TY - JOUR
T1 - Diminished post-rest potentiation of contractile force in human dilated cardiomyopathy
T2 - Functional evidence for alterations in intracellular Ca2+ handling
AU - Pieske, Burkert
AU - Sütterlin, Melanie
AU - Schmidt-Schweda, Stephan
AU - Minami, Kitzatomo
AU - Meyer, Markus
AU - Olschewski, Manfred
AU - Holubarsch, Christian
AU - Just, Hanjörg
AU - Hasenfuss, Gerd
PY - 1996/8/1
Y1 - 1996/8/1
N2 - 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.
AB - 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.
KW - aequorin
KW - calcium handling
KW - excitation-contraction-coupling
KW - myocardial function
KW - sarcoplasmic reticulum
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U2 - 10.1172/JCI118849
DO - 10.1172/JCI118849
M3 - Article
C2 - 8698869
AN - SCOPUS:0029862043
SN - 0021-9738
VL - 98
SP - 764
EP - 776
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 3
ER -