Monoamine oxidase A inhibition protects the myocardium after experimental acute volume overload

Abstract

Objective: The molecular pathway leading to myocardial cellular destruction after acute volume overload (AVO) may include monoamine oxidases. The aim of the present study was to investigate whether moclobemide (Mo), a monoamine oxidase inhibitor, protects the myocardium after AVO. Methods: Sixty syngeneic Fischer rats underwent surgical abdominal aortocaval fistula to induce AVO. Eighteen rats were treated with Mo 10 mg/kg/day and were compared with 42 untreated rats with AVO without treatment. Myocardial recovery was analyzed using quantitative reverse transcription polymerase chain reaction for hypoxia-inducible factor 1-alpha, inducible nitric oxide synthase, interleukin 6, E-selectin, atrial natriuretic peptide (ANP), brain natriuretic peptide, vascular endothelial growth factor-alpha, matrix metalloproteinase 9, chitinase 3-like protein (YKL-40), and transforming growth factor-beta. Results: After 3 days, the relative number of ischemic intramyocardial arteries in the left ventricle was lower in AVO treated with Mo than in without [0.04 (0.02–0.07) vs. 0.09 (0.07–0.14), point score unit]. After 1 day, ANP was lower in AVO treated with Mo than in without [0.95 (0.37–1.84) vs. 2.40 (1.33–3.09), fold changes from the baseline (FC), p=0.044], whereas after 1 and 3 days, YKL-40 was higher in AVO treated with Mo than in without [22.66 (14.05–28.83) vs. 10.06 (6.23–15.02), FC, p=0.006 and 6.03 (4.72–7.18) vs. 3.70 (2.62–5.35), FC, p=0.025]. Conclusion: Mo decreases intramyocardial arterial ischemia of the left ventricle after AVO while increases YKL-40, reflecting cellular protection during early cardiac remodeling. In the future, adding Mo may be a simple means for myocardial protection after AVO.