RESUMO
Enhanced cardiac sympathetic afferent reflex (CSAR) contributes to ventricular arrhythmia (VA) after acute myocardial infarction (AMI). However, central regulation mechanisms remain unknown. The aim of this study was to investigate whether local cardiac sympathetic afferent ablation (LCSAA) could reduce VA by inhibiting activated astrocytes in the hypothalamus paraventricular (PVN) in an AMI rat model. The rats were randomly divided into AMI, AMI + BD (baroreceptor denervation), AMI + LCSAA and AMI + BD+ LCSAA groups. Before the generation of AMI, BD and (or) LCSAA were performed. At 24 h after AMI, the incidence and duration of VA in AMI + LCSAA group and AMI + BD + LCSAA group were significantly reduced than AMI group (P < 0.05). Furthermore, LCSAA significantly reduced GFAP (a marker for activated astrocytes) positive cells and their projections as well as the level of TNF-α and IL-6 in the PVN of AMI + LCSAA group and AMI + BD+ LCSAA group, along with the decrease of neuronal activation in PVN and sympathetic nerve activity (P < 0.05). but BD had no obvious difference between AMI + LCSAA and AMI + BD + LCSAA group (P > 0.05). Therefore, LCSAA could decrease sympathoexcitation and VA occurrence in AMI rats by inhibiting astrocyte and neuronal activation in the PVN. Our study demonstrates that activated astrocytes may play an important role on CSAR in AMI.
Assuntos
Infarto do Miocárdio , Núcleo Hipotalâmico Paraventricular , Animais , Arritmias Cardíacas/etiologia , Astrócitos , Coração , Infarto do Miocárdio/complicações , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Malignant ventricular arrhythmia (VA) is the most common cause of death associated with acute myocardial infarction (MI). Recent studies have revealed direct involvement of the paraventricular nucleus (PVN) in the occurrence of VA. However, the underlying mechanisms remain incompletely understood. In this study, we investigated changes in the interleukin-6 (IL-6)-glycoprotein 130-signal transducer and activator of transcription 3 (STAT3) pathway in the PVN during acute MI and the effects of this pathway on ventricular stability. METHODS: Rats were divided into a control group, a MI group, a PVN-injected anti-IL-6 antibody group and a PVN-injected SC144 group to observe how IL-6 and its downstream glycoprotein 130-STAT3 pathway in the PVN affect ventricular stability. The left anterior descending coronary artery was ligated to induce MI. After that, an anti-IL-6 antibody and SC144 were injected into the PVNs of rats. All data are expressed as the mean ± SE and were analysed by ANOVA with a post hoc LSD test. p < 0.05 was considered to indicate statistical significance. RESULTS: After MI, the concentration of the inflammatory factor IL-6 increased, and its downstream glycoprotein 130-STAT3 pathway was activated in the PVN. After injection of MI rat PVNs with the anti-IL-6 antibody or glycoprotein 130 inhibitor (SC144), glutamate levels increased and γ-aminobutyric acid (GABA) levels decreased in the PVN. Plasma norepinephrine concentrations also increased after treatment, which increased the vulnerability to VA. CONCLUSIONS: In summary, IL-6 in the PVN exerts a protective effect in MI rats, and the glycoprotein 130-STAT3 pathway plays a key role in this process. We anticipate that our findings will provide new ideas for the prevention and treatment of arrhythmia after MI.
