RT Journal Article
SR Electronic
T1 Zamicastat decreases cardiac arrhythmias in a rat model of pulmonary arterial hypertension
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1483
DO 10.1183/13993003.congress-2020.1483
VO 56
IS suppl 64
A1 Nuno Pires
A1 Bruno Igreja
A1 Luis Magalhaes
A1 Maria-Joao Bonifacio
A1 Eric Chevalier
A1 Patricio Soares-Da-Silva
YR 2020
UL http://erj.ersjournals.com/content/56/suppl_64/1483.abstract
AB Pulmonary arterial hypertension (PAH) is characterized by a progressive increase in pulmonary vascular resistance causing right ventricular failure and premature death. Studies of PAH patients show a hyperstimulation of the sympathetic nervous system (SNS) indicating that PAH can be mediated, at least partly, by SNS hyperactivation. Zamicastat is a reversible dopamine β-hydroxylase inhibitor that modulate SNS by reducing the biosynthesis of noradrenaline in peripheral sympathetic nerves. Zamicastat treatment significantly improves survival rate in the monocrotaline (MCT) rat model of PAH.Here we assessed the effect of zamicastat in the MCT rat model on hemodynamic, cardiac contractility and electrocardiogram (ECG).Zamicastat treatment (30 mg/kg/day) was initiated 12 days after MCT, when the disease-related pathophysiology is already established, and prolonged until day 32. Zamicastat did not influence pulmonary hemodynamic or cardiac contractility but decreased heart rate, mean blood pressure and pulse pressure, compared to MCT-treated controls. Treatment with zamicastat eliminated the shortening of PR intervals and slightly widened the QRS complex, leading to significant increases in QTc duration. Zamicastat shortened JTc intervals but had no effect on Tpeak-Tend intervals. Zamicastat decreased the frequency of arrhythmic beats and the incidence of atrioventricular block, atrioventricular nodal reentrant tachycardia, bundle branch block and the incidence of ventricular fibrillation.FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 1483.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).