The contribution of inspiratory muscles function to exercise limitation in heart failure: pathophysiological mechanisms

Ribeiro, Jorge Pinto; Chiappa, Gaspar R.; Callegaro, Carine Cristina

doi:10.1590/s1413-35552012005000034

Cited by 55 publications

(65 citation statements)

References 70 publications

(102 reference statements)

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“…Inspiratory muscle weakness is noted in 30-50% of heart failure patients (Meyer et al, 2001;Ribeiro et al, 2012), and indices of diaphragm dysfunction and structural abnormalities have been noted in both patients and animal models of heart failure (Meyer et al, 2001;van Hees et al, 2008;Wong et al, 2011). LAD-HF rats in this study exhibited significant diaphragm atrophy and decreased sarcomeric Ca 21 sensitivity.…”

Section: Discussionmentioning

confidence: 57%

The Small-Molecule Fast Skeletal Troponin Activator, CK-2127107, Improves Exercise Tolerance in a Rat Model of Heart Failure

Hwee

Kennedy

Hartman

et al. 2015

J Pharmacol Exp Ther

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Heart failure-mediated skeletal myopathy, which is characterized by muscle atrophy and muscle metabolism dysfunction, often manifests as dyspnea and limb muscle fatigue. We have previously demonstrated that increasing Ca 21 sensitivity of the sarcomere by a small-molecule fast skeletal troponin activator improves skeletal muscle force and exercise performance in healthy rats and models of neuromuscular disease. The objective of this study was to investigate the effect of a novel fast skeletal troponin activator, CK-2127107 (2-aminoalkyl-5-N-heteroarylpyrimidine), on skeletal muscle function and exercise performance in rats exhibiting heart failure-mediated skeletal myopathy. Rats underwent a left anterior descending coronary artery ligation, resulting in myocardial infarction and a progressive decline in cardiac function [left anterior descending coronary artery heart failure (LAD-HF)]. Compared with sham-operated control rats, LAD-HF rat hindlimb and diaphragm muscles exhibited significant muscle atrophy. Fatigability was increased during repeated in situ isokinetic plantar flexor muscle contractions. CK-2127107 produced a leftward shift in the force-Ca 21 relationship of skinned, single diaphragm, and extensor digitorum longus fibers. Exercise performance, which was assessed by rotarod running, was lower in vehicle-treated LAD-HF rats than in sham controls (116 6 22 versus 193 6 31 seconds, respectively; mean 6 S.E.M.; P 5 0.04). In the LAD-HF rats, a single oral dose of CK-2127107 (10 mg/kg p.o.) increased running time compared with vehicle treatment (283 6 47 versus 116 6 22 seconds; P 5 0.0004). In summary, CK-2127107 substantially increases exercise performance in this heart failure model, suggesting that modulation of skeletal muscle function by a fast skeletal troponin activator may be a useful therapeutic in heart failure-associated exercise intolerance.

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Section: Discussionmentioning

confidence: 57%

The Small-Molecule Fast Skeletal Troponin Activator, CK-2127107, Improves Exercise Tolerance in a Rat Model of Heart Failure

Hwee

Kennedy

Hartman

et al. 2015

J Pharmacol Exp Ther

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“…On the contrary, it may change substantially depending on the physiological conditions. The decline of the muscle efficiency has vital consequences, such as heart failure (Mariunas et al 2008;Ribeiro et al 2012;Barclay 2008). About 600,000 people die of a heart disease only in the United States every year (Murphy et al 2013).…”

Section: Introductionmentioning

confidence: 99%

“…About 600,000 people die of a heart disease only in the United States every year (Murphy et al 2013). Decrease of the muscle efficiency, which may also be expressed as the "muscle weakness" occurs in 30 to 50% of the heart failure patients (Ribeiro et al 2012). People lose approximately 20 to 30% of their muscles between the ages of 20 and 80 (Kiriazis andGibbs 2000, Carmeli et al 2002); the age related loss of muscles is related with the mitochondrial functioning and the cellular energetics and accompanied with the loss of the efficiency (Carmeli et al 2002).…”

Section: Introductionmentioning

confidence: 99%

First and second law work production efficiency of a muscle cell

Sorgüven

Özilgen

2015

IJEX

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The absolute value of the muscle efficiency and its decrease over time has vital consequences. Among other diseases heart failure, which is the leading cause of death in developed countries is dramatically affected by muscle weakness. This paper provides an analogy between the Carnot engine and muscle to gain insight on the muscle work production process and estimate the maximum muscle efficiency under physiological conditions. An "ideal muscle" model, which operates steadily and reversibly, is defined and for this model energy and exergy analyses are performed. Theoretical results are compared with the experimental measurements.

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“…It contributes both to reduced exercise capacity [11,12] and the perception of dyspnea [2]. Furthermore, there is evidence that respiratory muscle dysfunction is an indicator of adverse prognosis in patients with CHF [13,14].…”

Section: Introductionmentioning

confidence: 99%

Biological variation, reference change value (RCV) and minimal important difference (MID) of inspiratory muscle strength (PImax) in patients with stable chronic heart failure

et al. 2015

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The contribution of inspiratory muscles function to exercise limitation in heart failure: pathophysiological mechanisms

Cited by 55 publications

References 70 publications

The Small-Molecule Fast Skeletal Troponin Activator, CK-2127107, Improves Exercise Tolerance in a Rat Model of Heart Failure

The Small-Molecule Fast Skeletal Troponin Activator, CK-2127107, Improves Exercise Tolerance in a Rat Model of Heart Failure

First and second law work production efficiency of a muscle cell

Biological variation, reference change value (RCV) and minimal important difference (MID) of inspiratory muscle strength (PImax) in patients with stable chronic heart failure

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