Analysis of the inotropic mechanism of enoximone in guinea pig ventricular muscle.
Force and action potentials were recorded in guinea pig papillary muscles. The peak force was 131.8 +/- 3.3% of control at 2 microM and 144.4 +/- 2.0% at 4 microM enoximone. Enoximone (2 microM) increased the rate of rise of force (131.0 +/- 4.9%) and time from peak to half-relaxation (106 +/- 1.1%). The time to peak twitch force shortened (96.7 +/- 0.6%). The action potential duration decreased at 2 microM (96.4 +/- 1.2%) and 4 microM (92.8 +/- 1.4%) enoximone. The action potential amplitude was 106.7 +/- 0.8% in 2 microM and 112.6 +/- 0.6% in 4 microM enoximone. The peak twitch force in response to a test stimulus given after varied intervals (i.e., mechanical restitution) was increased at all test intervals, whereas the time to full restitution was not affected at any concentration. The force in response to the preceding test interval (postextrasystolic potentiation) was also increased. Maximum potentiation was 11.9 +/- 3.0 mN/mm2 in controls, 15.9 +/- 3.3 mN/mm2 in 2 microM enoximone, and 17.02 +/- 3.2 mN/mm2 in 4 microM enoximone. During the decay of postextrasystolic potentiation, there was a linear relationship between the peak force of the postpotentiated contraction and peak force of the potentiated contraction. The slope of the line increased from 0.34 to 0.43 (n = 12, p less than 0.001) by enoximone (2 microM). The results suggest that enoximone exerts its positive inotropic effect by (a) increasing calcium inflow during the action potential and/or (b) reducing calcium outflow, thereby increasing the recirculation of activator calcium.
Jonas
S E
SE
Department of Pharmacology, University of Lund, Sweden.
Mörner
N
N
Christley
H M
HM
Wohlfart
B
B
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D017335:Enoximone; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D010210:Papillary Muscles / Q000187:drug effects
D015220:Calcium Channels; D002316:Cardiotonic Agents; D007093:Imidazoles; D017335:Enoximone