Osimertinib Improves the Immune Microenvironment of Lung Cancer by Downregulating PD-L1 Expression of Vascular Endothelial Cells and Enhances the Antitumor Effect of Bevacizumab.

Objective: To investigate the effect and mechanism of osimertinib combined with bevacizumab on lung cancer through cell and transplanted tumor animal experiments and to provide theoretical basis for further clinical trials. Methods: Immunohistochemistry was used to detect the expression of PD-L1 in tumor vessels of nonmetastatic lung adenocarcinoma and metastatic lung adenocarcinoma. At the same time, the expression of CD8 and FoxP3 in tumor tissue was detected. qRT-PCR was used to detect the effect of osimertinib on PD-L1 expression in HUVECs. The expression levels of p-Akt and p-ERK in HUVECs treated with osimertinib were analyzed by Western blot. AKT was blocked by AKT specific inhibitor Ly294002 to analyze the expression of PD-L1 in HUVECs. An animal model of transplanted tumor was constructed to analyze whether osimertinib could enhance the antitumor effect of bevacizumab. Results: PD-L1 was highly expressed in vascular endothelial cells of metastatic lung cancer. FoxP3 was highly expressed in metastatic lung adenocarcinoma, while CD8 expression was low. Osimertinib inhibits PD-L1 expression in endothelial cells. Mechanism studies have shown that osimertinib inhibits PD-L1 expression in endothelial cells through the AKT/ERK pathway. Osimertinib inhibited endothelial cell PD-L1 expression, increased CD8+T cell infiltration, inhibited tumor growth, and enhanced the tumor effect of bevacizumab. Conclusion: Osimertinib can significantly increase the killing ability of bevacizumab against tumor. Osimertinib can improve the tumor microenvironment and enhance the antitumor effect of bevacizumab by reducing the expression of PD-L1 in tumor blood vessels.

A novel immune checkpoint siglec-15 antibody inhibits LUAD by modulating mφ polarization in TME.

BACKGROUND: Siglec-15 (S15) is a type-I transmembrane protein and is considered a new candidate of immune checkpoint inhibitor for cancer immunotherapy. METHODS: In the present study, we first constructed and characterized a chimeric S15-specific monoclonal antibody (S15-4E6A). Then, the antitumor effectiveness and modulatory role of S15-4E6A in macrophages (mφs) were explored in vitro and in vivo. Finally, the underlying mechanism by which S15mAb inhibits LUAD was preliminarily explored. RESULTS: The results demonstrated the successful construction of S15-4E6A, and S15-4E6A exerted an efficacious tumor-inhibitory effect on LUAD cells and xenografts. S15-4E6A could promote M1-mφ polarization while inhibiting M2-mφ polarization, both in vitro and in vivo. CONCLUSIONS: S15-based immunotherapy that functions by modulating mφ polarization may be a promising strategy for the treatment of S15-positive LUAD.

PLOD2 increases resistance of gastric cancer cells to 5-fluorouracil by upregulating BCRP and inhibiting apoptosis.

