targets and molecular pathways were identified. CONCLUSIONS: AF alters the miRNA expression profiles of the left atria of MS patients. These findings may be useful for the biological understanding of AF in MS patients.

An antigenic recombinant serine protease from Trichinella spiralis induces protective immunity in BALB/c mice.

In this study, we report the cloning and characterization of a cDNA encoding a Trichinella serine protease gene (TspSP-1.3) from GenBank. The recombinant TspSP-1.3 protein (rTspSP-1.3) was expressed in an Escherichia coli expression system and purified with Ni-affinity chromatography. Real-time quantitative PCR analysis revealed that TspSP-1.3 was expressed at significantly higher levels in muscle larvae and adult worms than in newborn larvae. TspSP-1.3 was detected in excretory-secretory proteins of Trichinella spiralis with western blotting. Immunization with the rTspSP-1.3 antigen induced humoral immune responses, which manifested as elevated specific anti-rTspSP-1.3 IgG and IgE antibodies and a mixed Th1/Th2 response. To determine whether purified rTspSP-1.3 had good antigenicity and could be a vaccine candidate for the control of T. spiralis infection, we immunized BALB/c mice with rTspSP-1.3 and subsequently challenged the mice with T. spiralis larvae. The results showed that mice vaccinated with rTspSP-1.3 exhibited an average reduction in the muscle larvae burden of 39 % relative to the control group. These results suggest that TspSP-1.3 could be a novel vaccine candidate for controlling Trichinella infection.

Analysis of a novel cathepsin B circulating antigen and its response to drug treatment in Trichinella-infected mice.

In this paper, we cloned a novel full-length cDNA that encodes a Trichinella spiralis cathepsin B-like protease gene (TsCPB) using 3'-RACE PCR. The recombinant mature TsCPB protein (rTsCPB) was then expressed in an Escherichia coli expression system and purified with Ni-affinity chromatography. Real-time quantitative PCR revealed that TsCPB was expressed across all development stages of the parasite but had the highest expression level during the adult stage. Furthermore, rTsCPB was detected in Trichinella excretory-secretory products with anti-rTsCPB rabbit polyclonal antibodies. Interestingly, rTsCPB was strongly recognized by the T. spiralis-infected sera in Western blotting, implying that TsCPB protein appeared in the peripheral blood of Trichinella-infected mice as circulating antigens (CAg). We then analyzed the dynamic levels of TsCPB CAg and its antibodies in T. spiralis-infected sera by using an improved double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) and indirect ELISA, respectively. The results showed that TsCPB CAg can be detected much earlier compared to antibody detection in Trichinella-infected mice. In addition, we monitored the effects of albendazole drug therapy (a dosage of 370 mg/kg body weight, twice a day) on T. spiralis-infected mice by detecting the levels of TsCPB CAg and its antibody in the sera of drug-treated mice. The results showed that the levels of CAg dramatically decreased after successful drug treatment, while the antibody level remained unchanged. Overall, the novel Trichinella antigen TsCPB could be a promising novel circulating antigen molecule for the detection of Trichinella infection and for monitoring the efficacy of drug treatment of trichinellosis.

The altered expression profile of microRNAs in cardiopulmonary bypass canine models and the effects of mir-499 on myocardial ischemic reperfusion injury.

BACKGROUND: MicroRNAs were enrolled in various cardiovascular disease especially ischemic heart diseases, but the microRNA changes during myocardial ischemia reperfusion injury underwent cardiopulmonary bypass are still unknown. This study screens the microRNA differences in CPB canines and evaluates the relationship of microRNAs with myocardial ischemia reperfusion injury. METHODS: 13 healthy canines received CPB with 60 minutes of aortic clamping and cardioplegic arrest, followed by 90 minutes reperfusion. Left ventricular myocardial samples, blood samples and hemodynamic data were taken at different time points. We performed microRNAs microarray experiments upon the left ventricle myocardium tissue of canines before CPB and after reperfusion for 90 minutes by pooling 3 tissue samples together and used qRT-PCR for confirmation. RESULTS: Statistically significant difference was found in mir-499 level before CPB and after reperfusion (T1 vs. T4, p=0.041). We further examined the mir-499 levels by using qRT-PCR in all 13 canines at 4 different time points (T1 vs. T4, p=0.029). Mir-499 expression was negatively correlated with cardiac troponin T (cTnT) and creatine kinase- MB (CK-MB) levels of canines in all time points samples (r=0.469, p<0.001 and r=0.273, p=0.050 respectively). Moreover, higher mir-499 expression level was associated with higher dP/dtmax at 25 minutes and 90 minutes after reperfusion. CONCLUSION: Myocardial ischemic reperfusion injury with cardiopulmonary bypass results in declining level of mir-499 expression in left ventricle myocardium of canines, suggesting mir-499 would be a potential therapeutic target in cardiac protection during open heart surgery.

Simvastatin reduces myocardial injury undergoing noncoronary artery cardiac surgery: a randomized controlled trial.

