Pimobendan increases calcium sensitivity of skinned human papillary muscle fibers

The calcium sensitizing effects of the cardiotonic agent pimobendan on force production were investigated on chemically skinned human papillary muscle fibres. The papillary muscles were obtained from patients undergoing mitral valve replacement operations. Tension was produced by different free calcium concentrations and 100 mumol/l of pimobendan shifted the pCa-tension relationship significantly to the left. The effects of pimobendan were concentration dependent (10-300 mumol/l) but additionally also correlated with the state of left ventricular performance of the patients. Skinned papillary muscle fibres obtained from patients with reduced ventricular performance were more sensitive to calcium as well as pimobendan compared with fibres from patients with normal left ventricular performance. No differences in response to pimobendan were observed between fibres from NYHA II and NYHA III heart failure patients.