Pinacidil modifies the vulnerability to reentry during regional myocardial ischemia in a dose dependent manner: a simulation study

Potassium channel openers, such as pinacidil, are known to increase ATP-sensitive potassium current. Its activation changes markedly action potential configuration, specially during myocardial ischemia, creating inhomogeneities and favoring the occurrence of reentry. However, controversial effects of KCOs have been observed The aim of this work was to analyze the effects of pinacidil on reentry generation in a regional ischemic tissue using Luo-Rudy II model. Our results show that the vulnerable window (VW) width increases to 49 ms and reaches a maximum value of 54 ms for a dose of 0.001 mmol/L and 0.003 mmol/L respectively, compared to 45 ms in the absence of the drug. For higher doses, the VW width is reduced, and no reentry occurs for 0.01 mmol/L. We conclude that pinacidil modifies vulnerability to reentries during the acute phase of regional ischemia in a dose-dependent manner, and has antiarrhythmic effects for elevated doses.