Effects of simulated ischemia on spiral wave stability

Regional hyperkalemia during acute myocardial ischemia is a major factor pr omoting electrophysiological abnormalities leading to ventricular fibrillat ion (VF). However, steep action potential duration restitution, recently pr oposed to be a major determinant of VF, is typically decreased rather than increased by hyperkalemia and acute ischemia. To investigate this apparent contradiction, we simulated the effects of regional hyperkalemia and other ischemic components (anoxia and acidosis) on the stability of spiral wave r eentry in simulated two-dimensional cardiac tissue by use of the Luo-Rudy v entricular action potential model. We found that the hyperkalemic "ischemic " area promotes wavebreak in the surrounding normal tissue by accelerating the rate of spiral wave reentry, even after the depolarized ischemic area i tself has become unexcitable. Furthermore, wavebreak and fibrillation can b e prevented if the dynamical instability of the normal tissue is reduced si gnificantly by targeting electrical restitution properties, suggesting a no vel therapeutic approach.