Use of Ripple mapping to enhance localization and ablation of outflow tract premature ventricular contractions.

INTRODUCTION: Accurate localization of septal outflow tract premature ventricular contractions (PVCs) is often difficult due to frequent mid-myocardial or protected origin. Compared with traditional activation mapping, CARTO Ripple mapping provides visualization of all captured electrogram data without assignment of a specific local activation time and thus may enhance PVC localization. METHODS: Electroanatomic maps for consecutive catheter ablation procedures for septal outflow tract PVCs (July 2018-December 2020) were analyzed. For each PVC, we identified the earliest local activation point (EA), defined by the point of maximal -dV/dt in a simultaneously recorded unipolar electrogram, and the earliest Ripple signal (ERS), defined as the earliest point at which three grouped simultaneous Ripple bars appeared in late diastole. Immediate success was defined as full suppression of the clinical PVC. RESULTS: Fifty-seven unique PVCs in 55 procedures were included. When ERS and EA were in the same chamber (RV, LV, or CS), the odds ratio for the successful procedure was 13.1 (95% confidence interval [CI] 2.2-79.9, p = .005). Discordance between sites was associated with a higher likelihood of needing multi-site ablation (odds ratio [OR] 7.9 [1.4-4.6; p = .020]). Median EA-ERS distance in successful versus unsuccessful cases was 4.6 mm (interquartile range 2.9-8.5) versus 12.5 mm (7.8-18.5); (p = .020). CONCLUSION: Greater EA-ERS concordance was associated with higher odds of single-site PVC suppression and successful septal outflow tract PVC ablation. Visualization of complex signals via automated Ripple mapping may offer rapid localization information complementary to local activation mapping for PVCs of mid-myocardial origin.

Electronic alerts to initiate anticoagulation dialogue in patients with atrial fibrillation.

IMPORTANCE: The benefit of an electronic support system for the prescription and adherence to oral anticoagulation therapy among patients with atrial fibrillation (AF) and atrial flutter at heightened risk for of stroke and systemic thromboembolism is unclear. OBJECTIVE: To evaluate the effect of a combined alert intervention and shared decision-making tool to improve prescription rates of oral anticoagulation therapy and adherence. DESIGN, SETTING, AND PARTICIPANTS: A prospective single arm study of 939 consecutive patients treated at a large tertiary healthcare system. EXPOSURES: An electronic support system comprising 1) an electronic alert to identify patients with AF or atrial flutter, a CHA2DS2-VASc score ≥ 2, and not on oral anticoagulation and 2) electronic shared decision-making tool to promote discussions between providers and patients regarding therapy. MAIN OUTCOMES AND MEASURES: The primary endpoint was prescription rate of anticoagulation therapy. The secondary endpoint was adherence to anticoagulation therapy defined as medication possession ratio ≥ 80% during the 12 months of follow-up. RESULTS: Between June 13, 2018 and August 31, 2018, the automated intervention identified and triggered a unique alert for 939 consecutive patients with AF or atrial flutter, a CHA2DS2-VASc score ≥2 who were not on oral anticoagulation. The median CHA2DS2-VASc score among all patients identified by the alert was 2 and the median untreated duration prior to the alert was 495 days (interquartile range 123 - 1,831 days). Of the patients identified by the alert, 345 (36.7%) initiated anticoagulation therapy and 594 (63.3%) did not: 68.7% were treated with a non-Vitamin K antagonist oral anticoagulant (NOAC), 22.0% with warfarin, and 9.3 % combination of NOAC and warfarin. Compared with historical anticoagulation rates, the electronic alert was associated with a 23.6% increase in anticoagulation prescriptions. The overall 1-year rate of adherence to anticoagulant therapy was 75.4% (260/345). CONCLUSION AND RELEVANCE: An electronic automated alert can successfully identify patients with AF and atrial flutter at high risk for stroke, increase oral anticoagulation prescription, and support high rates of adherence.

Leadless pacemaker implantation after lead extraction for cardiac implanted electronic device infection.

