Diminished post-rest potentiation of contractile force in human dilated cardiomyopathy: Functional evidence for alterations in intracellular Ca2+ handling

Burkert Pieske, Melanie Sütterlin, Stephan Schmidt-Schweda, Kitzatomo Minami, Markus Meyer, Manfred Olschewski, Christian Holubarsch, Hanjörg Just, Gerd Hasenfuss

Research output: Contribution to journalArticlepeer-review

144 Scopus citations

Abstract

Post-rest contractile behavior of isolated myocardium indicates the capacity of the sarcoplasmic reticulum (SR) to store and release Ca2+. We investigated post-rest behavior in isolated muscle strips from nonfailing (NF) and end-stage failing (dilated cardiomyopathy [DCM]) human hearts. At a basal stimulation frequency of 1 Hz, contractile parameters of the first twitch after increasing rest intervals (2-240 s) were evaluated. In NF (n = 9), steady state twitch tension was 13.7±1.8 mN/mm2. With increasing rest intervals, post-rest twitch tension continuously increased to maximally 29.9±4.1 mN/mm2 after 120s (P < 0.05) and to 26.7±4.5 mN after 240 s rest. In DCM (n = 22), basal twitch tension was 10.0±1.5 mN/mm2 and increased to maximally 13.6±2.2 mN/mm2 after 20 s rest (P < 0.05). With longer rest intervals, however, post-rest twitch tension continuously declined (rest decay) to 4.7±1.0 mN/mm2 at 240 s (P < 0.05). The rest-dependent changes in twitch tension were associated with parallel changes in intracellular Ca2+ transients in NF and DCM (aequorin method). The relation between rest- induced changes in twitch tension and aequorin light emission was similar in NF and DCM, indicating preserved Ca2+-responsiveness of the myofilaments. Ryanodine (1 μM) completely abolished post-rest potentiation. Increasing basal stimulation frequency (2 Hz) augmented post-rest potentiation, but did not prevent rest decay after longer rest intervals in DCM. The altered post- rest behavior in failing human myocardium indicates disturbed intracellular Ca2+ handling involving altered function of the SR.

Original languageEnglish (US)
Pages (from-to)764-776
Number of pages13
JournalJournal of Clinical Investigation
Volume98
Issue number3
DOIs
StatePublished - Aug 1 1996
Externally publishedYes

Keywords

  • aequorin
  • calcium handling
  • excitation-contraction-coupling
  • myocardial function
  • sarcoplasmic reticulum

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