Association between high-density mapping of atypical atrial flutter, clinical outcomes and healthcare utilization.

BACKGROUND: Success of atypical atrial flutter (AAFL) ablation has historically been limited by difficulty mapping the complex re-entrant circuits involved. While high-density (HD) mapping has become commonplace in clinical practice, there are limited data on outcomes of HD versus non-HD mapping for AAFL ablation. OBJECTIVE: To compare clinical outcomes and healthcare utilization using HD mapping versus non-HD mapping for AAFL ablation. METHODS: Retrospective analysis of all AAFL procedures between 2005 and 2022 at an academic medical center was conducted. Procedures utilizing a 16-electrode HD Grid catheter and Precision mapping system were compared to procedures using prior generation 10-20 electrode spiral catheters and the Velocity system (Abbott, IL). Cox regression models and Poisson regression models were utilized to examine procedural and healthcare utilization outcomes. Models were adjusted for left ventricular ejection fraction, CHA2DS2-VASc, and history of prior ablation. RESULTS: There were 108 patients (62% HD mapping) included in the analysis. Baseline clinical characteristics were similar between groups. Use of HD mapping was associated with a higher rate of AAFL circuit delineation (92.5% vs. 76%; p = .014) and a greater adjusted procedure success rate, defined as non-inducibility at procedure end, (aRR (95% CI) 1.26 (1.02-1.55) p = .035) than non-HD mapping. HD mapping was also associated with a lower rate of ED visits (aIRR (95% CI) 0.32 (0.14-0.71); p = .007) and hospitalizations (aIRR (95% CI) 0.32 (0.14-0.68); p = .004) for AF/AFL/HF through 1 year. While there was a lower rate of recurrent AFL through 1 year among HD mapping cases (aHR (95% CI) 0.60 (0.31-1.16) p = .13), statistical significance was not met likely due to the low sample size and higher rate of ambulatory rhythm monitoring in the HD group (61% vs. 39%, p = .025). CONCLUSION: Compared to non-HD mapping, AAFL ablation with HD mapping is associated with improvements in the ability to define the AAFL circuit, greater procedural success, and a reduction in the number of ED visits and hospitalization for AF/AFL/HF.

Esophageal temperature management during cryoballoon ablation for atrial fibrillation.

INTRODUCTION: Esophageal thermal injury (ETI) is a well-recognized complication of atrial fibrillation (AF) ablation. Previous studies have demonstrated that direct esophageal cooling reduces ETI during radiofrequency AF ablation. The purpose of this study was to evaluate the use of an esophageal warming device to prevent ETI during cryoballoon ablation (CBA) for AF. METHODS: This prospective, double-blinded study enrolled 42 patients with symptomatic AF undergoing CBA. Patients were randomized to the treatment group with esophageal warming (42°C) using recirculated water through a multilumen, silicone tube inserted into the esophagus (EnsoETM®; Attune Medical) (WRM) or the control group with a luminal single-electrode esophageal temperature monitoring probe (LET). Patients underwent upper endoscopy esophagogastroduodenoscopy (EGD) the following day. ETI was classified into four grades. RESULTS: Baseline patient characteristics were similar between groups. Procedural characteristics including number of freezes, total freeze time, early freeze terminations, coldest balloon temperature, procedure duration, posterior wall ablation, and proton pump inhibitor and transesophageal echocardiogram use before procedure were not different between groups. The EGD was completed in 40/42 patients. There was significantly more ETI in the WRM group compared to the LET group (n = 8 [38%] vs. n = 1 [5%], p = 0.02). All ETI lesions were grade 1 (erythema) or 2 (superficial ulceration). Total freeze time in the left inferior pulmonary vein was predictive of ETI (360 vs. 300 s, p = 0.03). CONCLUSION: Use of a luminal heat exchange tube for esophageal warming during CBA for AF was paradoxically associated with a higher risk of ETI.

Patient-reported outcomes after cryoballoon ablation are equivalent between moderate sedation and general anesthesia.