BACKGROUND: Cardiac implanted electronic device (CIED) pocket and systemic infection remain common complications with traditional CIEDs and are associated with high morbidity and mortality. Leadless pacemakers may be an attractive pacing alternative for many patients following complete hardware removal for a CIED infection by eliminating surgical pocket-related complications as well as lower risk of recurrent complications. OBJECTIVE: To describe use and outcomes associated with leadless pacemaker implantation following extraction of a CIED system due to infection. METHODS: Patient characteristics and postprocedural outcomes were described in patients who underwent leadless pacemaker implantation at Duke University Hospital between November 11, 2014 and November 18, 2019, following CIED infection and device extraction. Outcomes of interest included procedural complications, pacemaker syndrome, need for system revision, and recurrent infection. RESULTS: Among 39 patients, the mean age was 71 ± 17 years, 31% were women, and the most frequent primary pacing indication was complete heart block (64.1%) with 9 (23.1%) patients being pacemaker dependent at the time of Micra implantation. The primary organism implicated in the CIED infection was Staphylococcus aureus (43.6%). Nine of the 39 patients had a leadless pacemaker implanted before or on the same day as their extraction procedure, and the remaining 30 patients had a leadless pacemaker implanted after their extraction procedure. During follow-up (mean 24.8 ± 14.7 months) after leadless pacemaker implantation, there were a total of 3 major complications: 1 groin hematoma, 1 femoral arteriovenous fistula, and 1 case of pacemaker syndrome. No patients had evidence of recurrent CIED infection after leadless pacemaker implantation. CONCLUSIONS: Despite a prior CIED infection and an elevated risk of recurrent infection, there was no evidence of CIED infection with a mean follow up of over 2 years following leadless pacemaker implantation at or after CIED system removal. Larger studies with longer follow-up are required to determine if there is a long-term advantage to implanting a leadless pacemaker versus a traditional pacemaker following temporary pacing when needed during the periextraction period in patients with a prior CIED infection.

Safety and efficacy outcomes of left atrial posterior wall isolation compared to pulmonary vein isolation and pulmonary vein isolation with linear ablation for the treatment of persistent atrial fibrillation.

BACKGROUND: Pulmonary wall isolation (PWI) is increasingly used as an adjunctive lesion set to compliment pulmonary vein isolation (PVI), especially in patients with persistent atrial fibrillation (AF). The objective was to compare outcomes of catheter ablation in patients with persistent AF undergoing PVI with and without adjunctive PWI. METHODS: We performed a retrospective study of 558 patients who underwent de novo and repeat ablation for persistent AF. Subjects were matched using propensity score adjustments. Outcomes were freedom from recurrent atrial arrhythmia and adverse events. RESULTS: Among 558 patients who underwent ablation for persistent AF, 78 (14%) underwent PVI + PWI, 255 (46%) underwent PVI, and 225 (40%) underwent PVI + linear ablation. Stratified logistic regression analysis with propensity matching revealed higher odds of recurrent arrhythmia with PVI + PWI when compared to PVI (odds ratio [OR] 2.25, 95% CI 1.08-4.69, P = .030) and when compared to PVI + linear (OR 2.31, 95% CI 1.01-5.28, P = .048). Within the PVI + PWI group, 57.7% of subjects were in normal sinus rhythm at 6 months compared to 73.9% and 72.2% in PVI and PVI + linear groups, respectively. Adverse events were rare, with 19 events total identified across all groups. CONCLUSIONS: PVI + PWI does not appear to be as effective as PVI or PVI + linear ablation in reducing the recurrence of arrhythmia within 6 months of the index procedure in patients with persistent AF. A prospective, randomized controlled trial comparing these ablation techniques is needed to clarify the role of extensive substrate modification for treatment of persistent AF. CONDENSED ABSTRACT: PWI is increasingly used as an adjunctive lesion set to compliment PVI in patients with persistent AF. We performed a retrospective study of 558 patients who underwent de novo and repeat ablation for persistent AF to compare the outcomes between PVI with and without adjunctive PWI. We found an increased incidence in recurrence of AF and other atrial arrhythmias at 6 months in the PVI + PWI cohort compared to PVI with or without additional linear ablation. A prospective, randomized controlled trial comparing these ablation techniques is needed to clarify the role of extensive substrate modification for treatment of persistent AF.

