LAUSR

RATIONALE: Heart failure (HF) following chronic myocardial infarction (MI) is associated with increased susceptibility for cardiac arrhythmias. However, the complex electrophysiological changes causing cardiac arrhythmias remain incompletely understood, especially in large animal models. METHOD: In a porcine model of ischemic HF we used action potential (AP)-clamp and sequential dissection of the major ionic currents during the cardiac AP in ventricular myocytes (from infarct border and remote zones 5 months after MI induction). RESULTS: (1) Compared to healthy controls, remote zone myocytes exhibited increased late sodium current, calcium-activated chloride current and calcium-activated potassium current, decreased rapid delayed rectifier potassium current and also altered sodium/calcium exchange current dynamics. These changes combine to lengthen the AP duration (APD) in the remote zone. (2) In the border zone, the above changes also occurred, but with additional pronounced decreases in L-type calcium current and inward rectifier potassium current, and calcium-activated potassium current was further enhanced to become a major repolarizing current. These additional changes shortened the APD in the border zone. CONCLUSIONS: Ischemic HF involves complex changes in many ionic currents. The changes in each individual current are modest; however, the combined changes in multiple currents integrate to cause APD shortening in the border zone but APD lengthening in the remote zone. Changes in many ionic currents significantly increase the APD dispersion surrounding the infarct to provide a substrate for cardiac arrhythmias.