Evaluation of Safety and Efficacy of Qinming8631 DR Implantable Cardiac Pacemaker in Chinese Patients: A Prospective, Multicenter, Randomized Controlled Trial of the First Domestically Developed Pacemaker of China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>High cost of imported pacemakers is a main obstacle for Chinese patients suffering from bradyarrhythmia, and a domestically developed pacemaker will help lower the burden. This study aimed to evaluate the safety and efficacy of Qinming8631 DR (Qinming Medical, Baoji, China), the first domestically developed dual-chamber pacemaker of China, compared with a commercially available pacemaker Talos DR (Biotronik, Berlin, Germany) in Chinese patients.</p><p><b>METHODS</b>A prospective randomized trial was conducted at 14 centers in China. Participants were randomized into trial (Qinming8631 DR) and control (Talos DR) groups. Parameters of the pacing systems were collected immediately after device implantation and during follow-ups. The effective pacing rate at 6-month follow-up was recorded as the primary end point. Electrical properties, magnet response, single- and double-pole polarity conversion, rate response function, and adverse events of the pacing system were analyzed. The Cochran-Mantel-Haenszel Chi-square test, paired t-test, and Wilcoxon signed-rank test were used for measuring primary qualitative outcomes and comparing normally and abnormally distributed measurement data.</p><p><b>RESULTS</b>A total of 225 patients with a diagnosis of bradyarrhythmia and eligible for this study were randomly enrolled into the trial (n = 113) and control (n = 112) groups. They underwent successful pacemaker implantation with acceptable postoperative pacing threshold and sensitivity. Effective pacing rates of trial and control groups were comparable both in the full analysis set and the per protocol set (81.4% vs. 79.5%, P = 0.712 and 95.4% vs. 89.5%, P = 0.143, respectively). In both data sets, noninferiority of the trial group was above the predefined noninferiority limit(-9.5%).</p><p><b>CONCLUSIONS</b>This study established the noninferiority of Qinming8631 DR to Talos DR. The safety and efficacy of Qinming8631 DR pacemaker were comparable to those of Talos DR in treating patients with cardiac bradyarrhythmia.</p>

Effects of different pacing algorithms on cumulative ventricular pacing proportion in patients with pacemakers / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It is well known that increased cumulative ventricular pacing proportion (CumVP%) is one of the most important causes for adverse cardiovascular events. Therefore, how to reduce CumVP% has been a treatment issue in recent years. This study aimed to investigate the effects of different pacing algorithms on CumVP% in patients with pacemakers.</p><p><b>METHODS</b>Pacemakers with three pacing algorithms, i.e., conventional dual chamber rate adaptive pacing (DDDR), search atrioventricular conduction plus (SAV+) and managed ventricular pacing (MVP), were implanted in 42 patients including 41 with bradycardia arrhythmias and one with ventricular tachycardia. Pacemakers were programmed to work in conventional DDDR, SAV+ and MVP during the follow-up periods of the first, the second and the third month. In each pacing algorithm, the time percentages of four pacing and sense status including atrial sense-ventricular sense (AS-VS), atrial sense-ventricular pacing (AS-VP), atrial pacing-ventricular sense (AP-VS) and atrial pacing-ventricular pacing (AP-VP) were calculated. Cumulative ventricular pacing proportions were compared in the three pacing algorithms in the first, the second and the third month postoperatively.</p><p><b>RESULTS</b>In the DDDR algorithm AS-VS, AS-VP, AP-VS and AP-VP were 2.4%, 52.3%, 2.5% and 42.8% respectively, while in SAV+ they were 19.3%, 34.9%, 33.9% and 12.0%, in MVP they were 38.9%, 13.2%, 41.6% and 6.4%. In the above the DDDR, SAV+ and MVP algorithms, cumulative ventricular pacing proportions were 95.1%, 46.9% and 19.6%, respectively (P < 0.05) and the percentages of CumVP% < 40% in patients were 0, 23.8% and 95.2.0% (P < 0.05).</p><p><b>CONCLUSIONS</b>Compared with the conventional DDDR algorithm, both SAV+ and MVP significantly reduced the CumVP%, especially the MVP algorithm. Patients may benefit from MVP algorithm due to reduced CumVP%.</p>