Stellate Ganglion Blockade: an Intervention for the Management of Ventricular Arrhythmias.

PURPOSE OF REVIEW: To highlight the indications, procedural considerations, and data supporting the use of stellate ganglion blockade (SGB) for management of refractory ventricular arrhythmias. RECENT FINDINGS: In patients with refractory ventricular arrhythmias, unilateral or bilateral SGB can reduce arrhythmia burden and defibrillation events for 24-72 h, allowing time for use of other therapies like catheter ablation, surgical sympathectomy, or heart transplantation. The efficacy of SGB appears to be consistent despite the type (monomorphic vs polymorphic) or etiology (ischemic vs non-ischemic cardiomyopathy) of the ventricular arrhythmia. Ultrasound-guided SGB is safe with low risk for complications, even when performed on anticoagulation. SGB is effective and safe and could be considered for patients with refractory ventricular arrhythmias.

Catheter ablation of atrial fibrillation in cardiac amyloidosis.

BACKGROUND: Cardiac amyloidosis is a progressive infiltrative disease involving deposition of amyloid fibrils in the myocardium and cardiac conduction system that frequently manifests with heart failure (HF) and arrhythmias, most frequently atrial fibrillation (AF), atrial flutter (AFL), and atrial tachycardia (AT). METHODS: We performed an observational retrospective study of patients with a diagnosis of cardiac amyloid who underwent catheter ablation at our institution between January 1, 2011 and December 1, 2018. Patient demographics, procedural characteristics, and outcomes were determined by manual chart review. RESULTS: A total of 13 catheter ablations were performed over the study period in patients with cardiac amyloidosis, including 10 AT/AF/AFL ablations and three atrioventricular nodal ablations. Left ventricular ejection fraction was lower at the time of AV node ablation than catheter ablation of AT/AF/AFL (23% vs 40%, P = .003). Cardiac amyloid was diagnosed based on the results of preablation cardiac MRI results in the majority of patients (n = 7, 70%). The HV interval was prolonged at 60 ± 15 ms and did not differ significantly between AV nodal ablation patients and AT/AF/AFL ablation patients (69 ± 18 ms vs 57 ± 14 ms, P = .36). The majority of patients undergoing AT/AF/AFL ablation had persistent AF (n = 7, 70%) and NYHA class II (n = 5, 50%) or III (n = 5, 50%) HF symptoms, whereas patients undergoing AV node ablation were more likely to have class IV HF (n = 2, 66%, P = .014). Arrhythmia-free survival in CA patients after catheter ablation of AT/AF/AFL was 40% at 1 year and 20% at 2 years. CONCLUSIONS: Catheter ablation of AT/AF/AFL may be a feasible strategy for appropriately selected patients with early to mid-stage CA, whereas AV node ablation may be more appropriate in patients with advanced-stage CA.

Predicting atrial fibrillation recurrence after ablation in patients with heart failure: Validity of the APPLE and CAAP-AF risk scoring systems.

BACKGROUND: Compared with medical therapy, catheter ablation of atrial fibrillation (AF) in patients with heart failure (HF) improves cardiovascular outcomes. Risk scores (CAAP-AF and APPLE) have been developed to predict the likelihood of AF recurrence after ablation, have not been validated specifically in patients with AF and HF. METHODS: We analyzed baseline characteristics, risk scores, and rates of AF recurrence 12 months postablation in a cohort of 230 consecutive patients with AF and HF undergoing PVI in the Duke Center for Atrial Fibrillation registry from 2009-2013. RESULTS: During a follow-up period of 12 months, 76 of 230 (33%) patients with HF experienced recurrent AF after ablation. The median APPLE and CAAP-AF scores were 1.5 ([Q1, Q3]: [1.0, 2.0]) and 4.0 ([Q1, Q3]: [3.0, 5.0]), respectively and were not different from those patients with and without recurrent AF. Freedom from AF was not different according to APPLE and CAAP-AF scores. Discrimination for recurrent AF with the CAAP-AF score was modest with a C-statistic of 0.60 (95% CI 0.52-0.67). Discrimination with the APPLE score was similarly modest, with a C-statistic of 0.54 (95% CI: 0.47-0.62). CONCLUSIONS: Validated predictive risk scores for recurrent AF after catheter ablation exhibit limited predictive ability in cohorts of AF and HF. Additional tools are needed to facilitate risk stratification and patient selection for AF ablation in patients with concomitant HF.

