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ABSTRACT: OBJECTIVE: To evaluate the long-term effects and analyze causes of non-response to cardiac resynchronization therapy (CRT) in heart failure (HF) patients with permanent atrial fibrillation (AF). METHODS: Thirty-three patients with HF and AF [29 men, mean age (61 ± 10) years, NYHA class III or IV, left ventricular ejection fraction (LVEF) ≤ 35%, QRS ≥ 120 ms in 31 cases] underwent bi-ventricular pacing (n = 26) or bi-ventricular pacing and atrioventricular node ablation (AVN-ablation, n = 7) were included in this study. Non-response was defined: the increase of left ventricular ejection fraction (LVEF) was less than 15%. Patients were followed-up for 4 years. RESULTS: Six patients died during follow up. Non-responder to CRT was observed in 6 out of 27 survived patients (22.22%). Six out of 7 patients underwent AVN-ablation were in responder group and 1 in non-responder group. Comparing with responder group, the baseline LVEF was significantly higher (37% vs. 32%, P = 0.003), and the history of HF was significantly longer (6.3 years vs. 4.1 years, P = 0.039), pulmonary artery pressure was significantly higher (53 vs. 32 mm Hg, P = 0.027), bi-ventricular pacing percentage (BIVP%) was significantly lower (75.86% vs. 91.73%, P = 0.007) in non-responder group. CONCLUSIONS: Higher LVEF, longer HF history, higher pulmonary artery pressure and lower BIVP% are factors linked with non-responses to CRT in this patient cohort. CRT plus AVN-ablation is associated with high response rate to CRT in this patient cohort.
Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 09/2012; 40(9):757-761.
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ABSTRACT: Tumor necrosis factor-α (TNF-α) is known to induce changes in endothelial cell morphology and permeability. The aim of this study is to determine the underlying signaling mechanisms involved in these responses.
Cultured human umbilical vein endothelial cells (HUVECs) were exposed to TNF-α, and HUVEC cytoskeletal changes were evaluated by observing fluorescence of F-actin following ligation with labeled antibodies. Endothelial permeability was detected by measuring the flux of horseradish peroxidase (HRP)-albumin across the EC monolayers. To explore the signaling pathways behind TNF-α-induced changes in HUVEC morphology and permeability, HUVECs were treated with either the Rho GTPase inhibitor Y27632 or the mitogen-activated protein kinases (MAPK) inhibitors PD98059 and SB203580 before TNF-α administration. To further elucidate possible involvement of the RhoA and ERK pathways in TNF-α-induced HUVEC changes, retrovirus-carried recombinant dominant-negative forms and constitutive-activative forms of RhoA, namely T19NRhoA and Q63LRhoA, were pre-infected into HUVECs prior to TNF-α exposure.
TNF-α induced F-actin cytoskeleton rearrangement and increased HUVEC permeability in a dose and time-dependent manner. The maximal increase in the HRP-BSA flux (40 ng/ml) was seen in cells exposed to TNF-α at 100 ng/ml after 2 h. Preconditioning of HUVEC monolayer with Y27632 or PD98059 significantly reduced TNF-α induced permeability increase (HRP concentration from 40 ng/ml decreased to 12.5 ng/ml, P < 0.05) and F-actin cytoskeleton rearrangement, HUVEC pre-infection with activated forms of Q63LRhoA increased HUVEC permeability and upregulated pERK compared to GFP infection, while HUVEC pre-infection with inhibited forms of T19NRhoA attenuated the effects of TNF-α on HUVEC permeability.
These results indicate that TNF-α-induced EC barrier dysfunction and morphological changes of the F-actin via activating RhoA-ERK/MAPK signal pathway.
Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 06/2011; 39(6):531-7.
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ABSTRACT: To observe the incidence and explore the potential factors of nonresponse to cardiac resynchronization therapy(CRT)in patients with severe chronic congestive heart failure.
