The positive inotropic effects of milrinone but not of digoxin are attenuated at short cycle lengths

The effects of inotropically active agents on the left ventricular force-in terval relation are a potential determinant of their clinical utility and s afety. However, little information is available concerning the effects of n oncatecholamine positive inotropic agents on this relation. Therefore this study compared the short-term effects of digoxin and milrinone on resting h emodynamics, frequency potentiation (FP), and mechanical restitution (MR) i n patients undergoing nonemergency cardiac catheterization. Both digoxin an d milrinone produced similar increases in LV + dP/dt at rest (12.2 +/- 1.3% , p < 0.000001 and 11.4 +/- 3.2%, p < 0.01, respectively). The positive ino tropic effects of digoxin were marginally attenuated during FP (by 8.5 +/- 4.2% and 4.6 +/- 2.9% at 10 and 60 s, respectively, both p = NS compared wi th baseline). Similarly, on MRC analysis, the parameter c (a measure of sen sitivity of contractile performance to reductions in cycle length) increase d by 3.6 +/- 3.7% (p = NS). Whereas the positive inotropic effects of milri none were not significantly attenuated during FP, they were abolished and p ossibly reversed at short cycle lengths on MR curve construction (6.8 +/- 5 .9% negative inotropic effect at 60% of resting cycle length; p = NS p < 0. 05 vs. resting cycle length). In conclusion, in patients with well-preserve d left ventricular systolic function, the positive inotropic effects of mil rinone but not of digoxin are markedly dependent on heart rate. These prope rties may influence both relative safety and efficacy of both agents.