These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Prolonged mechanical unloading reduces myofilament sensitivity to calcium and sarcoplasmic reticulum calcium uptake leading to contractile dysfunction.
    Author: Soppa GK, Lee J, Stagg MA, Siedlecka U, Youssef S, Yacoub MH, Terracciano CM.
    Journal: J Heart Lung Transplant; 2008 Aug; 27(8):882-9. PubMed ID: 18656802.
    Abstract:
    BACKGROUND: 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 Ca(2+) cycling and myofilament sensitivity to Ca(2+). METHODS: 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 [Ca(2+)] monitored using Indo-1. Myofilament sensitivity to Ca(2+) was assessed as the slope of the linear relationship between Indo-1 ratio and sarcomere shortening during relaxation. RESULTS: UN cardiomyocyte area was smaller compared with REC (mean +/- SEM: UN 2,503 +/- 78 microm(2) [n = 132], REC 3,856 +/- 89 microm(2) [n = 116]; p < 0.001). UN cardiomyocytes had a smaller sarcomere shortening amplitude (UN 0.08 +/- 0.01 microm [n = 37], REC 0.11 +/- 0.01 microm [n = 38]; p < 0.01), despite normal Ca(2+) transient amplitude (UN 0.13 +/- 0.01 Indo-1 ratio units [n = 37], REC 0.11 +/- 0.01 Indo-1 ratio units [n = 38]; p = non-significant). Myofilament sensitivity to Ca(2+) was reduced in UN (UN 2.0 +/- 1.2 microm/ratio unit [n = 20], REC 3.7 +/- 0.4 microm/ratio unit [n = 22]; p < 0.01). Sarcoplasmic reticulum (SR) Ca(2+) uptake (assessed by 20 mmol/liter caffeine) was also reduced in UN (UN 84.3 +/- 0.79% relative contribution [n = 22], REC 89.8 +/- 0.67% relative contribution [n = 24]; p < 0.001). CONCLUSIONS: Prolonged myocardial unloading causes depressed contractility due to reduced SR Ca(2+) uptake and myofilament sensitivity to Ca(2+). These effects may be relevant with regard to myocardial performance after prolonged LVAD support.
    [Abstract] [Full Text] [Related] [New Search]