Effects of pimobendan, a new cardiotonic agent, on contractile responses in single skeletal muscle fibres of the frog

Effects of a new cardiotonic agent, pimobendan, on contraction were investi gated in single intact skeletal muscle fibres of the frog. Pimobendan incre ased twitch tension in a concentration-dependent manner regardless of the p resence or absence of Ca2+ without any effect on tetanic tension, the resti ng membrane potential and the shape of the action potential. Pimobendan cau sed a further increase in twitch tension potentiated by caffeine (1 mM). Ad enine, an inhibitor of Ca2+-induced Ca2+ release from the sarcoplasmic reti culum, inhibited twitch tension potentiated by caffeine but not by pimobend an, suggesting that twitch potentiation by pimobendan is not attributed to increases in Ca2+-induced Ca2+ release, Pimobendan failed to increase cAMP levels in the skeletal muscle, though Forskolin significantly increased it without any effect on twitch tension. Contractile responses to high concent rations of caffeine and K+ were also potentiated by pimobendan. These resul ts: suggest that the potentiating effect of pimobendan on skeletal muscle c ontraction is mainly due to the increase in Ca2+ sensitivity to the contrac tile apparatus. (C) 2000 Editions scientifiques ct medicales Elsevier SAS.