Cardiovascular effects of milrinone.
The myocardial effects of milrinone are mediated through inhibition of myocardial phosphodiesterase III. This inhibition results in accumulation of cyclic adenosine monophosphate and consequently increased calcium influx through voltage-dependent channels. The vascular effects also result from increased cyclic adenosine monophosphate. Direct coronary artery infusion of milrinone causes a concentration-related increase in left ventricular +dP/dt and substantial improvement in pump function as indicated by increased stroke work at lower left ventricular end-diastolic pressures. Subsequent intravenous administration of milrinone produces additional hemodynamic improvement, which is associated with a further reduction in systemic vascular resistance and left and right heart filling pressures. There is also a downward displacement of the left ventricular pressure-volume curve and acceleration of isovolumic relaxation, findings which indicate improved diastolic filling and accelerated isovolumic myocardial relaxation, respectively. The former action may reflect unloading of the right ventricle, whereas the latter may be due to improved calcium reuptake in the myocardium. Myocardial oxygen demand is unaltered because peripheral vasodilatation reduces wall stress and counteracts the increased oxygen requirement necessary to support enhanced contractility. This therapeutic profile differs from that of inotropic agents such as dobutamine and vasodilators such as nitroprusside, and contributes significantly to the usefulness of phosphodiesterase III inhibitors such as milrinone in the short-term management of patients with heart failure.
Colucci
W S
WS
Cardiovascular Division, Brigham and Women's Hospital, Boston, MA.
D006321:Heart / Q000187:drug effects*; D006801:Humans; D020105:Milrinone; D009200:Myocardial Contraction / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011728:Pyridones / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; D020105:Milrinone