Overexpression of connexin 45 in rat mesenchymal stem cells improves the function as cardiac biological pacemakers / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Extensive research toward creating a biological pacemaker by enhancement of inward depolarizing current has been performed. However, studies have mainly focused on inducing spontaneous activity and have not adequately addressed ways to improve pacemaker function. In this study we attempted to improve pacemaker function by altering connexin expression in rat mesenchymal stem cells (MSCs) to a phenotype similar to native sinus node pacemaker cells.</p><p><b>METHODS</b>To generate a biological pacemaker, MSCs were transduced with a cardiac pacemaker gene-hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4), via transfection with a lentiviral vector. Funny current (I(f)) in HCN4(+) MSCs was recorded by voltage-clamp. Overexpression of connexin 45 (gene Gja7) in MSCs was achieved by transfection with the plasmid pDsRED2-N1-Gja7-RFP. Double-immunolabelling with anti-connexin 43 and anti-connexin 45 antibodies were used to identify the gap junction channels. The effects of the genetically modified MSCs on cardiomyocyte excitability were determined in MSCs cocultured with neonatal rat ventricular myocytes. Spontaneous action potentials of neonatal rat ventricular myocytes were recorded by current-clamp.</p><p><b>RESULTS</b>High level time- and voltage-dependent inward hyperpolarization current that was sensitive to 4 mmol/L Cs(+) was detected in HCN4(+) MSCs, confirming that HCN4 acted as I(f) channels in MSCs. Connexin 43 and connexin 45 were simultaneously detected in CX45(+) MSCs. Beating frequency was (82 +/- 8) beats per minute (n = 5) in myocytes cocultured with non-transfected control MSCs, versus (129 +/- 11) beats per minute (n = 5) in myocytes cocultured with HCN4(+) MSCs. Myocytes cocultured with MSCs cotransfected with HCN4 and connexin 45 had the highest beating frequency at (147 +/- 9) beats per minute (n = 5).</p><p><b>CONCLUSION</b>These findings demonstrate that overexpression of connexin 45 and subsequent formation of heteromeric connexin 45/connexin 43 gap junction channels in HCN4 expressing MSCs can improve their function as cardiac biological pacemakers in vitro.</p>

The study on the diagnostic value of pregnancy-associated plasma protein-A in acute coronary syndrome patients / 中国医师进修杂志

Objective To investigate the diagnostic value of pregnancy-associated plasma protein-A (PAPP-A) in acute coronary syndrome (ACS) patients. Methods Forty-nine cTnI-negative patients with coronary artery disease who were documented by angiography [31 cases with ACS,18 cases with stable angina (SAP)], and 28 healthy persons were selected as controls. PAPP-A and hs-CRP were analysed with enzyme-linked immunosorbent assay (ELISA). Results Circulating PAPP-A and ha-CRP levels were significandy higher in patients with ACS than those in patients with SAP and controls (P < 0.05). PAPP-A threshold value of 2.79 μg/ml identified patients who had ACS with a sensitivity of 81.0% and a specificity of 84.6%. PAPP-A levels were correlated with hs-CRP levels in patients with ACS (r = 0.418, P < 0.01). Conclusion PAPP-A is a strong candidate marker of ACS, especially to eTnl-negative patients.

Effects of docosahexaenoic acid on action potential and transient outward potassium current on ventricular myocytes of Sprague-Dawley rat / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of docosahexaenoic acid (DHA) on action potential (AP) and transient outward potassium current (I(to)) on ventricular myocytes of Sprague-Dawley rat.</p><p><b>METHODS</b>Calcium-tolerant ventricular myocytes were isolated by enzyme digestion. The changes of AP and I(to) with increasing DHA at concentrations of 0, 10, 20, 40, 60, 80, 100, 120 and 200 micromol/L were recorded by whole-cell patch clamp configuration.</p><p><b>RESULTS</b>(1) Action potential durations (APDs) were not affected by DHA at concentrations from 0 micromol/L to 30 micromol/L, while APDs were gradually prolonged in proportion with increasing DHA concentrations from 30 micromol/L to 200 micromol/L within 5 minutes and remained stable thereafter. APD(25), APD(50) and APD(75) were (7.7 +/- 2.0) ms, (21.2 +/- 3.5) ms, and (100.1 +/- 9.8) ms respectively at 100 micromol/L DHA. APD(25), APD(50), and APD(75) were (15.2 +/- 4.0) ms, (45.7 +/- 6.8) ms, and (215.6 +/- 15.7) ms respectively at 200 micromol/L DHA. (2) I(to) was gradually reduced with the increasing DHA concentrations from 10 micromol/L to 200 micromol/L. I(to) was blocked by DHA in a dose-dependent manner. I(to) current density was (30.1 +/- 7.2) pA/pF at DHA concentration of 60 micromol/L and its half-inhibition concentration was 58.3 micromol/L.</p><p><b>CONCLUSION</b>APDs are gradually prolonged while I(to) reduced with increasing concentrations of DHA which might contribute to the anti-arrhythmia mechanisms of DHA.</p>

