Cardiac, renal, and neurological benefits of preoperative levosimendan administration in patients with right ventricular dysfunction and pulmonary hypertension undergoing cardiac surgery: evaluation with two biomarkers neutrophil gelatinase-associated lipocalin and neuronal enolase

Guerrero-Orriach, José Luis; Ariza-Villanueva, Daniel; Florez-Vela, Ana; Garrido‐Sánchez, Lourdes; Moreno-Cortés, María Isabel; Galán-Ortega, Manuel; Ramirez-Fernandez, A; Torres, Juan Alcaide; Fernandez, Concepción Santiago; Arce, Isabel Navarro; Melero-Tejedor, José María; Rubio-Navarro, Manuel; Cruz-Mañas, Jose

doi:10.2147/tcrm.s102772

Cited by 24 publications

(12 citation statements)

References 43 publications

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“… 48 – 50 Preoperative administration of levosimendan decreased pulmonary artery pressure significantly in patients with right ventricular dysfunction and pulmonary hypertension. 51 As pulmonary hypertension is an important prognostic factor in cardiac surgery associated with increased morbidity and mortality, 52 levosimendan's efficacy could be pronounced in this subgroup and we warmly suggest to explore this setting.…”

Section: Discussionmentioning

confidence: 99%

Use of Levosimendan in Cardiac Surgery: An Update After the LEVO-CTS, CHEETAH, and LICORN Trials in the Light of Clinical Practice

Guarracino

Heringlake

Cholley

et al. 2018

Journal of Cardiovascular Pharmacology

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Abstract:Levosimendan is a calcium sensitizer and adenosine triphosphate–dependent potassium channel opener, which exerts sustained hemodynamic, symptomatic, and organ-protective effects. It is registered for the treatment of acute heart failure, and when inotropic support is considered appropriate. In the past 15 years, levosimendan has been widely used in clinical practice and has also been tested in clinical trials to stabilize at-risk patients undergoing cardiac surgery. Recently, 3 randomized, placebo-controlled, multicenter studies (LICORN, CHEETAH, and LEVO-CTS) have been published reporting on the perioperative use of levosimendan in patients with compromised cardiac ventricular function. Taken together, many smaller trials conducted in the past suggested beneficial outcomes with levosimendan in perioperative settings. By contrast, the latest 3 studies were neutral or inconclusive. To understand the reasons for such dissimilarity, a group of experts from Austria, Belgium, Finland, France, Germany, Italy, Switzerland, and Russia, including investigators from the 3 most recent studies, met to discuss the study results in the light of both the previous literature and current clinical practice. Despite the fact that the null hypothesis could not be ruled out in the recent multicenter trials, we conclude that levosimendan can still be viewed as a safe and effective inodilator in cardiac surgery.

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Section: Discussionmentioning

confidence: 99%

Use of Levosimendan in Cardiac Surgery: An Update After the LEVO-CTS, CHEETAH, and LICORN Trials in the Light of Clinical Practice

Guarracino

Heringlake

Cholley

et al. 2018

Journal of Cardiovascular Pharmacology

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“…Neurological complications can be observed after cardiac surgery, causing significant morbidity and mortality. Guerrero-Orriach and co-workers reported an 83% incidence of delirium and cognitive change after cardiac surgery [7] . LVS may be protective against these complications due to its neuroprotective effects [5] .…”

Section: Discussionmentioning

confidence: 99%

“…This mechanism of action may also modulate functions of other organs as well.. Thus, LVS can protect neurons indirectly by increasing cardiac output or cerebral blood flow [4][5][6][7][8] . It has been shown in in-vitro traumatic brain injury and middle cerebral artery occlusion models that LVS reduces neuronal damage [4,9] .…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective Effects of Levosimendan on the NB2a Mouse Neuroblastoma Cell Culture

Öztürk¹,

Vural²,

Aydemir³

et al. 2020

GKDA Derg

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Objective: Levosimendan (LVS) inhibits phosphodiestherase III and opens the ATP-sensitive K+ channels (KATP). It is cardioprotective due to its anti-oxidant, anti-inflammatuary, inotropic and vasodilatatory effects. The use of LVS is prefered in patients who have decreased ejection fraction during cardiac surgery. Therefore it has been reported that LVS protects neurons indirectly. Hovewer, its direct effects on neurons have not been known yet. We examined direct neuroprotective effects of LVS using neuroblastoma cell line of mouse origin (NB2a) in culture where drug interaction with cells occurs. Method: To this end, the neuroprotective effects of LVS (0,1, 0,3, 1, 3, 10, 30 and 100 µM) have been tested for its direct toxic effects by TUNEL method for apoptosis and by MTT for cell viability. We also examined moderate and chronic toxic effect of LSV by measure neurite outgrowth. Results: LVS didn't effect the cellular proliferation negatively. The number of apoptotic cells didn't differ from the number of control cells (p>0.05). Additionally, any moderate neurotoxic effects were not seen in all concentrations of NST which did not inhibit neurite outgrowth. Moreover, LVS at 1 µM concentration significantly increased the lengh of neurite showing clearly its neuroprotective and functional effects. Conclusion: These direct neuroprotective effects of LVS in culture might be important for clinical use. LVS can be used securely in patients that have a risk for a brain injury due to the nature of disease, trauma or the procedure itself.

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“…124 Much of the extant data come from noncardiac surgery patients suffering from the acute onset of pulmonary hypertension and/or right ventricular dysfunction; data on levosimendan in acute right ventricular failure are sparse though encouraging. 125…”

Section: Levosimendan In Pulmonary Hypertension and Right Ventricularmentioning

confidence: 99%

Use of Levosimendan in Intensive Care Unit Settings: An Opinion Paper

Herpain

Bouchez

Girardis

et al. 2019

Journal of Cardiovascular Pharmacology

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Abstract:Levosimendan is an inodilator that promotes cardiac contractility primarily through calcium sensitization of cardiac troponin C and vasodilatation via opening of adenosine triphosphate–sensitive potassium (KATP) channels in vascular smooth muscle cells; the drug also exerts organ-protective effects through a similar effect on mitochondrial KATP channels. This pharmacological profile identifies levosimendan as a drug that may have applications in a wide range of critical illness situations encountered in intensive care unit medicine: hemodynamic support in cardiogenic or septic shock; weaning from mechanical ventilation or from extracorporeal membrane oxygenation; and in the context of cardiorenal syndrome. This review, authored by experts from 9 European countries (Austria, Belgium, Czech republic, Finland, France, Germany, Italy, Sweden, and Switzerland), examines the clinical and experimental data for levosimendan in these situations and concludes that, in most instances, the evidence is encouraging, which is not the case with other cardioactive and vasoactive drugs routinely used in the intensive care unit. The size of the available studies is, however, limited and the data are in need of verification in larger controlled trials. Some proposals are offered for the aims and designs of these additional studies.

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Cardiac, renal, and neurological benefits of preoperative levosimendan administration in patients with right ventricular dysfunction and pulmonary hypertension undergoing cardiac surgery: evaluation with two biomarkers neutrophil gelatinase-associated lipocalin and neuronal enolase

Cited by 24 publications

References 43 publications

Use of Levosimendan in Cardiac Surgery: An Update After the LEVO-CTS, CHEETAH, and LICORN Trials in the Light of Clinical Practice

Use of Levosimendan in Cardiac Surgery: An Update After the LEVO-CTS, CHEETAH, and LICORN Trials in the Light of Clinical Practice

Neuroprotective Effects of Levosimendan on the NB2a Mouse Neuroblastoma Cell Culture

Use of Levosimendan in Intensive Care Unit Settings: An Opinion Paper

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