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 endstage 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/mm(2). With increasing rest intervals, post-rest twitch tension continuously increased to maximally 29.9+/-4.1 mN/mm(2) after 120 s (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/mm(2) and increased to maximally 13.6+/-2.2 mN/mm(2) 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/mm(2) 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 mu M) 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.