Inhibitory effect of 405 nm laser light on bacterial biofilm in urethral stent.

The clinical use of urethral stents is usually complicated by various adverse effects, including dysuria, fever, and urinary tract infection (UTI). Biofilms (formed by bacteria, such as Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus) adhering to the stent cause UTIs in stented patients (approximately 11%). The undesirable consequences of antibiotics use include bacterial resistance, weight gain, and type 1 diabetes, which occur when antibiotics are used for a long time. We aimed to assess the efficacy of a new optical treatment with a 405 nm laser to inhibit bacterial growth in a urethral stent in vitro. The urethral stent was grown in S. aureus broth media for three days to induce biofilm formation under dynamic conditions. Various irradiation times with the 405 nm laser light were tested (5, 10, and 15 min). The efficacy of the optical treatment on biofilms was evaluated quantitatively and qualitatively. The production of reactive oxygen species helped eliminate the biofilm over the urethral stent after 405 nm irradiation. The inhibition rate corresponded to a 2.2 log reduction of colony-forming units/mL of bacteria after 0.3 W/cm2 of irradiation for 10 min. The treated stent showed a significant reduction in biofilm formation compared with the untreated stent, as demonstrated by SYTO 9 and propidium iodide staining. MTT assays using the CCD-986sk cell line revealed no toxicity after 10 min of irradiation. We conclude that optical treatment with 405 nm laser light inhibits bacterial growth in urethral stents with no or minimal toxicity.

Facile synthesis of black phosphorus-zinc oxide nanohybrids for antibacterial coating of titanium surface.

Bacterial infection is a major complication associated with bioimplant materials, including titanium (Ti) based orthopedic joints and dental implants. Thus, the fabrication of Ti surfaces with antibacterial activity is highly important. Black phosphorus (BP) is a recently discovered promising two-dimensional semiconductor for various biomedical applications due to its tunable bandgap and physicochemical properties. The present study aimed to synthesize zinc oxide (ZnO) laden BP nanohybrids (NH) and their coatings on a Ti bioimplant surface for improving the antibacterial activities against pathogenic bacteria with and without near-infrared (NIR) light irradiation. Nanohybrids were produced with the slightly oxidized BP NF and electrostatically laden ZnO NP. The produced BP-ZnO NH was a NIR active nanomaterial (up to ∼1000 nm), demonstrating a photothermal effect against bacterial infection and showing improved activity by damaging the cell membrane towards S. aureus in comparison to E. coli. Ti surface coated with BP-ZnO NH embedded chitosan (CS) demonstrated better antibacterial activity than BP NF, especially with NIR light treatment. Additionally, the produced BP nanoflakes and BP-ZnO NH, and their coatings over the Ti surface were found to be toxic at a negligible level. Electrochemical studies revealed the high corrosion resistance of the Ti surface coated with the synthesized antibacterial agents without altering its characteristic passive behavior. Owing to the interactions between the charged groups between chitosan and cell surfaces, a slight increase in antibacterial activities was noticed. Chitosan-based coating matrix embedded with nanoagents has adhered well over the Ti surface due to its inherent film-forming and high adhesion properties.

Real-time monitoring of mono- and dual-species biofilm formation and eradication using microfluidic platform.

In a human host, bacterial Staphylococcus aureus and fungal Candida albicans pathogens form a mixed biofilm that causes severe mortality and morbidity. However, research on the formation and eradication of mixed biofilms under dynamic conditions is lacking. Thus, this study employed a microfluidic technique to analyze the real-time formation of mono- and dual-species (S. aureus and C. albicans) biofilms and noninvasive optical treatment of the established mature biofilm using 405-nm laser light. A herringbone mixer thoroughly mixed both bacterial and fungal cells in the growth media before being injected into the observation channels on the microfluidic chip. At a flow rate of 1.0 µL/min of growth media for 24 h, the bacterial biofilm coverage was up to 15% higher than that of the fungal biofilm (50% for bacteria vs. 35% for fungus). On the other hand, the dual-species biofilm yielded the highest coverage of ~ 96.5% because of the collective interaction between S. aureus and C. albicans. The number of cell proliferation events in S. aureus was higher than that of C. albicans for 12 h, which indicates that the S. aureus biofilm was developed faster than C. albicans. The novel in situ test platform showed a significant bactericidal effect (80%) of the 405-nm laser light at 1080 J/cm2 towards the established S. aureus biofilm, whereas the same treatment removed approximately 69% of the mixed cells in the dual-species biofilm. This study revealed that the developed microfluidic platform could be utilized to monitor the formation of dual-species biofilms in real-time and laser-induced antimicrobial effects on dual-species biofilms.

