198 Heart failure increases mitochondrial s-nitrosylation

Heart failure affects over 5 50 000 people living in the United Kingdom (1) and roughly half of those present with reduced cardiac ejection fraction (2). The electron transport chain (ETC) within the mitochondria is the principle source of ATP within cardiac muscle. Consequently, the regulation of the ETC in heart failure represents a potential rate limiting step to cardiac contraction in the disease state. The post-translational modification of proteins by nitric oxide, S-nitrosylation (S-NO) has previously been shown to have inhibitor effects on complex I activity (3). The aim of this study is therefore to investigate the role of S-NO and how this may regulate ETC activity in an ovine tachypaced model of heart failure. Tachypacing induced heart failure resulted in an increase in left ventricular diameter (3.100.06cm to 4.040.13cm, p This study demonstrates that in heart failure there is a gross increase in the level of myocardial S-NO. Within the mitochondria, S-NO of electron transport chain proteins is also increased, having an inhibitory effect on ATP production. This work therefore provides a novel insight into how S-NO may contribute to the deterioration of cardiac contractile function in heart failure. References . Townsend NWJ, Bhatnagar P, Wickramasinghe K, Rayner M. Cardiovascular disease statistics 2014. London: British Heart Foundation; 2014. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Executive Summary: Heart Disease and Stroke Statistics-2016 Update: A Report From the American Heart Association. Circulation. 2016;133(4):447-54. Epub 2016/01/27. . Chouchani ET, Methner C, Nadtochiy SM, Logan A, Pell VR, Ding SJ, et al. Cardioprotection by S-nitrosation of a cysteine switch on mitochondrial complex I. Nat Med. 2013;19(6):753.