Translational Research in Anatomy (Mar 2022)
Inflammatory degranulation of the cardiac resident mast cells suppresses the pacemaking and affects activation pattern in the sinoatrial node
Abstract
Background: Many bacterial and viral infections may cause sepsis or/and systemic or local proinflammatory responses that lead to life-threatening cardiovascular system failure. Severe bradycardia and/or bradyarrhythmias frequently accompany systemic inflammation and contribute to hemodynamic insufficiency. Markers for immunocompetent cells have been shown to be present in the tissue of the primary heart pacemaker, the sinoatrial node (SAN). However, the role of the resident cardiac immune cells in inflammation-induced bradycardia and SAN automaticity have still not been elucidated. Materials and methods: Confocal and bright field microscopy were used to identify toluidine blue-positive cells (TPC) in the SAN. Standard microelectrode technique and optical mapping were used to record action potentials (AP) and analyze activation pattern in the SAN tissue preparation from rats in presence of secretagogue C48/80. Results: Numerous TPC, which exhibit toluidine-accumulating granules, typical for mast cells, are revealed in the SAN region of the right atrium. The activation and degranulation of the resident mast cells by C48/80 leads to biphasic changes of the pacemaker AP rate in the SAN – an initial acceleration is followed by rate reduction. The activation of the resident mast cells causes an increase of the primary activation area in the SAN that probably underlies the AP rate increase in response to C48/80. In addition, the application of C48/80 causes the primary/leading activation point migration in the SAN and AP rate decrease is probably mediated by the shift of the primary pacemaker site to the region surrounding the coronary sinus. Moreover, inexcitable zones and conduction blocks induced in the central SAN myocardium by C48/80 underlie the suppression of automaticity. Conclusion: The degranulation of resident mast cells affects the pacemaker cardiomyocytes’ ability to generate spontaneous AP in the SAN tissue and causes shift of the dominant pacemaker site. Therefore, the activation of the resident mast cells in the SAN can be considered as a new mechanism of inflammatory induced bradyarrhythmias.
