Localized injury in cardiomyocyte network: a new experimental model of ischemia-reperfusion arrhythmias

We developed a new experimental approach to study the effects of local inju ry in a multicellular preparation and tested the ability of the method to i nduce reperfusion arrhythmias in cardiomyocyte monolayers. A small region o f injury was created using geometrically defined flows of control and ische mia-like solutions. Calcium transients were acquired simultaneously from in jured, control, and border zone cells using fluo 4. Superfusion with the in jury solution rapidly diminished the amplitude of calcium transients within the injury zone, followed by cessation of cell beating. Reperfusion caused an immediate tachyarrhythmic response in similar to 17% of experiments, wi th a wave front propagating from a single cell or small cell cluster within the former injury zone. Inclusion of a gap junction uncoupler (1 mM heptan ol) in the injury solution narrowed the functional border and sharply incre ased the number of ectopic foci and the incidence of reperfusion arrhythmia s. The model holds a potential to reveal both micro- and macroscopic featur es of propagation, conduction, and cell coupling in the normal and diseased myocardium and to serve as a new tool to test antiarrhythmic protocols in vitro.