Hemodynamic and neurohumoral effects of levosimendan, a new calcium sensitizer, at rest and during exercise in healthy men.
Levosimendan is a novel inodilator that increases the calcium sensitivity of troponin C in a calcium-dependent way. Cardiac function (impedance cardiography, systolic time intervals), neurohumoral responses at rest and during exercise at 2 workloads, and peripheral blood flow (plethysmography) were studied in 14 healthy young men. Vehicle and 2 doses of levosimendan (6.5 micrograms/kg, low dose [LD]; and 25 micrograms/kg, high dose [HD]) were given intravenously in a crossover study. Measurements taken 15 minutes after a supine rest showed HD levosimendan shortened electromechanical systole (QS2i) by 16 ms maximally (p < 0.001), and decreased systemic vascular resistance by 25% (p < 0.001), compared with baseline values. Diastolic blood pressure fell by 9 mm Hg (p < 0.01). When the changes after vehicle were compared with the changes after HD levosimendan, the difference was 2.1 L/min after 25 micrograms/kg (p < 0.001), caused by an increase in stroke volume, with the heart rate being unaffected. Leg blood flow increased by 35% (p < 0.001). During exercise at the lower workload, HD levosimendan increased cardiac output by 1.5 L/min (p < 0.05), compared with that caused by vehicle, by an increase in heart rate, with the stroke volume being unchanged. Electromechanical systole was shortened significantly (20 ms, p < 0.001 after HD; 12 ms, p < 0.01 after LD). At the higher workload, no effects on electromechanical systole or cardiac output compared with that associated with administration of vehicle were seen, but the mean heart rate increased (p < 0.001, LD and HD) and mean diastolic blood pressure decreased (p < 0.01, HD).(ABSTRACT TRUNCATED AT 250 WORDS)
Sundberg
S
S
Orion Research, Orion-Farmos, Espoo, Finland.
Lilleberg
J
J
Nieminen
M S
MS
Lehtonen
L
L
D000328:Adult; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002302:Cardiac Output / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002395:Catecholamines / Q000097:blood*; D018592:Cross-Over Studies; D005080:Exercise Test; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology*; D007866:Leg / Q000098:blood supply; D008297:Male; D011724:Pyridazines / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D012146:Rest; D000077464:Simendan; D013318:Stroke Volume / Q000187:drug effects; D013599:Systole / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D002316:Cardiotonic Agents; D002395:Catecholamines; D006835:Hydrazones; D011724:Pyridazines; D014665:Vasodilator Agents; D000077464:Simendan; D009320:Atrial Natriuretic Factor; D002118:Calcium