RESUMO
Cardiopulmonary sympathetic control is exerted via stellate ganglia (SG); however, little is known about how neuronal firing patterns in the stellate ganglion relate to dynamic physiological function in the heart and lungs. We performed continuous extracellular recordings from SG neurons using multielectrode arrays in chloralose-anesthetized pigs (n = 6) for 8-9 h. Respiratory and left ventricular pressures (RP and LVP, respectively) and the electrocardiogram (ECG) were recorded concomitantly. Linkages between sampled spikes and LVP or RP were determined using a novel metric to evaluate specificity in neural activity for phases of the cardiac and pulmonary cycles during resting conditions and under various cardiopulmonary stressors. Firing frequency (mean 4.6 ± 1.2 Hz) varied spatially across the stellate ganglion, suggesting regional processing. The firing pattern of most neurons was synchronized with both cardiac (LVP) and pulmonary (RP) activity indicative of cardiopulmonary integration. Using the novel metric to determine cardiac phase specificity of neuronal activity, we found that spike density was highest during diastole and near-peak systole. This specificity was independent of the actual LVP or population firing frequency as revealed by perturbations to the LVP. The observed specificity was weaker for RP. Stellate ganglion neuronal populations exhibit cardiopulmonary integration and profound specificity toward the near-peak systolic phase of the cardiac cycle. This novel approach provides practically deployable tools to probe stellate ganglion function and its relationship to cardiopulmonary pathophysiology.NEW & NOTEWORTHY Activity of stellate ganglion neurons is often linking indirectly to cardiac function. Using novel approaches coupled with extended period of recordings in large animals, we link neuronal population dynamics to mechanical events occurring at near-peak systole. This metric can be deployed to probe stellate ganglion neuronal control of cardiopulmonary function in normal and disease states.
Assuntos
Coração/fisiologia , Neurônios/fisiologia , Pressão , Fenômenos Fisiológicos Respiratórios , Gânglio Estrelado/fisiologia , Estresse Fisiológico/fisiologia , Pressão Ventricular/fisiologia , Animais , Aorta , Estimulação Cardíaca Artificial , Eletrocardiografia , Microeletrodos , Testes de Função Respiratória , Mecânica Respiratória , Análise Espaço-Temporal , Gânglio Estrelado/citologia , Sus scrofa , Suínos , Sistema Nervoso Simpático/fisiologia , Veia Cava InferiorRESUMO
BACKGROUND: Clinical trials for renal artery (RA) ablation have shown limited efficacy. OBJECTIVE: The purpose of this study was to investigate whether the aorticorenal ganglion (ARG) can be targeted for renal denervation. METHODS: Twenty-eight pigs were studied under isoflurane or alpha-chloralose to examine hemodynamic responses and catecholamine release in response to RA or ARG stimulation. To assess the efficacy of ARG ablation, we randomized 16 pigs to either sham, RA, or ARG ablation, followed by occlusion of the left anterior descending coronary artery (LAD). Hemodynamic responses, cardiac electrophysiological parameters, and arrhythmias/sudden cardiac death were assessed following LAD occlusion. Absent hemodynamic responses to stimulation confirmed ARG or RA ablation. In vivo stellate ganglion neural activity was recorded to assess cardiac sympathetic signaling. Cadaveric dissections were performed to localize the ARG in humans for comparison to swine. RESULTS: The ARG is a purely sympathetic ganglion with cholinergic inputs and pass-through sensory afferent fibers. Compared to RA stimulation, ARG stimulation yielded greater hemodynamic responses during alpha-chloralose anesthesia. However, neither site yielded significant responses under isoflurane. Radiofrequency ablation of the ARG eliminated responses to both RA and ARG stimulation, whereas RA ablation did not eliminate responses to ARG stimulation. Ablation of the ARG did not impact the kidneys or adrenal glands. Compared to control and RA ablation, ARG ablation was protective against ventricular arrhythmias and sudden death. Human and swine ARG are similarly located in the aorticorenal region. CONCLUSION: Our findings indicate that the ARG may be a novel target for renal neuromodulation. Further studies are warranted to validate these findings.