STIM1-Ca2+ signaling modulates automaticity of the mouse sinoatrial node.

Cardiac pacemaking is governed by specialized cardiomyocytes located in the sinoatrial node (SAN). SAN cells (SANCs) integrate voltage-gated currents from channels on the membrane surface (membrane clock) with rhythmic Ca(2+) release from internal Ca(2+) stores (Ca(2+) clock) to adjust heart rate to meet hemodynamic demand. Here, we report that stromal interaction molecule 1 (STIM1) and Orai1 channels, key components of store-operated Ca(2+) entry, are selectively expressed in SANCs. Cardiac-specific deletion of STIM1 in mice resulted in depletion of sarcoplasmic reticulum (SR) Ca(2+) stores of SANCs and led to SAN dysfunction, as was evident by a reduction in heart rate, sinus arrest, and an exaggerated autonomic response to cholinergic signaling. Moreover, STIM1 influenced SAN function by regulating ionic fluxes in SANCs, including activation of a store-operated Ca(2+) current, a reduction in L-type Ca(2+) current, and enhancing the activities of Na(+)/Ca(2+) exchanger. In conclusion, these studies reveal that STIM1 is a multifunctional regulator of Ca(2+) dynamics in SANCs that links SR Ca(2+) store content with electrical events occurring in the plasma membrane, thereby contributing to automaticity of the SAN.

Autonomic Modulation for the Treatment of Ventricular Arrhythmias: Therapeutic Use of Percutaneous Stellate Ganglion Blocks.

Ventricular tachycardia (VT), ventricular fibrillation (VF), and electrical storm are commonly encountered emergency conditions in cardiac and surgical intensive care units. In most cases, recurrent ventricular arrhythmias or electrical storm are associated with a heightened sympathetic tone. These arrhythmias can be difficult to treat and may be refractory to beta-blockade, antiarrhythmic therapy, sedation, and mechanical hemodynamic support. While monomorphic ventricular tachycardia and PVC-triggered polymorphic ventricular tachycardia may sometimes be amenable to successful ablation, some patients may be too critically ill to make such an approach feasible. We present 2 cases of minimally invasive stellate ganglion blocks for the treatment of electrical storm in patients with advanced heart failure on mechanical life support. These cases are part of a collaborative initiative at our institution to use percutaneous stellate ganglion block as an adjunctive intervention to achieve control of life-threatening ventricular arrhythmias.

Stellate ganglion blockade for the treatment of refractory ventricular arrhythmias: A systematic review and meta-analysis.

INTRODUCTION: Treatment refractory ventricular arrhythmias (VAs) are often driven and exacerbated by heightened sympathetic tone. We aim to conduct a systematic review and meta-analysis of published studies of a temporary percutaneous stellate ganglion block (SGB) on VA burden and defibrillation episodes in patients with treatment refractory VAs. METHODS: Relevant studies from January 1960 through May 2017 were identified in PubMed and Google Scholar. We performed a patient-level analysis using Student's t-test to compare outcomes before and after SGB. RESULTS: We identified 22 unique case series with a total of 35 patients. Patients were 57 ± 17 years old and 69% were males with a high burden of VA. A unilateral (left)-sided SGB was used in 85.7% (30 of 35) of cases and the remaining were bilateral SGB. The use of a unilateral or bilateral SGB resulted in a significant reduction of VA episodes (24-hours pre: mean 16.5 [CI 9.7-23.1] events vs. post: mean 1.4 [CI 0.85-2.01] events; P = 0.0002) and need for defibrillation (24-hours pre: mean 14.2 [CI 6.8-21.6] vs. post: mean 0.6 [CI 0.3-0.9]; P = 0.0026). Furthermore, SGB was significantly associated with a reduction of VA burden regardless of etiology of cardiomyopathy, type of ventricular rhythm, and degree of contractile dysfunction. SGB was followed by surgical sympathectomy in 21% of cases. CONCLUSIONS: Early experience suggests that SGB is associated with an acute reduction in the VA burden and offers potential promise for a broader use in high-risk populations. Randomized controlled studies are needed to confirm the safety and efficacy of this therapy.