Collective bacterial disinfection by opto-chemical treatment on mature biofilm in clinical endoscope.

The present study proposes an innovative opto-chemical treatment using a basket-integrated optical device (BIOD) to disinfect mature bacterial biofilm on endoscope channels. A BIOD was designed to position an optical diffuser on the central axis of an endoscope channel and to distribute laser light concentrically to the bacterial biofilm on the channel surface. To apply thermal damage and oxidative stress to the bacterial biofilm, a low concentration of a crosslinking agent (glutaraldehyde ~0.5%) was combined with 808 nm infrared (IR) and 405 nm blue (BL) laser lights. The applied irradiances of IR and BL were 10 W/cm2 and 1.6 W/cm2 for Teflon channel model and 20 W/cm2 and 3.2 W/cm2 for a clinical model, respectively. Individual irradiation of either IR or BL for 180 s induced the maximum temperatures of 62 ± 2 °C and 53 ± 3 °C on the biofilm, respectively. The simultaneous opto-chemical treatment reduced a significant population of the bacterial biofilms (7.5-log10 for Staphylococcus aureus and 7.1-log10 for Pseudomonas aeruginosa), which were 2.9-fold and 3.9-fold higher than that of the standard treatment with 2% glutaraldehyde (GA) solution, respectively. The proposed opto-chemical disinfection method can help reduce multi-drug resistant bacteria and prevent cross-infection during the clinical usage of a flexible endoscope.

Enhanced precision of real-time control photothermal therapy using cost-effective infrared sensor array and artificial neural network.

Photothermal therapy (PTT) requires tight thermal dose control to achieve tumor ablation with minimal thermal injury on surrounding healthy tissues. In this study, we proposed a real-time closed-loop system for monitoring and controlling the temperature of PTT using a non-contact infrared thermal sensor array and an artificial neural network (ANN) to induce a predetermined area of thermal damage on the tissue. A cost-effective infrared thermal sensor array was used to monitor the temperature development for feedback control during the treatment. The measured and predicted temperatures were used as inputs of fuzzy control logic controllers that were implemented on an embedded platform (Jetson Nano) for real-time thermal control. Three treatment groups (continuous wave = CW, conventional fuzzy logic = C-Fuzzy, and ANN-based predictive fuzzy logic = P-Fuzzy) were examined and compared to investigate the laser heating performance and collect temperature data for ANN model training. The ex vivo experiments validated the efficiency of fuzzy control with temperature method on maintaining the constant interstitial tissue temperature (80 ± 1.4 °C) at a targeted surface of the tissue. The linear relationship between coagulation areas and the treatment time was indicated in this study, with the averaged coagulation rate of 0.0196 cm2/s. A thermal damage area of 1.32 cm2 (diameter ∼1.3 cm) was observed under P-Fuzzy condition for 200 s, which covered the predetermined thermal damage area (diameter ∼1 cm). The integration of real-time feedback temperature control with predictive ANN could be a feasible approach to precisely induce the preset extent of thermal coagulation for treating papillary thyroid microcarcinoma.

Opto-chemical treatment for enhanced high-level disinfection of mature bacterial biofilm in a Teflon-based endoscope model.

Medical societies and public health agencies rigorously emphasize the importance of adequate disinfection of flexible endoscopes. The aim of this work was to propose a novel opto-chemical disinfection treatment against Staphylococcus aureus grown in mature biofilm on Teflon-based endoscope channel models. Laser irradiation using near-infrared and blue wavelengths combined with a low concentration of chemical disinfectant induced both irreversible thermal denaturation and intercellular oxidative stress as a combined mechanism for an augmented antimicrobial effect. The opto-chemical method yielded a 6.7-log10 reduction of the mature Staphylococcus aureus biofilms (i.e., approximately 1.0-log10 higher than current requirement of standard treatment). The proposed technique may be a feasible disinfection method for mitigating the risk associated with infection transmission.

Multiple cylindrical interstitial laser ablations (CILAs) of porcine pancreas in ex vivo and in vivo models.

