Analyses of risk factors and prognosis for new-onset atrial fibrillation in elderly patients after dual-chamber pacemaker implantation

Objective To retrospectively identify risk factors and the prognosis for new-onset atrial fibrillation (AF)after implantation of dual-chamber pacemakers in elderly patients.Methods Consecutive patients aged >65years who underwent their first implantation of a dual-chamber permanent pacemaker in Beijing Anzhen Hospital from October 2013to May 2016were enrolled.Their complete program- ming and follow-up data were recorded.Follow-up end points included new-onset AF and major adverse cardiovascular and cerebrovascular events.Restdts Altogether,322patients were enrolled,with new-onset AF observed in 79(24.5%)during their follow-up.Multivariable analysis identified four independent predictors of new-onset AF in elderly patients after pacemaker implantation:hypertension (HR =3.040, 95%CI:1.09-3.05,P =0.00),age (HR =1.966,95%CI:1.57-3.68,P =0.01);left atrial enlargement (HR =1.645,95%CI:1.05-1.25,P = 0.03);high ventricular pacing rate (HR =1.137,95%CI:1.01-1.06,P =0.01).Univariable analysis indicated that the CHA2DS2-VASc score was also a risk factor for AF (HR =1.368,95%CI:1.178-1.589,P =0.002),whereas multivariable regression analysis did not. Kaplan-Meier survival analysis showed that the risk for ischemic stroke was significantly higher in the new-onset AF group than in the non-AF group (P <0.05).Conclusion Hypertension,age,left atrial enlargement,and high ventricular pacing rate were independent predictors of new-onset AF in elderly patients after implantation of a permanent pacemaker.New-onset AF increased the risk for ischemic stroke.

Olmesartan Reduces New-onset Atrial Fibrillation and Atrial Fibrillation Burden after Dual-chamber Pacemaker Implantation in Atrioventricular Block Patients

Background： Atrial fibrillation （AF） is the rnost frequent tachyarrhythmia in patients with a permanent pacemaker. Angiotensin II receptor antagonists have a protective effect against the occurrence of AF in patients with heart diseases. This study aimed to assess the effectiveness of olmcsartan in the prevention of new-onset AF and AF burden in atrioventricular block （AVB） patients with dual-chamber （DDD） pacemaker implantation. Methods： This was a single-center, prospective, randomized, single-blind, controlled clinical study. A total of 116 AVB patients, who received DDD pacemakers implantation with the percentage of ventricular pacing （VP%） _〉40% from April 22, 2011 to December 24, 2012, were prospectively randomized to olrnesartan group （20 mg per day; n - 57） or control group （n = 59）. Patients were lbllowed up using pacernaker prograrnming± 12-lead electrocardiography in the intrinsic sinus rhythm, laboratory examinations, and transthoracic echocardiography at 24 months. Atrial high rate events （AHREs） were defined as 180 beats/min over a minimum of 5 min. AF burden was calculated by the number of hours with AHREs divided by the number of measurement hours. Results： Ten （17.5%） patients in the olmesartan group and 24 patients （40.7%） in the control group occurred new-onset AF, and the difference between two groups was statistically significant （P = 0.04）. AF burden was lower in olmesartan group than that in control group （8.02 ± 3.10% vs. 13.66 ± 6.14%, P = 0.04）. There were no significant differences in mean days to the first occurrence of AHREs and mean cumulative numbers of AHREs between two groups （P = 0.89 and P = 0.42, respectively）. Moreover, olmesartan group had smaller values of maximal P-wave durations and P-wave dispersion （PD） after 24 months follow-up compared with the control group （ 109.5 ± 7.4 ins vs. 113.4 ± 7.1 ms, P = 0.00; and 40.6 ± 4.5 ms vs. 43.3 ± 4.4 ins, P - 0.02, respectively）. Left ventricular end-diastolic diameter and left ventricular qiection traction were not significantly diiTerent between two groups （both P 〉 0.05）. Conclusion： This study suggested that 24-month ofolmesartan therapy could reduce new-onset AF and AF burden in patients with DDD pacemakers.