Intermittent Capture of the Left Bundle With Permanent His Bundle Pacing: Mechanistic Insights and Implications for an Emerging Field.

We present a case of a patient with elevated His lead capture thresholds and intermittent recruitment of the left bundle. The patient underwent a noninvasive electrophysiology study and was determined to have a left bundle branch block due to postrepolarization refractoriness. The nature of bundle branch block can have important implications for optimal patient selection and device programming in the emerging field of His bundle pacing.

Comparative Accuracy of Facial Models Fabricated Using Traditional and 3D Imaging Techniques.

PURPOSE: The purpose of this investigation was to compare the accuracy of facial models fabricated using facial moulage impression methods to the three-dimensional printed (3DP) fabrication methods using soft tissue images obtained from cone beam computed tomography (CBCT) and 3D stereophotogrammetry (3D-SPG) scans. MATERIALS AND METHODS: A reference phantom model was fabricated using a 3D-SPG image of a human control form with ten fiducial markers placed on common anthropometric landmarks. This image was converted into the investigation control phantom model (CPM) using 3DP methods. The CPM was attached to a camera tripod for ease of image capture. Three CBCT and three 3D-SPG images of the CPM were captured. The DICOM and STL files from the three 3dMD and three CBCT were imported to the 3DP, and six testing models were made. Reversible hydrocolloid and dental stone were used to make three facial moulages of the CPM, and the impressions/casts were poured in type IV gypsum dental stone. A coordinate measuring machine (CMM) was used to measure the distances between each of the ten fiducial markers. Each measurement was made using one point as a static reference to the other nine points. The same measuring procedures were accomplished on all specimens. All measurements were compared between specimens and the control. The data were analyzed using ANOVA and Tukey pairwise comparison of the raters, methods, and fiducial markers. RESULTS: The ANOVA multiple comparisons showed significant difference among the three methods (p < 0.05). Further, the interaction of methods versus fiducial markers also showed significant difference (p < 0.05). The CBCT and facial moulage method showed the greatest accuracy. CONCLUSIONS: 3DP models fabricated using 3D-SPG showed statistical difference in comparison to the models fabricated using the traditional method of facial moulage and 3DP models fabricated from CBCT imaging. 3DP models fabricated using 3D-SPG were less accurate than the CPM and models fabricated using facial moulage and CBCT imaging techniques.

Dissection of a quantitative trait locus for PR interval duration identifies Tnni3k as a novel modulator of cardiac conduction.

Atrio-ventricular conduction disease is a common feature in Mendelian rhythm disorders associated with sudden cardiac death and is characterized by prolongation of the PR interval on the surface electrocardiogram (ECG). Prolongation of the PR interval is also a strong predictor of atrial fibrillation, the most prevalent sustained cardiac arrhythmia. Despite the significant genetic component in PR duration variability, the genes regulating PR interval duration remain largely elusive. We here aimed to dissect the quantitative trait locus (QTL) for PR interval duration that we previously mapped in murine F2 progeny of a sensitized 129P2 and FVBN/J cross. To determine the underlying gene responsible for this QTL, genome-wide transcriptional profiling was carried out on myocardial tissue from 109 F2 mice. Expression QTLs (eQTLs) were mapped and the PR interval QTL was inspected for the co-incidence of eQTLs. We further determined the correlation of each of these transcripts to the PR interval. Tnni3k was the only eQTL, mapping to the PR-QTL, with an established abundant cardiac-specific expression pattern and a significant correlation to PR interval duration. Genotype inspection in various inbred mouse strains revealed the presence of at least three independent haplotypes at the Tnni3k locus. Measurement of PR interval duration and Tnni3k mRNA expression levels in six inbred lines identified a positive correlation between the level of Tnni3k mRNA and PR interval duration. Furthermore, in DBA/2J mice overexpressing hTNNI3K, and in DBA.AKR.hrtfm2 congenic mice, which harbor the AKR/J "high-Tnni3k expression" haplotype in the DBA/2J genetic background, PR interval duration was prolonged as compared to DBA/2J wild-type mice ("low-Tnni3k expression" haplotype). Our data provide the first evidence for a role of Tnni3k in controlling the electrocardiographic PR interval indicating a function of Tnni3k in atrio-ventricular conduction.

