Hemodynamic effects of the novel cardiotonic drug simendan: echocardiographic assessment in healthy volunteers.
Simendan is a novel cardiotonic drug with mixed properties, including calcium sensitization. Simendan was given intravenously to eight healthy volunteers in doses from 0.1 to 10.0 mg to define its safety and dose-response effects. Its effects on myocardial function were recorded by echocardiography with simultaneous measurement of heart rate (HR) and blood pressure (BP). A linear dose response was observed in all echocardiographic indices. Fractional shortening increased from a basal value of 29.5% to 32.4% (p < 0.05), 34.7% (p < 0.001), and 39.4% (p < 0.001) 10 minutes after doses of 1.0, 2.0, and 5.0 mg of simendan, respectively. The mean velocity of maximal circumferential fiber shortening increased from the baseline of 2.22 lengths/sec to 2.7 lengths/sec after the 2.0 mg dose (p < 0.05) and to 3.31 lengths/sec after the 5.0 mg dose (p < 0.001). Mean BP decreased slightly and mean HR increased only by 5.2 beats/min after the 5.0 mg dose. Because of the potent effect seen on hemodynamic indices and due to two vasovagal reactions, 10 mg was given to two subjects only. These results revealed that simendan has hemodynamic effects that can be explained by positive inotropy as well as vasodilatation, in agreement with preclinical findings. Further studies with patients disabled by heart failure are warranted.
Lilleberg
J M
JM
First Department of Medicine, Helsinki University Central Hospital, Finland.
Sundberg
S
S
Leikola-Pelho
T
T
Nieminen
M S
MS
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography; D004562:Electrocardiography / Q000187:drug effects; D004906:Erythrocyte Count / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D006835:Hydrazones / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009570:Nitriles / Q000009:adverse effects / Q000494:pharmacology*; D011724:Pyridazines; D015203:Reproducibility of Results; D000077464:Simendan; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D002316:Cardiotonic Agents; D006454:Hemoglobins; D006835:Hydrazones; D009570:Nitriles; D011724:Pyridazines; D000077464:Simendan