title: The contractility enhancing effect of the calcium sensitiser levosimendan is not attenuated by carvedilol in healthy subjects.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacology, University of Helsinki, Helsinki, Finland.
authors.forename: Lasse
authors.initials: L
authors.lastname: Lehtonen
authors.forename: Stig
authors.initials: S
authors.lastname: Sundberg
mesh_terms: 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
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D002316:Cardiotonic Agents; D006835:Hydrazones; D011412:Propanolamines; D011724:Pyridazines; D000077261:Carvedilol; D000077464:Simendan