Nicotine alters mucin rheological properties.

Tobacco smoke exposure, the major cause of chronic obstructive pulmonary disease (COPD), instigates a dysfunctional clearance of thick obstructive mucus. However, the mechanism underlying the formation of abnormally viscous mucus remains elusive. We investigated whether nicotine can directly alter the rheological properties of mucin by examining its physicochemical interactions with human airway mucin gels secreted from A549 lung epithelial cells. Swelling kinetics and multiple particle tracking were utilized to assess mucin gel viscosity change when exposed to nicotine. Herein we show that nicotine (≤50 nM) significantly hindered postexocytotic swelling and hydration of released mucins, leading to higher viscosity, possibly by electrostatic and hydrophobic interactions. Moreover, the close association of nicotine and mucins allows airway mucus to function as a reservoir for prolonged nicotine release, leading to correlated pathogenic effects. Our results provide a novel explanation for the maltransport of poorly hydrated mucus in smokers. More importantly, this study further indicates that even low-concentration nicotine can profoundly increase mucus viscosity and thus highlights the health risks of secondhand smoke exposure.

Outcomes of atrioesophageal fistula following catheter ablation of atrial fibrillation treated with surgical repair versus esophageal stenting.

INTRODUCTION: Atrioesophageal fistula (AEF) is a rare but devastating complication of radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF). Surgical repair and esophageal stents are available treatment options for AEF. We report outcomes of these 2 management strategies. METHODS: Nine patients with AEF post-RFCA for AF were included in this study. AEF was diagnosed based on symptoms and chest CT imaging. Of the 9 patients, 5 received stents and 4 underwent surgical repair of fistula. RESULTS: AF ablation was performed under general anesthesia (n = 4) or conscious sedation (n = 5). During ablation, RF power was maintained between 25 and 35 Watts in areas close to the esophagus and energy delivery discontinued when esophageal temperature reached 38 °C. Seven patients underwent ablation with 3.5-mm open-irrigated catheter, 1 with 8-mm nonirrigated catheter, and 1 had surgical epicardial ablation. Seven patients received proton pump inhibitor and sucralfate before and after procedure. AEF symptoms developed within 2­6 weeks from ablation. Esophageal stenting was performed in 5 patients (median age 58 years, median time from RFCA 4 weeks) and 4 underwent surgical repair (median age 54 years, median time from RFCA 4 weeks) within 2­4 hours from diagnosis. All 5 patients receiving stents died within 1 week of the procedure due to cerebral embolism, septic shock, or respiratory failure. On the other hand, the 4 patients that received surgical repair were alive at median follow-up of 2.1 years (P = 0.005). CONCLUSIONS: Esophageal stenting should be discouraged and prompt surgical repair is crucial for survival in patients with atrioesophageal fistula.

Magnolia polyphenols attenuate oxidative and inflammatory responses in neurons and microglial cells.