INTRODUCTION: Moderate sedation (MS) during cryoballoon ablation (CBA) avoids risks of general anesthesia (GA) and improves electrophysiology (EP) lab throughput. However, one barrier to the use of MS is the potential for patient discomfort. The objective of this study was to compare patient-reported outcome measures following CBA for paroxysmal atrial fibrillation (pAF) under MS and GA. METHODS AND RESULTS: Consecutive patients undergoing a first CBA for pAF under GA or MS were prospectively enrolled. The sedation method was assigned based on patient and provider preference, and perceived airway risk. The primary outcomes were quality of recovery (measured using a validated 40 question survey; QoR-40) and likelihood to recommend (LTR) the procedure and sedation method (measured by Likert scale). Secondary outcomes were acute pulmonary vein (PV) isolation rate, procedure, fluoroscopy and ablation times, and complication rates. Forty-seven GA and 53 MS patients were included. The mean age was 64.9 ± 9.4 years and mean CHA2 DS2 -VASc score was 2.0 ± 1.4. QoR-40 scores were 184.6 ± 16.4 for GA and 187.6 ± 10.2 for MS (P = .28). LTR responses were similar between groups. Mean procedure times were 148.2 ± 56.0 minutes for GA and 129.4 ± 31.4 minutes for MS (P = .038). Fluoroscopy and ablation times were similar between groups. A total of 100% (409/409) of PVs were acutely isolated. One hemopericardium occurred in the MS group requiring pericardiocentesis. CONCLUSION: MS for CBA offers an alternative to GA that is safe and well-tolerated by patients with comparable success rates and improved EP lab throughput.

Immortalization of Different Breast Epithelial Cell Types Results in Distinct Mitochondrial Mutagenesis.

Different phenotypes of normal cells might influence genetic profiles, epigenetic profiles, and tumorigenicities of their transformed derivatives. In this study, we investigate whether the whole mitochondrial genome of immortalized cells can be attributed to the different phenotypes (stem vs. non-stem) of their normal epithelial cell originators. To accurately determine mutations, we employed Duplex Sequencing, which exhibits the lowest error rates among currently-available DNA sequencing methods. Our results indicate that the vast majority of the observed mutations of the whole mitochondrial DNA occur at low-frequency (rare mutations). The most prevalent rare mutation types are C→T/G→A and A→G/T→C transitions. Frequencies and spectra of homoplasmic point mutations are virtually identical between stem cell-derived immortalized (SV1) cells and non-stem cell-derived immortalized (SV22) cells, verifying that both cell types were derived from the same woman. However, frequencies of rare point mutations are significantly lower in SV1 cells (5.79 × 10-5) than in SV22 cells (1.16 × 10-4). The significantly lower frequencies of rare mutations are aligned with a finding of longer average distances to adjacent mutations in SV1 cells than in SV22 cells. Additionally, the predicted pathogenicity for rare mutations in the mitochondrial tRNA genes tends to be lower (by 2.5-fold) in SV1 cells than in SV22 cells. While four known/confirmed pathogenic mt-tRNA mutations (m.5650 G>A, m.5521 G>A, m.5690 A>G, m.1630 A>G) were identified in SV22 cells, no such mutations were observed in SV1 cells. Our findings suggest that the immortalization of normal cells with stem cell features leads to decreased mitochondrial mutagenesis, particularly in RNA gene regions. The mutation spectra and mutations specific to stem cell-derived immortalized cells (vs. non-stem cell derived) have implications in characterizing the heterogeneity of tumors and understanding the role of mitochondrial mutations in the immortalization and transformation of human cells.

Moderate Sedation Reduces Lab Time Compared to General Anesthesia during Cryoballoon Ablation for AF Without Compromising Safety or Long-Term Efficacy.

