RESUMO
INTRODUCTION: The anatomical substrate for idiopathic left ventricular tachycardia (ILVT) remains speculative. Purkinje networks surrounding false tendons (FTs) might be involved in the reentrant circuit of ILVT. The objective was to evaluate the anatomical and electrophysiological features of false tendons FTs in relation to ILVT. METHODS: Intracardiac echocardiography (ICE) was conducted on patients with ILVT. The relationship of the FTs with ILVT was determined using electro-anatomical mapping. RESULTS: Electrophysiological evaluation and radiofrequency ablation were conducted in 23 consecutive patients with ILVT. FTs were identified in 19/23 cases (82.6%) with P1 potentials during VT recorded at the FT in 14 of these patients (73.7%). Three FT types were identified. In type 1, the FT attached the septum to the base of the posteromedial papillary muscle (PPM) (4/19); type 2 FTs ran between the septum and the PPM apex (3/19), while in type 3, the connection occurred between the septum and apex (11/19) or between the septum and the LV free wall (1/19). The effective ILVT ablation sites were situated at the FT-PPM (3/19) and the FT-septum (16/19) attachment sites. CONCLUSIONS: This series demonstrates the association between Purkinje fibers and FTs during catheter ablation of ILVT and verifies that left ventricular FTs are an important substrate in this type of tachycardia.
Assuntos
Ablação por Cateter , Cardiopatias Congênitas , Taquicardia Ventricular , Humanos , Eletrocardiografia , Ramos Subendocárdicos , Ventrículos do CoraçãoRESUMO
AIMS: Cardiomyopathy patients are prone to ventricular arrhythmias (VA) and sudden cardiac death. Current therapies to prevent VA include radiofrequency ablation to destroy slowly conducting pathways of viable myocardium which support re-entry. Here, we tested the reverse concept, namely that boosting local tissue viability in zones of slow conduction might eliminate slow conduction and suppress VA in ischaemic cardiomyopathy. METHODS AND RESULTS: Exosomes are extracellular vesicles laden with bioactive cargo. Exosomes secreted by cardiosphere-derived cells (CDCEXO) reduce scar and improve heart function after intramyocardial delivery. In a VA-prone porcine model of ischaemic cardiomyopathy, we injected CDCEXO or vehicle into zones of delayed conduction defined by electroanatomic mapping. Up to 1-month post-injection, CDCEXO, but not the vehicle, decreased myocardial scar, suppressed slowly conducting electrical pathways, and inhibited VA induction by programmed electrical stimulation. In silico reconstruction of electrical activity based on magnetic resonance images accurately reproduced the suppression of VA inducibility by CDCEXO. Strong anti-fibrotic effects of CDCEXO, evident histologically and by proteomic analysis from pig hearts, were confirmed in a co-culture assay of cardiomyocytes and fibroblasts. CONCLUSION: Biological substrate modification by exosome injection may be worth developing as a non-destructive alternative to conventional ablation for the prevention of recurrent ventricular tachyarrhythmias.
Assuntos
Cardiomiopatias , Ablação por Cateter , Isquemia Miocárdica , Taquicardia Ventricular , Animais , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/prevenção & controle , Cardiomiopatias/cirurgia , Ablação por Cateter/métodos , Cicatriz/prevenção & controle , Humanos , Isquemia Miocárdica/cirurgia , Isquemia Miocárdica/terapia , Proteômica , Suínos , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/prevenção & controleRESUMO
Two Autographa californica nucleopolyhedrovirus (AcMNPV) encoded miRNAs, AcMNPV-miR-1 and AcMNPV-miR-3, have been reported by us in 2013 and 2019, respectively. Here, we present an integrated investigation of AcMNPV-encoded miRNAs, which include the above two miRNAs and three additional newly identified miRNAs. Six candidate miRNAs were predicted through small RNA deep sequencing and bioinformatics, of which, five were validated. Three miRNAs are located opposite the coding sequences, the other two are located in the coding sequences of viral genes. Targets in both virus and host were predicted and subsequently tested using dual-luciferase reporter assays. The validated targets were found mainly in AcMNPV, except for the targets of AcMNPV-miR-4, which are all host genes. Based on reporter assays, the five miRNAs predominantly function by down-regulating their targets. The transcription start sites of these miRNAs were bioinformatic screened based on known baculovirus promoter motifs. Our study reveals that AcMNPV-encoded miRNAs function as fine modulators of the interactions between host and virus by regulating viral and/or host genes.
