title: The positive inotropic effects of milrinone but not of digoxin are attenuated at short cycle lengths.
abstract: The effects of inotropically active agents on the left ventricular force-interval relation are a potential determinant of their clinical utility and safety. However, little information is available concerning the effects of noncatecholamine positive inotropic agents on this relation. Therefore this study compared the short-term effects of digoxin and milrinone on resting hemodynamics, frequency potentiation (FP), and mechanical restitution (MR) in patients undergoing nonemergency cardiac catheterization. Both digoxin and 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 inotropic 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 with baseline). Similarly, on MRC analysis, the parameter c (a measure of sensitivity of contractile performance to reductions in cycle length) increased by 3.6 +/- 3.7% (p = NS). Whereas the positive inotropic effects of milrinone were not significantly attenuated during FP, they were abolished and possibly 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-preserved left ventricular systolic function, the positive inotropic effects of milrinone but not of digoxin are markedly dependent on heart rate. These properties may influence both relative safety and efficacy of both agents.
authors.affiliation: Cardiology Unit, The University of Adelaide, North Western Adelaide Health Service, The Queen Elizabeth Hospital, Woodville, South Australia.
authors.forename: C J
authors.initials: CJ
authors.lastname: Zeitz
authors.forename: R H
authors.initials: RH
authors.lastname: Ritchie
authors.forename: R G
authors.initials: RG
authors.lastname: Jarrett
authors.forename: J T
authors.initials: JT
authors.lastname: Hii
authors.forename: R D
authors.initials: RD
authors.lastname: Wuttke
authors.forename: J D
authors.initials: JD
authors.lastname: Horowitz
mesh_terms: D002316:Cardiotonic Agents / Q000494:pharmacology*; D004077:Digoxin / Q000494:pharmacology*; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020105:Milrinone / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D002316:Cardiotonic Agents; D010726:Phosphodiesterase Inhibitors; D004077:Digoxin; D020105:Milrinone