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Lochner, Amanda; Colesky, Frans J.; Sj, Genade

doi:10.1023/a:1007878523663

Cited by 25 publications

(4 citation statements)

References 22 publications

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“…It exerts its positive inotropic effect by sensitizing cardiac troponin C to calcium during systole, thus increasing cardiac performance without increasing myocardial oxygen consumption. Levosimendan also has a weak arrhythmogenic effect [22]. Our group demonstrated for the first time the efficacy of levosimendan in improving myocardial dysfunction after deep hypothermia-rewarming [11].…”

Section: Discussionmentioning

confidence: 99%

Role of calcium desensitization in the treatment of myocardial dysfunction after deep hypothermic circulatory arrest

et al. 2013

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IntroductionRewarming from deep hypothermic circulatory arrest (DHCA) produces calcium desensitization by troponin I (cTnI) phosphorylation which results in myocardial dysfunction. This study investigated the acute overall hemodynamic and metabolic effects of epinephrine and levosimendan, a calcium sensitizer, on myocardial function after rewarming from DHCA.MethodsForty male Wistar rats (400 to 500 g) underwent cardiopulmonary bypass (CPB) through central cannulation and were cooled to a core temperature of 13°C to 15°C within 30 minutes. After DHCA (20 minutes) and CPB-assisted rewarming (60 minutes) rats were randomly assigned to 60 minute intravenous infusion with levosimendan (0.2 μg/kg/min; n = 15), epinephrine (0.1 μg/kg/min; n = 15) or saline (control; n = 10). Systolic and diastolic functions were evaluated at different preloads with a conductance catheter.ResultsThe slope of left ventricular end-systolic pressure volume relationship (Ees) and preload recruitable stroke work (PRSW) recovered significantly better with levosimendan compared to epinephrine (Ees: 85 ± 9% vs 51 ± 11%, P<0.003 and PRSW: 78 ± 5% vs 48 ± 8%, P<0.005; baseline: 100%). Levosimendan but not epinephrine reduced left ventricular stiffness shown by the end-diastolic pressure-volume relationship and improved ventricular relaxation (Tau). Levosimendan preserved ATP myocardial content as well as energy charge and reduced plasma lactate concentrations. In normothermia experiments epinephrine in contrast to Levosimendan increased cTnI phosphorylation 3.5-fold. After rewarming from DHCA, cTnI phosphorylation increased 4.5-fold in the saline and epinephrine group compared to normothermia but remained unchanged with levosimendan.ConclusionsLevosimendan due to prevention of calcium desensitization by cTnI phosphorylation is more effective than epinephrine for treatment of myocardial dysfunction after rewarming from DHCA.

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Section: Discussionmentioning

confidence: 99%

Role of calcium desensitization in the treatment of myocardial dysfunction after deep hypothermic circulatory arrest

et al. 2013

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“…Xanthos et al 44 reported that the combination of epinephrine, atenolol, and levosimendan, when given during cardiac arrest and resuscitation in a pig model, resulted in improved 48-hour survival and postresuscitation cardiac function. Concurrently, Lochner et al 45 reported that the effects of levosimendan were not blunted by the presence of beta-blockers, as in the case of adrenergic inotropes.…”

Section: Origins Of a Unique Cardiovascular Agentmentioning

confidence: 97%

Levosimendan Efficacy and Safety: 20 Years of SIMDAX in Clinical Use

Papp

Agostoni

Álvarez

et al. 2020

Journal of Cardiovascular Pharmacology

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“…[ 44 ] Concurrently, Lochner et al reported that the effects of levosimendan were not blunted by the presence of beta-blockers, as in the case of adrenergic inotropes. [ 45 ]…”

Section: Origins Of a Unique Cardiovascular Agentmentioning

confidence: 99%

Levosimendan Efficacy and Safety: 20 years of SIMDAX in Clinical Use

Papp¹,

Agostoni²,

Álvarez³

et al. 2020

Cardiac Failure Review

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Levosimendan was first approved for clinic use in 2000, when authorisation was granted by Swedish regulatory authorities for the haemodynamic stabilisation of patients with acutely decompensated chronic heart failure. In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitisation and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced heart failure, right ventricular failure and pulmonary hypertension, cardiac surgery, critical care and emergency medicine. Levosimendan is currently in active clinical evaluation in the US. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and non-cardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, UK and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute heart failure arena in recent times and charts a possible development trajectory for the next 20 years.

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Cited by 25 publications

References 22 publications

Role of calcium desensitization in the treatment of myocardial dysfunction after deep hypothermic circulatory arrest

Role of calcium desensitization in the treatment of myocardial dysfunction after deep hypothermic circulatory arrest

Levosimendan Efficacy and Safety: 20 Years of SIMDAX in Clinical Use

Levosimendan Efficacy and Safety: 20 years of SIMDAX in Clinical Use

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