SARCOPLASMIC-RETICULUM AND MYOFILAMENT FUNCTION IN CHEMICALLY-TREATEDVENTRICULAR TRABECULAE FROM PATIENTS WITH HEART-FAILURE

Objectives: Assessment of sarcoplasmic reticulum calcium-loading abili ty, myofilament force production and myofilament calcium sensitivity i n ventricular trabeculae from patients with heart failure. Methods: Ri ght ventricular trabeculae (diameter 150-250 mu m) were obtained from 18 patients undergoing elective cardiac transplantation. These were mo unted 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 concentr ations (150-400 nM). The amplitude of caffeine-induced contractures wa s used as a quantitative measure of the SR calcium content and was cor related with the clinical severity of heart failure. The same trabecul a was then exposed to a solution containing Triton-X100 (1%) which des troys all cell membranes leaving only the myofilaments intact. The max imum calcium-activated force (C-max) and myofilament responsiveness to calcium was assessed. Results: Patients with ischaemic heart disease (IHD) and severe heart failure (PCWP > 20 mm Hg, ejection fraction < 1 5%, n = 8) demonstrated low SR Ca2+-loading ability compared with pati ents with IHD and moderate heart failure (PCWP-20 mmHg, LV ejection fr action > 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-sect ional area) was not significantly different between the three groups. Myofilament responsiveness to Ca2+ demonstrated no relationship with s everity 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 unaffecte d by severity of heart failure.