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1.
Artigo em Inglês | MEDLINE | ID: mdl-38924224

RESUMO

INTRODUCTION: Training in clinical cardiac electrophysiology (CCEP) involves the development of catheter handling skills to safely deliver effective treatment. Objective data from analysis of ablation data for evaluating trainee of CCEP procedures has not previously been possible. Using the artificial intelligence cloud-based system (CARTONET), we assessed the impact of trainee progress through ablation procedural quality. METHODS: Lesion- and procedure-level data from all de novo atrial fibrillation (AF) and cavotricuspid isthmus (CTI) ablations involving first-year (Y1) or second-year (Y2) fellows across a full year of fellowship was curated within Cartonet. Lesions were automatically assigned to anatomic locations. RESULTS: Lesion characteristics, including contact force, catheter stability, impedance drop, ablation index value, and interlesion time/distance were similar over each training year. Anatomic location and supervising operator significantly affected catheter stability. The proportion of lesion sets delivered independently and of lesions delivered by the trainee increased steadily from the first quartile of Y1 to the last quartile of Y2. Trainee perception of difficult regions did not correspond to objective measures. CONCLUSION: Objective ablation data from Cartonet showed that the progression of trainees through CCEP training does not impact lesion-level measures of treatment efficacy (i.e., catheter stability, impedance drop). Data demonstrates increasing independence over a training fellowship. Analyses like these could be useful to inform individualized training programs and to track trainee's progress. It may also be a useful quality assurance tool for ensuring ongoing consistency of treatment delivered within training institutions.

2.
Pacing Clin Electrophysiol ; 47(1): 113-116, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37310105

RESUMO

BACKGROUND: Power-on reset (PoR) is most commonly due to electromagnetic interference. Full PoR results in a switch to an inhibited mode (VVI) pacing and resets pacing outputs to maximal unipolar settings, leading to extracardiac stimulation. METHODS: We present a case of PoR occurrence in the absence of electromagnetic interference, resulting in pectoral stimulation triggered by violation of the atrial rate limit. CONCLUSIONS: It is useful for clinicians to recognizethe occurrence of PoR in the setting of atrial limit violation andthe appropriate management in such circumstances.


Assuntos
Marca-Passo Artificial , Humanos , Marca-Passo Artificial/efeitos adversos , Átrios do Coração , Estimulação Cardíaca Artificial/métodos
7.
Cardiovasc Revasc Med ; 42: 154-158, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35181265

RESUMO

BACKGROUND: Ticagrelor or prasugrel are recommended to reduce ischemic events in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). However, in clinical practice, patients are often switched from a potent P2Y12 inhibitor to clopidogrel prior to or at discharge ('de-escalation'). We sought to assess the incidence and predictors of de-escalation. METHODS: Consecutive patients who received either a ticagrelor or prasugrel loading dose for AMI PCI at two tertiary centers between Jan 2015-Mar 2019 who survived to discharge were included. Data were obtained from the electronic health record and institutional NCDR CathPCI data. Patients who were de-escalated to clopidogrel were compared with those who remained on potent P2Y12 inhibitors through the time of discharge. RESULTS: Of the1818 patients in the cohort, 1146 (63%) were de-escalated. Patients in the de-escalation group were older, more often Black, had lower prevalence of co-morbidities, less often had private insurance, and had less complex PCI. After adjustment, older age remained positively associated (OR 1.2, CI 1.08-1.34, p = .001) and Caucasian race (OR 0.5, CI 0.33-0.77, p = .002), prior MI (OR 0.7, CI 0.5-0.97, p = .032), bifurcation lesion (OR 0.71, CI 0.53-0.95, p = .019), and greater number of stents (OR 0.82, CI 0.75-0.91, p = .0001) were negatively associated with de-escalation. In de-escalated patients, the rationale was not documented in 75.9% of cases. CONCLUSIONS: De-escalation occurred frequently in patients with AMI and was associated with both non-clinical and clinical factors. Medical decision making was poorly documented and represent an area for improvement.


