RESUMO
Olfaction has not been explored in virtual reality environments to the same extent as the visual and auditory senses. Much less research has been done with olfactory devices, and very few of them can be easily integrated into virtual reality applications. The inclusion of odor into virtual reality simulations using a chemical device involves challenges such as possible diffusion into undesired areas, slow dissipation, the definition of various parameters (e.g., concentration, frequency, and duration), and an appropriate software solution for controlling the diffusion of the odor. This paper aims to present a non-intrusive, mobile, low cost and wearable olfactory display, and a software service that allows the developer to easily create applications that include olfactory stimuli integrated with virtual reality headset glasses. We also present a case study conducted with 32 people to evaluate their satisfaction when using the olfactory display. Our findings indicate that our solution works as expected, producing odor properly and being easy to integrate to applications. Supplementary Information: The online version contains supplementary material available at 10.1007/s00530-022-00908-8.
RESUMO
BACKGROUND: Ventricular tachycardia or fibrillation (VT/VF) of focal origin due to triggered activity (TA) from delayed afterdepolarizations (DADs) is reproducibly inducible after anterior coronary artery occlusion. Both VT/VF and TA can be blocked by reducing reactive oxygen species (ROS). We tested the hypothesis that inhibition of NADPH oxidase and xanthine oxidase would block VT/VF. METHODS: 69 dogs received apocynin (APO), 4 mg/kg intraveneously (IV), oxypurinol (OXY), 4 mg/kg IV, or both APO and OXY (BOTH) agents, or saline 3 h after coronary occlusion. Endocardium from ischemic sites (3-D mapping) was sampled for Rac1 (GTP-binding protein in membrane NADPH oxidase) activation or standard microelectrode techniques. Results (mean±SE, * p<0.05): VT/VF originating from ischemic zones was blocked by APO in 6/10 *, OXY in 4/9 *, BOTH in 5/8 * or saline in 1/27; 11/16 VT/VFs blocked were focal. In isolated myocardium, TA was blocked by APO (10(-6) M) or OXY (10(-8) M). Rac1 levels in ischemic endocardium were decreased by APO or OXY. CONCLUSION: APO and OXY suppressed focal VT/VF due to DADs, but the combination of the drugs was not more effective than either alone. Both drugs inhibited ischemic Rac1 with inhibition by OXY suggesting ROS-induced ROS. The inability to totally prevent VT/VF suggests that other mechanisms also contribute to ischemic VT.
Assuntos
Isquemia Miocárdica/enzimologia , NADPH Oxidases/metabolismo , Taquicardia Ventricular/enzimologia , Fibrilação Ventricular/enzimologia , Xantina Oxidase/metabolismo , Acetofenonas/farmacologia , Acetofenonas/uso terapêutico , Potenciais de Ação/efeitos dos fármacos , Animais , Western Blotting , Modelos Animais de Doenças , Cães , Feminino , Masculino , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/fisiopatologia , NADPH Oxidases/antagonistas & inibidores , Oxipurinol/farmacologia , Oxipurinol/uso terapêutico , Taquicardia Ventricular/complicações , Taquicardia Ventricular/tratamento farmacológico , Taquicardia Ventricular/fisiopatologia , Ultrassonografia , Fibrilação Ventricular/complicações , Fibrilação Ventricular/tratamento farmacológico , Fibrilação Ventricular/fisiopatologia , Xantina Oxidase/antagonistas & inibidores , Proteínas rac1 de Ligação ao GTP/metabolismoRESUMO
Increasing evidence suggests that cardiac pacemaking is the result of two sinoatrial node (SAN) cell mechanisms: a 'voltage clock' and a Ca(2+) dependent process, or 'Ca(2+) clock.' The voltage clock initiates action potentials (APs) by SAN cell membrane potential depolarization from inward currents, of which the pacemaker current (I(f)) is thought to be particularly important. A Ca(2+) dependent process triggers APs when sarcoplasmic reticulum (SR) Ca(2+) release activates inward current carried by the forward mode of the electrogenic Na(+)/Ca(2+) exchanger (NCX). However, these mechanisms have mostly been defined in rodents or rabbits, but are unexplored in single SAN cells from larger animals. Here, we used patch-clamp and confocal microscope techniques to explore the roles of the voltage and Ca(2+) clock mechanisms in canine SAN pacemaker cells. We found that ZD7288, a selective I(f) antagonist, significantly reduced basal automaticity and induced irregular, arrhythmia-like activity in canine SAN cells. In addition, ZD7288 impaired but did not eliminate the SAN cell rate acceleration by isoproterenol. In contrast, ryanodine significantly reduced the SAN cell acceleration by isoproterenol, while ryanodine reduction of basal automaticity was modest ( approximately 14%) and did not reach statistical significance. Importantly, pretreatment with ryanodine eliminated SR Ca(2+) release, but did not affect basal or isoproterenol-enhanced I(f). Taken together, these results indicate that voltage and Ca(2+) dependent automaticity mechanisms coexist in canine SAN cells, and suggest that I(f) and SR Ca(2+) release cooperate to determine baseline and catecholamine-dependent automaticity in isolated dog SAN cells.