Defibrillation efficacy of a newly developed automated external defibrillator in a swine ventricular tachycardia/fibrillation model / 中华心血管病杂志

<p><b>OBJECTIVE</b>The aim of this study was to evaluate the recognition and defibrillation efficiency of a newly developed automated external defibrillator (AED).</p><p><b>METHOD</b>Ventricular tachycardia (VT)/ventricular fibrillation (VF) was induced by alternating current (50 Hz) through an electrode placed on apex of right ventricle in 23 anesthetized swine and recorded, recognized and defibrillated by a newly developed AED.</p><p><b>RESULTS</b>A total of 96 VF was induced and 145 defibrillations were recorded. We analyzed available 167 electrocardiosignal with a total length of 103,740 seconds. The accuracy, sensitivity and the specificity of the AED on VT/VF recognition are 99.5%, 98.2% and 99.6%, respectively. The success rate of defibrillation was 33.4% which increased in proportion to defibrillation energy. The defibrillation threshold of energy is 29.10-116.91 (78.75 +/- 35.64) J, the defibrillation threshold of electric quantity is (0.11 +/- 0.04) C and the defibrillation threshold of voltage is (1216.67 +/- 260.87) V.</p><p><b>CONCLUSIONS</b>This newly developed AED has high sensitivity and the specificity on recognizing VT/VF. The lower success rate of defibrillation of this AED is associated with the low defibrillation energy during defibrillation which needs to be improved on further development.</p>

The changes of funny currents in the ventricular myocytes of neonatal rats and adult rats / 中国应用生理学杂志

<p><b>AIM</b>To record funny currents (If) of ventricular myocytes and to analysize hyperpolarization-activated cation channel(HCN) expression in the rats of different ages.</p><p><b>METHODS</b>Fresh ventricular myocytes were isolated from 3 days rats and adult rats.HCN expressions were measured by real-time quantitative polymerase chain reaction(real-time PCR). It was recorded through whole-cell patch clamp.</p><p><b>RESULTS</b>HCN1, HCN2, HCN3, HCN4 mRNA represented 0.23% +/- 0.01%, 83.58% +/- 0.04%, 0.79% +/- 0.01%, 15.44% +/- 0.01% of total HCN mRNA in the neonatal rats, respectively. If was recorded and the threshold for activation was -75 mV. In the adult rat, HCN1, HCN2, HCN3, HCN4 mRNA represented 0.72% +/- 0.02%, 91.58% +/- 0.08%, 0.27% +/- 0.02%, 7.12% +/- 0.02% of total HCN mRNA. The ratio of HCN2 to HCN4 was approximately (13.06 +/- 0.21):1. The threshold for activation of If was approximately -115 mV in the adult rats.</p><p><b>CONCLUSION</b>With the development of rats, the value of If is smaller. The threshold for activation of If is more negative. The ratio of HCN2 to HCN4 is bigger.</p>