Assuntos
Arritmias Cardíacas/terapia , Pressão Sanguínea/fisiologia , Frequência Cardíaca/fisiologia , Rim/inervação , Gânglio Estrelado/cirurgia , Simpatectomia/métodos , Animais , Arritmias Cardíacas/fisiopatologia , Modelos Animais de Doenças , Feminino , Masculino , Gânglio Estrelado/fisiopatologia , SuínosRESUMO
BACKGROUND: The mechanisms underlying premature ventricular contraction (PVC)-induced cardiomyopathy (PIC) remain unknown. Transient receptor potential vanilloid-1 (TRPV1) afferent fibers are implicated in the reflex processing of cardiac stress. OBJECTIVE: The purpose of this study was to determine whether cardiac TRPV1 afferent signaling promote PIC. METHODS: A PIC swine model (50% PVC burden) was created via an implanted pacemaker. We selectively depleted cardiac TRPV1 afferent fibers using percutaneous epicardial application of resiniferatoxin (RTX). Animals were randomized to PVC only (n = 11), PVC+RTX (n = 11), or control (n = 6). We examined early-stage (4 weeks after implantation; n = 5) and late-stage PIC (8 weeks after implantation; n = 6). At terminal experimentation, animals underwent echocardiography, serum sampling, and physiological and autonomic reflex testing. RESULTS: Depletion of cardiac TRPV1 afferents by RTX treatment was confirmed by absent sensory fibers and absent functional responses to TRPV1 activators. Left ventricular ejection fraction was worse in late-stage than early-stage PIC (P <.01). At 4 weeks (early stage), left ventricular ejection fraction was higher in PVC+RTX vs PVC animals (51.7% ± 1.6% vs 45.0% ± 2.1%; P = .030), whereas no significant difference between PVC and PVC+RTX was observed at 8 weeks (late stage). Histologic studies demonstrated reduced fibrosis in PVC+RTX vs PVC alone at 4 weeks (2.27% ± 0.14% vs 3.01% ± 0.21%; P = .020), suggesting that RTX mitigated profibrotic pathways induced by persistent PVCs. CONCLUSION: TRPV1 afferent depletion alleviates left ventricular dysfunction in early- but not late-stage PIC. This temporal effect suggests that multiple pathways promote PIC, of which TRPV1 afferents are a part.
Assuntos
Vias Aferentes/fisiopatologia , Cardiomiopatias , Coração/inervação , Transdução de Sinais , Canais de Cátion TRPV/agonistas , Complexos Ventriculares Prematuros , Animais , Cardiomiopatias/etiologia , Cardiomiopatias/patologia , Cardiomiopatias/fisiopatologia , Diterpenos/farmacologia , Ecocardiografia/métodos , Fibrose , Modelos Animais , Neurotoxinas/farmacologia , Volume Sistólico , Suínos , Função Ventricular Esquerda , Complexos Ventriculares Prematuros/complicações , Complexos Ventriculares Prematuros/fisiopatologiaRESUMO
BACKGROUND: Cardiac sympathoexcitation leads to ventricular arrhythmias. Spinal anesthesia modulates sympathetic output and can be cardioprotective. However, its effect on the cardio-spinal reflexes and network interactions in the dorsal horn cardiac afferent neurons and the intermediolateral nucleus sympathetic neurons that regulate sympathetic output is not known. The authors hypothesize that spinal bupivacaine reduces cardiac neuronal firing and network interactions in the dorsal horn-dorsal horn and dorsal horn-intermediolateral nucleus that produce sympathoexcitation during myocardial ischemia, attenuating ventricular arrhythmogenesis. METHODS: Extracellular neuronal signals from the dorsal horn and intermediolateral nucleus neurons were simultaneously recorded in Yorkshire pigs (n = 9) using a 64-channel high-density penetrating microarray electrode inserted at the T2 spinal cord. Dorsal horn and intermediolateral nucleus neural interactions and known markers of cardiac arrhythmogenesis were evaluated during myocardial ischemia and cardiac load-dependent perturbations with intrathecal bupivacaine. RESULTS: Cardiac spinal neurons were identified based on their response to myocardial ischemia and cardiac load-dependent perturbations. Spinal bupivacaine did not change the basal activity of cardiac neurons in the dorsal horn or intermediolateral nucleus. After bupivacaine administration, the percentage of cardiac neurons that increased their activity in response to myocardial ischemia was decreased. Myocardial ischemia and cardiac load-dependent stress increased the short-term interactions between the dorsal horn and dorsal horn (324 to 931 correlated pairs out of 1,189 pairs, P < 0.0001), and dorsal horn and intermediolateral nucleus neurons (11 to 69 correlated pairs out of 1,135 pairs, P < 0.0001). Bupivacaine reduced this network response and augmentation in the interactions between dorsal horn-dorsal horn (931 to 38 correlated pairs out of 1,189 pairs, P < 0.0001) and intermediolateral nucleus-dorsal horn neurons (69 to 1 correlated pairs out of 1,135 pairs, P < 0.0001). Spinal bupivacaine reduced shortening of ventricular activation recovery interval and dispersion of repolarization, with decreased ventricular arrhythmogenesis during acute ischemia. CONCLUSIONS: Spinal anesthesia reduces network interactions between dorsal horn-dorsal horn and dorsal horn-intermediolateral nucleus cardiac neurons in the spinal cord during myocardial ischemia. Blocking short-term coordination between local afferent-efferent cardiac neurons in the spinal cord contributes to a decrease in cardiac sympathoexcitation and reduction of ventricular arrhythmogenesis.