No adaptation to digitalization as evaluated by digitalis receptor (Na,K-ATPase) quantification in explanted hearts from donors without heart disease and from digitalized recipients with end-stage heart failure

Thomas A. Schmidt*, Paul D. Allen, Wilson S. Colucci, James D. Marsh, Keld Kjeldsen

*Corresponding author af dette arbejde

    Publikation: Bidrag til tidsskriftArtikelForskningpeer review

    Abstract

    Speculations about development of tolerance to the inotropic effect of digitalis have been engendered since studies in various in vitro systems and tissues not representative of the heart have shown up-regulation of sodium potassium adenosine triphosphatase (Na,K-ATPase) when exposed to digitalis. Moreover the digitalis receptor (i.e., Na,K-ATPase) concentration in the normal, vital human left ventricle has not been previously determined. On this basis, digitalis receptor concentration was quantified in the left ventricle of explanted hearts from subjects without heart disease and from patients with end-stage heart failure who had received digitalis therapy. This was performed using vanadate-facilitated 3H-ouabain binding to intact tissue samples giving values of 728 ± 58 (n = 5) and 467 ± 55 pmol/g wet weight (n = 6) (mean ± SEM) (p < 0.005), respectively. However, Some of the digitalis receptors may have retained digoxin before 3H-ouabain binding and thus may have escaped detection. To eliminate this effect of retained digoxin, samples were exposed to prolonged washing in buffer containing excess digoxin antibody, a method recently shown to clear digoxin from receptors and allow subsequent complete digitalis receptor quantification by 3H-ouabain binding. After washing in digoxin specific antibody, specific digitalis receptor concentration was 760 ± 58 pmol/g (n = 5) and 614 ± 47 pmol/g (n = 6) wet weight in samples of the normal and failing hearts, respectively (p < 0.08). Thus, digitalization was associated with occupancy of digitalis receptors in the failing human heart of 24% (p < 0.02). After washing with antibody, the digitalis receptor concentration tended to be lower (19%) in the failing than in the normal hearts. Thus, there was no evidence for development of adaptation to digitalization due to up-regulation of the digitalis receptor concentration when comparing the failing and healthy human heart.

    OriginalsprogEngelsk
    Sider (fra-til)110-114
    Antal sider5
    TidsskriftThe American Journal of Cardiology
    Vol/bind71
    Udgave nummer1
    DOI
    StatusUdgivet - 1 jan. 1993

    Fingeraftryk

    Udforsk hvilke forskningsemner 'No adaptation to digitalization as evaluated by digitalis receptor (Na,K-ATPase) quantification in explanted hearts from donors without heart disease and from digitalized recipients with end-stage heart failure' indeholder.

    Citationsformater