Background: Gastric cancer (GC) is one of the most common cancers, and it is the third most common cause of cancer-related mortality worldwide. Fluorouracil (5-FU)-based chemotherapy is frequently used for the treatment of advanced GC. However, a substantial proportion of patients eventually experience refractory disease due to drug resistance. PLOD2 was reported to increase invasion and migration in several GC cell lines, but the roles of PLOD2 in chemoresistance are still unclear. The present study aimed to determine whether PLOD2 could confer 5-FU resistance in GC. Methods: The expression of PLOD2 in GC cell lines was assessed by Western blotting. The cells were transfected by lentiviral transduction. The IC50 values were determined by the CCK-8 assay. The migration and invasion abilities of cells were analyzed by the Transwell assay. The proportion of apoptotic cells was assessed by flow cytometry. The protein levels of P-gp (MDR1), MRP1, BCRP (ABCG2), Bax and Bcl2 were analyzed by Western blotting. Furthermore, tumor xenograft models in nude mice were established to test tumor growth and weight. Result: The knockdown of PLOD2 in BGC823 cells significantly decreased the IC50 values of 5-FU. It also contributed to reducing the cell migration and invasion and promoting the apoptosis of GC cells. The opposite results appeared in PLOD2-overexpressing MGC803 GC cells. In vivo experiments showed that the knockdown of PLOD2 increased the growth inhibition of transplanted tumors in nude mice in response to 5-FU. Our mechanistic studies revealed that PLOD2-overexpressing cells appear to be resistant to the therapeutic characteristics of 5-FU in GC cells by upregulating BCRP and that PLOD2 confers resistance to 5-FU-induced apoptosis in GC cells by affecting the expression of Bax and Bcl2. Conclusion: PLOD2 contributed to increasing resistance of gastric cancer cells to 5-fluorouracil by upregulating BCRP and inhibiting apoptosis.

Tricuspid leaflet resection in an open beating heart for the creation of a canine tricuspid regurgitation model.

OBJECTIVES: Outcomes of tricuspid valve replacement are poor, partly due to right heart remodelling. The research on its underlying mechanisms is hampered by a lack of animal models of tricuspid regurgitation (TR). Our objective was to create a reproducible and clinically compatible TR animal model to study right heart remodelling caused by TR. METHODS: Fourteen juvenile male Beagle dogs were divided randomly into an intervention group (n = 11) and a sham-operated control group (n = 3). The intervention group underwent thoracotomy and right atrial incision following superior and inferior vena caval occlusion. The anterior leaflet, together with the chordae, of the tricuspid valve was resected in eight dogs ('one leaflet' group), whereas both anterior and posterior leaflets, together with the chordae, were resected in three dogs ('two leaflets' group). The right atrium and chest were then closed. The control group underwent the same procedure, except leaflet resection. One dog from the 'two leaflets' group and one control dog were sacrificed and autopsy was performed at 12 months post-surgery. RESULTS: All dogs survived over the 1-year observation period postoperatively. TR grade IV occurred immediately postoperatively in the 'one leaflet' group, and TR grade IV plus in the 'two leaflets' group. The overall procedure lasted 30-40 min, and the mean time of vena caval occlusion was 87 ± 10 s. Central venous pressure increased from 6 ± 1.2 at baseline to 13 ± 1.7 mmHg (P < 0.01). By 12 months after TR creation, both in the 'one leaflet' group and in the 'two leaflets' group, the right atrial area, tricuspid annular diameter and right ventricular index of myocardial performance increased significantly, right ventricular fractional area change and tricuspid annular plane systolic excursion decreased significantly. Autopsy of the intervention dog revealed oedema, ascites and cirrhosis. CONCLUSIONS: Our surgical technique to create a TR animal model was reproducible with high success and survival rates. This animal model would prove suitable to investigate the mechanisms of right heart remodelling.

Downregulated protein expression of transcriptional activator ELK-1 in atrial myocardium of chronic AF patients.

BACKGROUND: The structural alterations in atrial myocytes appear to be an adaptive response of dedifferentiation during chronic atrial fibrillation (AF). Transcriptional activator ELK-1, one of the members of ETS family, has been shown to play an important role in regulating cell differentiation, It is reasonable to presume that ELK-1 participate in the molecular and structural remodeling by which AF is sustained. To prove this hypothesis, the expression of ELK-1 protein in chronically fibrillating atria compared to that in normal rhythmic atria was detected. METHODS: Right atrial myocardium were obtained from twenty-four patients undergoing valve replacement surgery, twelve patients were in chronic AF (>6 months), whereas the others were in sinus rhythm (SR). The protein expression level of ELK-1 was quantified by Western blot analysis, and the cellular localization and expression pattern of ELK-1 was examined by immunohistochemical staining and indirect immunofluorescence. RESULTS: Western blot analysis showed that the protein expression of ELK-1 was significantly reduced in the atrial tissue of chronic AF patients compared to that in the controls. Immunohistochemistry showed that ELK-1 immunostaining occurred in both cytosolic and nuclear compartments of atrial myocardium. Indirect immunofluorescence showed that the nuclei of normal rhythmic atrial cells were densely labeled, whereas the nuclei in chronically fibrillating atrial cells were very faintly labeled. CONCLUSIONS: Our results suggest that the downregulated expression of transcriptional activator ELK-1 may play an important role in the pathogenesis of AF.

