Late exercise training improves non-uniformity of transmural myocardial function in rats with ischaemic heart failure

Mou, Younss Aït; Reboul, Cyril; André, Lucas; Lacampagne, Alain; Cazorla, Olivier

doi:10.1093/cvr/cvn229

Cited by 48 publications

(62 citation statements)

References 41 publications

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“…This contrasts with a study in mouse ventricular cardiomyocytes that described transmural differences in action potential waveforms, SR Ca 2+ release, and Na + -Ca 2+ exchanger function that underlie differences in [Ca 2+ ] i and EC coupling across the left ventricular free wall [39]. We also observed a similar gradient of EC coupling from epicardium to endocardium in rats [3]. These data indicate that the regional contractile heterogeneity is not limited to the excitation and Ca 2+ release steps and that heterogeneous properties and/or regulation of the contractile machinery should be considered as well.…”

Section: Introductioncontrasting

confidence: 99%

“…The impact of muscle length in this sensitization was however not investigated. Nevertheless, we have recently demonstrated that stretch can induce phosphorylation of MLC-2 which contributes to LDA [2,3,25]. The role of TnI phosphorylation in LDA regulation has also been extensively explored (see for review [33]).…”

Section: Lda Molecular Basismentioning

confidence: 99%

“…The involvement of cardiac TnI Thr 144 in LDA remains to be confirmed. It is also interesting to note that, in physio-pathological conditions, alteration of LDA has been attributed to changes in the phosphorylation status of MLC2 and/or TnI [3,25,61].…”

Section: Lda Molecular Basismentioning

confidence: 99%

“…Our experience is that stretch sensitization of myofilament activation across the ventricular wall is not uniform in normal heart. LDA at room temperature increases from the subepicardium to the subendocardium in permeabilized cardiomyocytes isolated from rat [3,20,25] to guinea pig hearts [2] (Fig. 2a).…”

Section: Lda Heterogeneity In the Heartmentioning

confidence: 99%

“…Indeed, titin degradation results in reduced passive tension. This is crucial since transmural LDA is correlated with the level of passive tension in cardiomyocytes isolated from rat [3,20,25] to guinea pig hearts [2]. Similarly, the group of Henk Granzier showed that, in bovine, the LV is stiffer than the left atrium (LA) and is associated with higher LDA [48].…”

Section: Lda Heterogeneity In the Heartmentioning

confidence: 99%

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Regional variation in myofilament length-dependent activation

Cazorla

Lacampagne

2011

Pflugers Arch - Eur J Physiol

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The Frank-Starling law is an important regulatory mechanism of the heart that links the end-diastolic volume with the systolic ejection fraction. This beat-to-beat regulation of the heart, underlined at the cellular level by higher myofilament calcium sensitivity at longer sarcomere length, is known as length-dependent activation or stretch sensitization of activation. However, the heart is structurally and functionally heterogeneous and asymmetrical. Specifically, contractile properties are not uniform within the left ventricle partly due to transmural differences in action potential waveforms and calcium homeostasis. The present review will focus on the role of the contractile machinery in the transmural contractile heterogeneity and its adaptation to changes in muscle strain. The expression of different myosin isoforms, the level of titin-based passive tension, and thin and thick sarcomeric regulatory proteins are considered to explain the regional cellular contractile properties. Finally, the importance of transmural heterogeneity of length-dependent activation and the consequences of its modification on the heart mechanics are discussed. Despite extensive research since the characterization of the Frank-Starling law, the molecular mechanisms by which strain information is transduced to the contractile machinery have not been fully determined yet.

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Section: Introductioncontrasting

confidence: 99%

Section: Lda Molecular Basismentioning

confidence: 99%

Section: Lda Molecular Basismentioning

confidence: 99%

Section: Lda Heterogeneity In the Heartmentioning

confidence: 99%

Section: Lda Heterogeneity In the Heartmentioning

confidence: 99%

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Regional variation in myofilament length-dependent activation

Cazorla

Lacampagne

2011

Pflugers Arch - Eur J Physiol

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Carbon monoxide exposure enhances arrhythmia after cardiac stress: involvement of oxidative stress

et al. 2011

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Arrhythmias following cardiac stress are a key predictor of death in healthy population. Carbon monoxide (CO) is a ubiquitous pollutant promoting oxidative stress and associated with hospitalization for cardiovascular disease and cardiac mortality. We investigated the effect of chronic CO exposure on the occurrence of arrhythmic events after a cardiac stress test and the possible involvement of related oxidative stress. Wistar rats exposed chronically (4 weeks) to sustained urban CO pollution presented more arrhythmic events than controls during recovery after cardiac challenge with isoprenaline in vivo. Sudden death occurred in 22% of CO-exposed rats versus 0% for controls. Malondialdehyde (MDA), an end-product of lipid peroxidation, was increased in left ventricular tissue of CO-exposed rats. Cardiomyocytes isolated from CO-exposed rats showed higher reactive oxygen species (ROS) production (measured with MitoSox Red dye), higher diastolic Ca(2+) resulting from SR calcium leak and an higher occurrence of irregular Ca(2+) transients (measured with Indo-1) in comparison to control cells after a high pacing sequence. Acute treatment with a ROS scavenger (N-acetylcysteine, 20 mmol/L, 1 h) prevented this sequence of alterations and decreased the number of arrhythmic cells following high pacing. Chronic CO exposure promotes oxidative stress that alters Ca(2+) homeostasis (through RYR2 and SERCA defects) and thereby mediates the triggering of ventricular arrhythmia after cardiac stress that can lead to sudden death.

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Exercise training in adverse cardiac remodeling

Duncker

Deel

Waard

et al. 2014

Pflugers Arch - Eur J Physiol

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Cardiac remodeling in response to a myocardial infarction or chronic pressure-overload is an independent risk factor for the development of heart failure. In contrast, cardiac remodeling produced by regular physical exercise is associated with a decreased risk for heart failure. There is evidence that exercise training has a beneficial effect on disease progression and survival in patients with cardiac remodeling and dysfunction, but concern has also been expressed that exercise training may aggravate pathological remodeling and dysfunction. Here we present studies from our laboratory into the effects of exercise training on pathological cardiac remodeling and dysfunction in mice. The results indicate that even in the presence of a large infarct, exercise training exerts beneficial effects on the heart. These effects were mimicked in part by endothelial nitric oxide synthase (eNOS) overexpression and abrogated by eNOS deficiency, demonstrating the importance of nitric oxide signaling in mediating the cardiac effects of exercise. Exercise prior to a myocardial infarction was also cardioprotective. In contrast, exercise tended to aggravate pathological cardiac remodeling and dysfunction in the setting of pressure-overload produced by an aortic stenosis. These observations emphasize the critical importance of the underlying pathological stimulus for cardiac hypertrophy and remodeling, in determining the effects of exercise training. Future studies are needed to define the influence of exercise type, intensity and duration in different models and severities of pathological cardiac remodeling. Together such studies will aid in optimizing the therapy of exercise training in the setting of cardiovascular disease.

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Late exercise training improves non-uniformity of transmural myocardial function in rats with ischaemic heart failure

Abstract: This study shows that exercise performed at a late stage after MI restored a transmural non-uniformity of myocardium lost during HF. Recoveries of Ca(2+) homeostasis and myofilament function of cardiomyocytes contribute to this beneficial effect.

Cited by 48 publications

References 41 publications

Regional variation in myofilament length-dependent activation

Regional variation in myofilament length-dependent activation

Carbon monoxide exposure enhances arrhythmia after cardiac stress: involvement of oxidative stress

Exercise training in adverse cardiac remodeling

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