Disease relevance of milrinone

• We conclude that milrinone shows promise for the longterm treatment of congestive heart failure [1].
• Furthermore, our data suggest that milrinone may aggravate ventricular arrhythmias [2].
• Patients treated with milrinone had more hospitalizations (44 vs. 39 percent, P = 0.041), were withdrawn from double-blind therapy more frequently (12.7 vs. 8.7 percent, P = 0.041), and had serious adverse cardiovascular reactions, including hypotension (P = 0.006) and syncope (P = 0.002), more often than the patients given placebo [3].
• We randomly assigned 1,088 patients with severe chronic heart failure (New York Heart Association class III or IV) and advanced left ventricular dysfunction to double-blind treatment with (40 mg of oral milrinone daily (561 patients) or placebo (527 patients) [3].
• Chronic milrinone therapy after acute myocardial infarction improves cardiac hemodynamic indexes and attenuates progressive left ventricular dilation [4].

Psychiatry related information on milrinone

• In patients with erectile dysfunction as well as in rabbits, intracavernous injections of milrinone were done [5].

High impact information on milrinone

• The left ventricular ejection fraction at rest was not significantly changed by milrinone (+0.2 percent; 95 percent confidence limits, -1.5 and 1.9), but it was increased by digoxin (+1.7 percent; P less than 0.01; 95 percent confidence limits, -0.03 and 3.4) and decreased by placebo (-2.0 percent; 95 percent confidence limits, -3.8 and -0.1) [2].
• We conclude that milrinone significantly increased exercise tolerance and reduced the frequency of worsened heart failure [2].
• In 20 patients with severe congestive heart failure, intravenous milrinone resulted in significant decreases in left ventricular end-diastolic pressure (from 27 +/- 2 to 18 +/- 2 mm Hg), pulmonary wedge pressure, right atrial pressure, and systemic vascular resistance, as well as a slight reduction in mean arterial pressure [1].
• In this study, we show that NOS3 and mRNA and protein levels in cardiac myocytes are reduced both in vitro after treatment with cAMP elevating drugs, and in vivo after 3 d of treatment with milrinone, a type III cAMP phosphodiesterase inhibitor [6].
• Because, in frog heart, the stimulatory effect of SIN-1 on ICa was found to be due to cGMP-induced inhibition of cGMP-inhibited phosphodiesterase (cGI-PDE), we compared the effects of SIN-1 and milrinone, a cGI-PDE selective inhibitor, on ICa in human [7].

Chemical compound and disease context of milrinone

• Positive inotropic and vasodilator actions of milrinone in patients with severe congestive heart failure. Dose-response relationships and comparison to nitroprusside [8].
• Systemic and coronary effects of intravenous milrinone and dobutamine in congestive heart failure [9].
• We changed the residues to alanine using site-directed mutagenesis technique, expressed the mutants in a baculovirus/Sf9 cell system, and analyzed the kinetic characteristics of inhibition of the mutant enzymes by milrinone and cilostazol, specific inhibitors of PDE3 [10].
• We measured systemic hemodynamics, regional blood flow, and neurohormonal parameters in 13 patients with severe chronic congestive heart failure before and after 1 month of therapy with oral milrinone, a bipyridine cardiotonic agent [11].
• Treatment with the cAMP-PDE inhibitors rolipram and milrinone in combination (inhibiting PDE IV and PDE III isoenzymes) at day 2 and onward completely prevented the hypercalcemia-induced downregulation of AQP2 and AQP3 (but not AQP1) and completely prevented the development of polyuria [12].

Biological context of milrinone

• Milrinone caused heart rate, stroke volume, and dP/dt to increase, and systemic vascular resistance to decrease in a concentration-related manner [8].
• After intravenous administration of milrinone, peak negative dP/dt increased (+ 18%; p less than .01) and T decreased (-30%; p less than .01), while heart rate increased by only 8% (87 +/- 12 to 94 +/- 15 beats/min; p less than .01), left ventricular systolic pressure did not change, and mean aortic pressure fell by 11% (p less than .01) [13].
• This forearm vasodilatation occurred without change in systemic hemodynamics or therapeutic milrinone plasma concentrations in the pulmonary artery [14].
• The pharmacokinetics of milrinone were studied in sequential ascending doses in New York Heart Association Class III and IV patients receiving oral and intravenous medication [15].
• Milrinone (0.2 to 20 micrograms/ml) caused no major changes in the action potential characteristics, refractoriness, or conduction velocity in fibers exposed to normal Tyrode's solution, but markedly improved conduction and abbreviated or eliminated postrepolarization refractoriness in the ischemic gap preparations [16].

