Effects of cell-to-cell uncoupling and catecholamines on Purkinje and ventricular action potentials: implications for phase-1b arrhythmias

Objective: The delayed phase of ventricular arrhythmias during acute ischem ia (phase-lb arrhythmia) is associated with depletion of catecholamines and cell-to-cell uncoupling between depressed depolarized intramural ischemic region and surviving cells in subepicardium and subendocardium. In the pres ent study we determined the effects of uncoupling and catecholamines on dev elopment of proarrhythmic afterdepolarizations. Methods: Depressed depolari zed ischemic region was simulated by a passive electronic circuit with a po tential of -73, -53, -33 or -13 mV. Using patch-clamp methodology, single s heep Purkinje and ventricular cells were coupled to the simulated ischemic region via a variable conductance. By varying coupling conductance, we were able to selectively study the effects of various degrees of uncoupling. Re sults: At strong coupling, cells were inexcitable and depolarized to potent ials near those of the simulated ischemic region. Excitability. action pote ntial duration and resting potential increased with progressive uncoupling. In a critical range of uncoupling, ventricular and 'high-plateau' Purkinje cells developed early afterdepolarization when the potential of the simula ted ischemic region was -13 mV. Norepinephrine (1 muM) frequently induced e arly and delayed afterdepolarizations in both ventricular and Purkinje cell s, but these afterdepolarizations were only present during uncoupling when the potential of the simulated ischemic region was -33 mV or more positive. Conclusions: In a critical range of uncoupling, afterdepolarization were p resent when the potential of the simulated ischemic region was -33 or -13 m V, suggesting that triggered activity plays a role in phase-lb arrhythmias when surviving layers uncouple from a highly depolarized intramural ischemi c region. (C) 2001 Elsevier Science B.V. All rights reserved.