Effects of different amlodipine isomers on L-type calcium current of rat ventricular myocytes / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of different amlodipine isomers on L-type calcium current (ICa-L) and kinetics of rat ventricular myocytes.</p><p><b>METHODS</b>Rat ventricular myocytes were isolated by enzyme digestion. ICa-L, peak currents, I-V curves, steady state activation curves, steady state inactivation curves and recovery curves from inactivation with S-amlodipine, R-amlodipine and R, S-amlodipine at concentrations of 0.1, 0.5, 1, 5, and 10 micromol/L were recorded by whole-cell patch clamp configuration.</p><p><b>RESULTS</b>At the concentrations of 0.1, 0.5, 1, 5, and 10 micromol/L, ICa-L were blocked in a dose-dependent manner by S-amlodipine [(1.5 +/- 0.2)%, (25.4 +/- 5.3)%, (65.2 +/- 7.3)%, (78.4 +/- 8.1)%, and (94.2 +/- 5.0)%] and by R, S-amlodipine [(0.9 +/- 0.1)%, (10.4 +/- 3.2)%, (69.1 +/- 5.3)%, (75.2 +/- 7.0)%, and (81.6 +/- 6.4)%]. I-V curves were significantly shifted upward, steady state activation and inactivation curves were significantly shifted to left by S-amlodipine and R, S-amlodipine (0.1 micromol/L to 10 micromol/L). Recovery time from inactivation was also significantly prolonged by S-amlodipine [(210.1 +/- 19.5) ms, (225.2 +/- 21.3) ms, (241.7 +/- 20.3) ms, (252.3 +/- 24.2) ms, and (282.6 +/- 23.2) ms] and by R, S-amlodipine [(208.7 +/- 17.4) ms, (215.8 +/- 18.3) ms, (225.2 +/- 21.3) ms, (235.8 +/- 22.7) ms, and (252.3 +/- 24.2) ms] in a dose-dependent manner. The observed effects of S-amlodipine were more potent than those of R, S-amlodipine (P < 0.05). However, all these parameters were not affected by R-amlodipine at various concentrations (P > 0.05).</p><p><b>CONCLUSION</b>L-type calcium current of rat ventricular myocytes could be blocked by R, S-amlodipine and S-amlodipine in a dose-dependent manner.</p>

Effects of amiodarone on funny current I(f) channel gene expression in neonatal rat ventricular myocytes / 中华心血管病杂志

<p><b>OBJECTIVE</b>To analysis the effect of amiodarone on funny current (I(f)) and hyperpolarization-activated cation channel (HCN) gene expressions of the neonatal rat ventricular myocytes.</p><p><b>METHODS</b>Ventricular myocytes of 1 - 3 days-old rats were isolated and cultured. The cardiomyocytes were treated by amiodarone (0.01, 0.1, 1, 10, 100 micromol/L) for 3 hours or amiodaron (10 micromol/L) for 0, 0.5, 1, 3, 6 hours. The I(f) and HCN 1 - 4 gene expressions were measured through the whole-cell configuration of the patch-clamp technique and real-time quantitative polymerase chain reaction (real-time PCR) using SYBR Green PCR kit.</p><p><b>RESULTS</b>(1) HCN1, HCN2, HCN3 and HCN4 represented (0.23 +/- 0.01)%, (83.58 +/- 0.04)%, (0.79 +/- 0.01)% and (15.44 +/- 0.01)% of total HCN mRNA, respectively. (2) Amiodaron resulted in a dose-dependent I(f) [(3.1 +/- 0.9)%, (9.7 +/- 2.4)%, (36.7 +/- 5.8)%, (80.3 +/- 1.8)% and (85.9 +/- 3.1)%, respectively at -145 mV, IC(50) (1.32 +/- 0.28) micromol/L], HCN2 [(2.1 +/- 0.8)%, (8.9 +/- 3.6)%, (30.1 +/- 4.2)%, (78.3 +/- 3.6)% and (81.1 +/- 1.9)%, respectively] and HCN4 decrease [(0.5 +/- 0.2)%, (2.1 +/- 2.6)%, (8.8 +/- 3.2)%, (60.1 +/- 4.6)% and (59.6 +/- 6.5)%, respectively]. (3) Amiodaron (10 micromol/L) also induced a time-dependent I(f) [(1.1 +/- 0.1)%, (12.6 +/- 2.3)%, (80.6 +/- 2.2)% and (80.1 +/- 2.1)%, respectively], HCN2 [(1.0 +/- 0.1)%, (9.8 +/- 3.9)%, (82.9 +/- 4.6)% and (83.9 +/- 1.7)%, respectively] and HCN4 decrease [(0.1 +/- 0.1)%, (1.9 +/- 1.1)%, (59.4 +/- 7.8)% and (60.9 +/- 3.1)%, respectively]. However, HCN1 and HCN3 expressions were not affected by amiodaron treatment.</p><p><b>CONCLUSION</b>Current density of I(f) and the expression of HCN2 and HCN4 were decreased by amiodaron which might be the possible antiarrhythmic working mechanisms of amiodaron.</p>

