Title: Effects of milrinone on inflammatory response-related gene expressions in cultured rat cardiomyocytes

Authors: Archana G. Venakatesh1, Johann J. Mathew1, Scott Coleman1, Longqiu Yang2, Geoffrey L. Liu3, Marilyn M. Li3, Henry Liu1

Institutions: 1Department of Anesthesiology & Perioperative Medicine, Drexel University College of Medicine, Hahnemann University Hospital, Philadelphia, PA 19102, USA; 2Department of Anesthesiology, Huangshi Central Hospital, Huangshi, Hubei 435002, China; 3Division of Genomic Diagnostics, Department of Pathology & Laboratory Medicine, Childrens Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.

Abstract: Congestive heart failure (CHF) is defined as a cardiac dysfunction leading to low cardiac output and inadequate tissue perfusion. Intravenous positive inotropes are used to increase myocardial contractility in hospitalized patients with advanced heart failure. Milrinone is a phosphodiesterase inhibitor and used most commonly for inotropic effect. The well-known PROMISE study investigated the effects of milrinone on mortality in patients with severe CHF, and concluded that long-term therapy with milrinone increased morbidity and mortality among patients with advanced CHF. Previous studies have suggested that phosphodiesterase inhibitors can have potential effects on inflammatory pathways. Hence, we hypothesized that milrinone may alter inflammatory gene expressions in cardiomyocytes, thus leading to adverse clinical outcomes. We used rat cardiomyocyte cell line H9C2 and studied the impact of exposing cardiomyocytes to milrinone (10 mmol/L) for 24 hours on inflammatory gene expressions. RNA extracted from cultured cardiomyocytes was used for whole rat genome gene expression assay (41,000 genes). The following changes in inflammatory response-related gene expressions were discovered. Genes with increased expressions included: THBS2 (+ 9.98), MMP2 (+ 3.47), DDIT3 (+ 2.39), and ADORA3 (+ 3.5). Genes with decreased expressions were: SPP1 ( 5.28) and CD14 ( 2.05). We found that the above mentioned gene expression changes seem to indicate that milrinone may hinder the inflammatory process which may potentially lead to adverse clinical outcomes. However, further in vivo and clinical investigations will be needed to illustrate the clinical relevance of these gene expression changes induced by milrinone.

Keywords: milrinone, gene expression, cardiomyocyte, inflammation

Full TextJBR-2017-0085.pdf

J Biomed Res published on 29 October 2017, https://doi.org/10.7555/JBR.32.20170085