Influence of the positive inotropic substance pimobendan (UD-CG 115 BS) on contractile economy of guinea pig papillary muscles.
Using antimony-bismuth myothermal equipment, we measured simultaneously the initial heat liberated from and the stress-time integral developed by guinea pig papillary muscles before and after application of UD-CG 115 BS (200 microM) at an experimental temperature of 21 degrees C. By means of the shortening method, the initial heat was subdivided into the activation heat, which is associated with the calcium turnover, and the tension-dependent heat, which represents the ATP splitting by contractile proteins. The activation heat increased slightly but not significantly from 0.24 +/- 0.05 to 0.34 +/- 0.09 mcal/g. The increase in the tension-dependent heat (from 0.23 +/- 0.07 to 0.49 +/- 0.22 mcal/g) was directly proportional to the increase in the developed stress-time integral (from 0.95 +/- 0.24 to 2.37 +/- 0.76 g.s/mm2). The data indicate that the economy of force generation by contractile proteins is unchanged by UD-CG 115 BS, whereas the activation heat may be slightly increased by this compound. A comparison of UD-CG 115 BS with other substances like isoproterenol or classic phosphodiesterase inhibitors reveals that UD-CG 115 BS increases myocardial force in a more economical way that may have clinical implications. The mode of action of this compound is attributed to its calcium-sensitizing effect on the contractile proteins.
Holubarsch
C
C
Department of Internal Medicine, University of Freiburg, F.R.G.
Hasenfuss
G
G
Just
H
H
Blanchard
E
E
Mulieri
L A
LA
Alpert
N R
NR
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006358:Hot Temperature; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D010042:Ouabain / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects* / Q000502:physiology; D011724:Pyridazines / Q000494:pharmacology*; D013268:Stimulation, Chemical
D002316:Cardiotonic Agents; D011724:Pyridazines; C041648:pimobendan; D010042:Ouabain; D007545:Isoproterenol