Feasibility of Atrial AutoCaptureTM to Detect Atrial Evoked Response： Experience from 102 Patients Implanted with Dual-chamber Pacemakers

Background： Atrial AutoCaptureTM （ACapTM） was a new technological development that confirmed atrial capture by analyzing evoked response （ER） with a new method - paced depolarization integral ER detection- and optimized energy output to changes in the stimulation threshold. The purpose of this study was to evaluate the clinical performance ofACapTM function. Methods： This was a prospective, observational, nonrandomized two-center study. Between November 2008 and August 2014, 102 patients were enrolled from two different institutions. Data were collected by case report forms at enrollment, hospital discharge, and in-office follow-ups scheduled at 1, 2, 3, 6, and 12 months postimplantation. Results： Ambulatory ACapTM function started to become available for 20.6% of patients at 1 day, then progressed to 30.4% at 7 days, 38.6% at 1 month, 41.6% at 2 months, 47.5% at 3 months, 53.5% at 6 months, and 63.4% at 1 year. The cause of the unsuccessful attempts to perform ACapTM threshold was ER/polarization 〈2：1. Availability for SD, BND, and HOCM indications had shown better results than AVB indication. For SD indication cases, feasibility was significantly better for SD with paroxysmal atrial fibrillation （pAF） than SD without pAF （78.4% vs. 35.0% at 1 year, n = 71, P 〈 0.001）. At each stage of the clinical follow-ups, there had been a strict correlation between ACapTM measurements and those conducted manually with P 〈 0.001 （n = 299）. Conclusions： It has been concluded that ACapTM function was safe and effective to confirm atrial threshold and reduce energy output automatically. ACapTM function is unavailable for some patients at early stages of the implantation; however, availability has been progressively increasing during follow-up.

Impact of single chamber and dual chamber permanent pacemaker implantation on left ventricular function:An observational study

BACKGROUND Permanent pacemaker implantation has the potential to impact left ventricular(LV)function and hence quality of life(QoL)in the long term.AIM To assess the effect of single-and dual-chamber pacing on LV function and QoL.METHODS This study included 56 patients who underwent permanent pacing:Dual pacing,dual sensing,dual responsive and rate responsive(DDDR)for the initial 3 months,ventricular sensing,inhibited response and rate responsive(VVIR)for the next 3 months,and DDDR mode for the last 3 months.Throughout the study period,various echocardiographic parameters,functional status,and QoL were measured to assess the impact of pacing on LV function compared with baseline and at every 3 months interval.RESULTS A significant change appeared in cardiac function after VVIR pacing which was in diastolic properties of LV as shown by increase in isovolumic relaxation time from(85.28±9.54 ms)to(89.53±9.65 ms).At the 3-,6-,and 9-month follow-up,reduction in LV ejection fraction was observed to be 62.71±4.66%,61.07±4.41%,and 58.48±3.89%,respectively.An increase in the QoL scores was noted at every follow-up visit.CONCLUSION An apparent depressant effect on LV function due to right ventricular pacing,with a higher incidence of adverse outcomes in the VVIR mode.In addition,an upsurge in QoL scores for the study population was noted,which indicates improvement in the QoL of patients post-pacing,irrespective of the mode.Generally,the DDDR mode is a highly preferable pacing mode.

Current knowledge for the risk factors of early permanent pacemaker implantation following transcatheter aortic valve replacement and what is next for the primary prevention?

In this editorial,we comprehensively summarized the preoperative risk factors of early permanent pacemaker implantation after transcatheter aortic valve replacement(TAVR)among patients with severe aortic stenosis from several renowned clinical studies and focused on the primary prevention of managing the modifiable factors,e.g.,paroxysmal atrial fibrillation before the TAVR.