Anti-diabetic effects of shubat in type 2 diabetic rats induced by combination of high-glucose-fat diet and low-dose streptozotocin.

ETHNOPHARMACOLOGICAL RELEVANCE: Shubat, probiotic fermented camel milk, has been used both as a drink with ethnic flavor and a medicine among Kazakh population for diabetic patients. Kazakh people have lower diabetic prevalence and impaired fasting glucose (IFG) than do other ethnic groups living in Xinjiang China, which might be related to the beneficial properties of shubat. We therefore prepared shubat in laboratory and tested anti-diabetic activity and evaluated its possible hypolipidemic and renoprotective effects in type 2 diabetic rats. MATERIALS AND METHODS: Type 2 diabetic rats were induced by an administration of high-glucose-fat diet for 6 weeks and an intraperitoneal injection of streptozotocin (STZ, 30mg/kg). Diabetic rats were divided randomly into four groups and treated for 28 days with sitagliptin (30mg/kg) or shubat (6.97×10(6) lactic acid bacteria+2.20×10(4) yeasts) CFU/mL, (6.97×10(7) lactic acid bacteria+2.20×10(5) yeasts) CFU/mL and (6.97×10(8) lactic acid bacteria+2.20×10(6) yeasts) CFU/mL. In addition, a normal control group and a diabetic control group were used for comparison. All drugs were given orally once daily 10mL/kg for 4 weeks. Fasting blood glucose (FBG) and body weight (BW) were measured before treatment and every week thereafter. Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol (HDL-c), serum creatinine (SCr), blood urea nitrogen (BUN), C-peptide, glycated hemoglobin (HbAlc), glucagon-like peptide-1 (GLP-1) levels and pancreas tissue sections were tested after 4 weeks. RESULTS: Shubat demonstrated positive hypoglycemic activity on FBG, HbAlc, C-peptide and GLP-1 levels, high dose shubat decreased FBG (P<0.01) and HbAlc (P<0.05), increased C-peptide (P<0.05) and GLP-1 (P<0.01), decreased serum TC, TG, LDL-c (P<0.05), increased HDL-c (P<0.01), and improved the reduction of body weight as well as decreased SCr and BUN levels (P<0.01) compared to diabetic controls. Histological analysis showed shubat protected the function of islets of type 2 diabetic rats. CONCLUSION: The results of this study indicate that shubat has significant hypoglycemic potential in T2D rats and may modulate lipid metabolism and protect renal function in the type 2 diabetic condition, which might be related to various probiotics acting through promoting the release of GLP-1 and improving the function of ß-cells.

PI3K/Akt signaling pathway modulates influenza virus induced mouse alveolar macrophage polarization to M1/M2b.

Macrophages polarized to M1 (pro-inflammation) or M2 (anti-inflammation) phenotypes in response to environmental signals. In this study, we examined the polarization of alveolar macrophage (AM), following induction by different influenza virus strains (ST169 (H1N1), ST602 (H3N2) and HKG9 (H9N2)). Macrophages from other tissues or cell line exert alternative responding pattern, and AM is necessary for investigating the respiratory system. AM polarized toward the M1 phenotype after 4 hours of infection by all three virus strains, and AM to presented M2b phenotype after 8 hours induction, and immunosuppressive phenotype after 24 hours of induction. Protein expression assay showed similar results as the gene expression analysis for phenotype verification. The ELISA assay showed that TNF-α secretion was up-regulated after 4 and 8 hours of infection by influenza viruses, and it returned to basal levels after 24 hours of infection. IL-10 expression was elevated after 8 and 24 hours of infection. Immunofluorescence showed that iNOS expression was up-regulated but not Arg1 expression. Influenza virus notably increased phospho-Akt but not phospho-Erk1/2 or phospho-p38, and the AM polarization pattern have been changed by LY294002 (PI3K inhibitor). In conclusion, our results demonstrate the dynamic polarization of AM induced by influenza viruses, and suggested that PI3K/Akt signaling pathway modulates AM polarization to M1/M2b.

