Effect of tedisamil on cell communication, impulse propagation, and excitability of the failing heart

In the present work, the effect of tedisamil on gap junctional conductance (gj) and conduction velocity was investigated in the failing heart of cardi omyopathic hamsters (TO-2 strain). It was found that tedisamil (10(-7) M) i ncreased gj by 53.8 +/- 1% (n = 23) in cell pairs isolated from 2 months ol d cardiomyopathic hamsters. The effect of tedisamil was suppressed by intra cellular dialysis of an inhibitor of protein kinase A and also by adenosine indicating that the drug increases gj through the activation of adenylcycl ase. Tedisamil also increased the conduction velocity and cardiac refractor iness of ventricular muscle from young cardiomyopathic hamsters. At an adva nced stage of the disease, however, when the beta-adrenoceptor, adenylcycla se signaling system is impaired, tedisamil was unable to increase gj. The p resent results indicate that the antiarrhythmic action of tedisamil is in p art related to an increase in junctional conductance and conduction velocit y. (C) 1999 Elsevier Science B.V. All rights reserved.