UMLS:C0018801 - FACTA Search

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Query: UMLS:C0018801 (heart failure)
72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of toborinone (OPC-18790) and milrinone on cardiac function and energetics were compared in microembolized guinea pig hearts. Male guinea pig hearts were perfused according to the Langendorff method and microembolization was induced by injecting microspheres. The hearts were then treated with toborinone (10 microM), milrinone (4 microM), and vehicle. Energy metabolism in hearts was assessed by 31-phosphorus magnetic resonance spectroscopy (31P-MRS). Microembolization produced a decrease in coronary perfusion flow (CPF), left ventricular developed pressure (LVP), and peak LVdP/dt by about 50% concomitantly with a decrease in creatine phosphate (PCr) and ATP and an increase in inorganic phosphate (Pi) and Pi/PCr ratio. Toborinone and milrinone increased peak LVdP/dt, an index of contractility, by 15 +/- 2% and 18 +/- 3%, respectively. Milrinone increased heart rate (HR) by 22 +/- 4% but toborinone did not change HR. Toborinone did not change PCr, ATP, Pi, Pi/PCr, and intracellular pH (pHi) compared with the vehicle. On the other hand, milrinone decreased PCr and increased Pi and Pi/PCr compared with toborinone or vehicle. These results suggest that the different effects between toborinone and milrinone on energy metabolism in microembolized hearts may be due to the difference of chronotropic action between these drugs. Thus toborinone, a positive inotropic agent without chronotropic action, may be effective in acute treatment of ischemic heart failure.
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PMID:Comparative study of toborinone (OPC-18790) and milrinone on energy metabolism in microembolized guinea pig hearts. 940 58

This study evaluated the efficacy of intravenous milrinone in improving hemodynamics and facilitating the titration of high-dose oral vasodilator therapy to improve clinical status. Fourteen patients (mean age 52 +/- 12 years) with severe heart failure and a left ventricular ejection fraction of 18 +/- 6% underwent right-side heart catheterization and an intravenous milrinone infusion followed by titration of oral vasodilator and diuretic therapy. Milrinone significantly (p <0.05) improved right atrial pressure (12 +/- 5 to 8 +/- 5 mm Hg), pulmonary capillary wedge pressure (23 +/- 7 to 15 +/- 7 mm Hg), cardiac index (1.9 +/- 0.4 to 3.4 +/- 0.5 L/min/m2), systemic vascular resistance (1,809 +/- 526 to 891 +/- 144 dynes/s/cm(-5)), and pulmonary vascular resistance (285 +/- 151 to 163 +/- 68 dynes/s/cm(-5)), which was maintained in 10 patients with titration of high-dose oral vasodilator therapy. Oral angiotensin-converting enzyme inhibitor and diuretic doses were increased 318% and 89%, respectively. Four patients also received hydralazine to optimize hemodynamics. New York Heart Association functional class improved from 3.8 +/- 0.4 to 2.6 +/- 0.6 following therapy. Ten patients who responded to therapy had fewer hospitalized days during the subsequent year compared with the year before treatment (4 +/- 17 vs 17 +/- 15), and no patient died. In contrast, the 3 patients who responded poorly to therapy tended to have more hospitalized days at 12 months compared with pretreatment (31 +/- 11 vs 20 +/- 18; NS); 1 patient died. We conclude that intravenous milrinone followed by optimization of oral medical therapy may be used as a therapeutic trial to identify patients in need of cardiac transplantation.
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PMID:Effects of intravenous milrinone followed by titration of high-dose oral vasodilator therapy on clinical outcome and rehospitalization rates in patients with severe heart failure. 981 82

The goal of this study was to determine the extent to which the effects of milrinone were desensitized in heart failure (HF) and to determine the mechanisms, i.e., whether these effects could be ascribed to changes in cAMP or phosphodiesterase (PDE) activity in HF. Accordingly, we examined the effects of milrinone in seven conscious dogs before and after HF was induced by rapid ventricular pacing at 240 beats/min. The dogs were chronically instrumented for measurements of left ventricular (LV) pressure and first derivative of LV pressure (dP/dt), arterial pressure, LV internal diameter, and wall thickness. Milrinone (10 micrograms . kg-1. min-1 iv) increased LV dP/dt by 1,854 +/- 157 from 2,701 +/- 105 mmHg/s (P < 0.05) before HF. After HF the increase in LV dP/dt in response to milrinone was attenuated significantly (P < 0.05); it increased by 615 +/- 67 from 1,550 +/- 107 mmHg/s, indicating marked desensitization. In the presence of ganglionic blockade the increases in LV dP/dt (+445 +/- 65 mmHg/s) in response to milrinone were markedly less (P < 0.01), and milrinone increased LV dP/dt even less in HF (+240 +/- 65 mmHg/s). cAMP and PDE activity were measured in endocardial and epicardial layers in normal and failing myocardium. cAMP was decreased significantly (P < 0.05) in LV endocardium (-26%) but not significantly in LV epicardium (-14%). PDE activity was also decreased significantly (P < 0.05) in LV endocardium (-18%) but not in LV epicardium (-4%). Thus significant desensitization to milrinone was observed in conscious dogs with HF. The major effect was autonomically mediated. The biochemical mechanism appears to be due in part to the modest reductions in PDE activity in failing myocardium, which, in turn, may be a compensatory mechanism to maintain cAMP levels in HF. Reductions in cAMP and PDE levels were restricted to the subendocardium, suggesting that the increased wall stress and reduced coronary reserve play a role in mediating these changes.
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PMID:Mechanisms of desensitization to a PDE inhibitor (milrinone) in conscious dogs with heart failure. 1033 Feb 56

