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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Cardiovascular drugs and therapy 8 (1994), S. 761-768 
    ISSN: 1573-7241
    Keywords: heart failure ; digoxin ; oral inotropes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Digoxin and other low doses of drugs that have inotropic properties may have an important role to play in the therapy of patients with chronic heart failure. There is convincing evidence that digoxin is effective in relieving the signs and symptoms of heart failure due to systolic dysfunction. While earlier results with some of the other agents have been disappointing, recent data suggest that a reevaluation of these agents is necessary. There is now compelling evidence that lower doses of these agents may be clinically useful without necessarily having any significant hemodynamic effects. The recent experience with vesnarinone is especially promising in showing that therapy with these agents may improve survival in addition to improving clinical status. It is becoming recognized that hemodynamic activity should not necessarily be a prerequisite for clinical utility for these agents. The neuroendocrine and electrophysiologic effects of many of these agents, including digitalis, remain incompletely characterized and may play an important role in their therapeutic benefit. It appears that certain drugs that have inotropic properties may be effective only when their inotropic effects are not readily demonstrated. Further research into the appropriate mechanisms of action and proper dosing of these drugs may lead to a renewed interest in the use of positive inotropes for chronic heart failure.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-7241
    Keywords: heart failure ; dobutamine ; nitroprusside ; enalaprilat ; digoxin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The hemodynamic effects of acute intravenous administration of nitroprusside, dobutamine, enalaprilat, and digoxin was investigated in a canine model of chronic heart failure (CHF) produced by multiple sequential intracoronary microembolizations. Dobutamine (4 µg/kg/min) increased cardiac output (2.4±0.1 vs. 4.0±0.4 l/min; p〈.001) and LV ejection fraction (LVEF; 26±1 vs. 30±4%; p〈.01), and decreased systemic vascular resistance (SVR; 3620±170 vs. 2470±190 dynes sec cm−5; p〈.001). Nitroprusside (3 µg/kg/min) acted as a venodilator; it decreased pulmonary artery wedge pressure (16±1 vs. 13±1 mmHg; p〈.01) and SVR (3730±440 vs. 3210±280 dynes sec cm−5; NS) but had no effect on cardiac output. Enalaprilat (1.875 mg) produced a significant increase of cardiac output (3.0±0.5 vs. 3.8±0.5 l/min; p〈.001) and LVEF (22±1 vs. 30±1%; p〈.01), and decreased SVR (3280±400 vs. 2450±250 dynes sec cm−5; p〈.01). Intravenous digoxin at a cumulative dose of 0.75 mg increased LVEF (23±2 vs. 31±2%; p〈.01) but had no effect on SVR. These data indicate that this canine model of CHF responds to acute pharmacologic intervention in a manner comparable to that seen in patients with CHF. Accordingly, this model may be a useful tool for the preclinical evaluation of new drugs targeted toward the treatment of CHF and for investigating the mechanisms of action of drugs currently used for the treatment of this disease state.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Cardiovascular drugs and therapy 11 (1997), S. 279-283 
    ISSN: 1573-7241
    Keywords: chronic heart failure ; digoxin ; hemodynamics ; neuroendocrine effects ; clinical efficacy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Digitalis has been used for more than 250 years, but its role in the treatment of chronic heart failure has been intensively investigated only during the past two decades. Digoxin increases cardiac output both at rest and during exercise, alone or in combination with ACE inhibitors, and these hemodynamic effects are sustained during chronic therapy. A daily dose of digoxin that achieves a serum concentration of approximately 1.2 ng/ml is associated with a significant improvement in central hemodynamics, particularly in patients with impaired cardiac function despite pretreatment with diuretics and ACE inhibitors. Acute administration of digoxin in patients with chronic heart failure has an immediate sympathoinhibitory effect, and chronic therapy is associated with a sustained decrease in serum norepinephrine concentration. Discontinuation of digoxin in patients with chronic heart failure resulted in hemodynamic deterioration, which was reversed when the drug was readministered. Randomized withdrawal of digoxin in patients receiving only diuretics (PROVED study), or its withdrawal in patients receiving diuretics and ACE inhibitors (RADIANCE study), was associated with worsening of the clinical evidence of heart failure and a decrease in left ventricular systolic function in both studies. In the only large-scale, placebo-controlled mortality study reported thus for (DIG Trial), 7788 patients received standard drug treatment for chronic heart failure in addition to either digoxin or placebo. Digoxin had no impact on survival over the 37 months of follow-up, but the incidence of hospitalizations due to worsening heart failure was significantly reduced in patients receiving the drug compared with those receiving placebo.
    Type of Medium: Electronic Resource
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