Assuntos
MicroRNAs/genética , Nucleopoliedrovírus/genética , Spodoptera/virologia , Proteínas Virais/metabolismo , Animais , Sequência de Bases , Genes Virais , Nucleopoliedrovírus/isolamento & purificação , Células Sf9 , Spodoptera/genética , Proteínas Virais/genética , Replicação Viral/genéticaRESUMO
BACKGROUND: Post-ablation atrial tachycardias (ATs) are characterized by low-voltage signals that challenge current mapping methods. In this study, we analyzed common mistakes during activation mapping and delineated a mapping strategy for correct interpretation of tachycardia mechanisms in patients with challenging underlying substrate. METHODS AND RESULTS: Thirty-one patients referred for AT ablation were selected for the study. Three types of incorrect activation patterns were identified, which were referred to as unrecognized block line (pseudo-macroreentry and pseudo-fig-8 reentry), incorrect activation timing window of interest (WOI) (chaotic activation), and mis-annotation of complex signals (multiple sites of "early meets late"). Pseudo-macroreentry and chaotic activation occur in focal or localized reentry AT with the error related to the WOI selection (four cases), incorrect annotation of local activation time (six cases), or a previous line of atrial block in (seven cases). Pseudo-fig-8 reentry (five cases) and multiple sites of "early meets late" (nine cases) occur in macroreentrant AT with blocked areas and low-voltage atrial substrate. All ATs were successfully eliminated at the origin site. CONCLUSIONS: We delineated a series of ATs in the setting of a disordered pattern of activation mapping encountered in patients after previous extensive ablation or atriotomy. The algorithm proposed rapidly corrects the activation map and identifies the mechanism of the AT.
Assuntos
Ablação por Cateter , Técnicas Eletrofisiológicas Cardíacas , Átrios do Coração , Taquicardia Supraventricular/fisiopatologia , Taquicardia Supraventricular/cirurgia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We present a case of wide-complex tachycardia in which the clinical electrophysiological diagnosis was considered to be bundle branch re-entry ventricular tachycardia. A series of ventricular entrainment attempts were performed from the left and right ventricular septum to confirm the diagnosis. Entrainment pacing with a general current output (10 mA) was performed from the right ventricular septum with manifest fusion and a post-pacing interval similar to tachycardia cycle length. Thereafter, another entrainment attempt with a greater current output (20 mA) was performed from the same site. Paradoxically, concealed fusion was demonstrated by selective RB capture only, though there was no clear "RB" potential seen. In this case, we attempt to explain and illustrate the mechanism of paradoxical near-field inability to capture with increasing current strength.
Assuntos
Potenciais de Ação , Fascículo Atrioventricular/fisiopatologia , Estimulação Cardíaca Artificial , Eletrocardiografia , Técnicas Eletrofisiológicas Cardíacas , Frequência Cardíaca , Taquicardia Ventricular/diagnóstico , Adulto , Feminino , Humanos , Valor Preditivo dos Testes , Taquicardia Ventricular/fisiopatologia , Fatores de TempoRESUMO
BACKGROUND: Three-dimensional electroanatomic mapping systems have demonstrated a significant reduction in radiation exposure during radiofrequency catheter ablation procedures. We aimed to investigate the safety, feasibility and efficacy of a completely zero-fluoroscopy approach for catheter ablation of supraventricular tachycardia using the Ensite NavX navigation system compared with a conventional fluoroscopy approach. METHODS: A multicenter prospective non-randomized registry study was performed in seven centers from January 2013 to February 2018. Consecutive patients referred for catheter ablation of supraventricular tachycardia were assigned either to a completely zero-fluoroscopic approach (ZF) or conventional fluoroscopy approach (CF) according to the operator's preference. Patients with atrial tachycardia were excluded. RESULTS: Totally, 1020 patients were enrolled in ZF group; 2040 patients ablated by CF approach were selected for controls. There was no significant difference between the zero-fluoroscopy group and conventional fluoroscopy group as to procedure time (60.3 ± 20.3 vs. 59.7 ± 22.6 min, P = 0.90), immediate success rate of procedure (98.8% vs. 99.2%, P = 0.22), arrhythmia recurrence (0.4% vs. 0.5%, P = 0.85), total success rate of procedure (98.4% vs. 98.8%, P = 0.39) or complications (1.1% vs. 1.5%, P = 0.41). Compared with the conventional fluoroscopy approach, the zero-fluoroscopy approach provided similar outcomes without compromising the safety or efficacy of the procedure. CONCLUSION: The completely zero-fluoroscopy approach demonstrated safety and efficacy comparable to a conventional fluoroscopy approach for catheter ablation of supraventricular tachycardia, and mitigated radiation exposure to both patients and operators. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03042078; first registered February 3, 2017; retrospectively registered.