BACKGROUND: The therapeutic capacity of multiple cylindrical interstitial laser ablations (CILAs) of pancreatic tissue was evaluated with 1064 nm laser light in ex vivo and in vivo porcine pancreatic models. METHODS: A diffusing applicator was sequentially employed to deliver 1064 nm laser light in a cylindrical distribution to ablate a large volume of pancreatic tissue. Ex vivo tissue was tested at various power levels (5, 7, and 10 W) under US imaging. An in vivo porcine model was used to evaluate the clinical feasibility of multiple CILAs on pancreatic tissue at 5 W via laparotomy (N = 3). RESULTS: Multiple CILAs symmetrically ablated a range of ex vivo tissue volumes (2.4-6.0 cm3) at various power levels. Multiple CILAs warranted a therapeutic capacity of symmetrically ablating in vivo pancreatic tissue. Both ex vivo and in vivo pancreatic tissues after multiple CILAs at 5 W confirmed the absence of or minimal thermal injury to the peripheral tissue and carbonization. CONCLUSIONS: The current findings suggest that the collective thermal effects from multiple CILAs can help widely ablate pancreatic tissue with minimal thermal injury. Further in vivo studies will investigate the safety of the proposed CILA treatment as well as acute/chronic responses of pancreatic tissue for clinical translations.

Endoscopic ultrasound (EUS)-guided cylindrical interstitial laser ablation (CILA) on in vivo porcine pancreas.

This study aims to demonstrate the feasibility of cylindrical interstitial laser ablation (CILA) in porcine pancreatic tissue to develop a EUS-guided PC ablation technique with enhanced safety. A diffusing applicator created a uniformly symmetrical laser ablation in pancreatic tissue. Ex vivo tests presented that both ablation thickness and volume increased linearly with the applied power (R2 = 0.96 and 0.90, respectively) without carbonization and fiber degradation. The numerical simulations matched well with the experimental results in terms of temperature development and thermal damage (deviation of ≤ 15%). In vivo tests with EUS confirmed easy insertion and high durability of the diffusing applicator. EUS-guided CILA warranted a feasible therapeutic capacity of ablating in vivo pancreatic tissue. The proposed EUS-guided CILA can be a feasible therapeutic approach to treat PC with predictable thermal ablation and enhanced safety.

Effect of optical energy modulation on the thermal response of biological tissue: computational and experimental validations.

This study develops an energy modulation technique to attain a constant interstitial tissue temperature and to induce the predetermined thermal coagulation without carbonization in tissue. An optical diffuser was employed to deliver 1064 nm light to the biological tissue. The combined mode maintained the interstitial temperature at 70 °C for longer durations compared to the continuous wave mode. Coagulation volumes increased linearly with the time and met the predetermined treatment volume range (0.32-0.52 cm3) after the combined treatment for 100 s. The combined modulation can be a feasible modality to induce the predetermined extent of thermal coagulation for treating papillary thyroid microcarcinoma.

Re-entrant ventricular tachycardia as a complication of ablation of idiopathic ventricular premature beats from the right outflow tract: a case report.

BACKGROUND: We report an unusual case of non-sustained ventricular tachycardia (NSVT) from the epicardial part of the right ventricular outflow tract (RVOT). CASE SUMMARY: A 37-year-old woman who underwent in 2006 an ablation for idiopathic ventricular premature beats (VPBs) from the RVOT presented with pre-syncopal NSVT in 2016. A cardiac workup showed no coronary disease, normal biventricular function, and no enhancement on cardiac magnetic resonance imaging. A metabolic positron emission tomography scan excluded inflammation. Biopsies revealed normal desmosomal proteins. An endocardial mapping revealed an area of low voltage potential (<0.5 mV) at the antero-septal aspect of the RVOT corresponding to the initial site of ablation from 2006. Activation mapping revealed poor prematurity and pace-mapping showed unsatisfactory morphologies in the RVOT, the left ventricle outflow tract and the right coronary cusp. An epicardial map revealed a low voltage area at the antero-septal aspect of the RVOT with fragmented potentials opposite to the endocardial scar. Pace-mapping demonstrated perfect match. An NSVT was induced and local electrocardiogram showed mid-diastolic potentials. Ablation was applied epicardially and endocardially without any complication. The patient was arrhythmia free at 4-year follow-up. DISCUSSION: Cardiac workup allowed to exclude specific conditions such as arrhythmogenic cardiomyopathy, tetralogy of Fallot, sarcoidosis, or myocarditis as a cause for NSVT from the RVOT. The epi and endocardial map showed residual scar subsequent to the first ablation which served as substrate for the re-entrant NSVT. This is the first case which describes NSVT from the epicardial RVOT as a complication from a previous endocardial ablation for idiopathic VPB.