BACKGROUND: Cryoballoon ablation (CBA) for paroxysmal atrial fibrillation (pAF) can be performed under general anesthesia (GA) or moderate sedation (MS). Our objective was to compare the effectiveness, safety, procedure duration, and time spent in the electrophysiology (EP) laboratory for CBA performed under GA and MS. METHODS: Patients undergoing a first CBA for pAF were identified. Patients received either GA administered by an anesthesiologist or MS with midazolam and fentanyl administered by EP laboratory staff. Total time in laboratory (sum of procedure and nonprocedure time); fluoroscopy time; freedom from documented AF, atrial flutter, and atrial tachycardia (FFAF); acute pulmonary vein isolation (PVI) rate; and 30-day complication rate were assessed. RESULTS: A total of 55 patients received GA and 119 patients received MS. PVI success rate was 100% in GA and 98.1% in MS (P = 0.04). Total laboratory time was longer for GA (280.4 ± 54.1 minutes vs 245.5 ± 54.7 minutes; P < 0.001), related to longer nonprocedure time (92.2 ± 28.8 minutes GA vs 71.0 ± 30.0 minutes MS; P < 0.001), but not procedure time (188.3 ± 49.3 minutes GA vs 174.5 ± 50.2 minutes MS; P = 0.09). FFAF was not significantly different over a median follow-up duration of 0.9 (interquartile range 0.4-1.9) years (61.8% GA vs 63.0% MS; log-rank P = 0.90). There was no significant difference in complication rate. CONCLUSION: Compared to GA, MS during CBA for pAF was independently associated with shorter total EP laboratory time without compromising FFAF or complication rates.

Cryoballoon versus radiofrequency catheter ablation for paroxysmal atrial fibrillation.

BACKGROUND: Catheter ablation is an established treatment for atrial fibrillation (AF). Cryoballoon ablation (CBA) has emerged as an alternative to radiofrequency ablation (RFA). However, there are few data comparing these modalities for treatment of paroxysmal AF (pAF) in the U.S. POPULATION: The purpose of this study was to compare procedural times, safety, and efficacy of CBA against RFA. METHODS: A single-center prospective cohort study evaluated patients who underwent catheter ablation for pAF using CBA or RFA between January 1, 2010 and October 31, 2013. Patients with prior ablation and those without rhythm follow-up for at least 3 months were excluded. The primary end point was freedom from AF, atrial flutter, and atrial tachycardia (FFAF) >30 seconds after a 3-month blanking period without requirement for antiarrhythmic drugs. We also compared rates of successful pulmonary vein isolation (PVI), fluoroscopy and procedure times, and major complication rates. RESULTS: A total of 201 patients were included (CBA = 101, RFA = 100). The rate of successful PVI was 99.3% in CBA versus 97.4% in RFA (P = 0.08). Procedure times were shorter with CBA (192.9 ± 44.0 minutes vs 283.7 ± 78.0 minutes, P < 0.001) as well as total fluoroscopy times (46.0 ± 22.4 minutes vs 73.0 ± 30.1 minutes, P < 0.001). Overall complication rates were equivalent; however, fewer cardiac perforations occurred with CBA (0% vs 4%, P = 0.042). The 1-year FFAF rates were 60.3% for CBA and 61.1% for RFA (log rank P = 0.93). CONCLUSION: CBA was associated with equivalent 1-year FFAF rate as RFA for pAF. Procedure and fluoroscopy times were shorter for CBA and fewer cardiac perforations occurred.

Sleep deprivation impairs cAMP signalling in the hippocampus.

Millions of people regularly obtain insufficient sleep. Given the effect of sleep deprivation on our lives, understanding the cellular and molecular pathways affected by sleep deprivation is clearly of social and clinical importance. One of the major effects of sleep deprivation on the brain is to produce memory deficits in learning models that are dependent on the hippocampus. Here we have identified a molecular mechanism by which brief sleep deprivation alters hippocampal function. Sleep deprivation selectively impaired 3', 5'-cyclic AMP (cAMP)- and protein kinase A (PKA)-dependent forms of synaptic plasticity in the mouse hippocampus, reduced cAMP signalling, and increased activity and protein levels of phosphodiesterase 4 (PDE4), an enzyme that degrades cAMP. Treatment of mice with phosphodiesterase inhibitors rescued the sleep-deprivation-induced deficits in cAMP signalling, synaptic plasticity and hippocampus-dependent memory. These findings demonstrate that brief sleep deprivation disrupts hippocampal function by interfering with cAMP signalling through increased PDE4 activity. Thus, drugs that enhance cAMP signalling may provide a new therapeutic approach to counteract the cognitive effects of sleep deprivation.

