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 cardiomyopathic hamsters (TO-2 strain). It was found that tedisamil (10(-7) M) increased gj by 53.8+/-1% (n = 23) in cell pairs isolated from 2 months old cardiomyopathic hamsters. The effect of tedisamil was suppressed by intracellular dialysis of an inhibitor of protein kinase A and also by adenosine indicating that the drug increases gj through the activation of adenylcyclase. Tedisamil also increased the conduction velocity and cardiac refractoriness of ventricular muscle from young cardiomyopathic hamsters. At an advanced stage of the disease, however, when the beta-adrenoceptor, adenylcyclase signaling system is impaired, tedisamil was unable to increase gj. The present results indicate that the antiarrhythmic action of tedisamil is in part related to an increase in junctional conductance and conduction velocity.
Department of Pharmacology, School of Medicine, UPR, San Juan, PR 00936-5067, USA.
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De Mello
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D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000627:therapeutic use; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology* / Q000627:therapeutic use; D002450:Cell Communication / Q000187:drug effects*; D006224:Cricetinae; D003521:Cyclopropanes / Q000494:pharmacology* / Q000627:therapeutic use; D004553:Electric Conductivity; D017629:Gap Junctions / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006333:Heart Failure / Q000517:prevention & control; D008297:Male; D008647:Mesocricetus
D000889:Anti-Arrhythmia Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003521:Cyclopropanes; C059921:tedisamil