Assuntos
Cálcio/metabolismo , Cálcio/fisiologia , Nó Sinoatrial , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Cães , Feminino , Coração , Isoproterenol/metabolismo , Isoproterenol/farmacologia , Masculino , Miócitos Cardíacos/metabolismo , Marca-Passo Artificial , Rianodina/metabolismo , Rianodina/farmacologia , Retículo Sarcoplasmático/metabolismo , Nó Sinoatrial/citologia , Nó Sinoatrial/metabolismo , Nó Sinoatrial/fisiologiaRESUMO
Ischemic focal ventricular tachycardia (VT) occurs in animals and humans. Angiotensin-converting enzyme inhibitors and receptor blockers reduce sudden death in patients with ischemic heart disease. In our dog model of coronary artery occlusion (CAO), we tested the hypothesis that angiotensin II (AGII) will selectively promote focal VT and that the specific AT(2) blocker PD-123319 (PD), or AT(1) blocker losartan, will affect this VT. Anesthetized dogs (n = 90) underwent CAO, followed by three-dimensional activation mapping of inducible VT. Dogs without VT in 1-3 h after CAO received AGII, and those with VT received either PD or losartan. Focal endocardium excised from ischemic sites was studied in vitro with standard microelectrode. Of 33 dogs with no inducible VT, AGII infusion resulted in sustained VT of only focal Purkinje origin in 13 (39%) compared with 0 of 20 dogs with saline. Of 26 dogs with inducible VT at baseline, given PD, reinduction was blocked in 8 of 10 (P < 0.05) focal VT, but only 1 of 15 with reentry. In contrast, of 11 dogs given losartan, reinduction of either mechanism was not blocked. In vitro triggered activity in Purkinje was blocked by PD in 13 of 19 (P < 0.05), but not by losartan in 8. Also, triggered activity was promoted by AGII, losartan, or the combination in 9 of 12 tissues. AGII promotes only focal, mainly Purkinje ischemic VT. PD, but not losartan, preferentially blocked focal VT, which is likely due to triggered activity due to delayed afterdepolarizations in Purkinje.
Assuntos
Angiotensina II/metabolismo , Isquemia Miocárdica/metabolismo , Miocárdio/metabolismo , Receptor Tipo 2 de Angiotensina/metabolismo , Transdução de Sinais , Taquicardia Ventricular/metabolismo , Potenciais de Ação , Angiotensina II/administração & dosagem , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Bloqueadores do Receptor Tipo 2 de Angiotensina II , Animais , Antiarrítmicos/farmacologia , Estimulação Cardíaca Artificial , Modelos Animais de Doenças , Cães , Eletrocardiografia , Técnicas Eletrofisiológicas Cardíacas , Endocárdio/metabolismo , Endocárdio/fisiopatologia , Feminino , Imidazóis/farmacologia , Infusões Intravenosas , Losartan/farmacologia , Masculino , Isquemia Miocárdica/complicações , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/fisiopatologia , Ramos Subendocárdicos/metabolismo , Ramos Subendocárdicos/fisiopatologia , Piridinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/fisiopatologia , Taquicardia Ventricular/prevenção & controle , Fatores de TempoRESUMO
Nitric oxide-releasing solution (NORS) is a liquid formulation that releases nitric oxide, a broad spectrum antimicrobial, single electron nitroxide radical. This solution was investigated as a potential antimicrobial treatment for bovine mastitis (BM). Three experiments were performed: a) NORS' effect on Staphylococcus aureus and Escherichia coli in an in vitro model; b) NORS' effect on milk obtained from dairy cows showing symptoms of clinical mastitis; and c) the consequences of administering NORS to healthy milking cattle using a dose-escalating in vivo study. Metabolite concentrations were estimated in their blood for methaemoglobin and nitrite; also, milk nitrite concentration and somatic cell count (SCC) were measured to study possible mammary gland inflammation following treatment. NORS lowered the bacterial concentration in all infected samples, in a time- and milk-diluted dependant fashion. Blood methemoglobin concentrations following treatment were all within the normal range for cattle. However, blood and milk nitrite concentrations increased initially but, during the next 24â¯h, returned to normal range, as did SCC, without any clinical signs of mammary gland inflammation. NORS, if shown to be effective, could be an alternative treatment for mastitis with a shorter clearance time.
