Ticagrelor reduces reperfusion arrhythmias in a metabolic syndrome

EMILIANO DIEZ; ROBERTO MIATELLO; NICOLÁS RENNA

Buenos Aires

Congreso; ISHR XXII World Congress; 2016

International Society for Heart Research

BACKGROUND: Ticagrelor (TICA) is a potent inhibitor of the P2Y12 receptor. In addition, TICA increases adenosine concentration by interfering with its cellular reuptake. Higher tissular levels of adenosine during ischemia and reperfusion protects against ischemia-reperfusion injury. In this study, we used TICA to prevent cardiovascular remodeling and ventricular arrhythmias in Langendorff-perfused hearts from SHR rats fed with fructose to induce metabolic syndrome.METHODS: Male WKY and SHR were separated into two groups whether receiving tap water or 10% (w/v) fructose solution during all 6 weeks and designated as fructose-fed rat (FFR) or fructose-fed hypertensive rat (FFHR), respectively. These four groups were divided into vehicle or TICA: (30 mg/kg intraesophageal for 6 weeks) (n=8 each group). Metabolic variables and systolic blood pressure were measured weekly through the 12 weeks. Cardiac and vascular remodeling were evaluated by macroscopic and microscopic measurements. Reperfusion ventricular arrhythmias were determined in Langendorff-perfused hearts after 10 min of regional ischemia. Connexin-43 and PKC-epsilon expression was determinate by western blot.RESULTS: The FFHR experimental model presented metabolic syndrome criteria, vascular and cardiac remodeling. Chronic treatment with TICA reduced ventricular fibrillation incidence in all groups. Connexin 43 and its phosphorylated form by PKC-epsilon were reduced in the pathological models. TICA reversed changes in this pathway.CONCLUSIONS: We conclude that FFHR model increases arrhythmogenesis and TICA protects against these changes. TICA preserve phosphorylated connexin 43, possibly stabilizing the intercellular communication and this effect is mediated by PKC.