Modulating Cardiac Conduction during Metabolic Ischemia with Perfusate Sodium and Calcium in Guinea Pig Hearts.

INTRODUCTION: We previously demonstrated that altering extracellular sodium (Nao ) and calcium (Cao ) can modulate a form of electrical communication between cardiomyocytes, termed ephaptic coupling, especially during loss of gap junction coupling. We hypothesized that altering Nao and Cao modulates conduction velocity (CV) and arrhythmic burden during ischemia.

METHODS: Electrophysiology was quantified by optically mapping Langendorff-perfused guinea pig ventricles with modified Nao (147 or 155mM) and Cao (1.25 or 2.0mM) during 30 minutes simulated metabolic ischemia (pH=6.5, anoxia, aglycemia). Gap junction adjacent perinexal width (WP ), a candidate cardiac ephapse, Cx43 protein expression and Cx43-S368 phosphorylation were quantified by transmission electron microscopy and Western immunoblotting, respectively.

RESULTS: Metabolic ischemia slowed CV in hearts perfused with 147mM Nao and 2.0mM Cao , but theoretically increasing EpC with 155mM Nao was arrhythmogenic and CV could not be measured. Reducing Cao to 1.25mM expanded WP , as expected during ischemia, consistent with reduced EpC, but attenuated CV slowing while delaying arrhythmia onset. These results were further supported by osmotically reducing WP with albumin, which exacerbated CV slowing and increased early arrhythmias during ischemia while mannitol expanded WP , permitted conduction, and delayed the onset of arrhythmias. Cx43 expression patterns during the various interventions insufficiently correlated with observed CV changes and arrhythmic burden.

CONCLUSIONS: Decreasing perfusate calcium during metabolic ischemia enhances perinexal expansion, attenuates conduction slowing, and delays arrhythmias. Thus, perinexal expansion may be cardioprotective during metabolic ischemia.