CRT was performed in 119 patients with NYHA function class III-IV and left ventricular ejection fraction ≤ 35% [96 men and 23 women, age (60.5 ± 11.3) years].
Seven patients died for different reasons between 1 - 6 months post CRT and clinical and echocardiographic (Echo) data at 6 months post CRT were analyzed from the remaining 112 patients. The incidence of nonresponse to CRT was 28.57%. Compared to the response group, complete right bundle branch block, longer course of congestive heart failure, higher pulmonary systolic pressure and serum creatinine level and non-optimal target vessels positioning of the left ventricle lead (the great cardiac vein and the middle cardiac vein) were the independent predictors for nonresponse after CRT (all P < 0.05). Compared with nonresponse group, the dosages of digoxin and diuretics used for heart failure were significantly reduced in response group (P < 0.01).
The incidence of nonresponse after CRT was 28.57% in this patient cohort. Higher pulmonary systolic pressure and serum creatinine level and non-optimal target vessels positioning of the left ventricle lead (the great cardiac vein and the middle cardiac vein) were the independent predictors for nonresponse after CRT.
Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 10/2010; 38(10):895-900.
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ABSTRACT: The purpose of this study was to analyze the anatomy variation of coronary vein system in patients with ischemic heart disease (IHD) and non-ischemic heart disease (NIHD).
Forty-one patients with IHD and 87 patients with NIHD [101 men, mean age (63.5 +/- 10.6) years] were included in this study.
Coronary sinuses were successfully cannulated and venographies were obtained in 127 cases. Transvenous LV pacing leads were successfully placed in optimal coronary vein in 123 cases (96.09%). The majority (76.38%) patients had at least one or more vessel abnormalities (thinness, stenosis, tortuousity, lack of lateral marginal vein or postero-lateral vein). The incidence of thin and tortuousity was significantly higher in lateral marginal vein than that in postero-lateral vein (P < 0.05-0.01). The incidence of lack of postero-lateral marginal vein was more frequent than the lack of lateral vein (P < 0.05). The rate of abnormality in both vessels was 25.2%. Incidence of vein lack in male was more frequent than in female (P < 0.05). The thin and tortuousity of vessels in female were more frequent than in male (P < 0.05). The incidence of thin and tortuousity of postero-lateral and abnormality of both vessels was significantly higher in IHD than in NIHD patients (P < 0.05). All coronary sinus myocardial bridges occurred in NIHD. Stenoses of left anterior descending (LAD) and left circumflex (LCX) were mostly associated with abnormality of lateral vessels.
The anatomic variations of lateral and postero-lateral coronary vein were more frequent in this patient cohort. Vein lack in male was more frequent and the thin and tortuousity of vessels were less in male than in female patients. The ratio of vessel abnormality is higher in patients with IHD. Coronary arteries stenosis and position of infarction are associated with anatomic variations of coronary vein system.
Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 06/2010; 38(6):522-6.
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ABSTRACT: Long-term efficacy and safety of tacrolimus-eluting stent (Janus) for treatment of coronary artery disease in percutaneous coronary interventions (PCI) "real world" is uncertain. The aim of this study was to evaluate the efficacy and safety of Janus stent for treating coronary heart disease in PCI daily practice, the safety of 4-month clopidogrel therapy after Janus stent implantation and the feasibility for treating patients with acute myocardial infarction (AMI) for first time.
From February 20, 2006 to August 26, 2006, a total of 200 patients were enrolled and randomly assigned to receive either Janus stent (n = 100) or bare metal stent (Tecnic Carbostent, n = 100). All patients were administered with clopidogrel for 4 months and aspirin for life long after stenting.