Outcome of video-assisted thoracoscopic implantation of epicardial left ventricular leads with visual targeting for cardiac resynchronization therapy.

OBJECTIVES: Our goal was to analyse the implantation and outcome of thoracoscopic epicardial leads after a failed endovascular approach or follow-up (FU) complications after endovascular implantation. METHODS: We reviewed the records of patients with failed endovascular left ventricular (LV) lead placement or complications during FU, who were subsequently referred to cardiac surgeons for treatment with thoracoscopic LV lead implantation. We analysed the reasons for endovascular failure; the indications for the surgical procedures; and the clinical, echocardiographic and device FU results. RESULTS: Between 2010 and 2013, a total of 23 patients were included. Among them, 17 of the patients had no previous cardiothoracic surgery, 13 (76%) had successful video-assisted thoracoscopy (VAT) LV lead implantation, 3 (18%) had a conversion to thoracotomy and 1 (6%) failed. Of the 6 patients with prior cardiothoracic surgery, 2 (33%) had VAT only, 3 (50%) had primary thoracotomies and 1 (17%) had a conversion. Two major complications occurred. The reasons for LV endovascular lead failure were subclavian vein occlusion (n = 2), implant failure (n = 13) and complications during the FU period (n = 8). FU information was available for 20 patients: 17 (85%) had improved symptoms. The median FU period was 33 months. A total of 78% of patients were in New York Heart Association (NYHA) functional class III-IV before the operation; 30% were in NYHA functional class III-IV at the last FU examination. The left ventricular ejection fraction increased from 25% before surgery to 31% at the last FU examination. Overall, sensing and pacing threshold values remained stable over time. In 1 patient, lead revision was necessary due to an increase in the pacing threshold. CONCLUSIONS: VAT implantation of LV leads had an excellent response rate with an improvement in NYHA functional class and left ventricular ejection fraction. The lead measurements were mainly stable over time.

Leadless pacing using the transcatheter pacing system (Micra TPS) in the real world: initial Swiss experience from the Romandie region.

AIMS: Leadless pacemakers are implanted in Switzerland since June 2015. Large worldwide registries have shown high implant success, low complication rates, and good electrical parameters up to 12 months' follow-up. However, data are scarce outside the investigational setting. The purpose of this study is to assess the real-world experience regarding clinical safety and efficacy of Micra TPS (transcatheter pacing system) leadless pacemakers. METHODS AND RESULTS: Retrospective observational, multi-centre study designed to assess initial safety and efficacy of the Micra TPS in the Swiss Romande region. A total of 92 patients were included from four different centres with an implantation success rate of 97.8% (90 of 92). Thresholds were overall low at implantation (median 0.38 V/0.24 ms, ranging from 0.13 to 2.88 V/0.24 ms) and remained stable over 1-year follow-up. The perioperative serious adverse event rate was 6.5% in six patients which lead to prolonged hospitalization in five patients and death in one patient. In addition, three further major events (3.3%) occurred during an average follow-up of 1 year, requiring implantation of a standard transvenous pacemaker in two patients, and surgical explantation of the Micra TPS in one patient due to intractable ventricular tachycardia. CONCLUSION: Leadless pacemakers are a valuable adjunct for treating selected patients requiring single-chamber pacing. However, in this initial experience, major complication rates were high (9.8%). The implant procedure requires proper training and should be performed in an adequate setting.

Computational analysis of linear energy modulation for laser thermal coagulation.

Accurate treatment planning and monitoring are critical factors to ensure safe and effective outcomes of laser thermal coagulation (LTC). Computational and experimental models based upon linear energy modulation were deployed to predict temperature distribution and thermal damage within ex vivo porcine liver. 1470-nm Gaussian emission was confirmed by using digital imaging and the customized goniometry. The tissue temperature was maintained in the pre-determined range (65~75 °C) to induce thermally destructive volumes of 0.23 cm3 (simulation) and 0.17 ± 0.05 cm3 (experiment) once the applied power was linearly reduced from 3.5 W to 0.2 W in 50 s ("3.5 W fast slope" laser modulation mode). The proposed model may be a useful tool to predict thermal responses of the tissue during LTC.

