Effects of milrinone and sulmazole on left ventricular mechanoenergetics in canine hearts.
BACKGROUND
The effect of cardiotonic drugs with calcium-sensitizing effect (Ca2+ sensitizers) on cardiac mechanoenergetics is not fully understood. Accordingly, the effects of milrinone (a phosphodiesterase inhibitor) and sulmazole (a calcium sensitizer with a phosphodiesterase-inhibiting effect) on left ventricular mechanics and energetics were studied.


RESULTS
In excised, cross-circulated canine hearts, myocardial oxygen consumption (Vo2), left ventricular contractility index (Emax), and systolic pressure-volume area (a measure of ventricular total mechanical energy) were measured before and during administration of either drug. Milrinone significantly increased Emax by 108.7 +/- 45.9% (mean +/- SD), from 6.3 +/- 3.5 to 13.1 +/- 6.8 mmHg.mL-1.100 g (P < .05), and sulmazole, by 73.6 +/- 54.2%, from 6.3 +/- 2.6 to 10.3 +/- 2.9 mmHg.mL-1.100 g (P < .05). Milrinone significantly abbreviated the contraction duration (Tmax) from 171 +/- 19 ms to 153 +/- 20 ms (P < .05), whereas sulmazole did not (164 +/- 36 ms to 161 +/- 31 ms, not significant), suggesting that the inotropic mechanisms of these two drugs differed. However, both drugs significantly increased the Vo2 intercept of the Vo2/pressure-volume area relation (milrinone: 0.027 +/- 0.004 to 0.036 +/- 0.003 mL O2/beat/100 g, P < .05; sulmazole: 0.025 +/- 0.005 to 0.032 +/- 0.006 mL O2/beat/100 g, P < .05) without significantly changing the slope (reciprocal of contractile efficiency). This parallel upward shift of the Vo2/pressure-volume area relation was similar to that observed with epinephrine and ouabain in our previous studies.


CONCLUSIONS
These results suggest that the two positive inotropic drugs exhibit similar mechanoenergetic effects in the normal canine heart despite the different mechanisms of action.
Department of Cardiovascular Dynamics, National Cardiovascular Center, Osaka, Japan.
K
K
Hata
Y
Y
Goto
S
S
Futaki
T
T
Takasago
A
A
Saeki
T
T
Nishioka
H
H
Suga
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004285:Dogs; D006321:Heart / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D020105:Milrinone; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D010101:Oxygen Consumption / Q000502:physiology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011728:Pyridones / Q000494:pharmacology*; D013268:Stimulation, Chemical; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology*; D017725:Ventricular Pressure / Q000187:drug effects
D002316:Cardiotonic Agents; D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; C029758:sulmazole; D020105:Milrinone