Levosimendan: a parenteral calcium-sensitising drug with additional vasodilatory properties.
Levosimendan (Simdax) is a new inodilator developed specifically for the treatment of decompensated heart failure. Its inotropic mechanism is based on calcium sensitisation of myofilaments and its vasodilator actions are related to the opening of ATP-dependent K-channels in the vasculature. Since the inotropic action of levosimendan does not require an increase in cytosolic free calcium, it is less arrhythmogenic than the conventional parenteral beta-agonist inotropes or PDE III inhibiting drugs. Due to the calcium-dependent binding of the drug to troponin C, levosimendan, unlike some other calcium-sensitising drugs, does not prolong diastolic relaxation of the myocytes but acts in synergy with the intramyocellular calcium levels. Furthermore, due to the anti-ischaemic effects of the K-channel opening in myocytes, levosimendan can be used during myocardial ischaemia. In clinical trials, levosimendan has dose-dependently increased cardiac output and decreased pulmonary capillary wedge pressure in patients with heart failure. On the other hand, it also increases heart rate and decreases blood pressure in these patients. In major clinical trials, where patients with decompensated heart failure have been treated with levosimendan, a reduction of overall mortality in comparison to placebo or dobutamine has been seen. This interesting finding should be verified in prospective outcome trials. In any case, the safety of levosimendan during myocardial ischaemia makes this drug valuable in the short-term treatment of decompensated heart failure.
Lehtonen
L A
LA
Department of Clinical Pharmacology, Helsinki University Central Hospital, PO Box 340, FIN-00029 HUS, Helsinki, Finland. lasse.lehtonen@hus.fi
D002118:Calcium / Q000378:metabolism*; D004335:Drug and Narcotic Control; D006333:Heart Failure / Q000188:drug therapy*; D006835:Hydrazones / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D011724:Pyridazines / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D000077464:Simendan; D014665:Vasodilator Agents / Q000494:pharmacology*
D006835:Hydrazones; D011724:Pyridazines; D014665:Vasodilator Agents; D000077464:Simendan; D002118:Calcium