Assuntos
Ablação por Cateter/instrumentação , Técnicas Eletrofisiológicas Cardíacas/instrumentação , Exposição à Radiação/prevenção & controle , Radiografia Intervencionista , Cirurgia Assistida por Computador/instrumentação , Taquicardia Supraventricular/cirurgia , Potenciais de Ação , Adulto , Ablação por Cateter/efeitos adversos , China , Técnicas Eletrofisiológicas Cardíacas/efeitos adversos , Feminino , Fluoroscopia , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Prospectivos , Exposição à Radiação/efeitos adversos , Radiografia Intervencionista/efeitos adversos , Recidiva , Sistema de Registros , Fatores de Risco , Cirurgia Assistida por Computador/efeitos adversos , Taquicardia Supraventricular/diagnóstico por imagem , Taquicardia Supraventricular/fisiopatologia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Contraction of the esophagus was observed during cryoablation for paroxysmal atrial fibrillation (PAF). The purpose of this study is to investigate the mechanism of esophageal contraction and the correlation between the contraction and esophageal thermal lesions. METHODS: This prospective study enrolled 64 patients with PAF undergoing second-generation cryoballoon (CB2) ablation for pulmonary vein isolation (PVI). During PVI for the left inferior pulmonary vein, contrast esophagography was performed before and during cryoablation. The sample population was divided into two groups: A (31 patients) and B (33 patients). Group A consisted of patients in whom the distal half of the CB was in proximity to the esophagus, while for group B the esophagus was away from the distal half of the CB. Esophageal contraction was recorded as a variation in the width of the esophageal lumen during PVI. Postablation esophageal endoscopy was done on all patients. RESULTS: The reduction in the width of the esophageal lumen in group A was greater than in group B during freezing (40.12 ± 23.24% vs 8.14 ± 10.35%, P < .001). Following endoscopy, no apparent esophageal lesion was detected in all patients. CONCLUSION: The extent of esophageal contraction is correlated with the positioning of the esophagus at the distal half of the CB. The findings of this study indicate that esophageal contraction during freezing may be a self-protective mechanism.
Assuntos
Fibrilação Atrial/cirurgia , Criocirurgia/métodos , Esôfago/lesões , Veias Pulmonares/cirurgia , Esofagoscopia , Esôfago/diagnóstico por imagem , Feminino , Fluoroscopia , Humanos , Complicações Intraoperatórias/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Atrial fibrillation (AF) and heart failure (HF) are two clinical entities that can present either separately or concurrently. One entity can lead to the other and vice versa as AF can not only be the underlying etiology of HF but also exacerbate HF due to other cardiac diseases. Besides prevention of cerebral and systemic embolism and elimination of AF-related symptoms, restoration of sinus rhythm for AF patients helps to avoid or reduce HF, irrespective of their underlying heart disease. Successful rates of medical therapy for AF are low in persistent AF, and much lower in long-standing AF, while invasive procedures for AF yield promising results. In this review, the authors evaluate the value of invasive therapies for HF patients complicated with non-valvular AF. We examine this clinical problem by interpreting the relationships between these two entities: the mechanism of tachycardia-induced cardiomyopathy (TIC), past opinions about rhythm control and rate control of AF, discrimination of HF-related AF and AF-induced HF, how to identify the AF patients that could benefit from invasive therapies, and how to select invasive therapies for different AF patients and peri-operative treatments.
