Effects of the new class-III antiarrhythmic drug D-sotalol on contractile function of postischemic myocardium.
The hemodynamic effects of the new class-III antiarrhythmic drug D-sotalol (2 mg/kg i.v.) on postischemic myocardium were investigated in comparison with the actions of the racemic D,L-sotalol (2 mg/kg i.v.) in rats. Drug infusion (7 min) was started 20 min after 3 x 4 min of global ischemic injury (oxygen deficiency). The left ventricular isovolumic pressure-generating capacity at the beginning of infusion was reduced by 15%, indicating postischemic dysfunction. Infusion of D-sotalol caused a highly significant (p less than 0.01) reduction of the left ventricular pressure-generating capacity (to 58 +/- 5%), as well as of the dp/dtmax (to 21 +/- 3%). Stroke volume (to 66 +/- 6%), ejection fraction (to 62 +/- 7%), and cardiac output (to 51 +/- 6%) were also decreased (p less than 0.01). Fifteen minutes after infusion a partial renormalization of the hemodynamic measures (dp/dtmax 41 +/- 5%; stroke volume 94 +/- 8%) was observed. Infusion of the racemic D,L-sotalol caused similar hemodynamic changes (left ventricular pressure-generating capacity 60 +/- 2%, dp/dtmax 25 +/- 2%), indicating its cardiodepressant action. In contrast to prior findings on normal myocardium, our present results indicate that D-sotalol, a potential new class-III antiarrhythmic drug, has a considerable negative inotropic effect on postischemic myocardium.
Hoffmeister
H M
HM
Medizinische Klinik, Abt. III, Universität Tübingen, Germany.
Müller
S
S
Seipel
L
L
D000818:Animals; D003327:Coronary Disease / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013015:Sotalol / Q000494:pharmacology*; D013237:Stereoisomerism
D013015:Sotalol