Dataset Information

Nerves projecting from the intrinsic cardiac ganglia of the pulmonary veins modulate sinoatrial node pacemaker function.

ABSTRACT:

Aims

Pulmonary vein ganglia (PVG) are targets for atrial fibrillation ablation. However, the functional relevance of PVG to the normal heart rhythm remains unclear. Our aim was to investigate whether PVG can modulate sinoatrial node (SAN) function.

Methods and results

Forty-nine C57BL and seven Connexin40+/EGFP mice were studied. We used tyrosine-hydroxylase (TH) and choline-acetyltransferase immunofluorescence labelling to characterize adrenergic and cholinergic neural elements. PVG projected postganglionic nerves to the SAN, which entered the SAN as an extensive, mesh-like neural network. PVG neurones were adrenergic, cholinergic, and biphenotypic. Histochemical characterization of two human embryonic hearts showed similarities between mouse and human neuroanatomy: direct neural communications between PVG and SAN. In Langendorff perfused mouse hearts, PVG were stimulated using 200-2000 ms trains of pulses (300 ?s, 400 µA, 200 Hz). PVG stimulation caused an initial heart rate (HR) slowing (36 ± 9%) followed by acceleration. PVG stimulation in the presence of propranolol caused HR slowing (43 ± 13%) that was sustained over 20 beats. PVG stimulation with atropine progressively increased HR. Time-course effects were enhanced with 1000 and 2000 ms trains (P < 0.05 vs. 200 ms). In optical mapping, PVG stimulation shifted the origin of SAN discharges. In five paroxysmal AF patients undergoing pulmonary vein ablation, application of radiofrequency energy to the PVG area during sinus rhythm produced a decrease in HR similar to that observed in isolated mouse hearts.

Conclusion

PVG have functional and anatomical biphenotypic characteristics. They can have significant effects on the electrophysiological control of the SAN.

SUBMITTER: Zarzoso M

PROVIDER: S-EPMC3718320 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Publications

Nerves projecting from the intrinsic cardiac ganglia of the pulmonary veins modulate sinoatrial node pacemaker function.

Zarzoso Manuel M Rysevaite Kristina K Milstein Michelle L ML Calvo Conrado J CJ Kean Adam C AC Atienza Felipe F Pauza Dainius H DH Jalife José J Noujaim Sami F SF

Cardiovascular research 20130403 3

<h4>Aims</h4>Pulmonary vein ganglia (PVG) are targets for atrial fibrillation ablation. However, the functional relevance of PVG to the normal heart rhythm remains unclear. Our aim was to investigate whether PVG can modulate sinoatrial node (SAN) function.<h4>Methods and results</h4>Forty-nine C57BL and seven Connexin40+/EGFP mice were studied. We used tyrosine-hydroxylase (TH) and choline-acetyltransferase immunofluorescence labelling to characterize adrenergic and cholinergic neural elements. ...[more]

PMID: 23559611

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Project description:BackgroundIncreasing evidence suggests that cardiac arrhythmias are frequent clinical features of coronavirus disease 2019 (COVID-19). Sinus node damage may lead to bradycardia. However, it is challenging to explore human sinoatrial node (SAN) pathophysiology due to difficulty in isolating and culturing human SAN cells. Embryonic stem cells (ESCs) can be a source to derive human SAN-like pacemaker cells for disease modeling.MethodsWe used both a hamster model and human ESC (hESC)-derived SAN-like pacemaker cells to explore the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the pacemaker cells of the heart. In the hamster model, quantitative real-time polymerase chain reaction and immunostaining were used to detect viral RNA and protein, respectively. We then created a dual knock-in SHOX2:GFP;MYH6:mCherry hESC reporter line to establish a highly efficient strategy to derive functional human SAN-like pacemaker cells, which was further characterized by single-cell RNA sequencing. Following exposure to SARS-CoV-2, quantitative real-time polymerase chain reaction, immunostaining, and RNA sequencing were used to confirm infection and determine the host response of hESC-SAN-like pacemaker cells. Finally, a high content chemical screen was performed to identify drugs that can inhibit SARS-CoV-2 infection, and block SARS-CoV-2-induced ferroptosis.ResultsViral RNA and spike protein were detected in SAN cells in the hearts of infected hamsters. We established an efficient strategy to derive from hESCs functional human SAN-like pacemaker cells, which express pacemaker markers and display SAN-like action potentials. Furthermore, SARS-CoV-2 infection causes dysfunction of human SAN-like pacemaker cells and induces ferroptosis. Two drug candidates, deferoxamine and imatinib, were identified from the high content screen, able to block SARS-CoV-2 infection and infection-associated ferroptosis.ConclusionsUsing a hamster model, we showed that primary pacemaker cells in the heart can be infected by SARS-CoV-2. Infection of hESC-derived functional SAN-like pacemaker cells demonstrates ferroptosis as a potential mechanism for causing cardiac arrhythmias in patients with COVID-19. Finally, we identified candidate drugs that can protect the SAN cells from SARS-CoV-2 infection.

Dataset Information

Nerves projecting from the intrinsic cardiac ganglia of the pulmonary veins modulate sinoatrial node pacemaker function.

Aims

Methods and results

Conclusion

Publications

Nerves projecting from the intrinsic cardiac ganglia of the pulmonary veins modulate sinoatrial node pacemaker function.

Similar Datasets

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