Effects of milrinone and sulmazole on left ventricular mechanoenergetics in canine hearts

Abstract

Background: The effect of cardiotonic drugs with calcium-sensitizing effect (Ca 2+ 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. Methods and Results: In excised, cross-circulated canine hearts, myocardial oxygen consumption (Vo 2), left ventricular contractility index (E max), and systolic pressure-volume area (a measure of ventricular total mechanical energy) were measured before and during administration of either drug. Milrinone significantly increased E max 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 (T max) from 171 ± 19 ms to 153 ± 20 ms ( P < .05), whereas sulmazole did not (164 ± 36 ms to 16131 ms, not significant), suggesting that the inotropic mechanisms of these two drugs differed. However, both drugs significantly increased the V O 2 intercept of the V O 2 /pressure-volume area relation (milrinone: 0.027 ± 0.004 to 0.036 ± 0.003 mL O 2/beat/100 g, P <.05; sulmazole: 0.025 ± 0.005 to 0.032 ± 0.006 mL O 2/beat/100 g, P < .05) without significantly changing the slope (reciprocal of contractile efficiency). This parallel upward shift of the V O 2 /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.