The Peripheral Hospital as Focal Point for Pacemaker Activity: Review of the Last 300 Implantations Carried out at the Haute Correze Hospital Center

Background: Pacemaker implantation is a very old activity which has revolutionized the cardiology practice throughout the world. This activity is effective at the Haute Correze Hospital Center since more than 20 years. Due to progress in this area, and the increasing request within this center located at the outskirts of town, we set out to evaluate our pacemaker activity in general and more specifically to assess the post-procedural complications in our series patients. Methodology: This was a retrospective longitudinal study. Data were recorded for period of 90 months from 27/05/2016 to 19/11/2023. This data collection was possible via a specific register completed by computerized patient data from the SillageTM software. All files of patients implanted with single or dual chamber pacemakers were included, generator replacements, upgrading procedures and addition of leads were excluded. The sampling was non-probabilistic, consecutive and non-exhaustive. Statistical analysis was carried out using the Excel 2019 spreadsheet and SPSS version 23 software. The quantitative variables were presented as mean ± standard deviation, the qualitative data as proportions. Results: A total of 303 first-time pacemaker’s implantations were carried out during the study period (rate of 40 per year). The average age in the population was 79.7 ± 9.4 years (44 - 99 years) with a male predominance of 63.7% (n = 193). Atrioventricular block (2nd and 3rd degree) was the main indication for pacemaker implantation in 42.9% of cases (n = 130). Patients were most often implanted with a dual-chamber pacemaker (57.7%, n = 175). The approach was most often cephalic in 72.6% of cases (n = 220), followed by the subclavian access in 27.4% of cases (n = 84). The average fluoroscopy time was 7.9 min ± 2.4 (1 - 43). The average irradiation dose in gray/cm2 was 12.4 ± 9.3 (0.22 - 117.5). The average length of hospitalization was 7 ± 4 (2 - 26) days. The overall complication rate at one year was 12.9% (n = 39). These complications are distributed as follows: Leads dislodgement in 8.2% (n = 25), hematoma 3.6% (n = 11) all without clinical consequences, pneumothorax 0.7% (n = 2), both cases of pneumothorax did not require specific care, infection (superficial) in 0.3% (n = 1). Leads dislodgement occurred after a median time of 18 days (IQR: 3 - 36). The earliest dislodgement was observed on D0 and the latest on D207. No serious complications were recorded. The average atrial threshold at implantation/first control/last follow-up was 0.7/1.3/0.8 V, respectively. The average ventricular threshold at implantation/first control/last follow-up was 0.5/1.08/0.87 V, respectively. The average atrial detection at implantation/first control/last follow-up was 3.2/2.3/ 2.05 mv, respectively. The average ventricular detection at implantation/first control/last follow-up was 10.3/11.03/10.8 mv. The average atrial impedance at implantation/first control/last follow-up was 610/457/457 ohms. The average ventricular impedance at implantation/first control/last follow-up was 754/547/563 ohms. Conclusion: Pacemaker implantation is safe at the Haute Correze Hospital Center with a relatively low rate of complications, in this case an almost zero major infection and no serious hematoma. The peripheral hospital should remain a focal point of this activity in order to respond more quickly to the needs of the populations.

Wireless Power Supply Based on MNG-MNZ Metamaterial for Cardiac Pacemakers

To solve the low power transfer efficiency and magnetic field leakage problems of cardiac pacemaker wireless powering, we proposed a wireless power supply system suitable for implanted cardiac pacemaker based on mu-negative(MNG) and mu-nearzero(MNZ) metamaterials. First, a hybrid metamaterial consisted of central MNG unit for magnetic field concentration and surrounding MNZ units for magnetic leakage shielding was established by theoretical calculation. Afterwards, the magnetic field distribution of wireless power supply system with MNG-MNZ metamaterial slab was acquired via finite element simulation and verified to be better than the distribution with conventional MNG slab deployed. Finally, an experimental platform of wireless power supply system was established with which power transfer experiment and system temperature rise experiment were conducted.Simulation and experimental results showed that the power transfer efficiency was improved from 44.44%,19.42%, 8.63% and 6.19% to 55.77%, 62.39%, 20.81%and 14.52% at 9.6 mm, 20 mm, 30 mm and 50 mm,respectively. The maximum SAR acquired by SAR simulation under human body environment was-7.14 dbm and maximum reduction of the magnetic field strength around the receiving coil was 2.82 A/m. The maximum temperature rise during 30min charging test was 3.85℃,and the safety requirements of human bodies were met.