Assuntos
Receptor gp130 de Citocina/metabolismo , Frequência Cardíaca , Interleucina-6/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Fator de Transcrição STAT3/metabolismo , Fibrilação Ventricular/prevenção & controle , Função Ventricular Esquerda , Potenciais de Ação , Animais , Modelos Animais de Doenças , Ácido Glutâmico/metabolismo , Masculino , Infarto do Miocárdio/complicações , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/fisiopatologia , Norepinefrina/sangue , Núcleo Hipotalâmico Paraventricular/fisiopatologia , Ratos Sprague-Dawley , Transdução de Sinais , Fibrilação Ventricular/etiologia , Fibrilação Ventricular/metabolismo , Fibrilação Ventricular/fisiopatologia , Ácido gama-Aminobutírico/metabolismoRESUMO
BACKGROUND: Sympathetic overactivation after acute myocardial infarction (AMI) contributes to ventricular arrhythmia (VA). Paraventricular nucleus (PVN) of the hypothalamus may play an important role on this context, however, the mechanisms remain unknown. In this study, we investigated whether inhibition of activated astrocytes in the PVN could reduce VA in rats with AMI. METHODS: The anesthetized rats were randomly divided into four groups of sham-operated, AMI, AMI + vehicle and AMI + fluorocitrate (FCA). Electrocardiogram was continuously recorded. RNA sequencing, sympathetic nerve activity (heart rate variability and norepinephrine levels) and ventricular electrical instability (ventricular effective refractory period and ventricular fibrillation inducibility) were measured. Furthermore, brain tissues were extracted to detect expression of inflammatory cytokines (IL-6, and TNF-α), astrocyte and neuro activation. RESULTS: RNA sequencing analysis showed that functions of differentially expressed genes in the PVN of AMI rats were significantly enriched in immune system- and neuroactive-related pathways, along with enhance expression of cytokines and Glial fibrillary acidic protein (GFAP). We further characterized that astrocytes were activated in PVN and intervention of activation astrocytes by FCA significantly inhibited sympathetic nerve activity and decreased the incidence of VA and ventricular electrical instability in rats with AMI. Moreover, FCA significantly attenuated neurons activation and downregulated expression of inflammatory cytokines in the PVN. CONCLUSIONS: Inhibition of activated astrocytes in the PVN could reduce VA occurrence and improve ventricular electrical instability in AMI rats by central neuro-immune pathway. These findings suggest that astrocytes are a potential target for prevention and treatment of VA complicating AMI.
Assuntos
Infarto do Miocárdio , Núcleo Hipotalâmico Paraventricular , Animais , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/prevenção & controle , Astrócitos , Infarto do Miocárdio/complicações , Ratos , Sistema Nervoso SimpáticoRESUMO
BACKGROUND: Modulation of the autonomic nervous system (ANS) has already been demonstrated to display antiarrhythmic effects in patients and animals with MI. In this study, we investigated whether local cardiac denervation has any beneficial effects on ventricular electrical stability and cardiac function in the chronic phase of MI. METHODS: Twenty-one anesthetized dogs were randomly assigned into the sham-operated, MI and MI-ablation groups, respectively. Four weeks after local cardiac denervation, LSG stimulation was used to induce VPCs and VAs. The ventricular fibrillation threshold (VFT) and the incidence of inducible VPCs were measured with electrophysiological protocol. Cardiac innervation was determined with immunohistochemical staining of growth associated protein-43 (GAP43) and tyrosine hydroxylase (TH). The global cardiac and regional ventricular function was evaluated with doppler echocardiography in this study. RESULTS: Four weeks after operation, the incidence of inducible VPC and VF in MI-ablation group were significantly reduced compared to the MI dogs (p<0.05). Moreover, local cardiac denervation significantly improved VFT in the infarcted border zone (p<0.05). The densities of GAP43 and TH-positive nerve fibers in the infarcted border zone in the MI-ablation group were lower than those in the MI group (p<0.05). However, the local cardiac denervation did not significantly improve cardiac function in the chronic phase of MI, determined by the left ventricle diameter (LV), left atrial diameter (LA), ejection fraction (EF). CONCLUSIONS: Summarily, in the chronic phase of MI, local cardiac denervation reduces the ventricular electrical instability, and attenuates spatial heterogeneity of sympathetic nerve reconstruction. Our study suggests that this methodology might decrease malignant ventricular arrhythmia in chronic MI, and has a great potential for clinical application.
