Depressed contractile reserve and impaired calcium handling of cardiac myocytes from chronically unloaded hearts are ameliorated with the administration of physiological treatment dose of T3 in rats

Abstract

These results suggest that the treatment with physiological treatment dose of thyroid hormone rescues the impaired myocyte relaxation and depressed contractile reserve at least partially through the restoration of PLB protein levels and its phosphorylation state in chronically unloaded hearts.

Prolonged Mechanical Unloading Reduces Myofilament Sensitivity to Calcium and Sarcoplasmic Reticulum Calcium Uptake Leading to Contractile Dysfunction

“…We chose 5 weeks of unloading because it has been reported that shorter periods are not associated with contractile dysfunction in normal hearts. 14,15 In contrast, other studies performed after 5 weeks of unloading demonstrated contractile dysfunction, 15,16 supporting the need for investigating the cellular mechanisms at this time-point.…”

“…Several studies have shown time-dependent changes in cardiomyocyte and papillary muscle contractile function and excitation-contraction (EC) coupling that can impair cardiac performance after prolonged unloading. [15][16][17][18] Myofilament sensitivity to Ca 2ϩ is an important determinant of cardiomyocyte contractile function and is reduced in human 19 and animal heart failure. 20 Myofilament contractile protein architecture is deranged in heart failure and partially normalized by mechanical unloading.…”

New insights into the role of thyroid hormone in cardiac remodeling: time to reconsider?

“…handling and myocyte contractility, which were associated with the shift of MHC isozymes and altered expressions of Ca 2? cycling-related proteins [132,133]. Physiological treatment dose of TH restored the expression levels of Ca 2?…”

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

“…The transplanted (atrophic) and the orthotopic (control) hearts of the recipient animal were removed in deep anaesthesia (thiopental-sodium, 100 mg/kg body weight) 2 weeks after transplantation. An unloading period of 2 weeks was chosen to induce a stable cardiac atrophy in accordance with previous studies [12,14,40,41] while avoiding the detrimental effects of prolonged unloading on cardiac excitation-contraction coupling and contractility [21,22,29,45]. For all experiments, the orthotopic hearts served as corresponding controls.…”

“…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 %).…”