Effects of Ticagrelor on Ionic Currents and Contractility in Rat Ventricular Myocytes.

PURPOSE

Antiplatelet therapy has been widely used for management of patients with ischaemic heart diseases or thrombotic events. Experimental studies have shown that ticlopidine and clopidogrel decreased L-type Ca(2+) currents (ICaL), altered action potential (AP) duration and thence exerted negative inotropic effects. In this study we tested if ticagrelor, a non-thienopyridine agent, has any influence on contractile and electrical properties of isolated ventricular myocytes.

METHODS

Cardiomyocytes were isolated from male rat hearts with an enzymatic dissociation procedure and left ventricular myocytes were used for experiments. The effects of ticagrelor (1 μM) on sarcomere shortening, ionic currents and action potentials were measured at 36 ± 1 °C.

RESULTS

Ticagrelor significantly reduced ICaL density (~18%, p < 0.01) of ventricular myocytes and this effect was reversible. In consistence, it also decreased sarcomere shortening of electrically stimulated cardiomyocytes (13%, p < 0.05), while it did not change relaxation rates. Repolarizing K(+) currents and AP duration were unaffected by 1 μM ticagrelor application.

CONCLUSIONS

Ticagrelor exerts a significant influence on contractile properties and membrane currents of ventricular myocytes similarly to thienopyridine agents. The impact of ticagrelor on cardiac excitation-contraction coupling elements is important, since it is widely used for the treatment of patients with heart diseases.