Inhibition of Monoamine Oxidase A in pulmonary artery banding-induced right heart failure

Abstract

Introduction: Oxidation of catecholamines and serotonin by monoamine oxidase–A (MAO-A) may play a role in pulmonary hypertension (PH). MAO-A inhibition (MAOi) decreased proliferation in pulmonary artery intima, and was beneficial in several models of left heart failure. We hypothesized that MAOi will be beneficial in the setting of PH. Methods: Male Wistar rats underwent surgical banding of the pulmonary trunk (PTB) or sham surgery (sham, n=7). Two weeks later, echocardiography was performed and PTB rats were randomized to MAOi (PTB+MAOi, n=12) and treated with clorgyline (2 mg/kg i.p. 3x/week) or saline (PTB, n=12). Rats were treated for five weeks before evaluation echo and pressure-volume-loops (PV loop) were obtained. During echo and PV loops rats where anesthetized with sevoflurane (mix in 1.5L/min O2, 7% for induction, 3.5% for maintainance). Results: MAO-A activity increased almost 3-fold in PTB compared to sham, whereas MAOi completely reversed this. PTB increased total heart- and RV weight, which was partly reversed by MAOi. The ratio of RV weight to left ventricle + septum weight did not change after MAOi. MAOi did not improve RV function or reduce RV dilatation as analyzed by echocardiography or PV loops (Fig. 1). Conclusion: Despite normalization of MAO-A activity in PTB rats, no functional improvements or changes in cardiac size were observed. Histological analyses will further elucidate these findings.