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.

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.

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.

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.

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.

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.

A Meta-analysis of Major Complications between Traditional Pacemakers and Leadless Pacemakers

Objectives:We aim to compare the major complications between leadless pacemakers and traditional pacemakers.Background:Leadless pacemakers,which are increasingly used in clinical practice,have several advantages compared with traditional pacemakers in avoiding pocket-and lead-related complications.However,the clinical effect of leadless pacemakers remains controversial.Methods:PubMed,Embase,the Cochrane Central Register of Controlled Trials(CENTRAL),the CNKI database,and the Wanfang database were searched from July 2013 to December 2019.Studies comparing leadless pacemakers and traditional pacemakers were included.The primary end point was major complications.The secondary end points were cardiac perforation/pericardial effusion,device revision or extraction,loss of device function,and death.Results:Six studies fulfi lled the inclusion criteria.Only four of the six studies reported data on major complications.Leadless pacemakers were associated with a lower incidence of major complications(risk ratio 0.33,95%confi dence interval 0.25–0.44,P<0.00001,I²=49%).We extracted data on cardiac perforation/pericardial effusion,device revision or extraction,loss of device function,and death from six studies.Our meta-analysis showed that leadless pacemakers have a higher risk of cardiac perforation or pericardial effusion(risk ratio 4.28,95%confi dence interval 1.66–11.08,P=0.003,I²=0%).No statistically signifi cant differences were found for mortality,device revision or extraction,and loss of device function.Conclusion:Compared with traditional pacemakers,leadless pacemakers have a signifi cantly decreased risk of major complications,but have a higher risk of cardiac perforation or pericardial effusion.

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。

Bow-and-arrow sign on point-of-care ultrasound for diagnosis of pacemaker lead-induced heart perforation:A case report and literature review

BACKGROUND Pacemaker lead-induced heart perforation is a rare but life-threatening complication of pacemaker implantation,and timely diagnosis remains a challenge for clinicians.Here,we report a case of pacemaker lead-induced cardiac perforation rapidly diagnosed by a“bow-and-arrow”sign on point-of-care ultrasound(POCUS).CASE SUMMARY A 74-year-old Chinese woman who had undergone permanent pacemaker implantation 26 d before suddenly developed severe dyspnea,chest pain,and hypotension.The patient had received emergency laparotomy for an incarcerated groin hernia and was transferred to the intensive care unit 6 d before.Computed tomography was not available due to unstable hemodynamic status,so POCUS was performed at the bedside and revealed severe pericardial effusion and cardiac tamponade.Subsequent pericardiocentesis yielded a large volume of bloody pericardial fluid.Further POCUS by an ultrasonographist revealed a unique“bow-and-arrow”sign indicating right ventricular(RV)apex perforation by the pacemaker lead,which facilitated the rapid diagnosis of lead perforation.Given the persistent drainage of pericardial bleeding,urgent off-pump open chest surgery was performed to repair the perforation.However,the patient died of shock and multiple organ dysfunction syndrome within 24 h post-surgery.In addition,we also performed a literature review on the sonographic features of RV apex perforation by lead.CONCLUSION POCUS enables the early diagnosis of pacemaker lead perforation at the bedside.A step-wise ultrasonographic approach and the“bow-and-arrow”sign on POCUS are helpful for rapid diagnosis of lead perforation.

Successful leadless pacemaker implantation in a patient with dextroversion of the heart:A case report

BACKGROUND Dextroversion is defined as the presence of dextrocardia with situs solitus,dextroloop ventricles,and normally related great arteries.Dextrocardia can pose technical challenges when interventional treatments are required.However,the challenges posed by dextroversion can be amplified due to the disruption of typical anatomical relationships,the unpredictable positioning and boundaries of cardiac structures resulting from the shift,and the pathological processes influencing rotation.CASE SUMMARY A 73-year-old woman with cardiac dextroversion suffered from a recurrence of atrial fibrillation after her radiofrequency catheter ablation and Despite the cessation of antiarrhythmic medications,there were episodes of sinus pauses and symptomatic bradycardia,with heart rates dropping as low as 28 beats per minute.CONCLUSION Dextroversion makes the implantation of leadless pacemakers more challenging,and appropriate adjustments in fluoroscope angles may be crucial for intracardiac operations.Additionally,when advancing delivery systems,attention should be paid to rotational direction during valve-crossing procedures;changes in the perspective of posture angle between normal cardiac position and dextroversion can serve as references.

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.

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.

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.

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.

Dynamic Expression of Hyperpolarization-activated Cyclic Nucleotide-gated Cation Channel 4 Involved in Microwave Induced Pacemaker Cell Injuries

To investigate the mechanisms of microwave induced pacemaker cell injuries, Wistar rats and the primary pacemaker cells of newborn Wistar rats were exposed to microwave at average power density of 50 mW/cm2. Slower spontaneous beating rate, intercellular Ca2＋ aggregation and cell membrane perforation were detected immediately after the exposure. Moreover, hyperpolarizationactivated cyclic nucleotide-gated cation channel 4 （HCN4） was down-regulated immediately after the exposure and up-regulated at 12 h after the exposure. In the sinoatrial node （SAN） of the rats,

Small balloon strategy associated with low pacemaker implantation rate after self-expanding transcatheter valve implantation

BACKGROUND: This study aims to investigate whether small balloon aortic valvuloplasty(BAV) reduces the need for permanent pacemaker implantation (PPMI) after transcatheter aortic valveimplantation (TAVI).METHODS: This was a retrospective analysis using data from our local TAVI database. SmallBAV was defined as a small balloon size (=18 mm) pre-dilatation. Normal BAV was defined as aballoon size >18 mm. The primary endpoint was the incidence of new PPMI.RESULTS: Of 99 consecutive TAVI patients, five patients were excluded due to pre-existingpermanent pacemaker. Patients in the small BAV group (n=57) had a signifi cantly lower PPMI ratecompared with the normal BAV group (n=37) (3.5% vs. 18.9%, P=0.026). Moderate or severe aorticvalve regurgitation post-procedure was similar between the small BAV and normal BAV groups (5.3%vs. 8.1%, P=0.480);likewise, the mean aortic gradient post-procedure did not differ significantly(11.5±5.2 mmHg vs. 12.2±7.3 mmHg, 1 mmHg=0.133 kPa, P=0.580) between the groups. Devicesuccess rates were also similar (94.7% vs. 91.8%, P=0.680). In multivariable analysis, small BAV(P=0.027), the ratio of prosthesis diameter to annulus diameter (P=0.048), and mean aortic gradientby echo in the basement (P=0.021) were independent predictors of PPMI.CONCLUSIONS: The small BAV strategy is associated with a low rate of permanentpacemaker implantation after transcatheter self-expanding valve implantation in this single-centerobservational study.

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.

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.

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.