Real-time three-dimensional transesophageal echocardiography to predict artificial chordae length for mitral valve repair.

BACKGROUND: Artificial chordae replacement is an effective technique for mitral valve repair, however, it is difficult to accurately determine the length of artificial chordae. This study aimed to assess the reliability and accuracy of real-time three-dimensional transesophageal echocardiography (TEE) to predict the length of artificial chordae preoperatively. METHODS: From December 2008 to December 2010, 48 patients with severe mitral regurgitation successfully underwent mitral valve repair using artificial chordae replacement. The patients were divided into a TEE pre-measurement group (n = 26) and a direct measurement group (n = 22), according to the method used to determine the length of artificial chordae. Cardiopulmonary bypass time, aortic cross-clamp time, and the recurrence rate of moderate or severe mitral regurgitation were compared between the two groups. RESULTS: There were no operative deaths in either group. The mean cardiopulmonary bypass time was 113.0 ± 18.7 min and 127.0 ± 28.9 min (p < 0.05), and the aortic cross-clamp time was 70.0 ± 16.6 min and 86.0 ± 20.7 min (p < 0.05) in the TEE pre-measurement group and direct measurement group, respectively. The difference between the pre-measured artificial chordal length and actual constructed artificial chordal length was not significant in the TEE pre-measurement group (p > 0.05). Although the difference in the incidence of moderate or severe mitral regurgitation between the two groups was not significant (p > 0.05), the incidence in the TEE pre-measurement group (3.8%) was lower than that in the direct measurement group (18.2%). CONCLUSIONS: Real-time three-dimensional transesophageal echocardiography can accurately predict the length of artificial chordae required for mitral valve repair, and shortens cardiopulmonary bypass time and aortic cross-clamp time while improving the results of mitral valve repair.

[Surgical correction of tetralogy of Fallot in adults over 40 years of age].

OBJECTIVE: To summarize the experience with surgical correction of tetralogy of Fallot in adults over 40 years of age. METHODS: From November 1985 to July 2008, 9 male and 11 female patients aged 41-53 years (mean 46.3±3.5 years) underwent total surgical correction for tetralogy of Fallot. Twelve patients had preoperative NYHA class III cardiac function. The common comorbidities included infective endocarditis, cerebral abscess, cerebral infarction, renal dysfunction, and tricuspid insufficiency. Surgical corrections were carried out at the anatomical or physiological level. RESULTS: Nineteen patients received right ventriculotomy to relieve right ventricular outflow obstruction and for ventricular septal defect closure, and 1 patient had Fontan operation. Two patients died after the surgery for heart failure and ventricular fibrillation. The average cardiopulmonary bypass time, aortic clamp time, and postoperative ventilation time was 142.9±36.3 min, 89.9±25.1 min, and 72.0±17.5 h, respectively. Postoperative low cardiac output syndrome occurred in 5 cases, septic shock in 1 case, secondary renal failure in 1 case, and bleeding in 2 cases. Echocardiography showed a significant postoperative reduction of the mean right ventricular outflow tract velocity from 4.29±1.36 m/s to 2.13±0.83 m/s (P<0.01); the right ventricular longitudinal dimension exhibited no significant changes postoperatively (57.1±6.7 mm vs 55.1±7.0 mm, P=0.65). CONCLUSIONS: Surgical correction of the tetralogy of Fallot in patients over 40 years is highly risky and requires appropriate management of cardiac failure, careful myocardial protection, and thorough intracardiac lesion correction to decrease surgical complications.

