Population pharmacokinetics of serelaxin in patients with acute or chronic heart failure, hepatic or renal impairment, or portal hypertension and in healthy subjects

Background: In chronic heart failure (CHF), cardiac cachexia is often associated with the terminal stage of this disease. In animal studies it has been demonstrated that myostatin, a key regulator of skeletal muscle mass, is elevated in advanced stages of this syndrome. Design: The aim of the present study was to investigate the expression of myostatin in patients with late stage CHF (NYHA IIIb) in comparison to healthy subjects. Furthermore the effects of physical exercise on myostatin were analyzed. Methods: Twenty-four patients were either randomized to a sedentary control group (CHF-S) or exercise training (CHF-E). At baseline and after 12 weeks mRNA and myostatin protein in the peripheral skeletal muscle as well as myostatin serum concentration were measured. Furthermore 12 age-matched healthy men were compared to all patients at baseline (HC). Results: CHF patients showed a two-fold increase of myostatin mRNA ( p = 0.05) and a 1.7-fold ( p = 0.01) augmentation of protein content in skeletal muscle compared to healthy subjects. In late-stage CHF, exercise training led to a 36% reduction of the mRNA and a 23% decrease of the myostatin protein compared to baseline. The serum concentration of myostatin revealed no significant alteration between the groups. Conclusion: In the skeletal muscle, myostatin increases significantly in the course of CHF. The observed effects of a significant reduction of myostatin in skeletal muscle after 12 weeks of exercise training demonstrate the reversibility of molecular changes that might be able to halt the devastating process of muscle wasting in chronic heart failure.

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Population Pharmacokinetics of Eplerenone in Japanese Patients With Chronic Heart Failure

The Journal of Clinical Pharmacology ◽

10.1002/jcph.861 ◽

2016 ◽

Vol 57 (6) ◽

pp. 730-738

Author(s):

Masayo Oishi ◽

Yoshiro Tomono ◽

Qinying Zhao ◽

Kevin Sweeney

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Population Pharmacokinetics ◽

Japanese Patients

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Cytochrome P450 2C9 is involved in flow-dependent vasodilation of peripheral conduit arteries in healthy subjects and in patients with chronic heart failure

European Journal of Heart Failure ◽

10.1016/j.ejheart.2007.05.005 ◽

2007 ◽

Vol 9 (8) ◽

pp. 770-775 ◽

Cited By ~ 36

Author(s):

Dieter Fischer ◽

Ulf Landmesser ◽

Stephan Spiekermann ◽

Denise Hilfiker-Kleiner ◽

Marian Hospely ◽

...

Keyword(s):

Heart Failure ◽

Cytochrome P450 ◽

Chronic Heart Failure ◽

Healthy Subjects ◽

Cytochrome P450 2C9

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The Correlation between Gut Microbiota and Serum Metabolomic in Elderly Patients with Chronic Heart Failure

Mediators of Inflammation ◽

10.1155/2021/5587428 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Zhenhua Wang ◽

Zhaoling Cai ◽

Markus W. Ferrari ◽

Yilong Liu ◽

Chengyi Li ◽

...

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Gut Microbiota ◽

Elderly Patients ◽

16S Rdna ◽

Healthy Subjects ◽

The Elderly ◽

Inflammatory Factors ◽

16S Rdna Sequencing ◽

Rdna Sequencing

Objective. Chronic heart failure (CHF) refers to a state of persistent heart failure that can be stable, deteriorated, or decompensated. The mechanism and pathogenesis of myocardial remodeling remain unknown. Based on 16S rDNA sequencing and metabolomics technology, this study analyzed the gut microbiota and serum metabolome in elderly patients with CHF to provide new insights into the microbiota and metabolic phenotypes of CHF. Methods. Blood and fecal samples were collected from 25 elderly patients with CHF and 25 healthy subjects. The expression of inflammatory factors in blood was detected by ELISA. 16S rDNA sequencing was used to analyze the changes in microorganisms in the samples. The changes of small molecular metabolites in serum samples were analyzed by LC-MS/MS. Spearman correlation coefficients were used to analyze the correlation between gut microbiota and serum metabolites. Results. Our results showed that the IL-6, IL-8, and TNF-α levels were significantly increased, and the IL-10 level was significantly decreased in the elderly patients with CHF compared with the healthy subjects. The diversity of the gut microbiota was decreased in the elderly patients with CHF. Moreover, Escherichia Shigella was negatively correlated with biocytin and RIBOFLAVIN. Haemophilus was negatively correlated with alpha-lactose, cellobiose, isomaltose, lactose, melibiose, sucrose, trehalose, and turanose. Klebsiella was positively correlated with bilirubin and ethylsalicylate. Klebsiella was negatively correlated with citramalate, hexanoylcarnitine, inosine, isovalerylcarnitine, methylmalonate, and riboflavin. Conclusion. The gut microbiota is simplified by the disease, and serum small-molecule metabolites evidently change in elderly patients with CHF. Serum and fecal biomarkers could be used for elderly patients with CHF screening.

