Disease relevance of Wincoram

• Thrombocytopenia and fever in a patient taking amrinone [1].
• Amrinone, a new cardiotonic drug active in humans with congestive heart failure, is shown to stimulate net Ca uptake by dog RBC [2].
• Milrinone, an amrinone analog, is a more potent cardiotonic agent with lower toxicity [3].
• The cardiotonic agent amrinone inhibits bone resorption in vitro [3].
• To determine the effects of vasodilator and inotropic therapy on hyponatremia in patients with severe heart failure, we measured serum sodium concentration before and after treatment with captopril (70 patients), hydralazine (42 patients), prazosin (22 patients), and amrinone (19 patients), while diuretic dosages were kept constant [4].

Psychiatry related information on Wincoram

• Vesnarinone, but not amrinone, (1) decreased fever and lethargy, consistent with decreased central nervous system effects of endotoxin, and (2) decreased lung leukocyte infiltration [5].

High impact information on Wincoram

• Milrinone, a derivative of amrinone, has nearly 20 times the inotropic potency of the parent compound and does not cause fever or thrombocytopenia in normal volunteers or in animals sensitive to amrinone [6].
• Both vesnarinone and amrinone suppressed the production of tumor necrosis factor-alpha [7].
• On the other hand, amrinone failed to inhibit natural killer cell activity [7].
• In contrast to amrinone, milrinone stimulated resorption in cultures of neonatal mouse calvaria and fetal rat limb bones [3].
• If Ca moves through myocardial sarcolemma as it does through dog RBC membranes, then the inotropic action of amrinone can be explained on the basis that the drug increases intracellular Ca levels [2].

Chemical compound and disease context of Wincoram

• The effects of amrinone, dobutamine, and a combination of the two drugs on peak positive left ventricular dP/dt and left ventricular performance were evaluated in 11 patients with chronic congestive heart failure [8].
• Hemodynamic and regional blood flow distribution responses to dextran, hydralazine, isoproterenol and amrinone during experimental cardiac tamponade [9].
• This association suggests that N-acetylamrinone, and not amrinone, may be the mediator of thrombocytopenia in children receiving amrinone [10].
• Our results suggest that rolipram and amrinone decrease the immune activation in endotoxemia through inhibition of the production of pro-inflammatory mediators IL-12, IFN-gamma, TNF-alpha and NO [11].
• In another model of heart failure, in which ouabain-induced arrhythmias preceded procainamide toxicity, amrinone was also an effective cardiotonic agent [12].

Biological context of Wincoram

• Tachyphylaxis with amrinone therapy: association with sequestration and down-regulation of lymphocyte beta-adrenergic receptors [13].
• The positive inotropic effects of amrinone were most pronounced at low frequencies of stimulation (0.01 to 0.25 Hz) and were nearly obliterated at more physiologic heart rates (0.5 to 1.25 Hz) [14].
• Hemodynamic effects of intravenous administration of amrinone include increases in dP/dt, cardiac output, and stroke work with decreases in left ventricular filling pressure and systemic vascular resistance [15].
• After nitroprusside was stopped, intravenous amrinone (3 mg/kg) caused decreases from baseline in pulmonary arterial end-systolic pressure in eight of nine patients (23 +/- 11% [overall mean +/- SE], p less than .05), and in pulmonary vascular resistance in all patients (38 +/- 6%, p less than .001) [16].
• The amrinone-induced decrease in right ventricular end-systolic volume was compared with that predicted for right ventricular afterload reduction alone based on the effect of amrinone on pulmonary arterial end-systolic pressure and the pressure-volume relationship observed during infusion of nitroprusside.(ABSTRACT TRUNCATED AT 250 WORDS)[16]

Anatomical context of Wincoram

• Effects of amrinone, a cardiotonic drug, on calcium movements in dog erythrocytes [2].
• STUDY OBJECTIVE: To determine whether intravenous therapy with amrinone changes number, location or function of the beta-adrenergic receptors on lymphocytes [13].
• To determine the hemodynamic and clinical effects of long-term positive inotropic stimulation on the myocardium, we treated 31 patients with severe chronic heart failure with oral amrinone (600 mg daily) and performed invasive hemodynamic studies during short- and long-term treatment with the drug [17].
• The amrinone-induced hemodynamic improvement in patients with congestive heart failure secondary to coronary artery disease was associated with reductions in MVO2 and CBF and no evidence of myocardial ischemia [18].
• The effects of amrinone and related agents were studied in mammalian cardiac and vascular smooth muscle preparations loaded intracellularly with aequorin, a bioluminescent calcium indicator that emits light when it combines with Ca++ [14].

Associations of Wincoram with other chemical compounds

• The dose-response curve of left ventricular dP/dt and performance during titration of dobutamine with and without the addition of intravenous amrinone was evaluated in seven patients [8].
• To determine whether amrinone and its induced increase of cyclic AMP releases nitric oxide and enhances endothelium-dependent vascular relaxation, we studied nitric oxide production and vascular relaxation of rat thoracic aorta on treatment with amrinone and forskolin, an activator of adenylate cyclase [19].
• NG-nitro L-arginine reversed the relaxation induced by amrinone or forskolin in ring segments with, but not without, endothelium [19].
• When 20 microM amrinone was applied to ring segments of aorta previously contracted with phenylephrine, relaxation was greater in segments with endothelium than in those without (% relaxation 94 +/- 4 vs 37 +/- 7%, P < 0.01) [19].
• Nitric oxide production in ring segments of aorta, following application of amrinone or forskolin, was detected by nitric oxide-selective electrode and electron paramagnetic resonance spin trapping methods [19].

Gene context of Wincoram

• Amrinone also inhibited upregulation of ICAM-1 (p < .001) at therapeutic concentrations, and VCAM-1 (p < .001) at higher concentrations [20].
• Intraperitoneal treatment of animals with amrinone (100 mg/kg) 30 min before LPS administration decreased both plasma IL-6 and IL-10 concentrations in the first phase of the response, but enhanced plasma levels of these cytokines in the second part [21].
• Immunohistochemical investigation further revealed the VEGF-expressed cells in the sponge granulation tissues to be fibroblasts, and the intensity of positive reactions was enhanced by bFGF, 8-bromo-cAMP, forskolin, and amrinone [22].
• All three PDE III inhibitors, amrinone, pimobendan and vesnarinone, inhibited TNF-alpha production, but vesnarinone's inhibitory effect was the most prominent [23].
• Amrinone at 26 mumol/l and NKH477 at 10 nmol/l also had a less marked inhibitory effect against the production of IL-6 [24].

Analytical, diagnostic and therapeutic context of Wincoram

• Long-term oral administration of amrinone for congestive heart failure: lack of efficacy in a multicenter controlled trial [25].
• Accordingly, the hemodynamic, myocardial metabolic and ECG responses to amrinone (2.5 mg/kg i.v. over 1 hour) were measured in nine patients with congestive heart failure secondary to coronary artery disease [18].
• In unanesthetized dogs, intravenous infusion of amrinone (10-100 microgram/kg per min) caused increases in left ventricular dp/dt max and only small changes in heart rate and blood pressure [26].
• Nineteen patients (aged 2 months to 8.3 years) with one or more left to right shunts were evaluated during cardiac catheterization with direct hemodynamic measurements made before and 10 min (peak effect) after administration of a bolus injection of amrinone, 3 mg/kg body weight [27].
• Amrinone did not significantly change Ees or k in the control group [28].

References