Antibacterial activity of Staphylococcus aureus biofilm under combined exposure of glutaraldehyde, near-infrared light, and 405-nm laser.

Healthcare-associated infections have increasingly become problematic in the endoscopic procedures resulting in several severe diseases such as carbapenem-resistant Enterobacteriaceae (CRE)-related infections, pneumonia, and bacteremia. Especially, some bacterial strains are resistant to traditional antimicrobials. Therefore, the necessity of developing new antibiotics or management to deal with bacterial infections has been increasing. The current study combined a low concentration of glutaraldehyde (GTA) with near-infrared (NIR) light and 405-nm laser to entail antibacterial activity on Staphylococcus aureus biofilm. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and colony forming unit (CFU) counting were used to quantify the viable cells while fluorescent and scanning electron microscopic images were used to qualitatively evaluate the cell membrane integrity and structural deformation, respectively. Practically, S. aureus biofilm was highly susceptible (7% cell viability and 6.8-log CFU/cm2 bacterial reduction for MTT assay and CFU analysis, respectively) to the combination of GTA (0.1%), NIR light (270 J/cm2), and 405-nm laser (288 J/cm2) exposure. GTA could form either DNA-protein or protein-protein crosslinks to inhibit DNA and protein synthesis. The NIR light induced the thermal damage on protein/enzymes while 405-nm laser could induce reactive oxygen species (ROS) to damage the bacterial membrane. Thus, the proposed technique may be a feasible modality for endoscope cleaning to prevent any secondary infection in the healthcare industry.

Effect of spatial light distribution on the thermal response of vascular tissue.

The aim of the current study is to investigate the effect of radial and cylindrical light distributions on the response of vascular tissue during 1470-nm irradiation in ex vivo models. Due to a low irradiance (5.3 W/cm2) and wide light distribution, cylindrically diffusing irradiation yielded uniform thermal coagulation while radial irradiation accompanied delamination of layers in leporine veins. Bovine foot model testing verified that the diffusing irradiation was associated with the steady maximum temperature and no tissue attachment, compared with the radial irradiation. The proposed cylindrical light application can be a feasible way to treat varicose veins in an effective manner.

[Cardiology update in 2016]. / Cardiologie.

In 2016 the European Society of Cardiology (ESC) published new guidelines. These documents update the knowledge in various fields such as atrial fibrillation, heart failure, cardiovascular prevention and dyslipidemia. Of course it is impossible to summarize these guidelines in detail. Nevertheless, we decided to highlight the major modifications, and to emphasize some key points that are especially useful for the primary care physician.

L'année 2016 en cardiologie a été marquée par la publication de nouvelles recommandations, par la Société européenne de cardiologie (ESC). Ces documents actualisent les connaissances dans des domaines variés que sont la fibrillation auriculaire, l'insuffisance cardiaque, la prévention cardiovasculaire et les dyslipidémies. Il est bien entendu impossible de synthétiser ces recommandations de façon exhaustive. Néanmoins, il nous a paru important de résumer les nouveautés majeures, mais également de rappeler certains points essentiels et surtout utiles pour le médecin de premier recours.

Spatial effect of conical angle on optical-thermal distribution for circumferential photocoagulation.

A uniformly diffusing applicator can be advantageous for laser treatment of tubular tissue. The current study investigated various conical angles for diffuser tips as a critical factor for achieving radially uniform light emission. A customized goniometer was employed to characterize the spatial uniformity of the light propagation. An ex vivo model was developed to quantitatively compare the temperature development and irreversible tissue coagulation. The 10-mm diffuser tip with angle at 25° achieved a uniform longitudinal intensity profile (i.e., 0.90 ± 0.07) as well as a consistent thermal denaturation on the tissue. The proposed conical angle can be instrumental in determining the uniformity of light distribution for the photothermal treatment of tubular tissue.

Thromboembolic events 7-11 years after catheter ablation of atrial fibrillation.

