Physiology and Molecular Biology of the Developing Circulation

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

“…Against the functional background of a physiologically limited contractile reserve [1][2][3], the presence of a CHD may further worsen ventricular performance by means of acidosis, hypoxia, neurohormonal activation [4], surgical manipulation, ischemia reperfusion injury, fluid overload, and systemic inflammatory response occurring during cardiac surgery [5]. As a consequence, in the first 6-12 postoperative hours, more than 20 % of patients exhibit a low cardiac output syndrome (LCOS), characterized by poor systemic perfusion and high vasoactive drugs requirement [6].…”

Initial Single-Center Experience With Levosimendan Infusion for Perioperative Management of Univentricular Heart With Ductal-Dependent Systemic Circulation

“…Neonatal hearts are known to have limited functional reserve as compared to adult hearts because of limited contractility with low contractile reserve, preload and afterload tolerance, and a poor response to catecholamine administration. 5 A few age-related myocyte histopathologic features might explain this poor contractile efficiency: (1) decreased sympathetic innervation on downregulated and insensitive adrenergic receptors, (2) immaturity of the dyads with impaired mechanism of calcium-induced calcium release, (3) poor control of intracytosolic calcium concentration from an underdeveloped sarcoplasmic reticulum with contractile dependence on free cytosolic Ca ++ fluxes, (4) immature mitochondria irregularly scattered between few and relatively disorganized sarcomeres, and (5) expression of myofibril fetal isoforms expressing low ATPase activity. 6 On this functional background, acidosis, hypoxia, and failing ventricle-associated neurohormonal activation may further desensitize myofilaments to a specific intracellular concentration of Ca ++ .…”