Sarcoplasmic reticulum and myofilament function in chemically-treated ventricular trabeculae from patients with heart failure

Objectives: Assessment of sarcoplasmic reticulum calcium-loading ability, myofilament force production and myofilament calcium sensitivity in ventricular trabeculae from patients with heart failure. Methods: Right ventricular trabeculae (diameter 150–250 μm) were obtained from 18 patients undergoing elective cardiac transplantation. These were mounted for isometric tension measurement and treated with saponin which permeabilises the sarcolemma leaving the sarcoplasmic reticulum (SR) functionally intact. The trabecula was bathed in a mock intracellular solution containing ATP and weakly buffered [Ca2+] at various concentrations (150–400 nM). The amplitude of caffeine-induced contractures was used as a quantitative measure of the SR calcium content and was correlated with the clinical severity of heart failure. The same trabecula was then exposed to a solution containing Triton-X100 (1%) which destroys all cell membranes leaving only the myofilaments intact. The maximum calcium-activated force (Cmax) and myofilament responsiveness to calcium was assessed. Results: Patients with ischaemic heart disease (IHD) and severe heart failure (PCWP > 20 mm Hg, ejection fraction < 15%, n = 8) demonstrated low SR Ca2+-loading ability compared with patients with IHD and moderate heart failure (PCWP-20 mmHg, LV ejection fraction > 20%, n = 6). Patients with dilated cardiomyopathy (DCM) (n = 4) demonstrated SR Ca2+-loading ability which was lower than either of the two IHD groups. Myofilament force production (per unit cross-sectional area) was not significantly different between the three groups. Myofilament responsiveness to Ca2+ demonstrated no relationship with severity of heart failure. Conclusions: In human heart failure, SR Ca2+-loading ability diminishes with increasing severity of heart failure. Myofilament force production and sensitivity to calcium are unaffected by severity of heart failure