Limited utility of current MRI criteria for distinguishing multiple sclerosis from common mimickers: primary and secondary CNS vasculitis, lupus and Sjogren's syndrome.

BACKGROUND: Magnetic resonance imaging (MRI) criteria play an important role in making an earlier diagnosis of multiple sclerosis (MS) in patients presenting with clinically isolated syndrome. OBJECTIVE: The objective of this paper is to determine whether MRI criteria may be used to distinguish MS from primary and secondary central nervous system (CNS) vasculitis, lupus, and Sjogren's syndrome. METHODS: MRI criteria were applied retrospectively to images for patients with clinically definite MS (CDMS), primary CNS vasculitis, secondary CNS vasculitis, and autoimmune disorders including systemic lupus erythematosus (SLE) and Sjogren's syndrome. Classical statistics and Bayesian analyses were performed. RESULTS: Overall modified Barkhof's MRI criteria were statistically significant in distinguishing CDMS (60%) from SLE/Sjogren's syndrome (17%, p = 0.0173) but not in distinguishing CDMS from primary CNS vasculitis (50%, p = 0.7376) or secondary CNS vasculitis (58%, p = 1.0000). Four of the five other MRI criteria tested were demonstrated to be superior to modified Barkhof's criteria in predicting MS: nine or more T2 lesions (a component of Barkhof's criteria), one or more ovoid periventricular T2 lesions, one or more perpendicular periventricular T2 lesions, and one or more T2 lesions larger than 6 mm. CONCLUSIONS: MRI criteria, including the modified Barkhof's criteria, were unsuccessful in distinguishing MS from primary CNS vasculitis or secondary CNS vasculitis and mildly successful in distinguishing MS from SLE/Sjogren's syndrome.

Safety and feasibility of intravenous sotalol loading for the prevention of ventricular arrhythmias.

BACKGROUND: The use of intravenous (IV) sotalol loading following recent U.S. Food and Drug Administration (FDA) approval of a 1-day loading protocol has reduced the obligatory 3-day hospital stay for sotalol initiation when given orally. Several studies have recently demonstrated the safety and feasibility of IV loading for patients with atrial arrhythmias. However, there is a paucity of data on the feasibility and safety of IV sotalol loading for patients with ventricular arrhythmias. This study aims to assess the safety, feasibility, and length of stay (LOS) outcomes of IV sotalol loading for the prevention of ventricular arrhythmias. METHODS: A retrospective analysis was performed of all patients undergoing IV sotalol loading and oral sotalol initiation for ventricular arrhythmias, or IV sotalol loading for atrial arrhythmias between August 2021 and December 2023 at Northwestern University. Baseline characteristics, success of sotalol initiation/loading, changes in heart rate (HR) and QT/QTc, safety, and LOS were compared between patients undergoing sotalol loading/initiation for ventricular arrhythmias (IV vs. PO) and between patients undergoing IV sotalol loading for ventricular arrhythmias vs. for atrial arrhythmias. RESULTS: A total of 28 patients underwent sotalol loading/initiation for ventricular arrhythmias (N = 15 IV and N = 13 PO) and 41 patients underwent IV sotalol loading for atrial arrhythmias. Baseline characteristics of congestive heart failure history and left ventricular ejection fraction were worse in the ventricular arrhythmias group. There was no significant difference in the successful completion of IV sotalol loading for ventricular arrhythmias compared to oral sotalol initiation for ventricular arrhythmias or IV sotalol loading for atrial arrhythmias (86.7% vs. 92.3% vs. 90.2%, p = 0.88). There was a significant increase in ΔQTc following IV sotalol infusion for ventricular arrhythmias compared to following PO sotalol initiation for ventricular arrhythmias (46.4 ± 29.2 ms vs. 8.9 ± 32.6 ms, p = 0.004) and following IV sotalol infusion for atrial arrhythmias (46.4 ± 29.2 ms vs. 24.0 ± 25.1 ms, p = 0.018). ΔHR following IV sotalol infusion for ventricular arrhythmias was similar to ΔHR following PO sotalol initiation for ventricular arrhythmias and ΔHR following IV sotalol infusion for atrial arrhythmias (- 7.5 ± 8.7 bpm vs. - 8.5 ± 13.9 bpm vs. - 8.3 ± 13.2 bpm, p = 0.87). There were no significant differences in discontinuation for QTc prolongation (6.7% vs. 1.7% vs. 2.4%, p = 0.64) and bradycardia (13.3% vs. 7.7% vs. 9.8%, p = 0.88) between IV sotalol loading for ventricular arrhythmias, PO sotalol initiation for ventricular arrhythmias, and IV sotalol loading for atrial arrhythmias. There were no instances of hypotension, life-threatening ventricular arrhythmias, heart failure, or death. Length of stay was significantly shorter for IV sotalol loading compared to PO sotalol initiation for ventricular arrhythmias (1.1 ± 0.36 days vs. 4.2 ± 1.0 days, p < 0.0001). CONCLUSION: IV sotalol loading appears feasible and safe for use in ventricular arrhythmias and results in a decreased length of stay. Despite increased comorbidities and greater increase in QTc interval following IV sotalol infusion in the ventricular arrhythmias group, there were no significant differences in successful completion of loading or adverse outcomes when compared to PO sotalol initiation for ventricular arrhythmias and IV loading for atrial arrhythmias.

