Mechanical unloading improves intracellular Ca2+regulation in rats with doxorubicin-induced cardiomyopathy

Takaseya, Tohru; Ishimatsu, Masaru; Tayama, Eiki; Nishi, Akinori; Akasu, Takashi; Aoyagi, Shigeaki

doi:10.1016/j.jacc.2004.08.057

Cited by 34 publications

(28 citation statements)

References 24 publications

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“…1d, e) were not significantly different. These findings confirm that the intracellular Ca 2+ transients remain unchanged in early cardiac atrophy [22,46].…”

Section: Systolic Casupporting

confidence: 83%

“…Given that the decay of the intracellular Ca 2+ transient is unaltered in atrophic myocardium (Fig. 1) [22,46], it seems likely that SERCA activity is reduced to a degree that the resulting slowing of the Ca 2+ uptake into the SR is fully compensated for by Ca 2+ transport via the Na + -Ca 2+ exchanger. Taken together, the data currently available indicate that the reduction in SR Ca 2+ load is predominantly a consequence of a moderately decreased SERCA activity, possibly mediated by reduced PLB phosphorylation and potentially in combination with a reduced set point of SR Ca 2+ content [24] or an increased nonspark diastolic Ca 2+ release [39].…”

Section: Discussionmentioning

confidence: 99%

“…Cardiac atrophy was induced in syngeneic male Lewis rats (270±5 g, n= 34, Charles River, Sulzfeld, Germany) by heterotopic abdominal heart transplantation as previously described [12,14,21,22,29,40,41,45,46]. The donor heart was harvested under deep anaesthesia (thiopental-sodium, 100 mg/kg body weight) and was transplanted into the abdominal cavity of the recipient rat under isoflurane anaesthesia (2-2.5 %).…”

Section: Animal Modelmentioning

confidence: 99%

“…Hence, one may expect that Ca 2+ release during systole is diminished and amplitudes of systolic Ca 2+ transients are dampened in atrophic hearts. The shape of the systolic Ca 2+ transient, however, was found to be unaltered in early atrophic remodelling [22,46].…”

Section: Introductionmentioning

confidence: 98%

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Enhanced Ca2+ influx through cardiac L-type Ca2+ channels maintains the systolic Ca2+ transient in early cardiac atrophy induced by mechanical unloading

Biermann¹,

Bernhardt²,

Neef³

et al. 2014

Thorac cardiovasc Surg

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Cardiac atrophy as a consequence of mechanical unloading develops following exposure to microgravity or prolonged bed rest. It also plays a central role in the reverse remodelling induced by left ventricular unloading in patients with heart failure. Surprisingly, the intracellular Ca 2+ transients which are pivotal to electromechanical coupling and to cardiac plasticity were repeatedly found to remain unaffected in early cardiac atrophy. To elucidate the mechanisms underlying the preservation of the Ca 2+ transients, we investigated Ca 2+ cycling in cardiomyocytes from mechanically unloaded (heterotopic abdominal heart transplantation) and control (orthotopic) hearts in syngeneic Lewis rats. Following 2 weeks of unloading, sarcoplasmic reticulum (SR) Ca 2+ content was reduced by~55 %. Atrophic cardiac myocytes also showed a much lower frequency of spontaneous diastolic Ca 2+ sparks and a diminished systolic Ca 2+ release, even though the expression of ryanodine receptors was increased by~30 %. In contrast, current clamp recordings revealed prolonged action potentials in endocardial as well as epicardial myocytes which were associated with a two to fourfold higher sarcolemmal Ca 2+ influx under action potential clamp. In addition, Cav1.2 subunits which form the pore of L-type

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“…1d, e) were not significantly different. These findings confirm that the intracellular Ca 2+ transients remain unchanged in early cardiac atrophy [22,46].…”

Section: Systolic Casupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Animal Modelmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

Enhanced Ca2+ influx through cardiac L-type Ca2+ channels maintains the systolic Ca2+ transient in early cardiac atrophy induced by mechanical unloading

Biermann¹,

Bernhardt²,

Neef³

et al. 2014

Thorac cardiovasc Surg

View full text Add to dashboard Cite

show abstract

“…Effects on Serca 2a gene expression and protein levels vary. Clinical and experimental studies have shown recovery (Takaseya et al 2004), as well as no change (Chaudhary et al 2004) to occur with MU, in addition to a biphasic response, i.e. initial recovery followed by subsequent decline coinciding with contractile function deterioration (Oriyanhan et al 2007).…”

Section: Serca 2amentioning

confidence: 99%

Myocardial Recovery Following Left Ventricular Assist Device Therapy

Navaratnarajah¹,

Ibrahim²,

Yacoub³

et al. 2011

New Aspects of Ventricular Assist Devices

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Enhanced Ca2+ influx through cardiac L-type Ca2+ channels maintains the systolic Ca2+ transient in early cardiac atrophy induced by mechanical unloading

Schwoerer

Neef

Broichhausen

et al. 2013

Pflugers Arch - Eur J Physiol

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Cardiac atrophy as a consequence of mechanical unloading develops following exposure to microgravity or prolonged bed rest. It also plays a central role in the reverse remodelling induced by left ventricular unloading in patients with heart failure. Surprisingly, the intracellular Ca2+ transients which are pivotal to electromechanical coupling and to cardiac plasticity were repeatedly found to remain unaffected in early cardiac atrophy. To elucidate the mechanisms underlying the preservation of the Ca2+ transients, we investigated Ca2+ cycling in cardiomyocytes from mechanically unloaded (heterotopic abdominal heart transplantation) and control (orthotopic) hearts in syngeneic Lewis rats. Following 2 weeks of unloading, sarcoplasmic reticulum (SR) Ca2+ content was reduced by ~55 %. Atrophic cardiac myocytes also showed a much lower frequency of spontaneous diastolic Ca2+ sparks and a diminished systolic Ca2+ release, even though the expression of ryanodine receptors was increased by ~30 %. In contrast, current clamp recordings revealed prolonged action potentials in endocardial as well as epicardial myocytes which were associated with a two to fourfold higher sarcolemmal Ca2+ influx under action potential clamp. In addition, Cav1.2 subunits which form the pore of L-type Ca2+ channels (LTCC) were upregulated in atrophic myocardium. These data suggest that in early cardiac atrophy induced by mechanical unloading, an augmented sarcolemmal Ca2+ influx through LTCC fully compensates for a reduced systolic SR Ca2+ release to preserve the Ca2+ transient. This interplay involves an electrophysiological remodelling as well as changes in the expression of cardiac ion channels.

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Mechanical unloading improves intracellular Ca2+regulation in rats with doxorubicin-induced cardiomyopathy

Abstract: Mechanical unloading increases functional sarcoplasmic reticulum Ca(2+) ATPase and improves [Ca(2+)](i) handling and contractility in rats with doxorubicin-induced cardiomyopathy. These beneficial effects of mechanical unloading were not observed in normal hearts.

Cited by 34 publications

References 24 publications

Enhanced Ca2+ influx through cardiac L-type Ca2+ channels maintains the systolic Ca2+ transient in early cardiac atrophy induced by mechanical unloading

Enhanced Ca2+ influx through cardiac L-type Ca2+ channels maintains the systolic Ca2+ transient in early cardiac atrophy induced by mechanical unloading

Myocardial Recovery Following Left Ventricular Assist Device Therapy

Enhanced Ca2+ influx through cardiac L-type Ca2+ channels maintains the systolic Ca2+ transient in early cardiac atrophy induced by mechanical unloading

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