Effects of metoprolol on cardiac function and myocyte calcium regulatory protein expressions in rabbits with experimental heart failure / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of metoprolol on cardiac function and myocyte calcium regulatory protein expressions in rabbits with heart failure.</p><p><b>METHODS</b>Rabbit heart failure model was established by aortic insufficiency induced volume overload followed 14 days later by pressure overload induced by abdominal aorta constricting (HF, n = 11), another 8 rabbits with heart failure were treated with metoprolol (ME) for 6 weeks, sham-operated rabbits (n = 11) served as control. Cardiac function was measured by echocardiography at the end of study. Caffeine-induced calcium transients of myocytes loaded by Fluo-3/AM were observed under Laser scanning confocal microscope. Calcium regulatory protein expression was determined by Western blot analysis.</p><p><b>RESULTS</b>Compared to control animals, the ejection fractions [EF, (45.7 +/- 3.0)% vs. (72. 6 +/- 5.0)%, P < 0.01] and the amplitude of caffeine-induced calcium transients [(16.0 +/- 3.5) FI vs. (43.5 +/- 6.2) FI, P < 0.01] were significantly decreased while its time to peak was significantly prolonged [(129.8 +/- 14.5) s vs. (52.2 +/- 7.4) s, P < 0.01] in HF rabbits. The RyR2 (0.106 +/- 0.007 vs. 0.203 +/- 0.021, P < 0.01) and the ratio of SERCA2a and NCX (1.22 +/- 0.23 vs. 1.96 +/- 0.12, P < 0.01) were also significantly reduced in myocytes of HF rabbits. Metoprolol significantly attenuated the decrease of EF [(60.2 +/- 5.1)%], the amplitude of calcium transient [(32.8 +/- 5.4) FI], the RyR2 expression (0.164 +/- 0.016) and the ratio of SERCA2a and NCX (1.68 +/- 0.17, all P < 0.05 vs. HF rabbits) and attenuated the increase of the time to peak of caffeine-induced calcium transients [(91.4 +/- 10.9) s, P < 0.05 vs. HF rabbits].</p><p><b>CONCLUSION</b>Metoprolol could improve the cardiac function possibly by preventing the alterations of calcium regulatory proteins and increasing calcium transients in failing heart.</p>

Effects of simvastatin on the left ventricular expression of transient outward potassium channel in rabbits with experimental heart failure / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of simvastatin on the left ventricular (LV) expression of transient outward potassium channel in rabbits with experimental heart failure (HF).</p><p><b>METHODS</b>HF model was established by ligating the left anterior descending coronary artery of rabbits. Rabbits were randomized into simvastatin group (HF + S, 10 mg x kg(-1) x d(-1) for 10 weeks, n = 8), HF group (n = 9), and sham group (n = 9). Left ventricular remodeling and function were evaluated by echocardiography and hemodynamic measurements 10 weeks after operation. The mRNA and protein expressions of K(v)1.4, K(v)4.2 and K(v)4.3 potassium channel alpha subunit in LV were determined by semi-quantitative RT-PCR and Western blot.</p><p><b>RESULTS</b>Simvastatin attenuated LV remodeling and improved cardiac function. The mRNA and protein expressions of K(v)1.4, K(v)4.2 and K(v)4.3 potassium channel alpha subunit in HF rabbits (0.48 +/- 0.09, 0.37 +/- 0.07, 0.42 +/- 0.11; 0.33 +/- 0.09, 0.22 +/- 0.07, 0.29 +/- 0.11) were significantly decreased compared with sham rabbits (0.85 +/- 0.08, 0.66 +/- 0.07, 0.67 +/- 0.08; 0.68 +/- 0.13, 0.53 +/- 0.15, 0.49 +/- 0.10, all P < 0.01), and these decreases could be attenuated by simvastatin (0.77 +/- 0.10, 0.50 +/- 0.10, 0.57 +/- 0.12; 0.58 +/- 0.10, 0.36 +/- 0.10, 0.43 +/- 0.12, all P < 0.01 vs. HF).</p><p><b>CONCLUSION</b>Simvastatin not only attenuated LV remodeling and improved LV function but also prevented the downregulation of LV transient outward potassium channel expressions in rabbits with experimental HF.</p>

Association between unique nucleotide polymorphism of 2350G→A in angiotensin converting enzyme and myocardial infarction in Han nationality / 中华急诊医学杂志

0.05).Conclusions SNP of 2350G→A in ACE gene is associated with MI,AA genotype is probably a genetic marker of MI in Han nationality.

