Effects of pinacidil on refractoriness in acutely ischemic tissue: insights from experiments and simulations

A controversy exits regarding the arrhythmogenic effect of potassium channel openers, such as pinacidil, during acute myocardial ischemia. In order to throw some insight into this issue, the effect of pinacidil on the refractoriness of normal and acutely ischemic tissue has been experimentally and theoretically studied. Experiments with Lungendom perjused rabbit hearts were conducted, as well as computer simulations based on Luo-Rudy phase II model of the cardiac action potential. Our results show that pinacidil significantly reduces the effective refractory period (ERP) in normal tissue. However, in spite of strongly reducing QT interval, pinacidil does not have a signijkanr efect on ERP in acutely ischemic tissue. In conclusion, during myocardial ischemia, despite action potential durution (APD) reduction provoked by pinacidil, ERP is not significantly modified by the drug due to the counteracting effect of 1
_K(ATP)
on depolarization currents