Assuntos
Antibacterianos/farmacologia , Mastite Bovina/tratamento farmacológico , Óxido Nítrico/farmacologia , Animais , Bovinos , Contagem de Células , Feminino , Leite , Staphylococcus aureusRESUMO
BACKGROUND: Use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor has been associated with reduced implantable defibrillator shocks in several multicenter trials, suggesting an antiarrhythmic effect. OBJECTIVE: The purpose of this study was to determine if lovastatin had an antiarrhythmic effect in a canine model of ischemic and inducible ventricular tachycardia (VT). METHODS: Forty-seven alpha-chloralose anesthetized dogs underwent left anterior descending coronary occlusion. Three-dimensional activation mapping identified the mechanism of reinducible VT and the response to lovastatin (0.5 mg/kg IV). The endocardium was excised from foci and studied using standard microelectrode techniques with Tyrode's solution. RESULTS: Lovastatin blocked focal VT in 8 of 13 dogs (P <.01) compared with only 1 of 12 saline-treated dogs with focal VT. Lovastatin had no effect on reentrant VT. Lovastatin did not alter the effective refractory period, arterial pressure, or percentage of ischemic electrograms. Effective plasma concentration of lovastatin hydroxy acid ranged from 21-157 ng/mL (0.8-3.7 x 10(-7) M). In vitro rapid pacing, mostly with isoproterenol (5 x 10(-7) M) superfusion, produced delayed afterdepolarizations and triggered activity (9 +/- 2 action potentials). Lovastatin (10(-7) M) produced no change in action potentials or delayed afterdepolarizations. However, triggered activity was attenuated to 2 +/- 1 action potentials with lovastatin (P <.05, n = 13) but not with vehicle alone. Triggered activity returned to control after lovastatin washout (20 minutes) as well as with co-superfusion with mevalonic acid (10(-6) M, n = 5). 2,2,6,6-Tetramethylpiperidine-N-oxyl, an antioxidant that enters tissues (10(-3) M, n = 8), prevented triggered activity in a fashion similar to lovastatin. CONCLUSION: Lovastatin, in concentrations achievable in human plasma, specifically suppresses triggered activity and focal VT due to ischemia. A prenylated protein downstream from mevalonic acid may act as an antioxidant, producing the antiarrhythmic effect.
Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Lovastatina/farmacologia , Isquemia Miocárdica/prevenção & controle , Isquemia Miocárdica/fisiopatologia , Fibrilação Ventricular/prevenção & controle , Fibrilação Ventricular/fisiopatologia , Potenciais de Ação/efeitos dos fármacos , Agonistas Adrenérgicos beta/farmacologia , Análise de Variância , Animais , Antiarrítmicos/sangue , Antiarrítmicos/farmacologia , Antioxidantes/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Mapeamento Potencial de Superfície Corporal , Estimulação Cardíaca Artificial , Óxidos N-Cíclicos/farmacologia , Modelos Animais de Doenças , Cães , Técnicas Eletrofisiológicas Cardíacas , Feminino , Inibidores de Hidroximetilglutaril-CoA Redutases/sangue , Isoproterenol/farmacologia , Lovastatina/sangue , Masculino , Ácido Mevalônico/farmacologia , Microeletrodos , Período Refratário Eletrofisiológico/efeitos dos fármacos , Projetos de PesquisaRESUMO
OBJECTIVE: In cultured endothelium, stretch induces release of growth factors that contribute to angiogenesis. We tested the hypothesis that bradycardia, which prolongs ventricular diastolic filling time and volume, promotes collateral vessel growth. METHODS AND RESULTS: An ameroid occluder was placed on coronary arteries of dogs with normal heart rates (AM) or bradycardia (55 bpm; AM+BC). A third group had normal heart rates and no ameroid (control [CON]). Four weeks after occluder placement, myocardial blood flow at rest and maximal vasodilation (adenosine) at equivalent heart rates and vascular morphometry of hearts were measured. In AM dogs, conductance (myocardial flow/diastolic pressure) of collateral-dependent myocardium was similar to collateral-independent myocardium during rest but increased to only one third of CON during maximal vasodilation. In contrast, in AM+BC dogs, conductance was similar in collateral-dependent and -independent regions during maximal vasodilation. Arteriolar length density in collateral-dependent myocardium was 80% greater in AM+BC than AM dogs. Capillary length density in collateral-dependent region of AM dogs was lower than CON but normal in AM+BC dogs. The angiopoietin receptor Tie-2 increased in collateral-dependent regions of AM and AM+BC groups, whereas vascular endothelial growth factor increased in collateral-dependent and -independent regions only in AM+BC dogs. CONCLUSIONS: Chronic bradycardia during gradual coronary artery occlusion facilitates angiogenesis/arteriogenesis in collateral-dependent myocardium and preserves maximal perfusion.
