Inoprotection: The Perioperative Role of Levosimendan

Abstract

Levosimendan is emerging as a novel cardioprotective inotrope. Levosimendan augments myocardial contractility by sensitising contractile myofilaments to calcium without increasing myosin adenosine triphosphatase activity or oxygen consumption. Levosimendan activates cellular adenosine triphosphate-dependent potassium channels, a mechanism which is postulated to protect cells from ischaemia in a manner similar to ischaemic preconditioning. Levosimendan may therefore protect the ischaemic myocardium during ischaemia-reperfusion as well as improve the contractile function of the heart. Adenosine triphosphate-dependent potassium channel activation by levosimendan may also be protective in other tissues, such as coronary vascular endothelium, kidney and brain. Clinical trials in patients with decompensated heart failure and myocardial ischaemia show levosimendan to improve haemodynamic performance and potentially improve survival. This paper reviews the known pharmacology of levosimendan, the clinical experience with the drug to date and the potential use of levosimendan as a cardioprotective agent during surgery.

Levosimendan infusion in newborns after corrective surgery for congenital heart disease: randomized controlled trial

“…In addition its vasodilator effects (including coronary arterial vasodilation) have been attributed to activation of sarcolemmal K-sensitive adenosine triphosphate (KATP) channels of vascular smooth muscle cells, recently suggested as a key target in the therapy of myocardial dysfunction [11,16,17]. Furthermore, another key feature of levosimendan is the activation of mitochondrial KATP channels, which are important mediators of ischemic preconditioning, and may also be protective in other tissues, such as kidney and brain [18].…”

Levosimendan improves contractilityin vivoandin vitroin a rodent model of post-myocardial infarction heart failure

“…In contrast, recent data show that LEV increases cyclic adenosine monophosphate (cAMP), specifically by inhibition of PDE, and activates protein kinase A (PKA) signalling in rats (Markou et al 2011). Interestingly, LEV also opens mitochondrial ATP-dependent potassium (K+) channels that is presented to be related both to cardioprotective and inotropic effects (Das & Sarkar 2007, Soeding et al 2007, du Toit et al 2008, Perjes et al 2012.…”

Use of levosimendan in patients with ischemic heart disease following mechanical reperfusion

“…In addition, it also exerts a protective effect on coronary vascular endothelial cells, the brain, and kidneys through the activation of K + -dependent ATP channels. 18 Levosimendan improves myocardial contractility without increasing the myocardial O 2 consumption. It exerts this effect in ischemic-origin heart failure through antiischemic, anti-stunning, and coronary vasodilatation effects (Table 1).…”

“…18 Levosimendan protects cardiac contractile function as well as the ischemic myocardium during ischemic reperfusion. During the administration of hypothermic cardioplegics in an isolated rat heart, ischemia-reperfusion damage is reported to be less in the levosimendan group.…”