Dual-chamber pacing confers better myocardial performance and improves clinical outcomes compared to single-chamber pacing

The deleterious effects of long term right ventricular pacing are increasingly being recognized today.Current clinical practice favors the implantation of dual-chamber permanent pacemaker which maintains atrioventricular synchrony and is associated with better quality of life.However,despite the popular belief and common sense surrounding the superiority of dual-chamber pacing over single chamber pacing,the same has never been conclusively verified in clinical trials.Some observational evidence however,does exists which supports the improved cardiac hemodynamics,lower the rate of atrial fibrillation,heart failure and stroke in dual-chamber pacing compared to single-chamber pacing.In the index study by Haque et al,right ventricular pacing,particularly in ventricular paced,ven-tricular sensed,inhibited response and rate responsive pacemaker adversely im-pacted the left ventricular functions over 9-months compared to dual pacing,dual sensing,dual responsive and rate responsive pacemaker.Although there are key limitations of this study,these findings does support a growing body of evidence reinstating the superiority of dual chamber pacing compared to single chamber pacing.

Application Effect of External Diaphragm Pacemaker Combined with Active Respiratory Circulation Technology in Pulmonary Rehabilitation of Perioperative Lung Cancer Patients

Aim: To explore the application effect of external diaphragm pacemaker combined with active respiratory circulation technology in pulmonary rehabilitation of perioperative lung cancer patients. Methods: A total of 98 lung cancer patients admitted to our hospital from April 2020 to November 2021 were selected as the observation objects, and then divided into a control group and an observation group using the random number table method, with 49 cases in each group. The control group received routine admission guidance and active respiratory circulation training, while the observation group was supplemented with external diaphragm pacemaker on the basis of the control group. The intervention effect was evaluated by blood gas indicators, pulmonary function indicators, diaphragm function indicators, sputum comfort degree, and activity tolerance indicators before and after intervention. Results: Before intervention, there were no significant differences in blood gas analysis indicators, pulmonary function indicators, diaphragm function indicators, sputum comfort degree, and activity tolerance indicators between the two groups (P > 0.05). After intervention, the improvement degree of the above indicators in the observation group was higher than that in the control group (P < 0.05). Conclusions: The application of external diaphragm pacemaker combined with active respiratory circulation technology in pulmonary rehabilitation of perioperative lung cancer patients is significant, which can effectively improve the pulmonary function, blood gas function, and diaphragm function of lung cancer patients after surgery, and improve the activities of daily living and quality of life of patients.

Risk of permanent pacemaker implantation following transcatheter aortic valve replacement:Which factors are most relevant?

Transcatheter aortic valve replacement(TAVR)has emerged as a formidable treatment option for severe symptomatic aortic stenosis ahead of surgical aortic valve replacement.The encouraging results from large randomized controlled trials has resulted in an exponential rise in the use of TAVR even in the low-risk patients.However,this is not without challenges.Need for permanent pacemaker(PPM)post-TAVR remains the most frequent and clinically relevant challenge.Naturally,identifying risk factors which predispose an individual to develop high grade conduction block post-TAVR is important.Various demographic factors,electrocardiographic features,anatomic factors and procedural characteristics have all been linked to the development of advanced conduction block and need for PPM following TAVR.Amongst these electrophysiological variables,most notably a prolonged QRS>120 ms regardless of the type of conduction block seems to be one of the strongest predictors on logistic regression models.The index study by Nwaedozie et al highlights that patients requiring PPM post-TAVR had higher odds of having a baseline QRS>120 ms and were more likely to be having diabetes mellitus that those who did not require PPM.

