The cardioprotective effects of levosimendan: preclinical and clinical evidence.
Levosimendan, a drug used in the treatment of acute and decompensated heart failure, has positive inotropic and antistunning effects mediated by calcium sensitization of contractile proteins, and vasodilatory and antiischemic effects mediated via the opening of ATP-sensitive potassium channels in vascular smooth-muscle cells. Recently, it also has been shown to act on mitochondrial ATP-sensitive potassium (mitoKATP) channels, an action thought to protect the heart against ischemia-reperfusion damage. This finding has suggested a possible application for levosimendan in clinical situations in which preconditioning would be beneficial (eg, in pre- and perioperative settings in cardiac surgery). The demonstration that levosimendan can prevent or limit myocyte apoptosis via the activation of mitoKATP channels provides a potential mechanism whereby this agent might protect cardiac myocytes during episodes of acute heart failure. This finding may explain why short-term treatment with levosimendan may improve longer-term survival. The present article reviews the literature on the cardioprotective actions of levosimendan, with particular emphasis on its recently recognized effects on mitoKATP channels and the putative preconditioning effects of that action. A therapeutic approach to acute heart failure that includes a cardioprotective strategy could have a clinically meaningful benefit on disease progression beyond alleviation of symptoms.
Pollesello
Piero
P
Orion Pharma, Cardiology and Critical Care, Espoo, Finland. piero.pollesello@orionpharma.com
Papp
Zoltán
Z
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology*; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D008929:Mitochondria, Heart / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D015221:Potassium Channels / Q000187:drug effects*; D011724:Pyridazines / Q000494:pharmacology*; D016032:Randomized Controlled Trials as Topic; D000077464:Simendan
D002316:Cardiotonic Agents; D006835:Hydrazones; D015221:Potassium Channels; D011724:Pyridazines; C117780:mitochondrial K(ATP) channel; D000077464:Simendan