Surgical outcome of isolated total anomalous pulmonary venous connection in adults: a 14-year experience.

AIM OF THE STUDY: To investigate the surgical result of adult total anomalous pulmonary venous connection (TAPVC). METHODS: From March 1997 to March 2011, 12 adult cases of isolated TAPVC, with an average age of 24.9 ± 6.7 years (from 18 to 41 years), underwent surgical repair in our department. All patients suffered from right-sided volume overload with clinical manifestations varying from mild cyanosis to severe heart failure. RESULTS: According to Darling's classification, eight cases were classified as supracardiac type, four as cardiac type. Unobstructed connections were established between the left atrium and the pulmonary common vein in all patients with external cardiac approach in four supracardiac cases, and internal cardiac approach in four cardiac and three supracardiac cases, and Warden technique in one supracardiac patient. Concomitant operations included De Vega's tricuspid annuloplasty in six patients, patent arteriosus ductus closure in two. All patients survived the operation, and postoperative follow-up was 100% complete with a period ranging from 10 months to 14 years. NYHA grade decreased from 2.33 ± 0.49 to 1.08 ± 0.29 (p < 0.01). Three patients had postoperative tricuspid insufficiency. Five patients had cardiac arrhythmia, among two symptomatic cases; one controlled with medication, another received a successful radiofrequency ablation for incision-related atrial flutter. CONCLUSIONS: Surgical correction of isolated adult TAPVC can be carried out safely with acceptable long-term outcome. Postoperative tricuspid insufficiency and cardiac arrhythmias may have a negative long-term impact, which should be evaluated preoperatively and managed individually during surgery.

Matrine inhibits disturbed flow-enhanced migration via downregulation of ERK1/2-MLCK signaling vascular smooth muscle cells.

BACKGROUND: To investigate the effects of matrine on the vascular smooth muscle cell (VSMC) migration modulated by disturbed flow and their underlying molecular mechanisms in vitro. METHODS: Isolated rat aortic VSMCs were grown to confluence on 20- × 80-mm fibronectin-coated glass cover slides, and then, denuded zones were made at the position calculated to be the oscillating flow-reattachment zone and also in the downstream laminar flow region. VSMCs were treated with different doses of matrine (0, 10, 20, 30, and 40 mg/L), or PD98059 (30 µM), ML-7 (10 µM) combined with matrine (40 mg/L) for 30 minutes before and during the experiments. Then, the wounded monolayers were kept under static conditions or were subjected to laminar or disturbed flow for 21 hours or 10 hours. The VSMC migration was assessed by microscopic images. The extracellular signal-regulated kinase 1/2 (ERK1/2) and myosin light chain kinase (MLCK) proteins were determined by Western blot. RESULTS: Disturbed flow significantly increased phosphorylation of ERK1/2. Selective inhibition of ERK1/2 phosphorylation by inhibitor PD98059 and matrine significantly suppressed VSMC migration under disturbed flow. Disturbed flow significantly enhanced phosphorylation of MLCK, whereas both matrine and PD98059 inhibited the phosphorylation of MLCK under disturbed flow. The complete inhibition of MLCK phosphorylation using the selective MLCK inhibitor ML-7 significantly inhibited VSMC migration under disturbed flow. CONCLUSION: Matrine inhibits VSMC migration under disturbed flow, in part, by downregulation of ERK1/2-MLCK signaling pathway.

Determination of olprinone in human plasma utilizing liquid chromatography tandem mass spectrometry.