Establishment of a HEK293 cell line stably expressing human HCN2 gene / 中国应用生理学杂志

<p><b>AIM</b>To create a model for studying ionic channels by means of the expressing human HCN2 and G418-resistant HEK293 cell lines established.</p><p><b>METHODS</b>pcDNA3-hHCN2 was transfected with Lipofectin2000 into HEK293 cell line. The transfected cells would be survived in the further culture medium containing G418 antibiotic as the hHCN2 gene could express a G418 resistant products. Whole-cell patch clamp investigated that hHCN2 gene was transfected into HEK293 cells.</p><p><b>RESULTS</b>The G418 resistant (600 ug/ml) HEK293 cell line was established successfully and whole-cell patch clamp recorded ionic currents of transfected hHCN2.</p><p><b>CONCLUSION</b>The G418 resistant HEK293 cell line was successfully established with transfection of plasmid pcDNA3-hHCN2 by Lipofectin, which might be useful for studying the relationship between the structure and function of cloned ionic channels.</p>

Abnormal abundances of calcium cycling regulatory proteins in rabbit myocytes with heart failure / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the abnormal abundances of calcium regulatory proteins in rabbit myocytes with failing hearts.</p><p><b>METHODS</b>Sixteen rabbits were divided into two groups: 8 rabbits with heart failure induced by volume plus pressure overload and 8 sham-operated animals. The hemodynamic parameters and cardiac structure and function were detected via catheterization and echocardiography respectively. L-type calcium channel (LTCC), Ryanodine receptor 2 (RyR2), Sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a), and Na(+)-Ca(2+) exchanger (NCX) protein abundances were determined by Western blot analysis.</p><p><b>RESULTS</b>The ratio of left ventricular mass to body weight, heart rate and left ventricular end diastolic pressure in heart failure rabbits were significantly increased compared with sham-operated rabbits (P < 0.01), but their left ventricular shorten fraction [(21.3 +/- 4.00)% vs. (36.5 +/- 1.36)%] and ejection fraction (0.45 +/- 0.07 vs. 0.70 +/- 0.02) were decreased (P < 0.01). In heart failure rabbits, the abundances of LTCC and RyR2 were significantly decreased (R(LTCC/actin): 0.287 +/- 0.029 vs. 0.624 +/- 0.009; R(RyR2/actin): 0.106 +/- 0.001 vs. 0.203 +/- 0.011; P < 0.01), whereas the expressions of SERCA2a and NCX were markedly increased (R(NCX/actin): 0.497 +/- 0.015 vs. 0.221 +/- 0.014; R(SERCA2a/actin): 0.611 +/- 0.036 vs. 0.433 +/- 0.008; P < 0.01).</p><p><b>CONCLUSIONS</b>Reductions of LTCC and RyR2 might contribute to risk factors of systolic dysfunction in failing hearts. In early stage of heart failure, upregulated SERCA2a and NCX protein levels may be helpful for maintaining cardiac performance.</p>

Pacemaker current gene expression of rat mesenchymal stem cells and identification of mesenchymal stem cells expressing human pacemaker current gene (hHCN2) / 中华心血管病杂志

<p><b>OBJECTIVE</b>To study pacemaker current gene expression of mesenchymal stem cells (MSCs) and the electrophysiological property of MSCs expressing human pacemaker current gene.</p><p><b>METHODS</b>Pacemaker current gene expression of MSCs were studied by real-time quantitative polymerase chain reaction (real-time PCR) and pcDNA3-hHCN2 was transfected with Lipofectin 2000 into MSCs. hHCN2 expression at mRNA and at protein levels in the transfected cells were identified by real-time PCR and Western blot, respectively. The ionic currents of cloned hHCN2 (IhHCN2) were recorded and the current characteristics were studied through the whole-cell patch clamp technique.</p><p><b>RESULTS</b>mHCN1, mHCN2, mHCN3, mHCN4 represent (0.08+/-0.01)%, (77.16+/-0.03)%, (0.24+/-0.01)%, (22.53+/-0.02)% of total HCN mRNA in MSCs as determined by real-time PCR. Transfected hHCN2 ionic currents were recorded by whole-cell patch clamp and current density-voltage curves were obtained. The threshold for activation of IhHCN2 was approximately -80 mV and this current could be blocked by Cs+ (4 mmol/L). hHCN2 expression in transfected MSCs was detected both at mRNA and protein levels.</p><p><b>CONCLUSIONS</b>1. mHCN2 and mHCN4 represent the major populations of total HCN mRNA in MSCs. 2. Plasmid pcDNA3-hHCN2 by Lipofectin could be successfully transfected into MSCs with IhHCN2 recorded by whole-cell patch clamp technique, this study provides a basis for future antiarrhythmic gene therapy.</p>