Reversible, complete atrioventricular block caused by primary cardiac lymphoma in a nonimmunocompromised patient.

Primary cardiac lymphoma (PCL) is a rare entity that commonly presents as a heart rhythm disorder. We describe a previously healthy, immunocompetent patient presenting with complete atrioventricular block (AVB). The patient was found to have a cardiac mass on magnetic resonance imaging and underwent percutaneous biopsy eventually diagnosing PCL. After pacemaker implantation, the patient's tumor responded rapidly to chemotherapy and the AVB completely resolved. In otherwise healthy patients presenting with AV block, cardiac tumor should be considered. Additionally, if PCL is diagnosed and the patient is clinically stable with AVB, it may be reasonable to delay pacemaker implantation until the clinical response to chemotherapy is evaluated.

Prevalence and predictors of cable extrusion and loss of electrical integrity with the Riata defibrillator lead.

INTRODUCTION: Recently, a medical advisory was issued regarding the Riata and Riata ST silicone endocardial defibrillator leads (St. Jude Medical, Sylmar, CA, USA) addressing the issue of conductor cables extruding in an "inside-out" fashion from the main body of the lead. However, little data exist to guide our management of patients with these leads. METHODS AND RESULTS: A retrospective analysis was performed of 84 patients with a Riata lead who underwent cine-fluoroscopy and electrical evaluation as part of a screening program to assess for cable extrusion. All leads screened were dual-coil except for one single-coil lead. Of 84 patients, 23 patients (27.4%) had fluoroscopic evidence of cable extrusion. Multivariate analysis showed that the duration of time since lead implant and the presence of multiple right ventricular leads were significantly associated with cable extrusion. All 23 patients had normal electrical parameters on routine device interrogation. Fifteen of these 23 patients (65%) with extruded cables had high-voltage shocks within 12 months of lead screening; only one patient demonstrated postshock electrical abnormalities. CONCLUSIONS: The prevalence of cable extrusion in dual-coil Riata leads is significantly higher at 27.4% than previously reported. The duration of time since implantation and the presence of multiple right ventricular leads are associated with cable extrusion. High-energy shocks did not reveal electrical abnormalities in most patients with cable extrusion.

Dialysis therapy and mortality in older adults with heart failure and advanced chronic kidney disease: A high-dimensional propensity-matched cohort study.