Assuntos
Síndrome Coronariana Aguda , Infarto do Miocárdio , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/terapia , Clopidogrel/efeitos adversos , Hospitais , Humanos , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Cloridrato de Prasugrel/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Ticagrelor/efeitos adversos , Resultado do Tratamento
8.
J Interv Card Electrophysiol ; 64(2): 349-357, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34031777

RESUMO

BACKGROUND: Percutaneous left atrial appendage occlusion (LAAO) devices have emerged as alternatives to anticoagulation for embolic stroke prevention in patients with non-valvular atrial fibrillation (NVAF). The left atrial appendage is known to produce vasoactive neuroendocrine hormones involved in cardiovascular homeostasis. The hemodynamic impact of LAA occlusion on cardiac function remains poorly characterized. METHODS: This is a single-center, retrospective study of sixty-seven consecutive patients who received LAAO utilizing the WATCHMAN device from May 2017 to June 2019. All patients received a comprehensive 2D transthoracic echocardiogram (TTE) prior to the procedure and a post-procedural TTE. 2D echocardiographic pre-/post-procedural measurements including left ventricular ejection fraction, tricuspid regurgitation, estimated pulmonary artery pressure, diastolic parameters, and left atrial and right ventricular strain were statistically analyzed using the paired t-test. RESULTS: Seventy percent of study patients were male with an overall mean age of 73.0 ± 9.0 years. Analysis of post-procedural LAAO revealed statistically significant improvement in left ventricular ejection fraction (52.4 ± 12.6 vs. 56.7 ± 12.7, p < 0.001), an increase in mitral E/e' (14.1 ± 6.5 vs. 18.3 ± 10.8, p < 0.001), and a decrease right ventricular global longitudinal strain (RVGLS) (- 17.5 ± 4.6 vs. - 19.6 ± 5.7, p = 0.027) as compared to pre-procedural TTE. Peak left atrial longitudinal strain (PALS) improved post-LAAO (20.6 ± 12.2 to 22.9 ± 12.9, p = 0.040) with adjustment for cardiac arrhythmias. Post-LAAO, heart failure hospitalizations occurred in 23.9% of patients. CONCLUSIONS: Percutaneous LAAO results in real-time atrial and ventricular hemodynamic changes as assessed by echocardiographic evaluation of LV filling pressures (E/e'), PALS, RVGLS, and LVEF.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Idoso , Idoso de 80 Anos ou mais , Apêndice Atrial/diagnóstico por imagem , Apêndice Atrial/cirurgia , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Volume Sistólico , Resultado do Tratamento , Função Ventricular Esquerda
12.
Pacing Clin Electrophysiol ; 43(9): 930-940, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32691859

RESUMO

BACKGROUND: Randomized clinical trial data have demonstrated catheter ablation (CA) as a viable treatment modality for atrial fibrillation (AF). Patients with heart failure (HF) undergoing AF CA appear to derive improvements in quality of life and mortality compared to those treated with medical therapy (MT). Contemporary national data on 30-day readmissions after CA compared to MT among patients with HF are lacking. METHODS: From the 2016 Nationwide Readmissions Databases, 749 776 (weighted national estimate: 1 421 673) AF HF patients were identified of which 2204 (0.3%) underwent CA and 747 572 (99.7%) received MT. Propensity matching balanced baseline clinical characteristics. Thirty-day readmission rates, causes, predictors, and costs of 30-day readmission were compared. RESULTS: Among both the unmatched and matched cohorts, 30-day readmissions were lower for patients treated with CA compared to MT (16.8% vs 20.1%, P < .001 and 16.8% vs 18.8%, P = .020). CA was associated with reduced risk of readmission compared to MT (odds ratio 0.86, 95% confidence interval [CI]: 0.77-0.97). HF exacerbation and arrhythmias were the most common cause for 30-day readmission after CA. CA costs were higher during index hospitalization but similar to MT during readmission among the matched cohort ($15 858 ± $21 636 vs $16 505 ± $29 171, P = .67). Predictors of readmission were largely nonmodifiable risk factors among both the CA and MT groups. CONCLUSIONS: Nearly one in six patients with HF is readmitted within 30-days after undergoing CA. In propensity matched analyses, CA was associated with decreased rate and risk for readmission compared to MT. CA has higher index hospitalization costs, but lower readmission costs.


Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Insuficiência Cardíaca/cirurgia , Readmissão do Paciente/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/complicações , Feminino , Insuficiência Cardíaca/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Estados Unidos
13.
Cardiol Res ; 11(3): 155-167, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32494325

RESUMO

BACKGROUND: Atrioventricular block requiring permanent pacemaker (PPM) implantation is a common complication of transcatheter aortic valve replacement (TAVR). The mechanism of atrioventricular (AV) block during TAVR is not fully understood, but it may be due to the mechanical stress of TAVR deployment, resulting in possible injury to the nearby compact AV node. Aortic valve calcification (AVC) may worsen this condition and has been associated with an increased risk for post-TAVR PPM implantation. We performed a retrospective analysis to determine if AVC is predictive for long-term right ventricular (RV) pacing in post-TAVR pacemaker patients at 30 days. METHODS: A total of 262 consecutive patients who underwent TAVR with a balloon-expandable valve were analyzed. AVC data were derived from contrast-enhanced computed tomography and characterized by leaflet sector and region. RESULTS: A total of 25 patients (11.1%) required post-TAVR PPM implantation. Seventeen patients did not require RV pacing at 30 days. Nine of these 17 patients had no RV pacing requirement within 10 days. The presence of intra-procedural heart block (P = 0.004) was the only significant difference between patients who did not require PPM and those who required PPM but they were not RV pacing-dependent at 30 days. Non-coronary cusp (NCC) calcium volume was significantly higher in patients who were pacemaker-dependent at 30 days (P = 0.01) and a calcium volume of > 239.2 mm3 in the NCC was strongly predictive of pacemaker dependence at 30 days (area under the curve (AUC) = 0.813). Pre-existing right bundle branch block (RBBB) (odds ratio (OR) 105.4, P = 0.004), bifascicular block (OR 12.5, P = 0.02), QRS duration (OR 70.43, P = 0.007) and intra-procedural complete heart block (OR 12.83, P = 0.03) were also predictive of pacemaker dependence at 30 days. CONCLUSIONS: In patients who required PPM after TAVR, quantification of AVC by non-coronary leaflet calcium volume was found to be a novel predictor for RV pacing dependence at 30 days. The association of NCC calcification and PPM dependence may be related to the proximity of the conduction bundle to the non-coronary leaflet. Further studies are necessary to improve risk prediction for long-term RV pacing requirements following TAVR.

14.
Ann Noninvasive Electrocardiol ; 25(6): e12753, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32198798

RESUMO

Patients with epilepsy suffer from a higher mortality rate than the general population, a portion of which is not due to epilepsy itself or comorbid conditions. Sudden unexpected death in epilepsy (SUDEP) is a common but poorly understood cause of death in patients with intractable epilepsy and often afflicts younger patients. The pathophysiology of SUDEP is poorly defined but does not appear to be related to prolonged seizure activity or resultant injury. Interestingly, a subset of patients with confirmed long QT syndrome (LQTS) present with a seizure phenotype and may have concurrent epilepsy. In this case, we present a patient who initially presented with a seizure phenotype. Further workup captured PMVT on an outpatient event monitor, and the patient was subsequently diagnosed with LQTS1. A substantial number of patients with LQTS initially present with a seizure phenotype. These patients may represent a subset of SUDEP cases resulting from ventricular arrhythmias. Appropriate suspicion for ventricular arrhythmias is necessary for proper arrhythmia evaluation and management in patients presenting with epilepsy.


