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Selected Publication:
Hasenfuss, G; Schillinger, W; Lehnart, SE; Preuss, M; Pieske, B; Maier, LS; Prestle, J; Minami, K; Just, H.
Relationship between Na+-Ca2+-exchanger protein levels and diastolic function of failing human myocardium.
Circulation. 1999; 99(5):641-648
Doi: 10.1161/01.CIR.99.5.641
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- Co-authors Med Uni Graz
- Pieske Burkert Mathias
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- Abstract:
- BACKGROUND: In the failing human heart, sarcoplasmic reticulum (SR) calcium handling is impaired, and therefore, calcium elimination and diastolic function may depend on the expression of sarcolemmal Na+-Ca2+ exchanger. METHODS AND RESULTS: Force-frequency relations were studied in ventricular muscle strip preparations from failing human hearts (n=29). Protein levels of Na+-Ca2+ exchanger and SR Ca2+-ATPase were measured in the same hearts. Hearts were divided into 3 groups by discriminant analysis according to the behavior of diastolic function when stimulation rate of muscle strips was increased from 30 to 180 min-1. At 180 compared with 30 min-1, diastolic force was increased by 160%, maximum rate of force decline was decreased by 46%, and relaxation time was unchanged in group III. In contrast, in group I, diastolic force and maximum rate of force decline did not change, and relaxation time decreased by 20%. Na+-Ca2+ exchanger was 66% higher in group I than in group III. Na+-Ca2+ exchanger was inversely correlated with the frequency-dependent rise of diastolic force when stimulation rate was increased (r=-0.74; P<0.001). Compared with nonfailing human hearts (n=6), SR Ca2+-ATPase was decreased and Na+-Ca2+ exchanger unchanged in group III, whereas Na+-Ca2+ exchanger was increased and SR Ca2+-ATPase unchanged in group I. Results with group II hearts were between those of group I and group III hearts. CONCLUSIONS: By discriminating failing human hearts according to their diastolic function, we identified different phenotypes. Disturbed diastolic function occurs in hearts with decreased SR Ca2+-ATPase and unchanged Na+-Ca2+ exchanger, whereas increased expression of the Na+-Ca2+ exchanger is associated with preserved diastolic function.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Aged -
- Calcium-Transporting ATPases - metabolism
- Cardiac Output, Low - metabolism
- Diastole - physiology
- Female - physiology
- Humans - physiology
- Male - physiology
- Middle Aged - physiology
- Myocardium - metabolism
- Sarcoplasmic Reticulum - enzymology
- Sodium-Calcium Exchanger - enzymology
- Find related publications in this database (Keywords)
- heart failure
- calcium
- myocardium
- sarcoplasmic reticulum
- diastole
- proteins