Levosimendan improves cardiac function and myocardial efficiency in rats with right ventricular failure

Hansen, Mads; Andersen, Asger; Tolbod, Lars Poulsen; Hansson, Nils Henrik; Nielsen, Roni; Vonk‐Noordegraaf, Anton; Nielsen‐Kudsk, Jens Erik

doi:10.1177/2045893217743122

Cited by 11 publications

(5 citation statements)

References 27 publications

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“…Additionally, Hansen et al. revealed that long-term treatment in the pulmonary trunk banding rat model improved RV function without increasing RV myocardial oxygen consumption leading to improved myocardial external efficiency, 29 which is consistent with the calcium sensitizing effect and emphasizes the potential therapeutic value of levosimendan therapy in PH.…”

Section: Levosimendan In Phmentioning

confidence: 75%

“…Effects on pulmonary vasculopathy was reported by attenuation of pulmonary arterial occlusive lesions, and reduced RV remodeling was demonstrated by increased capillary density, reduced cardiomyocyte size, and reduced atrial natriuretic peptide and B‐type natriuretic peptide. Additionally, Hansen et al revealed that long‐term treatment in the pulmonary trunk banding rat model improved RV function without increasing RV myocardial oxygen consumption leading to improved myocardial external efficiency, 29 which is consistent with the calcium sensitizing effect and emphasizes the potential therapeutic value of levosimendan therapy in PH.…”

Section: Levosimendan In Phmentioning

confidence: 75%

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Levosimendan in pulmonary hypertension and right heart failure

Hansen¹,

Andersen²,

Nielsen‐Kudsk³

2018

Pulm. circ.

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Pulmonary hypertension is a multifactorial disease with a high morbidity and mortality. Right ventricular function is the most important predictor of morbidity and mortality in patients suffering from pulmonary hypertension, but currently there are no approved treatments directly supporting the failing right ventricle. Levosimendan is a calcium sensitizing agent with inotropic, pulmonary vasodilatory, and cardioprotective properties. Given its pharmacodynamic profile, levosimendan could be a potential novel agent for the treatment of right ventricular failure caused by pulmonary hypertension. The aim of this review is to provide an overview of the current knowledge on the effects of levosimendan in pulmonary hypertension and right heart failure.

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Section: Levosimendan In Phmentioning

confidence: 75%

Section: Levosimendan In Phmentioning

confidence: 75%

Levosimendan in pulmonary hypertension and right heart failure

Hansen¹,

Andersen²,

Nielsen‐Kudsk³

2018

Pulm. circ.

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“…According to Louhelainen et al (2007) and Hansen et al (2018) , 3 mg/Kg Levosimendan (1 mg levosimendan was dissolved in 50 μL DMSO, and then diluted to 1 mg/mL levosimendan in 5%DMSO + 40%Peg400 + 5% Tween 80 + 50% water) was injected intraperitoneally 14 days after LAD, once a week, for four consecutive weeks. The solvent was injected intraperitoneally in the same way.…”

Section: Methodsmentioning

confidence: 99%

Exercise Capacity Is Improved by Levosimendan in Heart Failure and Sarcopenia via Alleviation of Apoptosis of Skeletal Muscle