Pacemaker post transcatheter aortic valve replacement:A multifactorial risk?

Pacemaker post-transcatheter aortic valve replacement is related to multifactorial risk.Nwaedozie et al brought to the body of evidence electrocardiogram and clinical findings.However,procedural characteristics have at least as much impact on the final need for a permanent pacemaker and potentially on the pacing rate.In this regard,long-term follow-up and understanding of the impact of long-term stimulation is of utmost importance.

利用DRBD和Pacemaker技术构建高可用数据容灾备份系统

为充分保证数据信息安全,提高数据中心容灾备份能力,以DRBD和Pacemaker技术为基础构建具有高可用性的数据容灾备份系统,实现生产数据在本地、异地之间三台服务器的镜像复制,并且实现应用和数据两个级别的高可用(HA),解决目前主流SAN存储环境下共享磁盘阵列的单点故障威胁,有效满足不断提升的数据恢复RTO和RPO的要求。本论述为数据中心业务系统高可用和数据异地备份提出了低成本的技术方案。

Small bowel capsule endoscopy in patients with cardiac pacemakers and implantable cardioverter defibrillators:Outcome analysis using telemetry review

AIM:To determine if there were any interactions between cardiac devices and small bowel capsules secondary to electromagnetic interference (EMI) in patients who have undergone small bowel capsule endoscopy (SBCE).METHODS:Authors conducted a chart review of 20 patients with a cardiac pacemaker (CP) or implantable cardioverter defibrillator (ICD) who underwent continuous electrocardiographic monitoring during their SBCE from 2003-2008.authors searched for unexplained electrocardiogram (ECG) findings,changes in CP andICD set parameters,any abnormality in transmitted capsule data,and adverse clinical events.RESULTS:There were no adverse events or hemodynamically significant arrhythmias reported.CP and ICD set parameters were preserved.The majority of ECG abnormalities were also found in pre-or post-SBCE ECG tracings and the CP behavior during arrhythmias appeared appropriate.Two patients seemed to have episodes of undersensing by the CP.However,similar findings were documented in ECGs taken outside the time frame of the SBCE.One patient was observed to have a low signal encountered from the capsule resulting in lack of localization,but no images were lost.CONCLUSION:Capsule-induced EMI remains a possibility but is unlikely to be clinically important.CPinduced interference of SBCE is also possible,but is infrequent and does not result in loss of images transmitted by the capsule.

Hwangryunhaedok-tang induces the depolarization of pacemaker potentials through 5-HT3 and 5-HT4 receptors in cultured murine small intestine interstitial cells of Cajal

AIM To investigate the effects of a water extract of Hwangryunhaedok-tang(HHTE) on the pacemaker potentials of mouse interstitial cells of Cajal(ICCs).METHODS We dissociated ICCs from small intestines and cultured. ICCs were immunologically identified using an antic-kit antibody. We used the whole-cell patch-clamp configuration to record the pacemaker potentials generated by cultured ICCs under the current clamp mode(I = 0). All experiments were performed at 30 ℃-32 ℃RESULTS HHTE dose-dependently depolarized ICC pacemaker potentials. Pretreatment with a 5-HT_3 receptor anta-gonist(Y25130) or a 5-HT_4 receptor antagonist(RS39604) blocked HHTE-induced pacemaker potential depolarizations, whereas pretreatment with a 5-HT7 receptor antagonist(SB269970) did not. Intracellular GDPβS inhibited HHTE-induced pacemaker potential depolarization and pretreatment with a Ca^(2+)-free solution or thapsigargin abolished the pacemaker potentials. In the presence of a Ca^(2+)-free solution or thapsigargin, HHTE did not depolarize ICC pacemaker potentials. In addition, HHTE-induced pacemaker potential depolarization was unaffected by a PKC inhibitor(calphostin C) or a Rho kinase inhibitor(Y27632). Of the four ingredients of HHT, Coptidis Rhizoma and Gardeniae Fructus more effectively inhibited pacemaker potential depolarization.CONCLUSION These results suggest that HHTE dose-dependently depolarizes ICC pacemaker potentials through 5-HT_3 and 5-HT_4 receptors via external and internal Ca^(2+) regulation and via G protein-, PKC-and Rho kinase-independent pathways.

