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• W1963609575 abstract "<h3>Background</h3> Prolonged unloading using left ventricular (LV) assist devices (LVADs) leads to unloading-induced atrophy with altered cardiomyocyte contractility. The causes for this time-dependent deterioration of myocardial function are unclear. Our aim was to determine the effects of prolonged mechanical unloading on cardiomyocyte function and, more specifically, on Ca²⁺ cycling and myofilament sensitivity to Ca²⁺. <h3>Methods</h3> LV unloading was induced by heterotopic abdominal transplantation (UN) in rats for 5 weeks. Recipient hearts were used as controls (REC). LV myocytes were isolated and cardiomyocyte area measured by planimetry, sarcomere length measured by Fourier analysis of digitized cardiomyocyte images, and cytoplasmic [Ca²⁺] monitored using Indo-1. Myofilament sensitivity to Ca²⁺ was assessed as the slope of the linear relationship between Indo-1 ratio and sarcomere shortening during relaxation. <h3>Results</h3> UN cardiomyocyte area was smaller compared with REC (mean ± SEM: UN 2,503 ± 78 μm² [<i>n</i> = 132], REC 3,856 ± 89 μm² [<i>n</i> = 116]; <i>p</i> < 0.001). UN cardiomyocytes had a smaller sarcomere shortening amplitude (UN 0.08 ± 0.01 μm [<i>n</i> = 37], REC 0.11 ± 0.01 μm [<i>n</i> = 38]; <i>p</i> < 0.01), despite normal Ca²⁺ transient amplitude (UN 0.13 ± 0.01 Indo-1 ratio units [<i>n</i> = 37], REC 0.11 ± 0.01 Indo-1 ratio units [<i>n</i> = 38]; <i>p</i> = non-significant). Myofilament sensitivity to Ca²⁺ was reduced in UN (UN 2.0 ± 1.2 μm/ratio unit [<i>n</i> = 20], REC 3.7 ± 0.4 μm/ratio unit [<i>n</i> = 22]; <i>p</i> < 0.01). Sarcoplasmic reticulum (SR) Ca²⁺ uptake (assessed by 20 mmol/liter caffeine) was also reduced in UN (UN 84.3 ± 0.79% relative contribution [<i>n</i> = 22], REC 89.8 ± 0.67% relative contribution [<i>n</i> = 24]; <i>p</i> < 0.001). <h3>Conclusions</h3> Prolonged myocardial unloading causes depressed contractility due to reduced SR Ca²⁺ uptake and myofilament sensitivity to Ca²⁺. These effects may be relevant with regard to myocardial performance after prolonged LVAD support." @default.
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• W1963609575 date "2008-08-01" @default.
• W1963609575 modified "2023-10-17" @default.
• W1963609575 title "Prolonged Mechanical Unloading Reduces Myofilament Sensitivity to Calcium and Sarcoplasmic Reticulum Calcium Uptake Leading to Contractile Dysfunction" @default.
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• W1963609575 doi "https://doi.org/10.1016/j.healun.2008.05.005" @default.
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