Baseline clinical and angiographic characteristics were comparable between the two groups. AMI was present in 37% of patients with Janus and 36% with Tecnic Carbostent. At an average of 246-day follow-up, major adverse cardiac events (MACE) was 6% with the Janus stent and 15% with the Tecnic Carbostent (P = 0.038). Primary events included 1 cardiac death, 1 myocardial infarction (MI) due to subacute stent thrombosis and 13 target lesion revascularizations (TLR) due to restenosis in patients with Tecnic Carbostent and 6 TLR due to restenosis in patients with Janus stent. Although all patients had discontinued clopidogrel for an average of 126 days, there was no additional thrombotic event in the two groups.
Janus stent is efficient in reducing MACE compared with Tecnic Carbostent at an average of 8-month follow-up. Discontinuation of clopidogrel at 4 months after PCI is safe for patients with Janus stent, including AMI patients. Long-term efficacy of Janus stent in reducing restenosis requires further study.
Chinese medical journal 05/2007; 120(7):552-6. · 0.86 Impact Factor
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ABSTRACT: To investigate the role and mechanism of Rac1 protein in the process of the human umbilical vein endothelial cell (HUVEC) senescence, we used hypoxia as a model for modulating HUVECs entering replicative senescence in vitro. Premature senescence of HUVECs was evidenced by detecting the SA-beta-Gal activity and PAI-1 expression. Meanwhile, cell cycle distribution and cell proliferation rate were investigated by flow cytometry assay and BrdU staining. The results indicated that the HUVECs became enlarged and flattened, both SA-beta-Gal activity and PAI-1 expression increased obviously, while cell proliferation was inhibited and G(1) phase cell cycle arresting occurred when HUVECs were treated with continued hypoxia for 96 h. Accompanied with these changes, the expression of activated Rac1 increased obviously in cells after hypoxia. All these observations suggested that endothelial senescence could be induced by continued hypoxia and it might correlate with the activity of Rac1. To further define the relationship between Rac1 and HUVEC senescence, HUVECs were transiently infected with the constitutively active form of Rac1 (V12Rac1) or dominant negative form of Rac1 (N17Rac1) using retrovirus vector pLNCX-V12Rac1 or pLNCX-N17Rac1. We observed the changes of these three kinds of HUVECs (HUVECs, N17Rac1-HUVECs, V12Rac1-HUVECs) after hypoxia for 48 h and 96 h, the expression and localization of serum response factor (SRF), which is one of the downstream signal molecules of Rac1, were also investigated. The results obtained indicated that after continued hypoxia for 48 h, HUVECs infected by V12Rac1 showed obvious senescence accompanied with SA-beta-Gal activation, PAI-1 expression increase, G(1) phase arrest and cell proliferation inhibition which were similar to HUVECs after continued 96-hour hypoxia treatment, while the senescence of HUVECs infected by N17Rac1 was significantly inhibited even if the cells were exposed to hypoxia for more than 96 h. All the results identified that the activation of Rac1 might accelerate HUVEC senescence induced by hypoxia and that inactivation of Rac1 could partly block the cell senescence. To further investigate the mechanism of HUVEC senescence induced by Rac1, we detected the expression of total SRF (tSRF) and nuclear SRF (nSRF) in these three kinds of HUVECs by immunofluorescent analysis and Western blot assay after hypoxia. The results showed that the expression of nSRF decreased obviously and the nuclear translocation of SRF was inhibited in HUVECs infected by V12Rac1 compared with those in the normal HUVECs. In contrast, the expression of nSRF increased obviously in the HUVECs infected by N17Rac1. These results suggest that activation of Rac1 accelerates endothelial cell senescence and inhibition of Rac1 activity prevents HUVECs from entering senescence induced by hypoxia, while the nuclear translocation of SRF regulated by Rac1 might play an important role in the process of senescence.
Sheng li xue bao: [Acta physiologica Sinica] 07/2006; 58(3):207-16.
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ABSTRACT: To evaluate the effects of cilostazol on long-term clinical outcomes in patients underwent coronary stent implantation.
One hundred patients who underwent coronary stenting were randomly assigned to receive cilostazol 200 mg/d for 6 months (n = 50) or ticlopidine 500 mg/d for 1 month (n = 50). Aspirin 100 mg/d was administrated concomitantly with cilostazol or ticlopidine. Angiographic follow-up was carried out at 6 months and clinical follow-up for 3 years after stenting.
