The effect of levosimendan during long-term amiodarone treatment in dogs.
The haemodynamic and electrophysiological effects of levosimendan were studied in conscious dogs receiving long-term oral amiodarone treatment. Instrumented dogs were administered increasing doses of levosimendan (up to 0.9 microg/kg/min. intravenously) in three successive 30 min. infusions. This schedule was repeated on the 21st day of treatment with oral amiodarone 100 mg/kg/day. The extent of increase in left ventricular systolic pressure (LVSP) and the decrease in left ventricular end-diastolic pressure (LVEDP) seen with levosimendan were similar before and after long-term treatment with amiodarone. The levosimendan-induced increases in isovolumic contraction (+dP/dt) and in left ventricular contractility (dP/dt/P) seen prior to amiodarone administration were augmented during amiodarone treatment, an effect that was statistically significant (P<0.05) at the highest doses of levosimendan. A tendency towards a shortening of the QT interval and a rise in heart rate was observed for levosimendan alone but they did not exceed the physiological range when the drug was given in combination with amiodarone. QTc value was unaffected by levosimendan either alone or with amiodarone. These effects were apparent in animals with therapeutically meaningful plasma levels of levosimendan, amiodarone and desethylamiodarone levels. The results of this study show that the improvement in ventricular contractile performance usually associated with administration of levosimendan was somewhat enhanced by chronic oral treatment with amiodarone. It seems reasonable to infer that the inotropic potency and electrophysiological safety of parenteral levosimendan will be maintained in patients with heart failure during long-term treatment with oral amiodarone.
Papp
Julius Gy
JG
Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical Center, University of Szeged, H-6701 Szeged, Hungary. Papp@phcol.szote.u.szeged.hu
Pollesello
Piero
P
Varró
András
A
Végh
Agnes
A
Udvary
Eva
E
D000638:Amiodarone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004347:Drug Interactions; D004562:Electrocardiography / Q000187:drug effects; D004594:Electrophysiology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006835:Hydrazones / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D011724:Pyridazines / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D000077464:Simendan; D013318:Stroke Volume / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan; D000638:Amiodarone