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Interrelationship between renin-angiotensin-aldosterone system and oxidative stress in chronic heart failure patients with or without renal impairment

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2020.110938 ◽

2021 ◽

Vol 133 ◽

pp. 110938 ◽

Cited By ~ 1

Author(s):

Marta Reina-Couto ◽

Joana Afonso ◽

Jorge Carvalho ◽

Luís Morgado ◽

Fernanda Aparecida Ronchi ◽

...

Keyword(s):

Oxidative Stress ◽

Heart Failure ◽

Chronic Heart Failure ◽

Renal Impairment ◽

Renin Angiotensin Aldosterone System ◽

Renin Angiotensin ◽

Heart Failure Patients ◽

And Oxidative Stress

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781 Endurance training in patients with stable chronic heart failure and healthy subjects: Effects on the expression of a muscle-specific E3-ligase in skeletal muscle biopsies

European Journal of Heart Failure Supplements ◽

10.1016/s1567-4215(07)60504-9 ◽

2007 ◽

Vol 6 (1) ◽

pp. 178-179

Author(s):

S GIELEN ◽

V ADAMS ◽

M SANDRI ◽

S ERBS ◽

A LINKE ◽

...

Keyword(s):

Heart Failure ◽

Skeletal Muscle ◽

Chronic Heart Failure ◽

Endurance Training ◽

Healthy Subjects ◽

E3 Ligase ◽

Muscle Biopsies

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Clinical Value of Cystatin C in Chronic Heart Failure Elderly Patients Without Advanced Renal Impairment

Journal of Cardiac Failure ◽

10.1016/j.cardfail.2012.08.295 ◽

2012 ◽

Vol 18 (10) ◽

pp. S179

Author(s):

Yasuhiko Mitsuke ◽

Akira Nakano ◽

Hiroyasu Uzui ◽

Naoki Amaya ◽

Kentaroh Ishida ◽

...

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Renal Impairment ◽

Elderly Patients ◽

Cystatin C ◽

Clinical Value

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Muscle sympathetic nerve activity response to heat stress is attenuated in chronic heart failure patients

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00355.2016 ◽

2017 ◽

Vol 312 (6) ◽

pp. R873-R882 ◽

Cited By ~ 3

Author(s):

Jian Cui ◽

John Boehmer ◽

Cheryl Blaha ◽

Lawrence I. Sinoway

Keyword(s):

Heart Failure ◽

Heat Stress ◽

Chronic Heart Failure ◽

Sympathetic Nerve ◽

Healthy Subjects ◽

Sympathetic Nerve Activity ◽

Muscle Sympathetic Nerve Activity ◽

Whole Body ◽

Nerve Activity ◽

Hot Environment

Heat stress evokes significant increases in muscle sympathetic nerve activity (MSNA) in healthy individuals. The MSNA response to heat stress in chronic heart failure (CHF) is unknown. We hypothesized that the MSNA response to heat stress is attenuated in CHF. Passive whole body heating was applied with water-perfused suits in 13 patients (61 ± 2 yr) with stable class II-III CHF, 12 age-matched (62 ± 2 yr) healthy subjects, and 14 young (24 ± 1 yr) healthy subjects. Mild heating (i.e., increases in skin temperature ΔTsk ~2–4°C, internal temperature ΔTcore <0.3°C) significantly decreased MSNA in CHF patients; however, it did not significantly alter the MSNA in the age-matched and young healthy subjects. Heat stress (i.e., ΔTsk ~4°C and ΔTcore ~0.6°C) raised MSNA in the age-matched (32.9 ± 3.2 to 45.6 ± 4.2 bursts/min; P < 0.001) and young (14.3 ± 1.7 to 26.3 ± 2.4 bursts/min; P < 0.001) controls, but not in CHF (46.2 ± 5.3 to 50.5 ± 5.3 bursts/min; P = 0.06). The MSNA increase by the heat stress in CHF (Δ4.2 ± 2.0 bursts/min) was significantly less than those seen in the age-matched (Δ12.8 ± 1.7 bursts/min, P < 0.05) and young (Δ12.0 ± 2.7 bursts/min, P < 0.05) control groups. These data suggest that the MSNA response to heat stress is attenuated in CHF patients. We speculate that the attenuated MSNA response to heat stress may contribute to impaired cardiovascular adjustments in CHF in a hot environment.

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