Knockout of the tumor necrosis factor a receptor 1 gene can up-regulate erythropoietin receptor during myocardial ischemia-reperfusion injury in mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Tumor necrosis factor a receptor 1 (TNFalphaR1) plays an important role in the signal pathway of apoptosis. The objective of this study was to investigate the effects of TNFalphaR1 knockout on the up-regulation of erythropoietin receptor (Epo-R) and the coordinated anti-apoptosis functions during myocardial ischemia-reperfusion injury in mice.</p><p><b>METHODS</b>The ischemia-reperfusion injury model for cardiomyocytes was performed by ligating the left circumflex branch artery of TNFalphaR1 knockout (P55(-/-)) C17 B6 mice, as well as wild-type (P55(+/+)) C17 B6 mice. Triphenyltetrazolium chloride (TTC) staining was performed to observe the damaged area of the heart. TUNEL staining and DNA fragmentation were used to identify apoptosis. Mitochondrial Bcl-2 and Bax as well as expression of Epo-R and its downstream genes (Jak-2, stat-5, Akt, IkB-alpha, HIF-1alpha) were measured by Western blotting. The gene knockout mice were assigned into those undergoing the apoptosis surgical model group (KO group), and those subjected to sham operation (KOs group). Similarly, wild-type mice were either exposed to the surgical model (WT group) or subject to a sham operation (WTs group).</p><p><b>RESULTS</b>The myocardial damage ratio of the wild-type group after the operation was significantly higher than that of the knockout group, (50.5 +/- 6.4)% vs (36.9 +/- 6.9)%, P < 0.01. Similarly, TUNEL positive ratio of the wild-type group was significantly higher than that of the knockout group, (63.1 +/- 5.6)% vs (42.1 +/- 4.7)%, P < 0.01. The gray value ratios of Epo-R, Jak-2, stat-5, Akt, IkB-alpha, HIF-1 and mitochondrial Bcl-2 in the KO group were significantly higher than those of the WT group, P < 0.05; however, mitochondrial Bax was significantly lower than that of the WT group significantly (P < 0.05).</p><p><b>CONCLUSIONS</b>Using the ischemia-reperfusion injury model in mice, cardiomyocytes of TNFalphaR1 knockouts exhibited anti-apoptotic characteristics. This information could be used to coordinate the prevention of myocardial apoptosis by up-regulating and activating the Epo-R pathway.</p>

Mechanism and re-ablation strategy for postablation atrial tachyarrhythmia in atrial fibrillation patients / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the mechanism and re-ablation strategy of recurrent atrial tachyarrhythmia (ATA) following circumferential ablation of pulmonary veins (PV) in patients with atrial fibrillation (AF).</p><p><b>METHODS</b>Fifteen patients with recurrent ATA following first AF ablation procedure were included in this study. Under CARTO guidance, PVs were remapped and ablated subsequently for relapse of left atrium to PV conduction. The whole atrium was then remapped and individualized ablation was made to eliminate inducible ATA.</p><p><b>RESULTS</b>Left atrium to PV conduction relapses were evidenced in 14 patients. After re-ablation, there were no inducible ATA in 9 patients, inducible left atrial macro-reentry tachycardia in 3 patients and all were terminated by further linear ablation on the roof and left atrial isthmus, inducible atrial focal tachycardia from left atrial isthmus in 1 patient and was eliminated after additional focal ablation, inducible right atrial macro-reentry tachycardia in 2 patients and were eliminated by right isthmus linear ablation. During 1 - 16 (5.5 +/- 4.4) months follow-up, ATA was disappeared in 13 patients and reduced in another 2 patients.</p><p><b>CONCLUSIONS</b>Relapse of left atrium to PV conduction is one of the main mechanisms for postablation ATA in patients with AF. Atrial macro-reentry tachycardia and focal atrial tachycardia were less common mechanisms for postablation ATA. Re-ablation focused on closing the PV gaps and additional individualized focal and lineal ablation strategies were helpful for treating postablation ATA in AF patients.</p>

A prospective, randomized, controlled trial of autologous mesenchymal stem cells transplantation for dilated cardiomyopathy / 中华心血管病杂志