Milrinone is a phosphodiesterase inhibitor that has been shown to improve hemodynamic parameters in patients with class III to IV heart failure when administered intravenously for < or =48 hours. This study examines the tolerability of long-term intravenous milrinone therapy and assesses its utility in allowing upward titration of oral vasodilator agents. A retrospective review of hospital records identified 63 patients who underwent hemodynamic monitoring and received intravenous milrinone for >24 hours in a critical care setting. Hemodynamics and medications were recorded before and after 24 hours of milrinone therapy. Additional medications, as well as any adverse events, were recorded throughout milrinone therapy. The mean dose of milrinone was 0.43 +/- 0.10 microg/kg/min, with a mean duration of 12 +/- 15 days (range 1 to 70). Therapy was continued for >48 hours in 89% of patients. After 24 hours of milrinone therapy, patients exhibited significant improvements in pulmonary artery pressures, pulmonary capillary wedge pressures, and cardiac index. When compared with baseline, significantly more patients received angiotensin-converting enzyme (ACE) inhibitors after 24 hours of milrinone and at the end of milrinone therapy (67% vs 86%, p <0.01). Likewise, significantly more patients also received oral hydralazine and/or nitrates at the end of milrinone therapy (38% vs 65%, p <0.01) when compared with baseline. The mean doses of most oral medications at the 3 time periods were similar. The ACE inhibitor dose was significantly higher at the end of milrinone therapy when compared with baseline, and hydralazine dose was significantly higher at the end of therapy when compared with 24 hours. Few adverse effects were noted, with only 10% of patients experiencing symptomatic ventricular tachycardia and 2 patients with significant hypotension requiring discontinuation of the drug. The adverse events were similar in the group of patients who received milrinone for > or =7 days compared with the entire cohort. Milrinone was well tolerated over the long term in a controlled inpatient setting, and allowed uptitration of oral vasodilator therapy.
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PMID:Tolerability of extended duration intravenous milrinone in patients hospitalized for advanced heart failure and the usefulness of uptitration of oral angiotensin-converting enzyme inhibitors. 1053 6

This is a summary of reports of presentation made at the American College of Cardiology 49th Scientific Sessions, Anaheim, 12-15 March 2000. Studies with a particular interest for heart failure physicians have been reviewed. OPTIME-CHF: Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure. OPTIME-CHF was a randomised-controlled trial comparing a 48-h infusion of Milrinone or standard therapy in 951 patients recruited over a 2-year period. Patients were excluded if the investigator believed their clinical condition mandated inotropic therapy. Patients were randomised within 48 h of admission for an acute exacerbation of chronic heart failure to receive Milrinone or placebo infision for 48 h. Of the patients 43% were diabetics, 70% were receiving an angiotensin converting enzyme inhibitor, 25% were already on a beta-Blocker, and 34% had atrial fibrillation. There was no significant difference between the two groups in length of hospital stay during the index admission, subsequent readmissions and days in hospital over the following 60 days. Subjective clinical assessment scores were also no different. There was an average admission rate over the next year of one per patient in both groups. However, there was a significant increase in the incidence of sustained hypotension in the Milrinone group, which accounted for all of the increased adverse event rates for the active therapy. The 60-day mortality was 10% in both groups. This and previous trials of the oral formulation of Milrinone have now clearly demonstrated a lack of benefit with Milrinone in either during acute exacerbations of or in stable severe chronic heart failure [Packer M, Carver JR, Rodeheffer RJ et al. Effect of oral Milrinone on mortality in severe chronic heart failure. N Engl J Med 1991;325:1468-1475.]. Medium sized studies of Milrinone in patients with milder severities of heart failure also suggested an adverse impact on prognosis in the presence or absence of digoxin [DiBianco R, Shabetai R, Kostuk W, Moran J, Schlant RC, Wright R. A comparison of oral Milrinone, digoxin, and their combination in the treatment of patients with chronic heart failure. N Engl J Med 1989;320:677-683.]. Whether Milrinone even has a role for the management of a haemodyamic crisis requiring inotropic therapy must also be questioned.
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PMID:Clinical trials update: OPTIME-CHF, PRAISE-2, ALL-HAT. 1085 36

A 19-year-old man with idiopathic dilated cardiomyopathy developed cardiogenic shock. A HeartMate left ventricular assist device was inserted as an emergency procedure, but removed after 189 days due to sepsis related to the device. Intravenous milrinone was administered because of recurrence of heart failure, and as a result the symptoms disappeared and the urinary output increased. Echocardiography showed improvement in the left ventricular ejection fraction. Subsequently, the patient successfully underwent heart transplantation. Milrinone was effective as a pharmacological bridge to heart transplantation in this patient with terminal and critical heart failure after removal of a left ventricular assist device.
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PMID:Clinical experience of milrinone as a pharmacological bridge to heart transplantation. 1096 21