A sensitive and rapid method was developed for quantification of olprinone in human plasma utilizing liquid chromatography tandem mass spectrometry (LC-MS/MS). An aliquot of 1 mL plasma sample was extracted with ethyl acetate-dichloromethane. Separation of olprinone and the milrinone (internal standard, IS) from the interferences was achieved on a C(18) column followed by MS/MS detection. The analytes were monitored in the positive ionization mode. Multiple reaction monitoring using the transition of m/z 251 → m/z 155 and m/z 212 → m/z 140 was performed to quantify olprinone and IS, respectively. The method had a total chromatographic run time of 3 min and linear calibration curves over the concentration range of 0.5-60 ng/mL. The lower limit of quantification (LLOQ) was 0.5 ng/mL. The intra- and inter-day precisions were less than 16.3% for low QC level, and 7.1% for other QC levels, respectively. The intra- and inter-day relative errors were ranged between -12.2% and 3.7% for three QC concentration levels. The validated method was successfully applied to the quantification of olprinone concentration in human plasma after intravenous (i.v.) administration of olprinone at a constant rate of infusion of 2 µg/(kg min) for 5 min in order to evaluate the pharmacokinetics.

Effects of leukocyte depletion on cardiopulmonary protection and inflammation after valve surgery.

BACKGROUND: To evaluate the effects of leukocyte-depleting filtration on myocardial and pulmonary protection and the inflammatory response in patients undergoing valve surgery. METHODS: Fifty-two patients who underwent mitral valve or mitral and aortic valve replacement were randomized into two groups with or without a leukocyte-depleting filter during surgery. The filter was used from 10 minutes before the release of the aortic cross-clamp to the end of cardiopulmonary bypass. RESULTS: Total leukocyte and neutrophil counts showed a short-term reduction in patients undergoing leukocyte filtration, but there was no significant difference between the two groups during the study. Serum levels of cardiac troponin I were lower than that of the control group (p=0.030). Leukocyte depletion resulted in a significantly higher oxygenation index (p=0.002) and a lower respiratory index (p=0.003) compared with the control group. Serum levels of interleukin-8 were significantly elevated in patients undergoing leukocyte filtration compared with patients without leukocyte filtration (p=0.001). There were no statistically significant differences between the two groups with regards to the concentration of interleukin-6 and TNFα, or the duration of intensive care and hospital stay. CONCLUSIONS: Leukocyte depletion is associated with improved myocardial and lung protection but does not appear to attenuate the inflammatory response in valve surgery.

[Surgical treatment of 128 cases of constrictive pericarditis].

OBJECTIVE: To summarize the experience with surgical treatment of constrictive pericarditis. METHODS: A retrospective analysis of the post-operative clinical data was conducted in 128 surgical patients with chronic constrictive pericarditis. RESULTS: Two early postoperative death occurred in this group due to severe low cardiac output syndrome, with the mortality rate of 1.57%. The postoperative complications included low cardiac output syndrome (13.2%), arrhythmia (7.02%), acute renal insufficiency (3.9%), respiratory insufficiency (3.1%), wound infection (2.3%), postoperative chest bleeding (1.6%) and cerebral infarction (0.78%). Relapse occurred in one case because of incomplete pericardial resection. CONCLUSIONS: Constrictive pericarditis should be confirmed as soon as possible with actively surgery, and the extent of pericardial resection should be decided according to the individual conditions. Complete untethering of the diseased pericardium should be performed with active prevention of postoperative complications.

The short-term pulsatile ventricular assist device for postcardiotomy cardiogenic shock: a clinical trial in China.