OBJECTIVE: Myocardial injury during cardiac surgery is a major cause of perioperative morbidity and mortality. We determined whether perioperative statin therapy is cardioprotective in patients undergoing noncoronary artery cardiac surgery and the potential mechanisms. METHODS AND RESULTS: One hundred fifty-one patients undergoing noncoronary artery cardiac surgery were randomly assigned to either a statin group (n=77) or a control group (n=74). Simvastatin (20 mg) was administered preoperatively and postoperatively. Plasma were analyzed for troponin T, isoenzyme of creatine kinase, C-reaction protein, interleukin-6, interleukin-8, creatinine, and blood urea nitrogen. Cardiac echocardiography was performed. Endothelial nitric oxide synthase (eNOS), Akt, p38, heat shock protein 90, caveolin-1, and nitric oxide (NO) in the heart were detected. Simvastatin significantly reduced plasma troponin T, isoenzyme of creatine kinase, C-reaction protein, blood urea nitrogen , creatinine, interleukin-6, interleukin-8, and the requirement of inotropic postoperatively. Simvastatin increased NO production, the expression of eNOS and phosphorylation at serine1177, phosphorylation of Akt, expression of heat shock protein 90, heat shock protein 90 association with eNOS and decreased eNOS phosphorylation at threonine 495, phosphorylation of p38, and expression of caveolin-1. Simvastatin also improved cardiac function postoperatively. CONCLUSIONS: Perioperative statin therapy can improve cardiac function and renal function by reducing myocardial injury and inflammatory response through activating Akt-eNOS and attenuating p38 signaling pathways in patients undergoing noncoronary artery cardiac surgery. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01178710.

Surgical technique for aortic regurgitation attributable to Behcet's disease: modified aortic valve replacement with reinforcement of the aortic wall.

Aortic regurgitation is a severe cardiovascular complication of Behcet's disease, resulting in high mortality rates within the Asian population. Standard surgical interventions have resulted in poor results in the long term. We herein report on a modified aortic valve replacement technique coupled with reinforcement of the aortic wall. During this procedure, Teflon felts and continuous mattress stitches were used to reinforce the aortic wall in order to prevent prosthetic valve detachment and formation of an aortic pseudoaneurysm. Postoperative examinations revealed that this procedure had satisfactory mid-term results.

Fibrosis of pulmonary vascular remodeling in carotid artery-jugular vein shunt pulmonary artery hypertension model of rats.

OBJECTIVE: The aim of the present study was to observe the changes of hemodynamics, stereology in pulmonary vascular remodeling and messenger RNA (mRNA) expressions of transforming growth factor beta 1, and receptors in carotid artery-jugular vein (CA-JV) shunt pulmonary artery hypertension model of rats. METHODS: Thirty-six Sprague-Dawley rats were randomized into three groups: CA-JV group, monocrotaline (MCT) administration group, and control group. Left CA-JV shunts were established in CA-JV group. Dorsal subcutaneous injections of MCT (60 mg kg(-1)) were received in MCT group. Ligations of left common carotid artery and external jugular vein were performed in control group. Right ventricular systolic pressure (RVSP) measurement, histological evaluation of the pulmonary tissue, and mRNA levels of transforming growth factor beta 1 (TGFß1), receptor 1 and receptor 2, were investigated after 6 weeks on MCT group, and after 12 weeks on both control and CA-JV groups. RESULTS: Compared with control group, RVSP, percentage of fibrous tissue (F%) in pulmonary arterioles, mRNA levels of TGFß1, and receptors of CA-JVand MCT groups increased significantly. Severe hemodynamics change was found in MCT groups. On the other hand, CA-JV group demonstrated more obvious fibrogenesis and TGFß1 signals' upregulation in two pulmonary artery hypertension (PAH) models. CONCLUSIONS: CA-JV shunt model of rats was a well-established PAH animal model simulating congenital heart disease with systemic-pulmonary shunt.

Successful surgical correction of total anomalous systemic venous drainage: a report of 2 cases.

Total anomalous systemic venous drainage is a rare malformation and only limited cases have been reported previously. Here we report two cases of total anomalous systemic venous drainage with successful surgical correction.

Surgical intervention for advanced valvular heart disease in 227 cases.

BACKGROUND: Although the results of surgical treatment in cardiac valve disease continue to improve, the postoperative mortality rate and the rate of complications in patients with advanced valvular heart disease (AVHD) are still very high. We did this retrospective study to summarize the surgical experience of heart valve replacement for patients with AVHD and discuss effective ways to improve the surgical outcome. METHODS: From January 1994 to October 2003, surgical procedures of heart valve replacement were performed on 227 (136 men and 91 women) patients with AVHD in our Department of Cardiothoracic Surgery. The clinical data of all patients were collected and analysed. Patients' age ranged from 10 years to 77 years. In preoperative cardiac function grading, 157 cases were NYHA III and 70 cases NYHA IV. Fifty-one patients had had cardiac operations. The ultrasonic cardiac graphs showed that 145 patients suffered from moderate or severe pulmonary hypertension and 73 had combined giant left ventricle. Mitral valve replacement was performed in 32 cases, aortic valve replacement in 90, tricuspid valve replacement in 1, combined mitral and aortic replacement in 103 and combined mitral and tricuspid replacement in 1. Nineteen patients also received surgical corrections for other minor abnormalities during the operations. A logistic model was established to evaluate the influence of perioperative factors on the mortality rate. RESULTS: The operative mortality rate was 13.2% (30/227). The main causes of death included multiple organ dysfunction syndrome (MODS), low cardiac output syndrome and ventricular fibrillation. From the results of the binary noncounterpart multivariate logistic regression, the following statistically significant factors were found to influence the operative mortality rate: redo operation, age >/= 55 years, preoperative NYHA cardiac function grading, extracorporeal circulation time >/= 120 minutes and postoperative usage of GIK (glucose, insulin and potassium) solution. All factors were risk ones except postoperative application of GIK. The Hosmer-Lemeshow goodness of fit coefficient of this model was 0.976. CONCLUSIONS: The risk factors associated with postoperative mortality rate in the patients with AVHD were redo operation, age >/= 55 years, preoperative NYHA cardiac function grading and extracorporeal circulation time >/= 120 minutes. Postoperative usage of GIK acted as a kind of metabolic therapy and will improve the recovery for patients with AVHD. Active perioperative management and care will play a very important role in reducing the operative risk and improving the short term outcome of surgical treatment for the patients with AVHD.