et al. 2022

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BackgroundPatients suffering from chronic heart failure (CHF) show an increased prevalence of sarcopenia. Levosimendan is an effective drug for the treatment of heart failure, but its effect on sarcopenia is still unclear. We aimed to explore whether levosimendan could enhance skeletal muscle contractibility, improve skeletal muscle atrophy, and thus improve exercise tolerance of individuals with heart failure.MethodsC57BL6/J mice were used to establish the heart failure with sarcopenia model and injected of levosimendan. Mice were separated into control group, sham operation group, HF group, HF + solvent group, HF + levosimendan group, HF + sarcopenia group, HF + sarcopenia + solvent group, HF + sarcopenia + levosimendan group (n = 5–12). After the treatment, exercise capacity and cardiac function were evaluated. Muscle morphology, inflammation level and apoptosis levels were detected, in which mitochondrial function and oxidative stress level were also assessed.ResultLevosimendan could increase forelimb grip strength/body weight, hanging impulse, maximum running distance and time in mice with HF and sarcopenia (P < 0.0001 for all), and these improvements were independent of EF (P = 0.0019 for hanging impulse, P < 0.001 for forelimb grip strength/body weight and maximum running distance). Levosimendan directly increased the CSA of gastrocnemius in mice with HF and sarcopenia (P < 0.0001). After levosimendan injection, the proportion of slow muscle fibers increased (P < 0.0001), but this improvement of muscle fiber typing might be attributed to improved cardiac function (P > 0.05). Levosimendan also maintained mitochondrial membrane potential, decreased cleaved caspase-3 (P = 0.034), cleaved caspase-9 (P < 0.0001), Bax expression (P < 0.0001), and increased Bcl2 expression (P = 0.0036). This effect is independent of improved cardiac function (P = 0.028 for bax, P < 0.001 for cleaved caspase-9 and Bcl2). IL-6, TNF-α expression (P < 0.0001 for both) decreased, and SOD activity (P = 0.0038), GSH/GSSG ratio (P = 0.002) significantly increased in skeletal muscle after injection of levosimendan. The improvement in oxidative stress level was attributed to improved cardiac function (P > 0.05).ConclusionLevosimendan reduce the loss of skeletal muscle mitochondrial membrane potential, decrease the apoptosis, alleviate the inflammation and oxidative stress, and ultimately improve the exercise capacity of mice with heart failure and sarcopenia. Therefore, levosimendan may be a potential drug for the treatment of heart failure with sarcopenia.

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“…Experimental data showed that Levo could attenuate pulmonary vascular remodeling in an animal model of PH, attributed to antiproliferative and anti-inflammatory effects mediated by K ATP channel activation [ 106 ]. Moreover, beneficial actions of Levo on adverse RV remodeling in experimental PH have been reported [ 107 , 108 ]. In humans, some limited evidence suggests that Levo may reduce PAP and PVR and improve RV function in patients with PAH [ 109 , 110 ].…”

Section: Therapeutic Management Of Ph-lhdmentioning

confidence: 99%

Pulmonary Hypertension in Left Heart Diseases: Pathophysiology, Hemodynamic Assessment and Therapeutic Management

Ltaief¹,

Yerly²,

Liaudet³

2023

IJMS

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Pulmonary hypertension (PH) associated with left heart diseases (PH-LHD), also termed group 2 PH, represents the most common form of PH. It develops through the passive backward transmission of elevated left heart pressures in the setting of heart failure, either with preserved (HFpEF) or reduced (HFrEF) ejection fraction, which increases the pulsatile afterload of the right ventricle (RV) by reducing pulmonary artery (PA) compliance. In a subset of patients, progressive remodeling of the pulmonary circulation resulted in a pre-capillary phenotype of PH, with elevated pulmonary vascular resistance (PVR) further increasing the RV afterload, eventually leading to RV-PA uncoupling and RV failure. The primary therapeutic objective in PH-LHD is to reduce left-sided pressures through the appropriate use of diuretics and guideline-directed medical therapies for heart failure. When pulmonary vascular remodeling is established, targeted therapies aiming to reduce PVR are theoretically appealing. So far, such targeted therapies have mostly failed to show significant positive effects in patients with PH-LHD, in contrast to their proven efficacy in other forms of pre-capillary PH. Whether such therapies may benefit some specific subgroups of patients (HFrEF, HFpEF) with specific hemodynamic phenotypes (post- or pre-capillary PH) and various degrees of RV dysfunction still needs to be addressed.

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Levosimendan improves cardiac function and myocardial efficiency in rats with right ventricular failure

Cited by 11 publications

References 27 publications

Levosimendan in pulmonary hypertension and right heart failure

Levosimendan in pulmonary hypertension and right heart failure

Exercise Capacity Is Improved by Levosimendan in Heart Failure and Sarcopenia via Alleviation of Apoptosis of Skeletal Muscle

Pulmonary Hypertension in Left Heart Diseases: Pathophysiology, Hemodynamic Assessment and Therapeutic Management

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