BACKGROUND: The bark of magnolia has been used in Oriental medicine to treat a variety of remedies, including some neurological disorders. Magnolol (Mag) and honokiol (Hon) are isomers of polyphenolic compounds from the bark of Magnolia officinalis, and have been identified as major active components exhibiting anti-oxidative, anti-inflammatory, and neuroprotective effects. In this study, we investigate the ability of these isomers to suppress oxidative stress in neurons stimulated by the ionotropic glutamate receptor agonist N-methyl-D-aspartate (NMDA) and oxidative and inflammatory responses in microglial cells activated by interferon-γ (IFNγ) and lipopolysaccharide (LPS). We also attempt to elucidate the mechanism and signaling pathways involved in cytokine-induced production of reactive oxygen species (ROS) in microglial cells. METHODS: Dihydroethidium (DHE) was used to assay superoxide production in neurons, while CM-H2DCF-DA was used to test for ROS production in murine (BV-2) and rat (HAPI) immortalized microglial cells. NADPH oxidase inhibitors (for example, diphenyleneiodonium (DPI), AEBSF, and apocynin) and immunocytochemistry targeting p47phox and gp91phox were used to assess the involvement of NADPH oxidase. Western blotting was used to assess iNOS and ERK1/2 expression, and the Griess reaction protocol was employed to determine nitric oxide (NO) concentration. RESULTS: Exposure of Hon and Mag (1-10 µM) to neurons for 24 h did not alter neuronal viability, but both compounds (10 µM) inhibited NMDA-stimulated superoxide production, a pathway known to involve NADPH oxidase. In microglial cells, Hon and Mag inhibited IFNγ±LPS-induced iNOS expression, NO, and ROS production. Studies with inhibitors and immunocytochemical assay further demonstrated the important role of IFNγ activating the NADPH oxidase through the p-ERK-dependent pathway. Hon and, to a lesser extent, Mag inhibited IFNγ-induced p-ERK1/2 and its downstream pathway for ROS and NO production. CONCLUSION: This study highlights the important role of NADPH oxidase in mediating oxidative stress in neurons and microglial cells and has unveiled the role of IFNγ in stimulating the MAPK/ERK1/2 signaling pathway for activation of NADPH oxidase in microglial cells. Hon and Mag offer anti-oxidative or anti-inflammatory effects, at least in part, through suppressing IFNγ-induced p-ERK1/2 and its downstream pathway.

Precision of fit between implant impression coping and implant replica pairs for three implant systems.

STATEMENT OF PROBLEM: The fabrication of an accurately fitting implant-supported fixed prosthesis requires multiple steps, the first of which is assembling the impression coping on the implant. An imprecise fit of the impression coping on the implant will cause errors that will be magnified in subsequent steps of prosthesis fabrication. PURPOSE: The purpose of this study was to characterize the 3-dimensional (3D) precision of fit between impression coping and implant replica pairs for 3 implant systems. The selected implant systems represent the 3 main joint types used in implant dentistry: external hexagonal, internal trilobe, and internal conical. MATERIAL AND METHODS: Ten impression copings and 10 implant replicas from each of the 3 systems, B (Brånemark System), R (NobelReplace Select), and A (NobelActive) were paired. A standardized aluminum test body was luted to each impression coping, and the corresponding implant replica was embedded in a stone base. A coordinate measuring machine was used to quantify the maximum range of displacement in a vertical direction as a function of the tightening force applied to the guide pin. Maximum angular displacement in a horizontal plane was measured as a function of manual clockwise or counterclockwise rotation. Vertical and rotational positioning was analyzed by using 1-way analysis of variance (ANOVA). The Fisher protected least significant difference (PLSD) multiple comparisons test of the means was applied when the F-test in the ANOVA was significant (α=.05). RESULTS: The mean and standard deviation for change in the vertical positioning of impression copings was 4.3 ±2.1 µm for implant system B, 2.8 ±4.2 µm for implant system R, and 20.6 ±8.8 µm for implant system A. The mean and standard deviation for rotational positioning was 3.21 ±0.98 degrees for system B, 2.58 ±1.03 degrees for system R, and 5.30 ±0.79 degrees for system A. The P-value for vertical positioning between groups A and B and between groups A and R was <.001. No significant differences were found for vertical positioning between groups B and R. The P-value for rotational positioning between groups A and B and between groups A and R was <.001. No significant differences were found for rotational positioning between groups B and R. CONCLUSIONS: The results of the study confirmed that implant systems differ in precision of fit. Vertical precision between paired implant components is a function of joint type and the tightening force applied to the guide pin. The magnitude of vertical displacement with applied torque is greater for conical connections than for butt joint connections. The rotational freedom between paired components is unique to the implant system and is presumably related to the machining tolerances specified by the manufacturer.