BACKGROUND: Heart failure (HF) and chronic kidney disease (CKD) frequently coexist, and the combination is linked to poor outcomes, but limited data exist to guide optimal management. We evaluated the outcome of dialysis therapy in older patients with HF and advanced CKD. METHODS: We examined adults aged ≥70 years with HF and eGFR ≤20 ml/min/1.73 m2 between 2008-2012 and no prior renal replacement therapy, cancer, cirrhosis or organ transplant. We identified patients who initiated chronic dialysis through 2013 and matched patients who did not initiate dialysis on age, gender, diabetes status, being alive on dialysis initiation date, and a high-dimensional propensity score for starting dialysis. Deaths were identified through 2013. We used Cox regression to evaluate the association of chronic dialysis and all-cause death. RESULTS: Among 348 adults with HF and advanced CKD who initiated dialysis and 947 matched patients who did not start dialysis, mean age was 80±5 years, 51% were women and 33% were Black. The crude rate of death was high overall but lower in those initiating vs. not initiating chronic dialysis (26.1 vs. 32.1 per 100 person-years, respectively, P = 0.02). In multivariable analysis, dialysis was associated with a 33% (95% Confidence Interval:17-46%) lower adjusted rate of death compared with not initiating dialysis. CONCLUSIONS: Among older adults with HF and advanced CKD, dialysis initiation was associated with lower mortality, but absolute rates of death were very high in both groups. Randomized trials should evaluate net outcomes of dialysis vs. conservative management on length and quality of life in this high-risk population.

Roles of fragile X mental retardation protein in dopaminergic stimulation-induced synapse-associated protein synthesis and subsequent alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-4-propionate (AMPA) receptor internalization.

Fragile X syndrome, the most common form of inherited mental retardation, is caused by the absence of the RNA-binding protein fragile X mental retardation protein (FMRP). FMRP regulates local protein synthesis in dendritic spines. Dopamine (DA) is involved in the modulation of synaptic plasticity. Activation of DA receptors can regulate higher brain functions in a protein synthesis-dependent manner. Our recent study has shown that FMRP acts as a key messenger for DA modulation in forebrain neurons. Here, we demonstrate that FMRP is critical for DA D1 receptor-mediated synthesis of synapse-associated protein 90/PSD-95-associated protein 3 (SAPAP3) in the prefrontal cortex (PFC). DA D1 receptor stimulation induced dynamic changes of FMRP phosphorylation. The changes in FMRP phosphorylation temporally correspond with the expression of SAPAP3 after D1 receptor stimulation. Protein phosphatase 2A, ribosomal protein S6 kinase, and mammalian target of rapamycin are the key signaling molecules for FMRP linking DA D1 receptors to SAPAP3. Knockdown of SAPAP3 did not affect surface expression of alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-4-propionate (AMPA) GluR1 receptors induced by D1 receptor activation but impaired their subsequent internalization in cultured PFC neurons; the subsequent internalization of GluR1 was also impaired in Fmr1 knock-out PFC neurons, suggesting that FMRP may be involved in subsequent internalization of GluR1 through regulating the abundance of SAPAP3 after DA D1 receptor stimulation. Our study thus provides further insights into FMRP involvement in DA modulation and may help to reveal the molecular mechanisms underlying impaired learning and memory in fragile X syndrome.

Initial experience using a radiofrequency powered transseptal needle.

INTRODUCTION: The purpose of this study was to determine the safety and efficacy of using a novel radiofrequency (RF) powered transseptal needle to perform transseptal puncture (TSP). METHODS: TSP was performed in 35 consecutive patients undergoing left-sided catheter ablation (mean age = 51 years; male = 71%) using a RF powered transseptal needle (NRG, Adult Large and Standard Curve C1, 71 cm, Baylis Medical Company, Inc.). Prior TSP had been performed in 34% of patients. The transseptal apparatus was positioned with the tip of the dilator engaged in the fossa ovalis. RF energy was delivered to the tip of the transseptal needle using a proprietary RF generator at 10 W for 2 seconds as gentle pressure was applied to the needle. RESULTS: In 5 of the 41 TSPs, the needle crossed into the left atrium before RF energy was delivered. In 35 of the remaining 36 punctures, the needle was successfully advanced into the left atrium after application of RF current. In 1 patient, the TSP with the powered needle was unsuccessful but was accomplished using a standard needle. The only complication was a transient right atrial thrombus, which occurred in 2 patients. CONCLUSION: A radiofrequency powered transseptal needle can be used to perform TSP safely and successfully without the need for significant mechanical force, even in patients who have undergone TSP previously. Additional studies are needed to determine whether a powered transseptal needle should be used routinely.

