Mechanisms of Action of Calcium-Sensitizing Drugs

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

“…So far, few data exist on levosimendan use in pediatric patients, mostly related to the treatment of heart failure [12]; nevertheless, its unique pharmacodynamics suggest a strong rationale for levosimendan use in immature hearts requiring surgery on cardiopulmonary bypass (CPB) [13]. As a calcium sensitizer, levosimendan enhances the sensitivity of contractile myofilaments to intracellular calcium concentration by binding to the C cardiac troponin [14]. The resulting inotropic effect is not mediated by adrenergic receptors and does not affect either calcium or intracellular cyclic adenosine monophosphate.…”

The Role of Potassium Channels in Relaxant Effect of Levosimendan in Rat Small Mesenteric Arteries

“…It has been reported that levosimendan exerts positive inotropic effect in isolated guinea pig heart in the concentration range of 0.03-1 µM and higher concentrations (0.3-10 µM) are needed in skinned myocardial fiber preparations [27]. We also recently showed that levosimendan produces increments in developed tension in isolated human atrial trabeculae with a pD 2 value of 6.819 ± 0.33 [28].…”

Levosimendan and severe pulmonary hypertension during open heart surgery

“…8 Beyond these two mechanism, especially at higher doses of levosimendan, vasodilatation occurs by the inhibition of phosphodiesterase (PDE) in vascular smooth muscle. 9 Inhibition of PDE by levosimendan creates an increased concentration of cAMP in the vascular smooth muscle of pulmonary vessels and cascade that ends in vasodilatation. In the two patients described herein, we were able to demonstrate that excessively high PAP can be controlled by levosimendan, an inodilator agent.…”