The action of medical drugs obtained from many vegetables aroused a great interest of naturalists and physicians in all time. Moreover, it was always required that those persons destined to medical practice have a good knowledge of botany. Among the medicinal plants utilized by ancient peoples of the Anahuac, yoloxochitl or heart flower (Talauma mexicana) is mentioned, which seems to have a digitalis-like action. Research in our century demonstrated a positive inotropic and bradycardic effect of the leavels of Magnolia grandiflora or Talauma mexicana extract. Since the end of the XVIII century, digitalis was employed. It was considered initially as a diuretic and later as a cardiotonic agent. The action of digitalic glycosides upon the cardiac tissues was studied experimentally in Mexico. At the present-time there are positive inotropic agents derived from pyridine, as is the case of Milrinone, which have a beneficial action on the failing human myocardium. However, following the opinion of distinguished pharmacologists, "in the case of heart failure associated to atrial fibrillation, digitalis cannot be substituted".
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PMID:[Digitalic therapy. Historical outline]. 1108 Sep 35

A randomized, open-label, parallel-group design was used to determine the percentage of patients achieving improvements in predetermined baseline hemodynamic end points (>20% to 30% increase in cardiac index depending on baseline values and >25% decrease in pulmonary capillary wedge pressure), assessed at hour 0 (end of initial dose titration) and 1, 2, 4, 8, and 24 hours after the infusion of milrinone or nitroglycerin. In total, 125 patients (60 milrinone, 65 nitroglycerin) enrolled in this study, and 119 (58 milrinone, 61 nitroglycerin) were evaluable for the efficacy analysis. A significantly greater proportion of milrinone-treated patients reached (45% v 14%, P =.005) and maintained (24% v 6%, P =.026) hemodynamic goals than did nitroglycerin-treated patients; the time to achieve hemodynamic goals was significantly less in milrinone-treated patients (33 +/- 2 v 54 +/- 10 minutes, P <.001). Milrinone was also significantly more effective in decreasing systemic vascular resistance (P =.004), increasing stroke volume (P =.008), and improving global clinical status. Inodilator therapy with milrinone seems more efficacious in attaining sustained hemodynamic improvement than does pure intravenous vasodilator therapy with nitroglycerin in treating patients with decompensated heart failure.
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PMID:A randomized multicenter study comparing the efficacy and safety of intravenous milrinone and intravenous nitroglycerin in patients with advanced heart failure. 1142 Jul 62

The objective of this study was to examine the efficacy of milrinone in chronic congestive heart failure. In this randomized, double-blind, placebo-controlled trial, 30 patients with class III or IV chronic congestive heart failure were randomly assigned to receive milrinone (n = 15) or placebo (n = 15). The results showed that in the milrinone group, stroke volume increased from 38.50 +/- 5.34 to 64.93 +/- 6.46 ml (P < 0.001), cardiac output increased from 3.39 +/- 0.42 to 5.28 +/- 0.55 L/min (P < 0.001), cardiac index increased from 2.01 +/- 0.42 to 3.21 +/- 0.57/min/m2 (P < 0.001) and ejection fraction increased from 0.23 +/- 0.05 to 0.35 +/- 0.06(P < 0.001). In the placebo group, no hemodynamic effects were found. Milrinone favourably influenced the symptoms and heart function in 11/15(73.3%) patients. In the placebo group, only 4/15(26.7%) patients had such response (P < 0.05). These data indicate that milrinone is effective for improving the hemodynamics status and heart function in patients with chronic heart failure.
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PMID:[Response to milrinone treatment in patients with chronic congestive heart failure]. 1251 50

Beta blockers have been shown to reduce morbidity and mortality in patients with heart failure without evidence of overt congestion. No data are available describing outcomes of patients admitted with exacerbated chronic heart failure who are receiving beta blockade at the time of admission. The purpose of this analysis was to evaluate clinical outcomes in patients from the Outcomes of the Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF) study who were prescribed beta blockers on admission compared with patients who were not prescribed beta blockers at admission. In all, 212 patients were treated with beta blockers at admission and 737 patients were not. Baseline characteristics were similar between groups, except that patients prescribed beta blockers on admission had slightly higher ejection fractions, fewer New York Heart Association class IV symptoms, and lower heart rates. There was no difference in clinical events between patients who were treated with beta blockers at the time of admission and those who were not. Exploratory analyses suggested that patients whose beta-blocker therapy was discontinued had a higher risk of adverse outcomes, particularly in the subset of patients randomized to milrinone. The data from this nonrandom comparison suggest that continuation of pre-existing beta-blocker therapy is not associated with an increased risk of adverse clinical events in patients admitted with worsening heart failure. These results also suggest that caution should be taken when withdrawing beta blockade in this population.
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PMID:Clinical outcomes in patients on beta-blocker therapy admitted with worsening chronic heart failure. 1252 29

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