Pacemaker therapy in very elderly patients: survival and prognostic parameters of single center experience

Background Permanent pacing is the therapy of choice for treating severe and/or symptomatic bradyarrhythmias. The number of very elderly patients receiving pacemakers is increasing and little is known about survival in this specific subgroup. This study is aimed at assessing the actual survival of patients requiring pacing therapy at age > 85 years and investigating variables associated with death. Methods Between 2010 and 2017, 572 patients aged ≥ 85 years underwent pacemaker implantation for conventional bradycardia indications in Department of Cardiology, S. Chiara Hospital, Italy. Results Thirty percent of patients were ≥ 90-year-old and comorbidities were frequent. Fifty-seven percent of patients required pacing for prognostic reasons(acquired atrioventricular block), and the remaining for relief of bradycardia symptoms. A dual-chamber pacemaker was implanted in 34% of patients. The 5-year survival was 45%(standard error: 3%), and the 8-year survival was 26%(standard error: 4%). The risk of death was similar in patients who received pacemaker for symptom relief and for prognostic reasons in the overall population(HR = 1.19, 95% CI: 0.93–1.52, P = 0.156), as well as in the ≥ 90-year-old group(HR = 1.39, 95% CI: 0.92–2.11, P = 0.102). At multivariate analysis, following variables were associated with death: higher age, lower ejection fraction, dementia/dysautonomia and diagnosis of cancer. The pacing indication and the implantation of a single chamber pacemaker were not associated with worse prognosis. Conclusions This study showed a good life expectancy in patients aged ≥ 85 years who received a pacemaker. Strong risk factors for all-cause death were non-cardiac. Pacemaker therapy seems a clinically effective therapeutic option to improve survival and to control bradyarrhythmia-related symptoms in very elderly patients.

Permanent transvenous pacemaker implantation in a patient with Cor triatriatum dextrum

Cor triatriatum dextrum is an extremely rare congenital heart abnormality in which the right atrium is separatedinto two chambers by a persistent fibrous membrane. A transvenous approach to place a dual-chamber pacemaker in such patients is technically challenging. We report the first case of a transvenous permanent pacemaker placement in a patient with cor triatriatum dextrum. An 87-year-old woman was diagnosed with paroxysmal atrial fibrillation. She was accidentally found to have cor triatriatum dextrum during the transesophageal echocardiography(TEE) prior to cardioversion. Later during her hospital stay, it was indicated to place a permanant pacemaker due to high grade atrioventricular block. After thorough reviewing TEE imagings, a transvenous catheter-based approach was decided feasible. Patient successfully received a dual chamber pacemaker through left subclavian venous approach. Furthermore in our case, using specially designed pacemaker leads and cautious intra-procedural maneuvering under fluoroscopic guidance ensured procedural success. In summary, a thorough pre-operative evaluation with transesophageal echocardiography is critical for the planning and eventual success of the transvenous placement of rightsided leads.

Transhepatic venous approach to permanent pacemaker placement in a patient with limited central venous access

The end-stage renal disease population poses a challenge for obtaining venous access required for life-saving invasive cardiac procedures. In this case report, we describe an adult patient with end-stage renal disease in whom the hepatic vein was the only available access to implant a single-lead permanent cardiac pacemaker. A 63-year-old male with endstage renal disease on maintenance hemodialysis and permanent atrial fibrillation/atrial flutter presented with symptomatic bradycardia. Imaging studies revealed all traditional central venous access sites to be occluded/non-accessible. With the assistance of vascular interventional radiology, a trans-hepatic venous catheter was placed. This was then used to place a right ventricular pacing lead with close attention to numerous technical aspects. The procedure was completed successfully with placement of a single-lead permanent cardiac pacemaker.