Despite the recent advances in myocardial protection, surgical techniques, intra-aortic balloon therapy, and maximal pharmacological support, postoperative ventricular dysfunction continues to occur in 0.5-1.0% of all patients undergoing cardiac surgery. Ventricular assist device (VAD) is an important therapeutic adjunct in treating patients with profound ventricular dysfunction with postcardiotomy cardiogenic shock. The purpose of this report was to describe the clinical results with the China-made Luo-Ye VAD as a short-term circulatory support. From May 1998 to December 2006, 17 patients with postcardiotomy cardiogenic shock were supported by the Luo-Ye VAD. Of these patients, 10 were males and seven were females with a mean age of 49.6 years (range 36-68 years). All cases were supported by left VAD (LVAD). Mean duration of support was 46.3 h (range 13-113 h). A criteria of insertion was established to standardize implantation criteria. Among the 17 patients treated with LVAD, eight (47.1%) patients were weaned from support and seven (41.2%) patients were discharged from hospital. Ten (58.8%) patients died while on LVAD support (nine cases) or shortly after weaning (one case). The causes of death in the entire group were cardiac (40%), renal failure (20%), neurologic (10%), sepsis (10%), and multiple organ system failure (20%). The complications were represented by bleeding, renal failure, neurologic event, infection, ventricular arrhythmias, etc. The Luo-Ye VAD functioned well and proved to be useful in patients with postcardiotomy cardiogenic shock. It carries a less-postoperative anticoagulant and a low incidence of VAD-related complications. The survival rate was encouraging in our small cohort of patients.

The orthotopic left lung transplantation in rats: a valuable experimental model without using cuff technique.

Advances in the field of clinical lung transplantation must rely on observations made in animal models. In this study, we introduced a new procedure in the rat, orthotopic left lung transplantation without using the cuff technique, in which the donor pulmonary artery, pulmonary vein, and membranous parts of the bronchus were anastomosed continuously in the lumen using a mattress suture under a surgical microscope; meanwhile, a second, low-pressure perfusion through the pulmonary artery and turnover of the vascular stump were made, which also made the vessel anastomosis easy. Transplantations were completed in 68 rats (89.5%), the mean time used for suturing the left lung hilar structure was 23.5 +/- 4.6 min. All lung grafts had good life-sustaining function because of there being no cuff-induced granulation tissue in bronchial anastomotic stoma, and three out of 12 allografts were observed with active bronchiolitis obliterans lesions at 8 weeks after transplantation. This model is a simple, valuable experimental model for studying lung transplantation and new therapies for preventing acute or chronic rejection.

Surgical treatment of late tricuspid regurgitation after left cardiac valve replacement.

BACKGROUND: The development of late tricuspid regurgitation (TR) following left cardiac valve replacement is an important complication, as it is associated with a severe impairment of exercise capacity and a poor symptomatic outcome. The pathogenesis of this condition remains poorly defined. It is still a challenge in terms of its prevention, treatment and indications for surgical correction. AIMS: To investigate the possible pathogenesis and report the surgical results of the late TR after left cardiac valve replacement. METHODS: There were 56 patients with moderate to severe TR after left cardiac valve replacement, divided into normal prosthesis group (10 patients with normal prosthetic valve function) and dysfunctional prosthesis group (46 patients with prosthetic valve dysfunction). In the normal prosthesis group, 4 patients underwent mitral valve replacement (MVR) and 6 patients underwent combined mitral and aortic valve replacement (DVR). Patients in the dysfunctional prosthesis group included MVR in 36, aortic valve replacement (AVR) in 4 and DVR in 6, with bioprosthetic valve dysfunction occurring in 18, mechanical prosthetic valve obstruction in 22 and periprosthetic valve leakage in 6 patients. At the initial operation, 10 patients underwent DeVega's tricuspid annuloplasty and 46 patients' tricuspid valves were normal. At the second operation, the surgical treatment of TR included tricuspid valve replacement (TVR) in 9 and tricuspid annuloplasty in 47. RESULTS: Two patients died postoperatively giving a 3.6% hospital mortality. The 54 survivors were followed up for 6-132 months (mean of 79.4 months). Heart function improved significantly in 8 with TVR and in 40 with tricuspid annuloplasty. Echocardiography showed moderate TR in 5 and severe TR in 1 patient with tricuspid annuloplasty who need a further surgical treatment. CONCLUSION: Pulmonary hypertension, myocardial dysfunction, and atrial fibrillation might be responsible for the development of late TR after left cardiac valve replacement. Tricuspid annuloplasty, as the surgical method of first choice, resulted in improvement in 87% of patients with late TR after left cardiac valve replacement. TVR can also be safely applied to repair organic disease and the extremely dilated tricuspid valve annulus. If the TR area is more than 25cm(2), the TVR is recommended.