<p><b>OBJECTIVE</b>Recent experimental and clinical observations have suggested that cell transplantation could be of therapeutic value for the treatment of heart failure. This study was performed to explore the efficacy and safety of intracoronary autologous mesenchymal stem cells (MSCs) transplantation for treating patients with idiopathic dilated cardiomyopathy.</p><p><b>METHOD</b>Twenty-four consecutive patients with idiopathic dilated cardiomyopathy received standard drug therapy were randomly divided into intracoronary injection of autologous mesenchymal stem cells (treated, n = 12) or saline (control, n = 12) groups. Serum IL-6, TNF-alpha and CRP, plasma brain natriuretic peptides (BNP) were determined and echocardiography, Holter electrocardiogram monitoring and six minutes walk test were performed at baseline, 3 and 6 months post injection.</p><p><b>RESULTS</b>IL-6, TNF-alpha and CRP remained unchanged after MSCs transplantation. Plasma BNP levels at 3 months and 6 months post MSCs injection were significantly higher than that of pre-injection (378.10 +/- 147.47, 420.40 +/- 148.50 vs. 292.40 +/- 148.54 ng/L, respectively, P < 0.05) but were significantly lower than that in control group at comparable time points (3 months: 378.10 +/- 147.47 vs. 473.10 +/- 106.31 ng/L; 6 months: 420.40 +/- 148.50 vs. 544.60 +/- 93.11 ng/L, P < 0.05). Six-minute-walking distance significantly increased at 6 months after MSCs injection compared with pre-injection level and which is also higher than that in control patients (519.00 +/- 43.28 vs. 396.33 +/- 42.19 and 464.00 +/- 76.5 m, respectively, P < 0.05). Left ventricular ejection fraction and LVEDd remained unchanged post MSCs injection. No malignant arrhythmias and severe side effects could be observed around transplantation and during six months follow-up. Survival was similar between the two groups during six months follow-up.</p><p><b>CONCLUSION</b>Percutaneous coronary autologous mesenchymal stem cells transplantation can attenuate the increase of plasma BNP, increase six-minute-walking capacity in patients with idiopathic dilated cardiomyopathy.</p>

Human bone marrow-derived mesenchymal stem cells transplanted into damaged rabbit heart to improve heart function / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

<p><b>OBJECTIVE</b>The present study was designed to test whether transplantation of human bone marrow-derived mesenchymal stem cells (hMSCs) in New Zealand rabbits with myocardial infarction can improve heart function; and whether engrafted donor cells can survive and transdifferentiated into cardiomyocytes.</p><p><b>METHODS</b>Twenty milliliters bone marrow was obtained from healthy men by bone biopsy. A gradient centrifugation method was used to separate bone marrow cells (BMCs) and red blood cells. BMCs were incubated for 48 h and then washed with phosphate-buffered saline (PBS). The culture medium was changed twice a week for 28 d. Finally, hematopoietic cells were washed away to leave only MSCs. Human MSCs (hMSCs) were premarked by BrdU 72 h before the transplantation. Thirty-four New Zealand rabbits were randomly divided into myocardial infarction (MI) control group and cell treated group, which received hMSCs (MI+MSCs) through intramyocardial injection, while the control group received the same volume of PBS. Myocardial infarction was induced by ligation of the left coronary artery. Cell treated rabbits were treated with 5 x 10(6) MSCs transplanted into the infarcted region after ligation of the coronary artery for 1 h, and the control group received the same volume of PBS. Cyclosporin A (oral solution; 10 mg/kg) was provided alone, 24 h before surgery and once a day after MI for 4 weeks. Echocardiography was measured in each group before the surgery and 4 weeks after the surgery to test heart function change. The hearts were harvested for HE staining and immunohistochemical studies after MI and cell transplantation for 4 weeks.</p><p><b>RESULTS</b>Our data showed that cardiac function was significantly improved by hMSC transplantation in rabbit infarcted hearts 4 weeks after MI (ejection fraction: 0.695+/-0.038 in the cell treated group (n=12) versus 0.554+/-0.065 in the control group (n=13) (P<0.05). Surviving hMSCs were identified by BrdU positive spots in infarcted region and transdifferentiated into cardiomyocytes characterized with a positive cardiac phenotype: troponin I.</p><p><b>CONCLUSION</b>Transplantation of hMSCs could transdifferentiate into cardiomyocytes and regenerate vascular structures, contributing to functional improvement.</p>