Paroxysmal Atrial Fibrillation on Flecainide Therapy.

Flecainide pill-in-the-pocket therapy is a pharmacologic treatment option for patients with infrequent episodes of symptomatic atrial fibrillation. We report a case of wide complex tachycardia due to atrial flutter with 1:1 atrioventricular conduction in a patient who took pill-in-the-pocket flecainide without concomitant atrioventricular nodalblockade.

Vasospastic Arrest:: A Heart-Stopping Case of Prinzmetal Angina.

Vasospastic angina is an uncommon cause of cardiac arrest. We describe a patient who presented with sudden cardiac arrest due to severe coronary vasospasm. Telemetry during the event revealed ventricular arrhythmias and asystole followed by spontaneous self-conversion back to normal sinus rhythm. The patient underwent implantable cardioverter-defibrillator therapy. (Level of Difficulty: Beginner.).

Presynaptic and postsynaptic amplifications of neuropathic pain in the anterior cingulate cortex.

Neuropathic pain is caused by a primary lesion or dysfunction in the nervous system. Investigations have mainly focused on the spinal mechanisms of neuropathic pain, and less is known about cortical changes in neuropathic pain. Here, we report that peripheral nerve injury triggered long-term changes in excitatory synaptic transmission in layer II/III neurons within the anterior cingulate cortex (ACC). Both the presynaptic release probability of glutamate and postsynaptic glutamate AMPA receptor-mediated responses were enhanced after injury using the mouse peripheral nerve injury model. Western blot showed upregulated phosphorylation of GluR1 in the ACC after nerve injury. Finally, we found that both presynaptic and postsynaptic changes after nerve injury were absent in genetic mice lacking calcium-stimulated adenylyl cyclase 1 (AC1). Our studies therefore provide direct integrative evidence for both long-term presynaptic and postsynaptic changes in cortical synapses after nerve injury, and that AC1 is critical for such long-term changes. AC1 thus may serve as a potential therapeutic target for treating neuropathic pain.

Effects of electrocautery on transvenous lead insulation materials.

INTRODUCTION: Insulation defects are a leading cause of transvenous lead failure. The purpose of this study was to determine the effects of electrocautery on transvenous lead insulation materials. METHODS: A preparation was done to simulate dissection of a transvenous lead from tissues. Radiofrequency energy was delivered using a standard cautery blade at outputs of 10, 20, and 30 W, for 3 and 6 seconds, using parallel and perpendicular blade orientations on leads with outermost insulations of silicone rubber, polyurethane, and silicone-polyurethane copolymer. Damage to each lead segment was classified after visual and microscopic analysis. RESULTS: Significant insulation damage occurred to almost all polyurethane leads. Full insulation breaches were observed with 30 W regardless of application duration with a parallel direction and with all power outputs with a perpendicular direction. Thermal insulation damage to copolymer insulation was similar to that of the polyurethane leads. In contrast, there was no thermal damage to silicone leads, regardless of the power output and duration of power delivery. However, mechanical insulation damage was observed to all silicone leads when at least 20 W was applied in a direction perpendicular to the lead. CONCLUSIONS: Polyurethane (PU55D) and copolymer materials have low thermal stability and are highly susceptible to thermal damage during cautery. Implanting physicians should be aware of the lead insulation materials being used during implant procedures and their properties. The use of direct contact cautery on transvenous leads should be minimized to avoid damage to the lead, especially on leads with polyurethane or copolymer outer insulations.