Metabolic syndrome (MetS) represents a worldwide health problem, affecting cardiovascular and mental health. People with MetS are often suffering from depression. We used hereditary hypertriacylglycerolemic (HTG) rats as an animal model of MetS, and these were fed a high-fat-high-fructose diet (HFFD) to imitate unhealthy eating habits of people having several MetS risk factors and suffering depression. Male HTG rats were fed a standard diet (HTG-SD) or HFFD for eight weeks (HFFD8). Venlafaxine was administered for the last three weeks of the experiment (HFFD8+VE). Heart function was observed on the level of intact organisms (standard ECG in vivo), isolated hearts (perfusion according to Langendorff ex vivo), and molecular level, using the RT-PCR technique. The function of the isolated perfused heart was monitored under baseline and ischemia/reperfusion conditions. Analysis of ECG showed electrical abnormalities in vivo, such as significant QRS complex prolongation and increased heart rate. Ex vivo venlafaxine significantly reduced QT interval after ischemia/reperfusion injury. Baseline values of contractile abilities of the heart tended to be suppressed by HFFD. A significant reduction of LVDP was present in the HFFD8 group. Molecular analysis of specific genes involved in cardiac electrical (Cacna1c, Scn5a), contractile (Myh6, Myh7), metabolic function (Pgc1alpha) and calcium handling (Serca2a, Ryr2) supported some of the functional findings in vivo and ex vivo. Based on the present effect of venlafaxine on heart function, further research is needed regarding its cardiometabolic safety in the treatment of patients with MetS suffering from depression. Keywords: Metabolic syndrome, Venlafaxine, ECG, Cardiac contraction, Ischemia/Reperfusion.

Department of Pharmacology and Toxicology Faculty of Pharmacy Comenius University Bratislava Slovak Republic

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