Assuntos
Morte Súbita , Eletrocardiografia/métodos , Epilepsia/complicações , Síndrome do QT Longo/complicações , Síndrome do QT Longo/diagnóstico , Adulto , Epilepsia/fisiopatologia , Evolução Fatal , Feminino , Humanos , Síndrome do QT Longo/fisiopatologia , Fenótipo
16.
J Am Heart Assoc ; 8(1): e010110, 2019 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-30620261

RESUMO

Background Image reconstruction thickness may impact quantitative coronary artery calcium scoring (CACS) from lung cancer screening computed tomography (LCSCT), limiting its application in practice. Methods and Results We evaluated Agatston-based quantitative CACS from 1.25-mm LCSCT and cardiac computed tomography for agreement in 87 patients. We then evaluated Agatston-based quantitative CACS from 1.25-, 2.5-, and 5.0-mm slice thickness LCSCT for agreement in 258 patients. Secondary analysis included the impact of slice thickness on predictive value of 4-year outcomes. Median age of patients who underwent 1.25-mm LCSCT and cardiac computed tomography was 63 years (interquartile interval, 57, 68). CACS from 1.25-mm LCSCT and cardiac computed tomography demonstrated a strong Pearson correlation, R=0.9770 (0.965, 0.985), with good agreement. The receiver operating characteristic curve areas under the curve for cardiac computed tomography and LCSCT were comparable at 0.8364 (0.6628, 1.01) and 0.8208 (0.6431, 0.9985), respectively ( P=0.733). Median age of patients who underwent LCSCT with 3 slice thicknesses was 66 years (interquartile interval, 63, 73). Compared with CACS from 1.25-mm scans, CACS from 2.5- and 5.0-mm scans demonstrated strong Pearson correlations, R=0.9949 (0.9935, 0.996) and R=0.9478 (0.9338, 0.959), respectively, though bias was largely negative for 5.0-mm scans. Receiver operating characteristic curve areas under the curve for 1.25-, 2.5-, and 5.0-mm scans were comparable at 0.7040 (0.6307, 0.7772), 0.7063 (0.6327, 0.7799), and 0.7194 (0.6407, 0.7887), respectively ( P=0.6487). When using individualized high-risk thresholds derived from respective receiver operating characteristic curves, all slice thicknesses demonstrated similar prognostic value. Conclusions Slice thickness is an important consideration when interpreting Agatston CACS from LCSCTs. Despite the absence of ECG gating, it appears reasonable to report CACS from either 1.25- or 2.5-mm slice thickness LCSCT to help stratify cardiovascular risk. Conversely, 5.0-mm scans largely underidentify calcium, limiting practical use within the established CACS values used to categorize cardiovascular risk.


Assuntos
Algoritmos , Doença da Artéria Coronariana/diagnóstico , Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/diagnóstico , Tomografia Computadorizada Multidetectores/métodos , Calcificação Vascular/diagnóstico , Idoso , Causas de Morte/tendências , Angiografia Coronária , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/mortalidade , Eletrocardiografia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Rhode Island/epidemiologia , Taxa de Sobrevida/tendências , Calcificação Vascular/complicações , Calcificação Vascular/mortalidade
17.
J Interv Card Electrophysiol ; 51(1): 77-86, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29260369