Angiographic restenosis occurred in 5 of 34 patients (14.7%) in cilostazol group and 10 of 37 patients (27.0%) in ticlopidine group (P = 0.204). At the end of three-year follow-up, the incidence of major adverse cardiac and cerebral events (MACCE) was greatly reduced in cilostazol group compared with ticlopidine group (16% vs 36%, P = 0.023). Changes of Seattle angina questionnaire (SAQ) physical limitation score showed no significant difference between two groups (21.8 +/- 12.3 vs 16.8 +/- 15.9, P = 0.086). However, changes the improvement of angina frequency score much more was significant in cilostazol group (22.6 +/- 12.7) compared with that in ticlopidine group (16.1 +/- 13.3, P = 0.015). Recurrent angina occurred in 38% of patients in cilostazol group and 54% in ticlopidine group, respectively (P = 0.105). Readmission due to cardiac and cerebral vascular diseases was much less in cilostazol group than that in ticlopidine group (20% vs 40%, P = 0.029).
Cilostazol treatment significantly reduced MACCE and improved the quality of life pf patients in three-year clinical follow-up after coronary stenting.
Zhonghua nei ke za zhi [Chinese journal of internal medicine] 12/2005; 44(11):814-7.
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ABSTRACT: RhoA is one of the main members of RhoGTPase family involved in cell morphology, smooth muscle contraction, cytoskeletal microfilaments and stress fiber formation. It has been demonstrated that RhoA modulates endothelial cell permeability by its effect on F-actin rearrangement, but the molecular mechanism of rearrangement of actin cytoskeleton remains unclear. Recent studies prove that RhoA/Rho kinase regulates smooth muscle specific actin dynamics by activating serum response factor (SRF)-dependent transcription. To further investigate the molecular mechanism of the rearrangement of vascular endothelial cell actin cytoskeleton, we explored the relationship between the activation of SRF and F-actin rearrangement induced by RhoA in human umbilical vein endothelial cells (HUVECs). HUVECs were infected with the constitutively active forms of RhoA (Q63LRhoA) or the dominant negative forms of RhoA(T19NRhoA) using retrovirus vector pLNCX-Q63LRhoA or pLNCX-T19NRhoA, the positive clone was obtained by G418 selection. The expression and distribution of SRF in normal and infected cells were evaluated by immunohistochemistry and Western blot in complete medium and in serum-free medium. The effect of F-actin polymerization was detected by Rhodamine-Phalloidine staining. Infection of PLNCX-Q63LRhoA induced F-actin rearrangement and stress fiber formation in HUVECs, as well as enhanced the expression of SRF in the nuclei. In contrast, the cells infected with T19NRhoA showed no distinct changes. With serum deprivation, the expression of SRF increased obviously in both normal and infected HUVECs, but the subcellular localization of SRF was evidently different. In HUVECs, the localization of SRF was in the nuclei after 3 d with serum deprivation, but it was redistributed outside the nuclei after 5 d with serum deprivation. In cells infected with Q63LRhoA, the immunolocalization of SRF was always in the nuclei compared with HUVECs infected with T19NRhoA, which was almost always localized in the cytoplasm. In HUVECs, the rearrangement of F-actin and formation of stress fiber increased after 3 d with serum deprivation, but appeared decreased and unpolymerized after 5 d with serum deprivation. The polymerization of F-actin and the formation of stress fiber in HUVECs infected with Q63LRhoA kept during the period of serum-free culture, whereas the rearrangement of F-actin in cells infected with T19NRhoA was not found. These results suggest that RhoA influences endothelial F-actin rearrangement in part by regulating the expression and subcellular localization of SRF.
Sheng li xue bao: [Acta physiologica Sinica] 07/2005; 57(3):295-302.
