Clofibric Acid has Positive Inotropic Effects on Cardiac Muscle

• Published in: The FASEB journal Vol. 24; no. S1; p. 622.3
• Main Authors: Kim, Seo‐Hyun, Mirza, Omer M, Stone, Jessica K, Touchberry, Chad D, Youssef, Jihan, Badr, Mostafa, Wacker, Michael J
• Format: Journal Article
• Language: English
• Published: Federation of American Societies for Experimental Biology 01-04-2010
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.24.1_supplement.622.3

Fibrates are a class of drugs used clinically to increase levels of HDL and to lower triglycerides. Preliminary data demonstrated that clofibric acid inhibited the Na+/K+ pump. Consequently, we hypothesized that blocking the Na+/K+ pump in cardiac tissue would lead to an increase in intracellular Na+. This would result in activation of the reverse mode of the Na+/Ca2+ exchanger and increase both intracellular Ca2+ and cardiac contractility. To test this hypothesis, mouse left ventricular heart strips were paced in the presence of either vehicle (DMSO) or clofibric acid (2 and 20 μM). Following a 20 minute exposure, analysis of individual contractions demonstrated increased height, slope, area under the curve, and tau (rate of decay) in clofibric acid‐treated strips as compared to vehicle. In summary, clofibric acid had a positive inotropic effect on mouse cardiac left ventricular muscle, most likely through a PPAR‐independent mechanism. It is possible that other analogs of clofibric acid currently prescribed in practice may also have positive inotropic effects on cardiac muscle.