RESUMO

PURPOSE: Transcatheter aortic valve replacement (TAVR) is an increasingly prevalent therapy in patients with severe symptomatic aortic stenosis. Conduction disturbances requiring permanent pacemaker (PPM) implantation are a known complication of TAVR. This study investigated the progression of cardiac conduction disease in the post-TAVR pacemaker population and identified predictors of post-TAVR right ventricular (RV) pacing dependence. METHODS: Prospectively collected echocardiographic, ECG, and PPM interrogation data of 262 consecutive patients who underwent TAVR with placement of a balloon-expandable valve at one institution from March 2012 to October 2016 were analyzed. RESULTS: A total of 25 patients (11.1%) required post-TAVR PPM implantation. Seventeen patients who received PPMs did not require RV pacing at 30 days. Nine of these 17 patients had no RV pacing requirement within 10 days. Pre-existing right bundle branch block (RBBB) (OR 105.4, 4.52-2458.5, p = 0.0002), bifascicular block (OR 12.50, 1.60-97.65, p = 0.02), intra-procedural complete heart block (OR 12.83, 1.26-130.52, p = 0.03), and QRS duration > 120 ms (OR 70.43, 3.23-1535.22, p = 0.0002) on pre-TAVR ECG were associated with RV pacing dependence at 30 days. CONCLUSIONS: Sixty-eight percent of patients meeting post-procedural guideline indications for PPM did not require RV pacing at 30 days. Fifty-two percent of these patients demonstrated recovery of sinus node function or AV conduction within 10 days post-implant. RBBB, intra-procedural complete heart block, bifascicular block, and QRS duration > 120 ms were associated with RV pacing dependence at 30 days. These findings suggest that post-TAVR conduction disturbances may be acutely reversible in a significant proportion of patients receiving PPM within 10-30 days of implant.


Assuntos
Estenose da Valva Aórtica/cirurgia , Bloqueio Atrioventricular/terapia , Estimulação Cardíaca Artificial/métodos , Próteses Valvulares Cardíacas , Substituição da Valva Aórtica Transcateter/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/mortalidade , Arritmias Cardíacas/diagnóstico por imagem , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/terapia , Bloqueio Atrioventricular/diagnóstico por imagem , Bloqueio Atrioventricular/etiologia , Estudos de Coortes , Intervalos de Confiança , Ecocardiografia/métodos , Feminino , Seguimentos , Sistema de Condução Cardíaco/fisiopatologia , Humanos , Masculino , Monitorização Fisiológica/métodos , Razão de Chances , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/terapia , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida , Fatores de Tempo , Substituição da Valva Aórtica Transcateter/métodos , Resultado do Tratamento
18.
Crit Pathw Cardiol ; 16(2): 76-80, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28509708

RESUMO

Premature ventricular contractions (PVCs) are common arrhythmias noticed in the clinical setting because of premature depolarization of the ventricular myocytes. Although often thought to be reflective of underlying disease rather than intrinsically harmful, PVCs have recently been linked with worse outcomes in patients without significant cardiac disease. Long-term exposure to a high PVC burden can lead to the development of PVC-induced cardiomyopathy. The pathogenesis of this condition is poorly understood at the current time. Many studies have suggested that catheter ablation of these PVCs may result in reversal of the PVC-induced cardiomyopathy. This article will go over the natural history of PVCs and PVC-induced cardiomyopathy, as well as review the current literature on the role of catheter ablation in treating PVC-induced cardiomyopathy.


Assuntos
Cardiomiopatias , Ablação por Cateter , Disfunção Ventricular Esquerda/etiologia , Complexos Ventriculares Prematuros , Cardiomiopatias/complicações , Cardiomiopatias/diagnóstico , Cardiomiopatias/cirurgia , Humanos , Volume Sistólico/fisiologia , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda/fisiologia , Complexos Ventriculares Prematuros/complicações , Complexos Ventriculares Prematuros/diagnóstico , Complexos Ventriculares Prematuros/fisiopatologia
19.
PLoS One ; 12(4): e0175678, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28437443