[Effects of biventricular support with Luo-Ye pump on hemodynamics during ischemic biventricular dysfunction].

To compare the effects on hemodynamics of univentricular support with that of biventricular support on experimental ischemic biventricular dysfunction so as to provide experimental basis for clinical usage of the Luo-Ye pump. Eight canines were placed with a left ventricular assist device (LVAD; left atrial-aorta bypass) and a right ventricular assist device (RVAD; right atrial-pulmonary artery bypass). Left anterior descending coronary artery(LAD) was ligated, three minutes later, the proximal of right coronary artery (RCA) was ligated to establish animal madel of acute ischemic biventricular dysfunction. First start the LVAD, and then RVAD was started five minutes later. The hemodynamic data were recorded including central venous pressure(CVP), cardiac output (CO), mean artery pressure(MAP), and pulmonary artery pressure(PAP) and pulmonary capillary wedge pressure (PCWP). During biventricular assist devices (BVAD) the hemodynamics were improved remarkably, MAP increased from 37.4 +/- 8.8 mmHg to 84.2 +/- 9.7 mmHg (P < 0.01) (the normal level), CO increased from 0.82 +/- 0.1 L/min to 1.33 +/- 0.12 L/min (P < 0.01), CVP decreased from 14.6 +/- 2.3 cmH2O to 4.2 +/- 1.5 cmH2O (P < 0.01), PCWP decreased significantly from 14 +/- 3.9 mmHg to 1.6 +/- 0.9 mmHg. These data suggest that LVAD during biventricular dysfunction could not improve the hemodynamics to normal level. Howere BVAD could increase CO and MAP to normal level and decrease heart work and myocardial oxygen consumption, which could help to improve myocardial metabolism and myocardial function. Therefore, BVAD is the first choice in treating severe biventricular dysfunction which was not respond to drug therapy and intra-aortic balloon pump (IABP).

[The delay time of pediatric LVAD of ECG-triggering mode].

Electrocardiac signal is one of the most important signals which is used to trigger ventricular assist device (VAD), and the delay time of VAD assistance is very important to get a satisfied result. Proper delay will give VAD relatively enough time to assist, avoiding left heart failure caused by the collision of the heart and VAD during systolic phase. This becomes much more important when the left atrium drainage is insufficient. The aim of our study is to set up an equation to calculate the delay time by RR interval. We try to set up an equation about RR and R-Ao like: R-Ao = A x (RR)n + B(A and B are constant). RR represents the RR interval and R-Ao represents the duration of the period between the peak point of QRS and the point of aortic valve closing; First, calculate RR according to weighting average method, and then, calculate the anticipant R-Ao according to the before-mentioned equation. After adjustment, R-Ao will be used as assistance delay time. R-R interval was measured in 457 selected pediatric patients who were undergiong left heart catheterization and who did not have arrhythmias. From the ECG recording during catheterization, R-R interval was measured while R-Ao was obtained from aortic pressure wave chart; Plot graphs with R-Ao as dependent variable and (RR)n as independent variable; find out correlating model and calculate the arguments A and B of R-Ao = A x (RR)n + B. The results showed that the relation between (RR)1/3 and R-Ao is the most significant, the relation coefficient is 0.733, the regress coefficient is -0.182 (P < 0.001) and the interception is 1.070. This means that R-Ao = (-0.182) (RR) 1/3 + 1.070. The likelyhood degrees of different sections differ markedly. When heart rate is less than 120 beats per min. The relation argument is about 0.733 while 0.45 when heart rate is more than 120 beats per min, Therefore, we can use the equation R-Ao = (-0.182) (RR)1/3 + 1.070 to calculate R-Ao when heart rate is less than 120 beats per min.