The contractility enhancing effect of the calcium sensitiser levosimendan is not attenuated by carvedilol in healthy subjects.
OBJECTIVE
It was assessed whether the contractility enhancing effect of the calcium sensitiser levosimendan is altered by carvedilol.


METHODS
Twelve healthy subjects received 2 mg levosimendan i.v. both alone and in addition to a 7-9-day treatment with 25 mg carvedilol orally, twice daily, in a cross-over, placebo-controlled, double-blind, randomised study. Systolic time intervals, heart rate, and blood pressure were measured at baseline and up to 2 h after drug administration.


RESULTS
When levosimendan was administered in addition to carvedilol, the shortening of electromechanical systole QS2i (indicating increased contractility) was similar to that found with levosimendan alone ( P=0.475). Also, the maximum heart rate change was similar, although a statistically significant difference in heart rate was detected due to minor differences at two time points during the 2-h follow-up ( P=0.018). There were no differences in diastolic blood pressure response ( P=0.962), but the systolic blood pressure response was attenuated by about 4 mmHg with the combination ( P=0.013).


CONCLUSIONS
The contractility enhancing effect of levosimendan was not altered in healthy subjects who had received carvedilol for at least 1 week. Heart rate and diastolic blood pressure responses were not altered either, while the systolic blood pressure response was blunted.
Lehtonen
Lasse
L
Department of Clinical Pharmacology, University of Helsinki, Helsinki, Finland.
Sundberg
Stig
S
D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002227:Carbazoles / Q000008:administration & dosage / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000077261:Carvedilol; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006835:Hydrazones / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D011412:Propanolamines / Q000008:administration & dosage / Q000494:pharmacology*; D011724:Pyridazines / Q000008:administration & dosage / Q000494:pharmacology*; D012016:Reference Values; D000077464:Simendan; D013599:Systole
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D002316:Cardiotonic Agents; D006835:Hydrazones; D011412:Propanolamines; D011724:Pyridazines; D000077261:Carvedilol; D000077464:Simendan