Reentrant tachycardia in a thin layer of ventricular subepicardium: effects of d-sotalol and lidocaine.
Ventricular tachycardia (VT) was induced by premature stimulation or fast pacing in 14 Langendorff-perfused rabbit hearts whose left ventricular endocardial and intramural cells had been selectively killed by freezing. VTs were caused by apparent reentrant excitation in the surviving thin (1 mm thick) subepicardial layer of anisotropically oriented cells having ostensibly normal membrane characteristics. During VT, 100 microM d-sotalol (seven hearts) or 30 microM lidocaine (seven hearts) was added to the perfusate. Electrophysiological variables were measured before and during drug exposure at both slow (S1 = 300 ms) and fast (S1 = 150-180 ms) pacing rates. Sotalol prevented VT reinduction in six of seven preparations, compared to only two of seven with lidocaine. Lidocaine prolonged the functional refractory period (FRP) and slowed conduction velocity (CV). Lidocaine prolonged the wavelength of the cardiac impulse (= FRP x CV) by 18% at slow rates but reduced it by 21% at fast rates. Sotalol, however, since it increased the FRP without reducing CV, caused wavelength prolongation at both rates (43% at slow rates, 26% at fast rates). Thus, this VT model may provide an important contrast of class I and class III drug action, with the drug effects on wavelength predicting susceptibility to VT induction.
Hill
B C
BC
Department of Cardiovascular Physiology and Biophysics, Palo Alto Medical Foundation, CA 94301.
Hunt
A J
AJ
Courtney
K R
KR
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004558:Electric Stimulation; D004594:Electrophysiology; D005615:Freezing; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology*; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology*; D011817:Rabbits; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D013015:Sotalol / Q000494:pharmacology*; D013610:Tachycardia / Q000503:physiopathology*
D008012:Lidocaine; D013015:Sotalol