Assuntos
Coração/inervação , Denervação Muscular , Infarto do Miocárdio/cirurgia , Simpatectomia , Fibrilação Ventricular/cirurgia , Animais , Doença Crônica , Modelos Animais de Doenças , Cães , Estimulação Elétrica , Feminino , Imuno-Histoquímica , Masculino , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miocárdio/patologia , Neurônios/patologia , Neurônios/fisiologia , Distribuição Aleatória , Gânglio Estrelado/patologia , Gânglio Estrelado/fisiopatologia , Fibrilação Ventricular/patologia , Fibrilação Ventricular/fisiopatologiaRESUMO
BACKGROUND: Augmentation of sympathetic nerve activity after acute myocardial infarction (AMI) contributes to fatal arrhythmia. In this study, we investigated whether local ablation of the coronary sinus (CS) and great cardiac vein (GCV) peripheral nerves could reduce ventricular arrhythmias (VA) in a canine AMI model. METHODS: Twenty-one anesthetized dogs were randomly assigned into the sham-operated, MI and MI-ablation groups, respectively. The incidence and duration of VA were monitored among different groups. The ventricular effective refractory period (ERP), the ERP dispersion and the ventricular fibrillation threshold (VFT) were measured during the experiments. Norepinephrine (NE) levels in CS blood and cardiac tissue were also detected in this study. RESULTS: The incidence and duration of VA in MI-ablation group were significantly reduced as compared to the MI dogs (p<0.05). Furthermore, local cardiac denervation drastically prolonged the ventricular ERP in the ischemia area, decreased the ERP dispersion, and reduced NE levels in CS blood (P<0.05). VFT also showed an increased trend in the AMI-ablation group. CONCLUSIONS: The results of this study indicate that, in the canine AMI model, local ablation of CS and GCV peripheral nerves reduces VA occurrence and improves ventricular electrical stability with no obvious effects on heart rate, mean arterial pressure and infarct size. This study suggests that local cardiac denervation may prevent ventricular arrhythmias complicating AMI.
Assuntos
Vasos Coronários/inervação , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/prevenção & controle , Simpatectomia/métodos , Fibrilação Ventricular/complicações , Fibrilação Ventricular/prevenção & controle , Animais , Cães , Feminino , MasculinoRESUMO
PURPOSE: The aim was to assess atrial fibrillation (AF) and vulnerability in Wolff-Parkinson-White (WPW) syndrome patients using two-dimensional speckle tracking echocardiography (2D-STE). METHODS: All patients were examined via transthoracic echocardiography and 2D-STE in order to assess atrial function 7 days before and 10 days after RF catheter ablation. A postoperative 3-month follow-up was performed via outpatient visit or telephone calls. RESULTS: Results showed significant differences in both body mass index (BMI) and supraventricular tachycardia (SVT) duration between WPW patients and DAVNP patients (both P<0.05). Echocardiography revealed that the maximum left atrial volume (LAVmax) and the left ventricular mass index (LVMI) in diastole increased noticeably in patients with WPW compared to patients with DAVNP both before and after ablation (all P<0.05). Before ablation, there were obvious differences in the levels of SRs, SRe, and SRa from the 4-chamber view (LA) in the WPW patients group compared with patients in the DAVNP group (all P<0.05). In the AF group, there were significant differences in the levels of systolic strain rate (SRs), early diastolic strain rate (SRe), and late diastolic strain rate (SRa) from the 4-chamber view (LA) both before and after ablation (all P<0.05). In the non-AF group, there were decreased SRe levels from the 4-chamber view (LA/RA) pre-ablation compared to post-ablation (all P<0.05). CONCLUSION: Our findings provide convincing evidence that WPW syndrome may result in increased atrial vulnerability and contribute to the development of AF. Further, RF catheter ablation of AAV pathway can potentially improve atrial function in WPW syndrome patients. Two-dimensional speckle tracking echocardiography imaging in WPW patients would be necessary in the evaluation and improvement of the overall function of RF catheter ablation in a long-term follow-up period.