Assuntos
Bradicardia/fisiopatologia , Circulação Coronária/fisiologia , Doença das Coronárias/fisiopatologia , Neovascularização Fisiológica/fisiologia , Animais , Arteríolas/fisiologia , Capilares/fisiologia , Doença Crônica , Vasos Coronários/fisiologia , Diástole/fisiologia , Cães , Receptor TIE-2/metabolismo , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Bovine respiratory disease complex (BRDc) is a multi-factorial disease, involving both viral and bacterial pathogens, that negatively impacts the cattle feedlot industry. A nitric oxide releasing solution (NORS) has been developed and shown to have potential in the prevention of BRDc. This study investigated the underlying immunological mechanisms through which the nitroslyating agent NORS provides protection against the development of BRDc in susceptible cattle. An in vitro BRDc experimental model was designed using bovine peripheral blood mononuclear cells (PBMCs) which were infected with bovine herpesvirus 1 (BHV-1) and subsequently cultured with lipopolysaccharides (LPS) extracted from Mannheimia haemolytica bacteria. The cells were treated with NORS following viral infection to reflect the timing of administering the NORS treatment in feedlots during initial processing. An expression and protein analysis of key genes involved in the innate immune response was carried out. The BRDc model produced significant increases in gene expression (p<0.01) and protein release (p<0.05) of the proinflammatory cytokines IL-1ß and TNF. Treatment with NORS reduced the protein levels of IL-1ß (0.39-fold↓) (p<0.05) and TNF (0.48-fold↓) (p<0.01) in the BRDc experimental group when compared against the non-treatment BRDc controls. TLR4 expression, having been significantly reduced under the BRDc experimental conditions (0.33-fold↓) (p<0.05), increased significantly (0.76-fold↑) (p<0.05) following NORS treatment. This study provides evidence suggesting that NO may protect against the development of BRDc by limiting deleterious inflammation while simultaneously increasing TLR4 expression and enhancing the ability of the host to detect and respond to bacterial pathogens.
Assuntos
Complexo Respiratório Bovino/imunologia , Herpesvirus Bovino 1/imunologia , Leucócitos Mononucleares/fisiologia , Lipopolissacarídeos/toxicidade , Mannheimia haemolytica/metabolismo , Óxido Nítrico/metabolismo , Animais , Bovinos , Células Cultivadas , Citocinas/genética , Regulação da Expressão Gênica/imunologia , Lipopolissacarídeos/imunologia , Mannheimia haemolytica/imunologiaRESUMO
BACKGROUND: The Dual-Chamber and VVI Implantable Defibrillator (DAVID) trial demonstrated a worse outcome in patients with implantable cardioverter-defibrillators (ICDs) programmed to DDDR at 70 bpm compared with patients who had ICDs programmed to VVI backup pacing at 40 bpm. Pacing was more frequent in the DDDR group. OBJECTIVES: The purpose of this study was to determine whether right ventricular pacing (RV) is an independent predictor of outcome in the DAVID trial. METHODS: We evaluated the relationship of percent RV pacing to the composite endpoint of death or hospitalization for congestive heart failure. Patients who had a 3-month follow-up and who had not yet reached an endpoint were included in the study. Using Cox regression analysis (VVI group N = 195; DDDR group N = 185), we examined multiple factors, including percent RV pacing at 3-month follow-up, that might be associated with adverse outcomes. RESULTS: Percent RV pacing as a continuous variable was correlated with the primary endpoint. As a dichotomous variable, the best separation for predicting endpoints occurred with DDDR RV pacing > 40% vs DDDR RV pacing < or = 40% (P = .025). Patients with DDDR RV pacing < or = 40% had similar or better outcomes to the VVI backup group (P = .07). Correction for baseline variables predictive of the composite outcome in the (nonpaced) VVI group (use of nitrates, increased heart rate, and increased age) did not change the findings for RV pacing (P = .008). In contrast, atrial pacing was not predictive of worse outcomes. CONCLUSION: These results suggest, but do not prove, a causal relationship between frequent RV pacing and adverse outcomes in patients with left ventricular ejection fraction < or = 40%.