RESUMO

Coronary artery calcium scores (CACS) from lung cancer screening computed tomography (LCSCT) or myocardial perfusion attenuation correction computed tomography (ACCT) are not routinely performed or reported. CACS from LCSCT and ACCT have not been directly compared in the same patient population. We identified 66 patients who underwent both LCSCT (non-gated) and ECG-gated cardiac CT (CCT) within a 2-year span. Of this population, 40 subjects had also undergone ACCT. Using the Agatston method, CACS for 264 individual vessels from the LCSCT population and for 160 vessels from ACCT population were calculated and evaluated for agreement with ECG-gated CCT as the gold standard. Secondary analysis included a comparison of individual vessel contribution to variations in agreement and a comparison of total CACS from CCT, LCSCT, and ACCT for respective MACE prediction. CACS from LCSCT demonstrated a strong Pearson correlation, r = 0.9017 (0.876-0.9223), with good agreement when compared to CACS from CCT. CACS from ACCT demonstrated a significantly (P < 0.00001) weaker correlation, r = 0.5593 (0.4401-0.6592). On an individual vessel basis, CACS from all major vessels (LM, LAD, LCX, and RCA) contributed to the weaker correlation. For total vessel CACS, LCSCT demonstrated comparable area under the curve (AUC) for the receiver operating characteristic (ROC) curve (LCSCT AUC = 0.8133 and CCT AUC = 0.8302, P = 0.691) for prediction of MACE. Although ACCT demonstrated a similar AUC (ACCT AUC = 0.7969, P = 0.662) for MACE prediction the cutoff value for elevated risk was extremely low. In conclusion, LCSCT outperformed ACCT at calcium scoring by providing better agreement and comparable risk assessment to CCT despite the absence of ECG-gating. It is therefore reasonable to use LCSCT images to derive and report Agatston-based CACS for cardiovascular risk assessment, whereas the use of ACCT images to report Agatston-based CACS is not currently practical.


Assuntos
Cálcio/análise , Vasos Coronários/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Imagem de Perfusão do Miocárdio/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Calcificação Vascular/diagnóstico por imagem
20.
J Neurosci ; 33(28): 11451-63, 2013 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-23843517

RESUMO

Transient Receptor Potential Vanilloid 1 (TRPV1) is a polymodal, Ca(2+)-permeable cation channel crucial to regulation of nociceptor responsiveness. Sensitization of TRPV1 by G-protein coupled receptor (GPCR) agonists to its endogenous activators, such as low pH and noxious heat, is a key factor in hyperalgesia during tissue injury as well as pathological pain syndromes. Conversely, chronic pharmacological activation of TRPV1 by capsaicin leads to calcium influx-induced adaptation of the channel. Paradoxically, both conditions entail activation of phospholipase C (PLC) enzymes, which hydrolyze phosphoinositides. We found that in sensory neurons PLCß activation by bradykinin led to a moderate decrease in phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2), but no sustained change in the levels of its precursor PI(4)P. Preventing this selective decrease in PI(4,5)P2 inhibited TRPV1 sensitization, while selectively decreasing PI(4,5)P2 independently of PLC potentiated the sensitizing effect of protein kinase C (PKC) on the channel, thereby inducing increased TRPV1 responsiveness. Maximal pharmacological TRPV1 stimulation led to a robust decrease of both PI(4,5)P2 and its precursor PI(4)P in sensory neurons. Attenuating the decrease of either lipid significantly reduced desensitization, and simultaneous reduction of PI(4,5)P2 and PI(4)P independently of PLC inhibited TRPV1. We found that, on the mRNA level, the dominant highly Ca(2+)-sensitive PLC isoform in dorsal root ganglia is PLCδ4. Capsaicin-induced desensitization of TRPV1 currents was significantly reduced, whereas capsaicin-induced nerve impulses in the skin-nerve preparation increased in mice lacking this isoform. We propose a comprehensive model in which differential changes in phosphoinositide levels mediated by distinct PLC isoforms result in opposing changes in TRPV1 activity.


Assuntos
Membrana Celular/metabolismo , Nociceptores/metabolismo , Fosfatidilinositóis/antagonistas & inibidores , Fosfatidilinositóis/metabolismo , Canais de Cátion TRPV/fisiologia , Animais , Capsaicina/farmacologia , Membrana Celular/efeitos dos fármacos , Células Cultivadas , Feminino , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Nociceptores/efeitos dos fármacos , Técnicas de Cultura de Órgãos , Xenopus laevis
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