Dual antiplatelet therapy increases pocket hematoma complications in Chinese patients with pacemaker implantation

Objective To assess the prevalence of the bleeding complications in pacemaker implanted patients receiving different antiplatelet regimens, and the influence of each regimen on hospital stays after device implantation. Methods We prospectively enrolled 364 patients receiving the cardiac rhythm device implantations in Fuwai Hospital from July 2012 to December 2013. Bleeding complications including pocket hematoma, hemothorax, cardiac tamponade and blood transfusion requirement were measured as endpoints. Post operation hospital stay was also included in the endpoints. Results Bleeding complications were detected in 15 patients （14 with hematoma, one with hemothorax） out of all 364 patients （4.12%）. Dual antiplatelet therapy （DAT） significantly increased hematoma （19.3%） compared with aspi- fin treatment （ASA） （3.2%, P = 0.001） and no antiplatelet therapy （1.9%, P 〈 0.001）. There was no significant difference in incidence of pocket hematoma between the ASA group and the control group （P = 0.45）. The post procedure hospital stay was longer in DAT group （5.45 ± 2.01 days） compared to those in the ASA group （3.65 ± 1.37 days, P 〈 0.05） or control group （3.99 ± 2.27 days, P 〈 0.05）. Pocket hema- toma was considered an independent predictor of hospital stay prolongation （OR： 5.26; 95% CI： 1.56-16.64; P = 0.007）. Conclusions Among the Chinese patients undergoing device implantation in this study, the use of dual antiplatelet agents significantly increased the risk of pocket hematoma complications and led to a longer hospital stay. Use of aspirin alone did not increase the risk.

基于Pacemaker的FreeSWITCH高可用解决方案

该文主要采用corosync＋pacemaker＋mysql技术方案，详细介绍了安装与配置策略，避免了传统的高可用集群的解决方案的弊端，提高了配置的弹性，从而使功能多元化。

Use of Rats Mesenchymal Stem Cells Modified with mHCN2 Gene to Create Biologic Pacemakers

The possibility of rats mesenchymal stem cells (MSCs) modified with murine hyperpolarization-activated cyclic nucleotide-gated 2 (mHCN2) gene as biological pacemakers in vitro was studied. The cultured MSCs were transfected with pIRES2-EGFP plasmid carrying enhanced green fluorescent protein (EGFP) gene and mHCN2 gene. The identification using restriction enzyme and sequencing indicated that the mHCN2 gene was inserted to the pIRES2-EGFP. Green fluorescence could be seen in MSCs after transfection for 24–48 h. The expression of mHCN2 mRNA and protein in the transfected cells was detected by RT-PCR and Western blot, and the quantity of mHCN2 mRNA and protein expression in transfected MSCs was 5.31 times and 7.55 times higher than that of the non-transfected MSCs respectively (P<0.05, P<0.05). IHCN2 was recorded by whole-cell patch clamp method. The effect of Cs+, a specific blocker of pacemaker current, was measured after perfusion by patch clamp. The results of inward current indicated that there was no inward current recording in non-transfected MSCs and a large voltage-dependent inward and Cs+-sensitive current activated on hyperpolarizations presented in the transfected MSCs. IHCN2 was fully activated around–140 mV with an activation threshold of –60 mV. The midpoint (V50) was –95.1±0.9 mV (n=9). The study demonstrates that mHCN2 mRNA and protein can be expressed and the currents of HCN2 channels can be detected in genetically modified MSCs. The gene-modified MSCs present a novel method for pacemaker genes into the heart or other electrical syncytia.