The Ca2+-sensitizers CGP 48506 and EMD 57033, but not the Na+-channel modulator BDF 9148, prolong the contractile twitch in guinea pig cardiomyocytes

The sodium channel modulator DPI 201-106 has been described to posses Ca2+- sensitizing properties. Therefore, the present study investigated the inotr opic effect of the Na+-channel modulator BDF 9148 (1 muM), a congener of DP I 201-106, in comparison with the Gaze-sensitizers CGP 48506 (1-50 mu mol/l ) and EMD 57033 (1-30 mu mol/l) in electrically driven left ventricular car diomyocytes isolated from guinea pigs. The changes of the contraction ampli tude in comparsion to the basal cell shortening (cell shortening in mum and %) were continuously recorded with a one-dimensional high speed camera. BD F 9148, CGP 48506, and EMD 57033 exerted a significant increase in the cont raction amplitude (p < 0.05 vs. control). The maximal positive inotropic ef fects of CGP 48506 (50 <mu>mol/l) and EMD 57033 (30 mu mol/l) were + 249 +/ - 30% and + 226 +/- 28%, respectively. The corresponding value for BDF 9148 (1 mu mol/l) was + 176 +/- 16%. However, only the Ca2+-sensitizers CGP 485 06 and EMD 57033, but not BDF 9148, prolonged the contractile twitch. Espec ially in patients with an already enhanced intracellular myocardial Ca2+-co ncentration, Ca sensitizers, which impair relaxation, may be disadvantageou s for therapeutial use despite their positive inotropic effect.