A new study has determined that in a rat model of pulmonary arterial hypertension (PAH), remodeling of ion channel, calcium-handling, and fibrosis genes leads to sinus node dysfunction and subsequent arrhythmias.
The study, published in Philosophical Transactions of the Royal Society B, observed a decrease in the intrinsic pacemaker activities in the sinus node late in PAH progression.
“Heart failure in general is known to cause dysfunction of the sinus node and the wider cardiac conduction system and a significant proportion of end-stage heart failure patients die as a result of bradyarrhythmias,” the authors wrote. “The aim of the present study was to investigate sinus node dysfunction in a rat model of monocrotaline-induced PAH in which cardiac conduction system dysfunction is recognized as a cause of death.”
The research team induced PAH in 34 Sprague-Dawley and Wistar rats via a 60 mg/kg injection of monocrotaline. Eight control rats received a saline injection. Three weeks after the injection, half of the PAH rats had died, and the remainder had evidence of heart failure. The pulmonary artery walls were significantly thicker in the PAH rats compared with controls, and atelectasis was also observed in the PAH rats.
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Lung weight was higher in the PAH rats, but body weight was lower. Interestingly, in these rats, the right atrium and right ventricle weights were significantly higher, but the left atrium and left ventricle weights were lower.
The authors observed a downregulation of ion channels and Ca2+-handling genes, which is known to slow pacemaking activity of the sinus node. There was also upregulation of fibrosis genes, including vimentin, collagen, elastin, fibronectin, and transforming growth factor β1.
The authors speculate that sinus node dysfunction could be the cause of death in PAH, given that bradyarrhythmias are a common cause of death in heart failure and given the evidence of significant remodeling and dysfunction of the sinus node in this rat model of PAH.
Logantha SJRJ, Yamanushi TT, Absi M, et al. Remodelling and dysfunction of the sinus node in pulmonary arterial hypertension. Phil. Trans. R. Soc. Published online May 1, 2023. doi.10.1098/rstb.2022.0178