Fig. 2.

Positive inotropic effects of levosimendan in mouse atrium only in the presence of rolipram. (A) Original recordings: Levosimendan ((-)-(R)-[[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl]hydrazono]propane-dinitrile) (10 nM to 10 µM) was cumulative applied alone (A, top) or the presence 0.1 µM rolipram ((RS)-4-(3-cyclopentyloxy-4-methoxy-phenyl)pyrrolidin-2-on) (A, bottom). Rolipram was used to inhibit the activity of phosphodiesterase IV. The positive inotropic effect of levosimendan in presence of rolipram was abrogated by subsequently applied 10 µM propranolol. Vertical bars indicate force in millinewton (mN). Horizontal bars indicate time in minutes (min). (B) Effects of isoprenaline (Iso: 1 µM), levosimendan (Levo: 10 µM), or both (Roli + Levo) in single high-speed contractions compared to control conditions (no drug addition: Ctr). Please note that we normalized in the ordinate the maximum developed force of contraction under all conditions as 100% in order to facilitate detection of changes in contraction and relaxation times (abscissa in milliseconds (ms)). Concentration-dependent effects of increasing concentrations of levosimendan on force of contraction, or rate of tension or times of contraction in electrically stimulated left atrial preparations of mice are summarized in C, D, or E. Levosimendan was cumulatively applied alone (open circles) or after addition of rolipram (closed circles) to the organ bath. See (A) for details of drug addition and incubation times. Ordinates indicate the effect of levosimendan on force of contraction in millinewton (mN, C), on rate of tension development (in mN/s: D), on rate tension of relaxation (mN/s: D), on time to peak tension in milliseconds (ms: E), and on time of relaxation (ms: E) in electrically stimulated (1 Hz) isolated left atrial preparations from mice. Abscissae: negative decadic logarithm of the concentrations of levosimendan. *p < 0.05 versus Ctr (t-test). Numbers in brackets indicate the number of experiments