Assuntos
Estimulação Cardíaca Artificial , Desfibriladores Implantáveis , Ventrículos do Coração/fisiopatologia , Taquicardia/terapia , Resultado do Tratamento , Insuficiência Cardíaca/fisiopatologia , Hospitalização , Humanos , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Volume Sistólico , Taquicardia/mortalidade , Fatores de TempoRESUMO
Because many episodes of ventricular fibrillation (VF) are believed to be triggered by ventricular tachycardia (VT), patients who present with VT or VF are usually grouped together in discussions of natural history and treatment. However, there are significant differences in the clinical profiles of these 2 patient groups, and some studies have suggested differences in their response to therapy. We examined arrhythmias occurring spontaneously in 449 patients assigned to implantable cardioverter-defibrillator (ICD) therapy in the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial to determine whether patients who receive an ICD after VT have arrhythmias during follow-up that are different from patients who present with VF. ICD printouts were analyzed both by a committee blinded to the patients' original presenting arrhythmia and by the local investigator. During 31 +/- 14 months of follow-up, 2,673 therapies were reported. Patients who were enrolled in the AVID trial after an episode of VT were more likely to have an episode of VT (73.5% vs 30.1%, p <0.001), and were less likely to have an episode of VF (18.3% vs 28.0%, p = 0.013) than patients enrolled after an episode of VF. Adjustment for differences in ejection fraction, previous infarction, and beta-blocker and antiarrhythmic therapy did not appreciably change the results. Ventricular arrhythmia recurrence during follow-up is different in patients who originally present with VT than in those who originally present with VF. These findings suggest there are important differences in the electrophysiologic characteristics of these 2 patient populations.
Assuntos
Antiarrítmicos/uso terapêutico , Arritmias Cardíacas/terapia , Desfibriladores Implantáveis , Taquicardia Ventricular/terapia , Fibrilação Ventricular/terapia , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/epidemiologia , Eletrocardiografia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Fatores de Risco , Volume Sistólico/efeitos dos fármacos , Volume Sistólico/fisiologia , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/epidemiologia , Fatores de Tempo , Resultado do Tratamento , Fibrilação Ventricular/diagnóstico , Fibrilação Ventricular/epidemiologiaAssuntos
Sistema Nervoso Autônomo/fisiopatologia , Barorreflexo , Morte Súbita Cardíaca/prevenção & controle , Frequência Cardíaca , Fibrilação Ventricular/fisiopatologia , Morte Súbita Cardíaca/etiologia , Humanos , Valor Preditivo dos Testes , Fatores de Risco , Fibrilação Ventricular/complicaçõesRESUMO
Cardiac resynchronization therapy (CRT) using a biventricular pacemaker is an invasive and expensive treatment option for left ventricular mechanical dyssynchrony (LVMD). The CRT candidate selection is a crucial issue due to the unreliability of the current standard CRT indicators. Real-time three-dimensional (3-D) echocardiography (RT3DE) provides four-dimensional (4-D) (3-D+time) information about the LV and is suitable for LVMD assessment. In this article, the complex left ventricle (LV) shape and motion of 50 RT3DE datasets are represented by novel 4-D descriptors - 4-D sphericity, volume and shape, from which novel indices were derived by principal component analysis (PCA) and subsequently analyzed by a support vector machine (SVM) classifier to assess their capability of LVMD characterization and CRT outcome prediction. These novel indices outperformed clinical indices and have promising capabilities in disease characterization and great potential in CRT outcome prediction. To enable efficient quantitative RT3DE analysis, a segmentation method was developed to combine the powers of active shape models and optimal graph search. Various aspects of the method were designed to handle varying RT3DE image quality among datasets and LV segments. An application with graphical user interface was developed to provide the user with simple and intuitive control. The developed method was robust to inter-observer variability and produced very good accuracy - 3.2±1.1 mm absolute surface positioning error, <1 mm mean signed error and <5% mean volume difference. The computer method's classification performance was compared with the independent standard, showing that the 4-D shape modal indices were not only the most capable of all tested options when employed for disease characterization but also the least sensitive to segmentation imperfections.
