Effects of ischemia on discontinuous action potential conduction in hybridpairs of ventricular cells

Background-Acute ischemia often occurs in cardiac tissue that has prior inj ury, resulting in spatially inhomogeneous distributions of membrane propert ies and intercellular coupling. Changes in action potential conduction with ischemia, which can be associated with release of catecholamines, may be p articularly important in tissue that has discontinuous conduction resulting from prior infarction, hypertrophy, or myopathy. Methods and Results-Isolated guinea pig ventricular myocytes were electrica lly coupled by a coupling-clamp circuit to a comprehensive computer model o f a guinea pig ventricular myocyte to assess alterations in the critical va lue of coupling conductance required for action potential conduction from t he real cell to the model cell when the real cell was exposed to a solution that included hypoxia, acidosis, and an elevated extracellular potassium c oncentration to simulate acute ischemia, The "ischemic" solution increased critical coupling conductance from 6.2+/-0.1 to 7.4+/-0.2 nS and decreased the associated maximum conduction delay from 31+/-1 to 23+/-1 ms (mean+/-SE M, n=11), The ischemic solution plus 1 mu mol/L norepinephrine decreased cr itical coupling conductance from 5.9+/-0.2 to 5.0+/-0.1 nS and increased ma ximum conduction delay from 31+/-2 to 54+/-4 ms (mean+/-SEM, n=8). Conclusions-The release of catecholamines with ischemia, in a setting of pa rtially uncoupled cells, may play a major role in producing long conduction delays, which may allow reentrant pathways.