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Functional-Molecular Mechanisms of Sympathetic-Parasympathetic Dysfunction in PVC-Induced Cardiomyopathy Revealed by Dual Stressor PVC-Exercise Challenge.
Shoureshi, Pouria; Ahmad, Zain; Myadam, Rahul; Wang, Li; Rose, Brianna; Balderas-Villalobos, Jaime; Medina-Contreras, Juana; Das, Anindita; Uzelac, Ilija; Kaszala, Karoly; Ellenbogen, Kenneth A; Huizar, Jose F; Tan, Alex Y.
Afiliação
  • Shoureshi P; Cardiology Division, Department of Internal Medicine, Central Virginia VA Health Care System/McGuire Veterans Affairs Medical Center, Richmond, Virginia, USA; Cardiology Division/Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.
  • Ahmad Z; Cardiology Division/Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.
  • Myadam R; Cardiology Division, Department of Internal Medicine, Central Virginia VA Health Care System/McGuire Veterans Affairs Medical Center, Richmond, Virginia, USA.
  • Wang L; Cardiology Division, Department of Internal Medicine, Central Virginia VA Health Care System/McGuire Veterans Affairs Medical Center, Richmond, Virginia, USA; Cardiology Division/Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.
  • Rose B; Cardiology Division, Department of Internal Medicine, Central Virginia VA Health Care System/McGuire Veterans Affairs Medical Center, Richmond, Virginia, USA.
  • Balderas-Villalobos J; Cardiology Division/Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.
  • Medina-Contreras J; Cardiology Division/Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.
  • Das A; Cardiology Division/Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.
  • Uzelac I; Cardiology Division/Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.
  • Kaszala K; Cardiology Division, Department of Internal Medicine, Central Virginia VA Health Care System/McGuire Veterans Affairs Medical Center, Richmond, Virginia, USA; Cardiology Division/Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.
  • Ellenbogen KA; Cardiology Division/Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.
  • Huizar JF; Cardiology Division, Department of Internal Medicine, Central Virginia VA Health Care System/McGuire Veterans Affairs Medical Center, Richmond, Virginia, USA; Cardiology Division/Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.
  • Tan AY; Cardiology Division, Department of Internal Medicine, Central Virginia VA Health Care System/McGuire Veterans Affairs Medical Center, Richmond, Virginia, USA; Cardiology Division/Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA. Electron
Article em En | MEDLINE | ID: mdl-39001761
ABSTRACT

BACKGROUND:

The significance of autonomic dysfunction in premature ventricular contraction-induced cardiomyopathy (PVC-CM) remain unknown.

OBJECTIVE:

Utilizing a novel "dual stressor" provocative challenge combining exercise with premature ventricular contraction (PVCs), the authors characterized the functional and molecular mechanisms of cardiac autonomic (cardiac autonomic nervous system) remodeling in a PVC-CM animal model.

METHODS:

In 15 canines (8 experimental, 7 sham), we implanted pacemakers and neurotelemetry devices and subjected animals to 12 weeks of bigeminal PVCs to induce PVC-CM. Sympathetic nerve activity (SNA), vagal nerve activity (VNA), and heart rate were continuously recorded before, during, and after treadmill exercise challenge with and without PVCs, at baseline and after development of PVC-CM. Western blot and enzyme-linked immunosorbent assay were used to evaluate molecular markers of neural remodeling.

RESULTS:

Exercise triggered an increase in both SNA and VNA followed by late VNA withdrawal. With PVCs, the degree of exercise-induced SNA augmentation was magnified, whereas late VNA withdrawal became blunted. After PVC-CM development, SNA was increased at rest but failed to adequately augment during exercise, especially with PVCs, coupled with impaired VNA and heart rate recovery after exercise. In the remodeled cardiac autonomic nervous system, there was widespread sympathetic hyperinnervation and elevated transcardiac norepinephrine levels but unchanged parasympathetic innervation, indicating sympathetic overload. However, cardiac nerve growth factor was paradoxically downregulated, suggesting an antineurotrophic counteradaptive response to PVC-triggered sympathetic overload.

CONCLUSIONS:

Sympathetic overload, sympathetic dysfunction, and parasympathetic dysfunction in PVC-CM are unmasked by combined exercise and PVC challenge. Reduced cardiac neurotrophic factor might underlie the mechanisms of this dysfunction. Neuromodulation therapies to restore autonomic function could constitute a novel therapeutic approach for PVC-CM.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: JACC Clin Electrophysiol Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: JACC Clin Electrophysiol Ano de publicação: 2024 Tipo de documento: Article