Assuntos
Terapia de Ressincronização Cardíaca , Ecocardiografia Tridimensional , Disfunção Ventricular Esquerda/diagnóstico por imagem , Automação , Ecocardiografia Quadridimensional , Ecocardiografia Tridimensional/métodos , Insuficiência Cardíaca/complicações , Humanos , Disfunção Ventricular Esquerda/terapiaRESUMO
T-wave alternans (TWA) has been investigated as a marker for susceptibility to lethal ventricular arrhythmia. In this article, we studied intracardiac TWA and ischemia as predictors of spontaneous ventricular tachycardia (VT) or ventricular fibrillation (VF) in a canine model of coronary artery occlusion (CAO). Anesthetized, open-chest dogs were studied. Electrograms from intracardiac bipolar electrodes (IBEs) were assessed for TWA and spontaneous VT or VF. TWA was defined on IBE as T wave voltage change on every other complex. In each heart, we examined 62 electrograms measured in the risk zone and surrounding normal sites, filtered from 3 to 1300 Hz. Ischemia was measured as percent of all IBE recorded that had QRS voltage drop >45%. Mapping localized the three-dimensional origin of spontaneous VT or VF. The data from dogs with VF (n = 5), VT (n = 8), or controls (no VT or VF, n = 8) were analyzed before left CAO, at the 20th min after CAO and times immediately preceding VT and VF. We found a correlation between intracardiac TWA and ischemia. More importantly, increases in intracardiac TWA peaked immediately preceding spontaneous VF and VT and were significantly higher compared to controls at comparable times. At VT/VF origins and adjacent sites, the mean TWA magnitude and discordance of TWA distinguished between VT/VF and controls at comparable times but not between VT and VF or between reentry and focal mechanisms. TWA was more common than ischemia at VT/VF origins. In summary, changes in intracardiac TWA and ischemia correlate with impending spontaneous VT/VF in a clinically applicable canine model of CAO.
Assuntos
Oclusão Coronária/complicações , Eletrocardiografia , Isquemia Miocárdica/fisiopatologia , Taquicardia Ventricular/etiologia , Fibrilação Ventricular/etiologia , Animais , Modelos Animais de Doenças , Cães , Feminino , MasculinoRESUMO
Heterochromatin bodies in single- and multichromocentered interphase cell nuclei of Triatoma infestans, a vector of Chagas disease, have been suggested to contain AT-rich DNA, based on their positive response to Q-banding and Hoechst 33248 treatment. No information exists on whether GC-rich DNA is also present in these nuclei and whether it plays a role on chromatin condensation. Considering that methodologies more precise than those previously used to determine DNA base composition in situ are currently available, and that the spatial distribution of chromatin areas differing in composition in interphase cell nuclei of different species is a matter of interest, the localization of AT- and GC-rich DNA in T. infestans nuclei is revisited here. The methodologies used included DAPI/AMD and CMA(3)/Distamycin differential staining, Feulgen-DNA image analysis following Msp I and Hpa II enzymatic digestion, 5-methylcytidine immunodetection, AgNOR response, confocal microscopy, and the 5-aza-2'-deoxycytidine (5-AZA) demethylation assay. The results identified the presence of AT-rich/GC-poor DNA in chromocenters and evenly distributed AT and GC sequences in euchromatin. A GC-rich DNA zone encircling the chromocenters was also found but it could not be associated with NOR regions. To corroborate the DNA AT-richness in T. infestans nuclei, bioinformatic analyses were also performed. Methylated cytosine was evident at some points of the chromocenters' edge in single- and multichromocentered nuclei and at the euchromatin of multichromocentered nuclei and could be transiently affected by the 5-AZA treatment. The present results suggest that in the particular case of chromocenters of the hemipteran T. infestans, cytosine methylation is not a relevant factor involved in chromatin condensation.
