Crataegus special extract WS 1442 increases force of contraction in human myocardium cAMP-independently

The mode of action of Crataegus extracts in the treatment of heart failure is still under examination. WS 1442, a standardized special extract from Cr ataegus 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 ventr icular myocardium from explanted hearts, NYHA IV, n = 8) as well as in nonf ailing controls (right auricular trabeculae from patients with coronary hea rt disease, n = 8). WS 1442 effectively displaced specifically bound H-3-ou abain but did not influence the activity of adenylate cyclase [control + Gp p(NH)p (10(-4) mu M) 3,500 pmol cyclic adenosine monophosphate (cAMP/20 min ). Ln isolated left Ventricular papillary muscle strips, WS 1442 significan tly increased the force of contraction [basal. 1.8 +/- 0.2 mN; WS 1442 (50 mu g/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 (ri ght atrial trabeculae), WS 1442 increased both the Ca2+-transient and force generation. These effects also wen observed in the lipophilic ethyl acetat e-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, W S 1442 improves the force-frequency relation in failing human myocardium.