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

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.