Assuntos
Núcleo Celular/química , DNA/análise , Interfase , Triatoma/química , Animais , Composição de Bases , Cromatina , Metilação de DNA , Heterocromatina , Mapeamento por Restrição , Triatoma/citologiaRESUMO
BACKGROUND: Catecholamines increase heart rate by augmenting the cAMP-responsive hyperpolarization-activated cyclic nucleotide-gated channel 4 pacemaker current (I(f)) and by promoting inward Na(+)/Ca(2+) exchanger current (I(NCX)) by a "Ca(2+) clock" mechanism in sinoatrial nodal cells (SANCs). The importance, identity, and function of signals that connect I(f) and Ca(2+) clock mechanisms are uncertain and controversial, but the multifunctional Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is required for physiological heart rate responses to ß-adrenergic receptor (ß-AR) stimulation. The aim of this study was to measure the contribution of the Ca(2+) clock and CaMKII to cardiac pacing independent of ß-AR agonist stimulation. METHODS AND RESULTS: We used the L-type Ca(2+) channel agonist Bay K8644 (BayK) to activate the SANC Ca(2+) clock. BayK and isoproterenol were similarly effective in increasing rates in SANCs and Langendorff-perfused hearts from wild-type control mice. In contrast, SANCs and isolated hearts from mice with CaMKII inhibition by transgenic expression of an inhibitory peptide (AC3-I) were resistant to rate increases by BayK. BayK only activated CaMKII in control SANCs but increased L-type Ca(2+) current (I(Ca)) equally in all SANCs, indicating that increasing I(Ca) was insufficient and suggesting that CaMKII activation was required for heart rate increases by BayK. BayK did not increase I(f) or protein kinase A-dependent phosphorylation of phospholamban (at Ser16), indicating that increased SANC Ca(2+) by BayK did not augment cAMP/protein kinase A signaling at these targets. Late-diastolic intracellular Ca(2+) release and I(NCX) were significantly reduced in AC3-I SANCs, and the response to BayK was eliminated by ryanodine in all groups. CONCLUSIONS: The Ca(2+) clock is capable of supporting physiological fight-or-flight responses, independent of ß-AR stimulation or I(f) increases. Complete Ca(2+) clock and ß-AR stimulation responses require CaMKII.
Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/farmacologia , Cálcio/farmacologia , Catecolaminas/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Nó Sinoatrial/efeitos dos fármacos , Taquicardia/tratamento farmacológico , Animais , Modelos Animais de Doenças , Cães , Frequência Cardíaca/fisiologia , Camundongos , Microscopia Confocal , Miocárdio/metabolismo , Miocárdio/patologia , Nó Sinoatrial/metabolismo , Taquicardia/metabolismoRESUMO
BACKGROUND: Focal ventricular tachycardia (VT) in acute myocardial ischemia is closely related to triggered activity (TA), which may be blocked by scavenging reactive oxygen species (ROS). OBJECTIVE: This study analyzed effects of acutely administered ROS scavenger-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) on VT in vivo and TA in vitro. METHODS: Forty-three alpha chloralose anesthetized dogs with coronary artery occlusion were studied. Three-dimensional activation mapping helped to locate the origin of focal or reentrant VT. TEMPO (30 mg/kg intravenously) or vehicle was given. Endocardium excised from the site of origin of VT was studied using standard microelectrode techniques and measures of ROS. RESULTS: Reentry and focal VT induction were both highly reproducible. TEMPO blocked focal VT in 6 of 11 dogs (P <.05), but 9 of 9 dogs with reentrant VT continued to have VT re-induced after TEMPO. TEMPO did not alter effective refractory period (168 +/- 3 to 171 +/- 3 ms), mean blood pressure (88 +/- 3 to 81 +/- 3 mm Hg), and size of ischemia (42% +/- 3% vs 40% +/- 4%). In vitro, TEMPO (10(-3) M, n = 14) produced no change in action potentials. Nevertheless, TA was reversibly attenuated from 5.3 +/- 1.1 to 0.4 +/- 0.4 complexes with TEMPO (n = 15, P <.05). Lucigenin-enhanced chemiluminescence and dihydroethidium staining showed increased ROS in ischemic endocardium; TEMPO dramatically reduced ROS in ischemic sites. CONCLUSION: TEMPO, a scavenger of ROS, prevented triggered activity associated with focal VT during myocardial ischemia in areas of increased ROS. Antioxidant therapy may play an important role in blockade of focal VT under the conditions of myocardial ischemia.
