The mode of action of Crataegus extracts in the treatment of
heart failure is still under examination.
WS 1442, a standardized special extract from Crataegus leaves with flowers, exerts direct positive inotropic effects. This study was designed to investigate the mode of inotropic action of
WS 1442 in human myocardium from patients with
congestive heart failure (left ventricular myocardium from explanted hearts; NYHA IV, n = 8) as well as in nonfailing controls (right auricular trabeculae from patients with
coronary heart disease, n = 8).
WS 1442 effectively displaced specifically bound 3H-ouabain but did not influence the activity of
adenylate cyclase [control, +
Gpp(NH)p (10(-4) microM) 3,500 pmol cyclic
adenosine monophosphate (cAMP)/20 min). In isolated left ventricular papillary muscle strips,
WS 1442 significantly increased the force of contraction [basal, 1.8+/-0.2 mN;
WS 1442 (50 microg/ml), 2.4+/-0.1 mN (130%)] and improved the frequency-dependent force generation (0.5 vs. 2.5 Hz: control, +0.1+/-0.01 mN;
WS 1442, +0.9+/-0.3 mN) even in failing human myocardium. In
fura-2-loaded muscle strips (right atrial trabeculae),
WS 1442 increased both the Ca2+-transient and force generation. These effects also were observed in the lipophilic
ethyl acetate-soluble fraction A, enriched in
flavone derivatives. In conclusion, these findings suggest a pharmacologic mechanism of
WS 1442 similar to the cAMP-independent positive inotropic action of
cardiac glycosides. In addition,
WS 1442 improves the force-frequency relation in failing human myocardium.