Malignant hypertrophic cardiomyopathy caused by the Arg723Gly mutation in beta-myosin heavy chain gene in a Chinese pedigree / 中华心血管病杂志

<p><b>OBJECTIVE</b>Hypertrophic cardiomyopathy (HCM) is a genetically and phenotypically heterogeneous disease and an Arg723Gly mutation in beta-myosin heavy chain (beta-MHC) gene was found in 3 Spanish families with malignant HCM. We detected this gene mutation in 5 Chinese pedigrees with hypertensive cardiomyopathy.</p><p><b>METHODS</b>Five Chinese pedigrees with HCM and 80 age-matched normal control subjects were chosen for the study. The exons in the functional regions of the beta-MHC gene were amplified with PCR and the products were sequenced, genotype and phenotype analyzed.</p><p><b>RESULTS</b>Arg723Gly mutation was identified in exon 20 in one pedigree. In this pedigree, 13 out of 25 family members were diagnosed as HCM, 5 died of heart failure, all HCM patients in this pedigree had Arg723Gly mutation and 3 of them had NYHA III and 2 of them were diagnosed as HCM before the age of 20.</p><p><b>CONCLUSIONS</b>Arg723Gly mutation was also one of the main disease-causing genes in Chinese familial HCM. The mutation of Arg723Gly is a malignant phenotype as shown by early progressive heart failure development and poor prognosis in this pedigree with Arg723Gly mutation.</p>

Mutation of Arg723Gly in beta-myosin heavy chain gene in five Chinese families with hypertrophic cardiomyopathy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hypertrophic cardiomyopathy (HCM) is a form of cardiomyopathy with an autosomal dominant inherited disease, which is caused by mutations in at least one of the sarcomeric protein genes. Mutations in the beta-myosin heavy chain (beta-MHC) are the most common cause of HCM. This study was to reveal the disease-causing gene mutations in Chinese population with HCM, and to analyze the correlation between the genotype and phenotype.</p><p><b>METHODS</b>The exons 3 to 26 of MYH7 were amplified by PCR, and the PCR products were sequenced in five non-kin HCM patients. A 17-year-old patient was detected to be an Arg723Gly mutation carrier. Then his family was gene-screened, and the correlation between genotype and phenotype was analyzed.</p><p><b>RESULTS</b>The mutation of Arg723Gly in a Chinese family with HCM was detected for the first time. With a C-G transversion in nucleotide 13,619 of the MYH7 gene, located at the essential light chain interacting region in S1, the replacement of arginine by glycine took place at amino acid residue 723. A two-dimensional echocardiogram showed moderate asymmetrical septal hypertrophy with left atria enlargement. There was no obstruction in the left ventricular outflow tract. In his family, a total of 13 individuals were diagnosed HCM and 5 of them were dead of congestive heart failure at a mean age of 66-year-old. Eight living members were all detected to carry the mutation, in which 3 developed progressive heart failure. Moreover, the heart function of the people evidently deteriorates when their age are older than 50. The mutation and the disease show co-separated.</p><p><b>CONCLUSION</b>The Arg723Gly mutation is a malignant type. In Chinese the mutation has the similar characters to the former report but has low degree malignant.</p>

Comparative Study on Different Methods for Measurement of Diameter of Patent Ductus Arteriosus in Transcatheter Interventions / 实用儿科临床杂志

Objective To evaluate the value of transthoracic echocardionraphy(TTE)and angiographic appearance for measurement of the diameter of patent ductus arteriosus(PDA)in transcatheter interventions.Methods In 52 patients,the position,diameter and length of ductus arteriosus between the descending aorta and the pulmonary artery were observed and the narrowest diameter of PDA was measured by TTE.In angiographic appearance,pig catheter was selected to perform left lateral aortography and measure the narrowest diameter of PDA.Comparative studies were performed on the numbers measured by 2 methods.Results Aortography showed that 45 patients had funnel shape PDA and 5 patients had tubular shape PDA,while 1 patient had funnel plus tubular shape PDA and 1 patient had residual shunt after operation.TTE showed that 46 patients had funnel shape PDA,4 patients had tubular shape PDA and 1 patient had window shape PDA,1 patient had residual shunt after operation.The mean diameter of PDA measured by angiographic appearance was(3.72?2.51)mm,which was statistically lower than those by TTE(4.47?2.31)mm(t=5.17 P