Impulse propagation in the ventricle depends on both sodium channel availability and cell-to-cell coupling through gap junctions. Sodium channel block has been shown to depress conduction velocity (&thetas;) more longitudinal (LONG) to than transverse (TRANS) to fiber orientation. Because exposure to CO2produces intracellular acidosis and decreased gap junction conductance in vitro, we tested the hypothesis that increased Pco2would result in preferential depression of transverse conduction in vivo.Methods and ResultsIn anesthetized dogs, when arterial pH was reduced to 6.70±0.04 by increasing the fraction of inhaled CO2to 40%,&thetas;TRANSfell from 0.23±0.04 to 0.19±0.02 m/s (−16±8%,P< .03), while &thetas;LONGwas unchanged (-3±7%,P=NS). In contrast, with the same degree of acidemia produced by HCI infusion, only &thetas;LONGfell (−8±7%), coincident with a rise in serum K+.ConclusionsThe observed effect of CO2on propagation in the intact heart is consistent with its previously described in vitro actions to uncouple cell-to-cell communication and may provide a model to study the role of cell-to-cell coupling in normal and abnormal propagation.