BACKGROUND: The results of catheter ablation of atrial fibrillation (AF) beyond 6 years remain unknown. The goal of this study is to assess the risk of thromboembolic events (TEs) and outcomes of AF ablation at long-term follow-up (FU). METHODS: All patients who had AF ablation from 2002 until 2005 in our center were contacted for a FU including a questionnaire, cardiac rhythm monitoring, and transthoracic echocardiography. RESULTS: Among the 264 eligible patients, 164 (62%) completed the study. The mean FU was 9.1 years (7.7-10.5). Seven patients had a TE during FU (event ratio 0.41 per 100 patient years [PY]) and their mean CHA2DS2-VASc score was 3.1 ± 1.3. Two patients died from stroke (0.14 per 100 PY) and five of the seven were considered in sinus rhythm (SR) and were off anticoagulation at the time of event. Prior to ablation, 13 patients had history of TE, and only one had a TE during FU. Overall, 14 deaths were documented (0.58 per 100 PY). Stable SR was present in 111 patients (68% of 164 patients) after 1.5 ± 0.6 procedures/patient. Univariate analysis showed that dyslipidemia (odds ratio [OR] = 2.95, P = 0.003), CHA2DS2-VASc ≥2 (OR = 3.22, P = 0.001), and amiodarone (OR = 5.64, P < 0.001) were predictors of long-term recurrence. Multivariate analysis showed that only CHA2DS2-VASc ≥2 (OR = 2.67, P = 0.023) and amiodarone (OR = 4.62, P = 0.001) were predictors. CONCLUSIONS: Our study shows low TE rates 9 years after ablation of AF that are lower than published data for AF patients with anticoagulation only. AF patients with a CHA2DS2-VASc ≥2 should, however, be maintained on anticoagulation.

Molecular epidemiology of rotavirus diarrhoea among children in Haiphong, Vietnam: the emergence of G3 rotavirus.

From September 2006- October 2007 hospital-based surveillance was conducted in Haiphong, Vietnam among children less than age 5 years hospitalized for diarrhoea to determine the distribution of G and P types and electropherotypes of rotavirus. Of note, the emergence of G3P[8] was identified and the strain was predominant among rotaviruses detected. More than 90% of G3P[8] electropherotyped strains shared an identical electropherotype, indicating they were of a single origin and their VP7 sequences were similar to those reported from Japan and China. This abrupt emergence of a novel G3 strains underscores the continued need for quality rotavirus surveillance.

Pacing-induced cardiac gap junction remodeling: modulation of connexin43 phosphorylation state.

BACKGROUND: Altered myocardial distribution of gap junctions and intercellular coupling have been implicated in nonuniform conduction of the depolarization wave and repolarization asynchrony in the mammalian heart. We tested the hypothesis that short-term cardiac pacing is associated with structural remodeling of gap junctions and their altered spatial distribution in cardiac myocytes in the immediate vicinity of the pacing site. MATERIALS AND METHODS: Isolated adult male rat hearts (n = 8) were perfused using a Langendorff apparatus. A multimicroelectrode array pacing catheter was positioned in the endocardial apical region of the right ventricle. Pacing (330 bpm; stimulus: 1.5 V, 5 milliseconds) was applied for 3 hours. Immunoblotting and immunohistochemical assays [using serine specific (Ser368) anti-connexin43 and anti-phosphoserine antibody] were used to determine the phosphorylation state of connexin43 (Cx43) and to determine its spatial distribution. RESULTS: Pacing was associated with a consistent, increased dephosphorylation state of Cx43 at the pacing site when compared to remote regions. In control hearts, Cx43 manifested a predominantly phosphorylated state; Western blotting analysis showed that dephosphorylated Cx43 was more abundant (1.5 +/- 0.33-fold) in the paced hearts than in controls (P < 0.02). Global cardiac function parameters, such as developed left ventricular pressure and oxygen demand index (rate-pressure product), did not differ significantly in paced hearts compared with controls (P > 0.05). CONCLUSIONS: A relatively short period of cardiac asynchronous pacing is associated with remodeling of gap junctions as manifested in the altered phosphorylation state of their constituent Cx43. This effect is confined to the myocardial tissue surrounding the pacing electrodes and does not alter global cardiac mechanics and energetics. These results, considered together with the known involvement of Ser368 in the gating of Cx43 and the putative role of Cx43 in the intercellular conductance, suggest that pacing-induced localized gap junctional remodeling could contribute to the creation of a reentrant substrate.