Assuntos
Antioxidantes/farmacologia , Óxidos N-Cíclicos/farmacologia , Isquemia Miocárdica/etiologia , Isquemia Miocárdica/prevenção & controle , Taquicardia Ventricular/complicações , Animais , Cães , Eletrocardiografia , Técnicas Eletrofisiológicas Cardíacas , Luminescência , Isquemia Miocárdica/fisiopatologia , Ramos Subendocárdicos/fisiopatologia , Reprodutibilidade dos Testes , Coloração e Rotulagem , Taquicardia Ventricular/fisiopatologiaRESUMO
OBJECTIVE: In this study we tested the hypothesis that alpha-2 adrenergic antagonism could facilitate induction of previously non-inducible ventricular tachycardia (VT) during acute ischemia. Previous reports suggest that VT during ischemia may be modulated by (alpha-2 adrenergic agonists. DESIGN: The left anterior descending artery was occluded after instrumentation of the ischemic risk zone with 21 multipolar plunge needles, each recording 6 bipolar electrograms. Three dimensional mapping characterized the mechanism of VT induced with extrastimuli. RESULTS: Of 16 non-inducible dogs included, eight which were given the alpha-2 adrenergic antagonist yohimbine all had inducible VT, while all eight in the control group remained non-inducible (p < 0.05). Six of the VTs were of focal Purkinje origin. The cycle length of the VTwas 119 +/- 4 ms. Mean arterial pressure (81+/- 8 to 82 +/- 8 mmHg, p = ns), ventricular effective refractory period (146 +/- 6 to 144 +/- 5 ms, p = ns) and ischemic zone size (55 +/-6% vs. 61 +/- 4%, p = 0.45) were not altered by yohimbine indicating minimal central or pre-junctional effects of the drug. CONCLUSIONS: Yohimbine facilitates induction of VT, especially those with focal Purkinje fiber origin, suggestive of an effect mediated through antagonism of post-junctional alpha-2 adrenoceptors on Purkinje fibers.
Assuntos
Antagonistas Adrenérgicos alfa/efeitos adversos , Isquemia Miocárdica/tratamento farmacológico , Taquicardia Ventricular/induzido quimicamente , Ioimbina/efeitos adversos , Animais , Modelos Animais de Doenças , Cães , Eletrocardiografia , Técnicas Eletrofisiológicas Cardíacas , Feminino , Masculino , Ramos Subendocárdicos/efeitos dos fármacos , Ramos Subendocárdicos/fisiopatologia , Receptores Adrenérgicos alfa 2/efeitos dos fármacos , Taquicardia Ventricular/fisiopatologiaRESUMO
Entrainment can be a useful method to identify reentry as a mechanism of ventricular tachycardia (VT). In this study, we evaluated the effect of gradually decreasing cycle lengths of overdrive pacing for stable VT induced in a canine model 1-3 h after coronary occlusion. Intact dogs underwent anterior descending coronary artery occlusion after instrumentation of the risk zone with 21 multipolar plunge needles, each recording 6 bipolar electrograms. Overdrive pacing was attempted if the animals had sustained hemodynamically stable VT, looking for evidence of entrainment. Subsequent three-dimensional mapping determined the mechanism of VT. Fifteen of the 21 dogs studied demonstrated entrainment with overdrive pacing by progressive QRS fusion alone (1), the first nonpaced QRS entrained to the paced cycle length only (7), or both (7). Five of these 15 dogs also had postpacing acceleration of the VT at a subsequent faster pacing cycle length. The mechanism of acceleration in four was a change to a VT with a focal origin. The prepacing mechanism in all 15 dogs was subsequently mapped to reentry. Regarding the six VTs, which demonstrated no evidence for entrainment, the site of earliest activity was mapped to a focal origin in all. These data showing entrainment of inducible reentrant VTs and lack of such for focal VTs support that the focal VTs seen in this study are unlikely the result of microreentry but possibly a mechanism as triggered activity.