Anatomical context of milrinone

• 0.5 microM indomethacin inhibited milrinone effects in calvaria but usually not in limb bones [17].
• The inotropic effects of amrinone and milrinone on neonatal and young canine cardiac muscle [18].
• We monitored forearm hemodynamics, systemic hemodynamics, and milrinone plasma concentration from both the forearm venous effluent and pulmonary artery [14].
• Preinfusion of the phosphodiesterase inhibitor, milrinone, into the coronary artery resulted in a significant increase in the response to intracoronary dobutamine [19].
• Reduction of the extracellular Na+ concentration of 75% of normal potentiated the inotropic response of papillary muscles to low concentrations of milrinone, suggesting possible activation of the Na+-Ca++ exchange mechanism [20].

Associations of milrinone with other chemical compounds

• To clarify further the role of a positive inotropic action, the relative effects of milrinone and nitroprusside on left ventricular stroke work and dP/dt were compared in each patient at doses matched to cause equivalent reductions in mean arterial pressure or systemic vascular resistance, indices of left ventricular afterload [8].
• Both the heart rate-blood pressure product (9624 +/- 2272 to 9380 +/- 2428 mm Hg-beats/min; p = NS) and regional left ventricular myocardial oxygen consumption (7.6 +/- 2.9 to 8.1 +/- 3.1 ml O2/min; p = NS) were unchanged after milrinone, resulting in a 45% increase in calculated left ventricular external efficiency (p = .004) [21].
• Femoral vein oxygen content was increased by milrinone from 7.9 +/- 2.6 to 9.8 +/- 3.0 ml/100 ml (p less than .05) and was not changed by captopril [22].
• X-ray crystallographic analysis of milrinone and amrinone revealed structural homologies between the phenolic ring of thyroxine and the substituted ring of milrinone, whereas amrinone did not share these homologies [23].
• Pimobendan, in a dose-dependent manner, increased active tension developed by chemically-skinned dog heart muscle fibers at submaximally activating concentrations of Ca2+, whereas milrinone did not [24].

Gene context of milrinone

• In contrast, the mutants T844A, F972A and Q975A showed increased K(i) for cilostazol but no difference for milrinone from the recombinant PDE3A [10].
• The distribution pattern of the mRNA for the isoenzymes PDE3A and PDE5A may explain the pharmacological effects as well as the side effects of milrinone and sidenafil [25].
• The PDE activity of HCP1 is not sensitive to cGMP or other inhibitors of the cGMP-inhibitable PDEs, such as milrinone [26].
• Ro-20, 1724, etazolate, amrinone, milrinone and pentoxifylline inhibited unstimulated TNF-alpha production, with IC50 values of 1.87, 2.07, 13.9, 153 and 201 microM, respectively [27].
• The selective PDE 4 inhibitors, and to a certain extent the PDE3 inhibitors amrinone and milrinone, reduced the GM-CSF release in a concentration dependent manner [28].

Analytical, diagnostic and therapeutic context of milrinone

• In 10 patients receiving long-term oral milrinone (greater than or equal to 6 months) radionuclide ventriculography showed continued responsiveness, with a 27 per cent increase in left ventricular ejection fraction after 7.5 mg of the drug [1].
• Cardiotonic agent milrinone stimulates resorption in rodent bone organ culture [17].
• In nine patients radionuclide ventriculographic studies were performed during left heart catheterization, allowing calculation of left ventricular peak filling rate, volumes, and the diastolic pressure-volume relationship before and after milrinone [13].
• Dobutamine and milrinone were administered intravenously according a graded titration schedule up to maximum doses (14 micrograms/kg/min and 75 micrograms/kg, respectively) or until increased ventricular ectopy or a reduction in left ventricular end-diastolic pressure to 10 mm Hg or less occurred [29].
• In this study microelectrode techniques were used to assess the electrophysiologic effects of milrinone in canine false tendons homogeneously superfused with either normal or high-K Tyrode's solution and in Purkinje fibers mounted in a three-compartment chamber in which the central segment was depressed with an "ischemic" solution [16].

References