Assuntos
Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/cirurgia , Animais , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/etiologia , Cardiomiopatia Dilatada/cirurgia , Humanos , Prognóstico , Fatores de Risco , Taquicardia/complicações , Resultado do TratamentoRESUMO
BACKGROUND: Esophageal injury is related to a reduction in luminal esophageal temperature (LET) in second-generation cryoballoon (CB) ablation; however, methods to prevent these reductions in temperature have not been well characterized. METHODS: Esophageal temperature was continuously monitored using a LET probe in patients undergoing pulmonary vein (PV) isolation using the second-generation CB. A rotational maneuver of the CB was performed if the initial ablation resulted in a decrease of more than 4â in LET. The refrigerant injector near the distal CB pole was used as a fluoroscopic marker to measure the nearest distance between the CB and the LET probe. RESULTS: A total of 52 consecutive patients were enrolled in this study. The rotation was applied in 19 patients and 20 PVs (seven left superior pulmonary veins [LSPVs], seven left inferior PVs [LIPVs], and six right inferior PVs [RIPVs]) with a reduction in LET of more than 4â during freezing. The nadir temperature of CB applications was similar before and after CB rotation in all PVs. There was significant difference in the minimum LET before and after rotation during freezing in LSPVs (28.4 ± 3.7 vs 32.4 ± 2.3â, P = .02), LIPVs (28.4 ± 1.4 vs 32.6 ± 2.7, P = .01) and RIPVs (26.1 ± 4.3 vs 34.0 ± 1.3â, P = .002). The differences in mean balloon to LET distance were measured for all veins before and after rotation; LSPV (right anterior oblique [RAO], 11.0 ± 1.7 vs 13.8 ± 4.5 mm, P = .05); LIPV (RAO, 10.7 ± 4.3 vs 14.6 ± 6.1 mm, P = .03); RIPV (LAO, 11.8 ± 5.5 vs 14.2 ± 5.7 mm, P = .01). CONCLUSIONS: CB rotational maneuvers during ablation can prevent significant reduction in LET and may prevent esophageal injury during the procedure.
Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter , Criocirurgia/instrumentação , Criocirurgia/métodos , Esôfago/lesões , Complicações Intraoperatórias/prevenção & controle , Idoso , Temperatura Baixa , Criocirurgia/efeitos adversos , Feminino , Humanos , Complicações Intraoperatórias/etiologia , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória , Estudos Prospectivos , Veias Pulmonares/cirurgiaRESUMO
UNLABELLED: An Autographa californica nucleopolyhedrovirus-encoded microRNA (miRNA), AcMNPV-miR-1, downregulates the ac94 gene, reducing the production of infectious budded virions and accelerating the formation of occlusion-derived virions. In the current study, four viruses that constitutively overexpress AcMNPV-miR-1 were constructed to further explore the function of the miRNA. In addition to the ac94 gene, two new viral gene targets (ac18 and ac95) of AcMNPV-miR-1 were identified, and the possible interacting proteins were verified and tested. In the context of AcMNPV-miR-1 overexpression, ac18 was slightly upregulated, and ac95 was downregulated. Several interacting proteins were identified, and a functional pathway for AcMNPV-miR-1 was deduced. AcMNPV-miR-1 overexpression decreased budded virus infectivity, reduced viral DNA replication, accelerated polyhedron formation, and promoted viral infection efficiency in Trichoplusia ni larvae, suggesting that AcMNPV-miR-1 restrains virus infection of cells but facilitates virus infection of larvae. IMPORTANCE: Recently, microRNAs (miRNAs) have been widely reported as moderators or regulators of mammalian cellular processes, especially disease-related pathways in humans. However, the roles played by miRNAs encoded by baculoviruses, which infect numerous beneficial insects and agricultural pests, have rarely been described. To explore the actions of virus-encoded miRNAs, we investigated an miRNA encoded by Autographa californica nucleopolyhedrovirus (AcMNPV-miR-1). We previously identified this miRNA through the exogenous addition of AcMNPV-miR-1 mimics. In the current study, we constitutively overexpressed AcMNPV-miR-1 and analyzed the resultant effects to more comprehensively assess what is indeed the function of this miRNA during viral infection. In addition, we widely explored the target genes for the miRNA in the viral and host genomes and proposed a possible functional network for AcMNPV-miR-1, which provides a better general understanding of virus-encoded miRNAs. In brief, our study implied that AcMNPV-miR-1 constrains viral replication and cellular infection but enhances larval infection.
