Sotalol exhibits reverse use-dependent action on monophasic action potentials in normal but not in infarcted canine ventricular myocardium.
In 12 anesthetized mongrel dogs (30 mg/kg pentobarbital), a thoracotomy was performed, and the left anterior descending coronary artery was ligated proximally. Eight to 12 days later, monophasic action potentials were recorded endocardially from the apex of the noninfarcted right ventricle and infarcted areas of the left ventricle, and the effects of 1.5 mg/kg intravenous sotalol were evaluated. Monophasic action potentials from the infarcted zone of the left ventricle were obtained from areas where fractionated bipolar electrograms could be recorded; this was histologically confirmed. After sotalol, in sinus rhythm, the monophasic action potential duration at 90% repolarization of the infarcted zone increased from 186 +/- 31 to 226 +/- 45 ms (+ 22%, p less than 0.05), and monophasic action potential duration of the noninfarcted zone increased from 184 +/- 31 to 225 +/- 47 ms (+ 22%, p less than 0.05). Programmed ventricular stimulation was performed with single extrastimuli at a basic drive cycle length of 300 ms. With long coupling intervals (290 ms), monophasic action potential duration of the infarcted zone increased from 165 +/- 23 to 183 +/- 25 ms (+ 11%, p less than 0.05) after sotalol; and monophasic action potential duration of the noninfarcted zone increased from 159 +/- 20 to 180 +/- 25 ms (+ 13%, p less than 0.05). With short coupling intervals (200 ms), the monophasic action potential duration of the noninfarcted zone increased from 157 +/- 19 to 173 +/- 18 ms (+ 10%, p less than 0.05), and monophasic action potential duration of the noninfarcted zone increased from 150 +/- 18 to 157 +/- 18 ms (+ 5%, NS).(ABSTRACT TRUNCATED AT 250 WORDS)
Schmitt
C
C
Department of Cardiology, University of Heidelberg, Germany.
Beyer
T
T
Karch
M
M
Montero
M
M
Hilbel
T
T
Brachmann
J
J
Kübler
W
W
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004285:Dogs; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D006329:Heart Conduction System / Q000187:drug effects*; D009203:Myocardial Infarction / Q000503:physiopathology*; D013015:Sotalol / Q000494:pharmacology*
D013015:Sotalol