The inotropic and hemodynamic effects of intravenous milrinone when reflex adrenergic stimulation is suppressed by beta-adrenergic blockade.
Milrinone is an inotropic and vasodilator agent proven to be effective in the treatment of heart failure. This study evaluated whether milrinone produces inotropic and hemodynamic effects independent of reflex adrenergic stimulation. Eleven stable heart failure patients (New York Heart Association class II to III) undergoing cardiac catheterization received intravenous (i.v.) milrinone (50 micrograms/kg for 10 minutes followed by 0.5 micrograms/kg/min for 50 minutes) during beta-adrenergic blockade. After beta-blockade with a 50-mg oral dose of metoprolol, heart rate decreased by a mean of 16.6%. The peak inotropic response to i.v. milrinone measured using the maximum rate of rise of left ventricular pressure (LV dP/dt) was fully developed at 20 minutes. Mean absolute inotropic response of LV dP/dt from baseline was statistically significant at 10, 20, 30, and 40 minutes (P < 0.05). Mean percentage increase in cardiac index from baseline was statistically significant at 20 and 30 minutes, and mean absolute decline from baseline for pulmonary capillary wedge pressure was statistically significant at 20 and 40 minutes (P < 0.05). The inotropic and hemodynamic effects of i.v. milrinone were thus preserved during beta-adrenergic blockade. This finding is consistent with a mechanism of action of i.v. milrinone--myocardial phosphodiesterase inhibition--that is independent of reflex adrenergic stimulation.
Charing Cross and Westminister Medical School, Department of Cardiology, Charing Cross Hospital, London, England.
C M
CM
Travill
S
S
Pugh
M I
MI
Noble
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000368:Aged; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D006333:Heart Failure / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D020105:Milrinone; D009200:Myocardial Contraction / Q000187:drug effects*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D011728:Pyridones / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D012018:Reflex / Q000187:drug effects*; D016037:Single-Blind Method; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D002316:Cardiotonic Agents; D011728:Pyridones; D020105:Milrinone