Assuntos
MicroRNAs/genética , Nucleopoliedrovírus/genética , Spodoptera/virologia , Proteínas do Envelope Viral/metabolismo , Vírion/genética , Replicação Viral/genética , Animais , Células Cultivadas , Replicação do DNA , Regulação Viral da Expressão Gênica , Larva/genética , Larva/virologia , Spodoptera/genética , Proteínas do Envelope Viral/genéticaAssuntos
Arritmias Cardíacas/fisiopatologia , Arritmias Cardíacas/cirurgia , Fascículo Atrioventricular/fisiopatologia , Fascículo Atrioventricular/cirurgia , Ablação por Cateter , Técnicas Eletrofisiológicas Cardíacas , Mapeamento Epicárdico , Ventrículos do Coração/fisiopatologia , Ventrículos do Coração/cirurgia , HumanosRESUMO
AIMS: Radiofrequency catheter ablation (RFCA) is well established as a definitive therapy of accessory pathways (APs). Successful RFCA of anteroseptal APs at the non-coronary cusp (NCC) have been reported in several case reports. We aimed to evaluate the prevalence, safety, efficacy, and long-term outcome of RFCA at the NCC for the treatment of para-hisian APs. METHODS AND RESULTS: Our study included 17 patients (58.8% female, mean age 46.9 ± 15.9 years) with para-hisian APs. We performed two different ablation approaches which targeted at either the right anterior septum (RAS) (n = 10) or the NCC (n = 7) as the initial target. We compared safety, efficacy, and long-term outcome between these two approaches. The para-hisian APs were successfully ablated in 15 patients and damaged in 1 patient, for the remaining patients, the ablation was abandoned for the suspicion of no atrioventricular conduction. Considering all ablation sites of the para-hisian APs, radiofrequency (RF) delivered at the NCC had a higher success rate (11/12 vs. 5/12, P < 0.05) and a lower complication rate (0/12 vs. 4/12, P < 0.05) compared with the RAS. During a mean follow-up period of 22.4 ± 15.0 months, all the patients were free of arrhythmias without any anti-arrhythmic drugs. CONCLUSION: Para-hisian APs can be safely and effectively ablated at the NCC. Compared with the ablation at the RAS, RF delivered at the NCC has a higher immediate success, lower complication rate, and good long-term outcome.
Assuntos
Feixe Acessório Atrioventricular/cirurgia , Valva Aórtica/cirurgia , Fibrilação Atrial/cirurgia , Septo Interatrial/cirurgia , Ablação por Cateter/métodos , Átrios do Coração/cirurgia , Taquicardia Supraventricular/cirurgia , Síndrome de Wolff-Parkinson-White/cirurgia , Feixe Acessório Atrioventricular/fisiopatologia , Adolescente , Adulto , Idoso , Fibrilação Atrial/fisiopatologia , Fascículo Atrioventricular/fisiopatologia , Estudos de Coortes , Mapeamento Epicárdico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Taquicardia Supraventricular/fisiopatologia , Resultado do Tratamento , Síndrome de Wolff-Parkinson-White/fisiopatologia , Adulto JovemRESUMO
BACKGROUND: To explore the association between atrial fibrillation (AF) and serum uric acid (SUA) in a general population in rural China. METHODS: From January 2013 to August 2013, we performed a cross-sectional study involving 11,956 permanent residents ≥ 35 years old in the rural Liaoning province of China. All participants completed a questionnaire, had a physical examination, and underwent an electrocardiogram (ECG) and echocardiogram. AF was diagnosed from ECG findings and/or a history of physician-confirmed AF. Blood samples were drawn for laboratory analyses and hyperuricemia was defined as an SUA level > 7.0 mg/dL in men and > 5.7 mg/dL in women, based on the NHANES-III laboratory definition. Logistic regression analyses were performed to estimate the crude and independent associations between hyperuricemia and the prevalence of AF. RESULTS: A total of 139 participants were diagnosed with AF, of which, 72 were self-reported, 45 were ECG-diagnosed, and 22 were both. There was a higher prevalence of AF in participants with hyperuricemia than those with normal SUA levels (2.4 vs. 1.0 %; P < 0.001). The odds ratios (OR) and 95 % confidence intervals (CI) were 2.37 (1.61-3.49) when compared to participants with normal SUA. After adjustment for other cardiovascular and AF risk factors, the independent association remained (OR = 1.94, 95 % CI: 1.26-3.00). Similar associations were observed between SUA as a continuous variable and AF prevalence (adjusted OR = 1.20, 95 % CI: 1.06-1.36). The independent associations were significant in men (Ps < 0.05) but not in women (Ps > 0.05), although the interaction logistic regression analyses presented these differences as not being statistically significant (Ps > 0.05). CONCLUSIONS: SUA is positively associated with the prevalence of AF in rural China.
