The Protective Effects of Levosimendan on Ischemia/Reperfusion Injury and Apoptosis

Levosimendan is a calcium sensitizer with positive inotropic and vasodilating properties. It increases the sensitivity of troponin C for calcium, opens adenosine triphosphate-dependent potassium (K+) channels and inhibits phosphodiesterase III. Levosimendan is approved for use in cardiac failure but large clinical trials have raised doubts whether levosimendan is superior to β-adrenergic agonists regarding long-term survival of patients. Despite this controversy, there is growing evidence of beneficial effects of levosimendan in ischemia/reperfusion (I/R) injury due to its effect on K+ channels. As a consequence, patents on K+ channel agonists have been granted recently for reducing injury in organs or tissue in transplants and trauma therapy. Moreover, experimental studies and clinical trials have shown that levosimendan effectively inhibits cardiomyocyte apoptosis. The underlying molecular mechanism is currently unclear. However, it is tempting to assume that levosimendan inhibits cardiomyocyte apoptosis due to its beneficial effect on I/R injury. However, the link between these two phenomena has not been well established. This review summarizes experimental studies and clinical trials on the effects of levosimendan in I/R injury and apoptosis also discussing recent patents.