Intracoronary Infusion of Levosimendan to Treat Postpericardiotomy Heart Failure

Management of Acute Cardiac Failure by Intracoronary Administration of Levosimendan

“…As IC infusion is a selective route of administration without systemic side effects, it was felt that a maximal dose of 24 mg/kg of levosimendan could safely be utilized. 17,18 Correspondingly, a number of other studies have reported using a similar intravenous dose of levosimendan safely. [19][20][21][22] The results generated in this series are consistent with previous experiences in animal models.…”

“…10,16 However, to date, the clinical usage of IC administered levosimendan has only anecdotically been reported in the literature. [17][18][19] We thus report herewith the first clinical series of using levosimendan administered via an IC route to treat acute heart failure in cardiac surgical procedures in an attempt of establishing a ''proof of concept'' in a human cohort and speculate on the potential applicability during cardiac surgery and percutaneous coronary interventions (PCIs).…”

Modulation of Programmed Forms of Cell Death by Intracoronary Levosimendan During Regional Myocardial Ischemia in Anesthetized Pigs

“…These effects on coronary blood flow were accompanied by a significant reduction of both area at risk and necrotic area (p<0.05). Area at risk amounted to 17.8%±2 (16)(17)(18)(19)(20)(21)(22)(23) in the pigs treated with LEV in comparison with that measured in animals treated with vehicle alone of about 23.4%±2.1 (20)(21)(22)(23)(24)(25)(26)(27). In the treated animals and in control pigs, the necrotic area amounted to 41%±2.6 (37-45) and 45.5%± 2.5 (42-50) of area at risk, respectively.…”

“…We have previously shown that such interactions can be avoided by giving intracoronary levosimendan in doses corresponding to those clinically given [15] as a bolus in the anaesthetized pig; using such doses levosimendan was found to induce an increase of coronary blood flow without lowering arterial blood pressure [16]. Furthermore, intracoronary administration of a bolus of levosimendan in a patient suffering from postpericardiotomy heart failure elicited beneficial cardiac effects, in absence of changes in other hemodynamic variables [17]. It is also noteworthy that the pharmacological activation of mitochondrial potassium channels by levosimendan has been reported to inhibit apoptosis induced by oxidative stress in cardiac myocytes [18] though levosimendan has been known to enhance contraction by increasing calcium transients [18] and myofilament sensitivity to calcium [19], a messenger of cell death.…”

“…1) through a catheter for a period of 15 min at a dose of 0.2 µg per each ml/min of measured blood flow with an infusion pump (Model 22, Harvard Apparatus) working at constant rate of 1 ml/min. The infused dose was similar to the one used clinically as bolus administration (12 µg/kg) [15,17] and previously used as intracoronary administration in pigs [16]. In the remaining 10 pigs (control animals) the about 4 h regional myocardial ischemia was followed by administration of vehicle only, infused for 15 min.…”