Assuntos
Fibrilação Atrial/complicações , Fibrilação Atrial/epidemiologia , Hiperuricemia/complicações , Adulto , Fatores Etários , China/epidemiologia , Estudos Transversais , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , População Rural , Fatores SexuaisRESUMO
BACKGROUND: Endocardial mapping for scars and abnormal electrograms forms the most essential component of ventricular tachycardia ablation. The utility of ultra-high resolution mapping of ventricular scar was assessed using a multielectrode contact mapping system in a chronic canine infarct model. METHODS: Chronic infarcts were created in five anesthetized dogs by ligating the left anterior descending coronary artery. Late gadolinium-enhanced magnetic resonance imaging (LGE MRI) was obtained 4.9 ± 0.9 months after infarction, with three-dimensional (3D) gadolinium enhancement signal intensity maps at 1-mm and 5-mm depths from the endocardium. Ultra-high resolution electroanatomical maps were created using a novel mapping system (Rhythmia Mapping System, Rhythmia Medical/Boston Scientific, Marlborough, MA, USA) Rhythmia Medical, Boston Scientific, Marlborough, MA, USA with an 8.5F catheter with mini-basket electrode array (64 tiny electrodes, 2.5-mm spacing, center-to-center). RESULTS: The maps contained 7,754 ± 1,960 electrograms per animal with a mean resolution of 2.8 ± 0.6 mm. Low bipolar voltage (<2 mV) correlated closely with scar on the LGE MRI and the 3D signal intensity map (1-mm depth). The scar areas between the MRI signal intensity map and electroanatomic map matched at 87.7% of sites. Bipolar and unipolar voltages, compared in 592 electrograms from four MRI-defined scar types (endocardial scar, epicardial scar, mottled transmural scar, and dense transmural scar) as well as normal tissue, were significantly different. A unipolar voltage of <13 mV correlated with transmural extension of scar in MRI. Electrograms exhibiting isolated late potentials (ILPs) were manually annotated and ILP maps were created showing ILP location and timing. ILPs were identified in 203 ± 159 electrograms per dog (within low-voltage areas) and ILP maps showed gradation in timing of ILPs at different locations in the scar. CONCLUSIONS: Ultra-high resolution contact electroanatomical mapping accurately localizes ventricular scar and abnormal myocardial tissue in this chronic canine infarct model. The high fidelity electrograms provided clear identification of the very low amplitude ILPs within the scar tissue and has the potential to quickly identify targets for ablation.
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Técnicas de Imagem de Sincronização Cardíaca/métodos , Cicatriz/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Infarto do Miocárdio/fisiopatologia , Taquicardia Ventricular/fisiopatologia , Animais , Meios de Contraste , Modelos Animais de Doenças , Cães , Eletrocardiografia , Gadolínio DTPA , Processamento de Imagem Assistida por ComputadorRESUMO
Baculovirus-encoded microRNAs (miRNAs) have been described in Bombyx mori nucleopolyhedrovirus; however, most of their functions remain unclear. Here we report the identification and characterization of an miRNA encoded by Autographa californica nucleopolyhedrovirus. The identified miRNA, AcMNPV-miR-1, perfectly matched a segment in the coding sequence of the viral gene ODV-E25 and downregulated ODV-E25 mRNA expression, which likely resulted in a reduction of infectious budded virions and accelerated the formation of occlusion-derived virions.
Assuntos
Regulação Viral da Expressão Gênica , MicroRNAs/metabolismo , Nucleopoliedrovírus/genética , RNA Viral/metabolismo , Proteínas do Envelope Viral/genética , Animais , Sequência de Bases , Linhagem Celular , Regulação para Baixo , MicroRNAs/química , MicroRNAs/genética , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Nucleopoliedrovírus/química , Nucleopoliedrovírus/metabolismo , RNA Viral/química , RNA Viral/genética , Spodoptera , Proteínas do Envelope Viral/metabolismoRESUMO
Codon optimized genes have two major advantages: they simplify de novo gene synthesis and increase the expression level in target hosts. Often they achieve this by altering codon usage in a given gene. Codon optimization is complex because it usually needs to achieve multiple opposing goals. In practice, finding an optimal sequence from the massive number of possible combinations of synonymous codons that can code for the same amino acid sequence is a challenging task. In this article, we introduce COStar, a D-star Lite-based dynamic search algorithm for codon optimization. The algorithm first maps the codon optimization problem into a weighted directed acyclic graph using a sliding window approach. Then, the D-star Lite algorithm is used to compute the shortest path from the start site to the target site in the resulting graph. Optimizing a gene is thus converted to a search in real-time for a shortest path in a generated graph. Using in silico experiments, the performance of the algorithm was shown by optimizing the different genes including the human genome. The results suggest that COStar is a promising codon optimization tool for de novo gene synthesis and heterologous gene expression.
Assuntos
Algoritmos , Códon/genética , Sequência de Aminoácidos , Biologia Computacional/métodos , Simulação por Computador , Regulação da Expressão Gênica , Genes Sintéticos/genética , Genoma Humano/genética , Humanos , Modelos Genéticos , SoftwareRESUMO
BACKGROUND: Cryoablation to achieve pulmonary vein (PV) isolation has become one of the standard approaches for atrial fibrillation (AF) ablation. The Arctic Front series cryoballoon and Achieve circular mapping catheter (Medtronic) inherently possess design defects that have been associated with unfavorite clinical outcomes. Lately, a new cryoablation system (Nordica Cryoablation System, Synaptic Medical) was developed with improved design of the cryoballoon and circular mapping catheter to address the inadequacies of current cryoablation technology. An animal study was conducted to test the efficacy and safety in performing PVI with the Nordica Cryoablation System. METHODS: Pulmonary vein isolation with the Nordica Cryoablation System was performed on 12 PVs of six healthy canines. Acute PVI and peri-procedural complications were recorded. All animals underwent a repeat EP study at least 4 weeks after index procedures followed by pathological and histological assessments of the heart and collateral/downstream organs after planned euthanasia. RESULTS: Acute PV isolation was achieved in all targeted PVs with 50% of PVs being isolated with a single cryoablation application. There were no major peri-procedural complications or device malfunction events. All PVs remained isolated after 29-30 days follow-up. Histological examination showed transmural cryo-lesions at treated sites with minimal inflammation, neovascularization, and neointima formation but no significant injury to adjacent tissue or embolization in downstream organs. CONCLUSION: Acute and durable PVI can be achieved by using the novel Nordica Cryoablation System. Ablation with this new cryoablation system is associated with transmural lesions at targeted myocardium but creates no injury to the collateral tissues or downstream organs.
RESUMO
BACKGROUND: Late potential elimination has been proposed as a surrogate endpoint for scar-related VT ablation procedures. The characteristics, distribution, and predictors of persistent LPs (pLP) after ablation have not been studied. OBJECTIVE: We sought to characterize the spatial distribution and features of pLP after catheter ablation of VT substrate with high-resolution mapping. METHODS: Cases of scar-related VT ablation with adequate pre- and post-ablation electroanatomical maps (EAM) acquired exclusively using a high-density grid (HDG) catheter were reviewed from 2021-2023. RESULTS: A total of 62 EAM (pre- and post-ablation) from 31 cases using HDG were reviewed. Persistent late potentials (pLP) were observed in 19 cases after ablation (61%). New LP, spatially distinct from pre-ablation LP, at the periphery of the ablation area comprised the majority of pLP (16/19, 84%). Isolated pLP were more prevalent than fractionated pLP with a median amplitude of 0.26mV (0.09-0.59mV). The presence of pLP was associated with a significantly lower LVEF and septal ablation but not low voltage, late potential, or ablation area as compared to absence of pLP (22.8±7.8% vs 31.5±8.0% [p =0.008] for LVEF, and 83% vs 44% [p = 0.033] for septal ablation). CONCLUSIONS: Formation of spatially distinct new LP after targeted VT ablation is common especially in patients with lower LVEF and septal substrate independent of ablation burden. This finding highlights the limitations of complete LP elimination as an endpoint to VT ablation procedures.