Improved exercise ejection fraction with long-term prazosin therapy in patients with heart failure

Goldman, Stephen A.; Johnson, Lynne L.; Escala, Edith; Cannon, Paul J.; Weiss, Melvin B.

doi:10.1016/0002-9343(80)90158-8

Cited by 79 publications

(11 citation statements)

References 25 publications

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“…reduction of the infarct size or work overload on the heart because scar wt/LV wt ratio as well as heart rate in MI rats were not altered by treatment with prazosin. Although it is generally believed that the beneficial actions of α-AR blockers in heart failure are due to a decrease in the afterload [12][13][14][15], we did not observe any change in MAP in experimental rats upon prazosin treatment. This may be due to adjustment in blood pressure during 8 wks of prazosin administration or difference in drug responses in rats and humans upon chronic treatment.…”

Section: +contrasting

confidence: 88%

“…Although some clinical studies have shown the improvement of cardiac function upon treatment with α-AR blockers [12][13][14][15], others have failed to show any beneficial effects [20,21]. In spite of these controversial investigations, the results reported in this study provide experimental evidence that the use of α-AR blockers may prove to be of some value for the treatment of heart failure.…”

Section: +mentioning

confidence: 72%

“…On the other hand, α-AR associated mechanisms have been indicated to be intimately involved during the development of heart failure [11]. This view is supported by several clinical studies, which have shown beneficial effects of different α-AR blockers including prazosin in heart failure [12][13][14][15]. The combination therapy with prazosin and enalapril (an angiotensin converting enzyme inhibitor) produced greater effects than the monotherapy with enalapril in chronic heart failure [16].…”

Section: Introductionmentioning

confidence: 97%

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Reversal of Cardiac Remodeling and Subcellular Defects by Prazosin in Heart Failure Due to Myocardial Infarction

Babick¹,

Elimban²,

Dhalla³

2012

J Clinic Experiment Cardiol

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Background: This study was undertaken to test if α-Adrenoceptor (AR) blockade with prazosin reverses cardiac remodeling and ameliorates subcellular defects in heart failure due to Myocardial Infarction (MI).Methods: Heart failure in rats was induced by MI for 12 wks and then treated with or without prazosin (10 mg/kg/ day) for 8 wks. Both control and experimental animals were assessed hemodynamically and echocardiographically for evaluating changes in heart function and cardiac remodeling, respectively. Left Ventricle (LV) was used for determining biomedical and molecular activities.Results: Cardiac dysfunction, as evident from depressed LV systolic pressure, rates of changes in pressure development and decay, cardiac output, ejection fraction and fractional shortening as well as increased LV end diastolic pressure, in 20 wks infarcted animals, was corrected partially by prazosin treatment. Different parameters of cardiac remodeling including increased LV posterior wall thickness and LV systolic diameter in failing hearts were fully or partially reversed whereas increased LV diastolic diameter was unaltered by prazosin therapy. Reversal of lung congestion and cardiac hypertrophy in MI animals by prazosin was associated with depression in the elevated levels of plasma norepinephrine, unlike epinephrine or dopamine. Depressions in Sarcoplasmic Reticular (SR) Ca 2+ -uptake activity as well as protein content for Ca 2+ -pump ATPase and phospholamban in failing hearts were reversed partially whereas depressed SR Ca 2+ -release activity and myofibrillar Ca 2+ -stimulated ATPase activity were not affected by prazosin. Alterations in mRNA levels for SR Ca 2+ -pump ATPase, SR Ca 2+ -release channels, and α-myosin heavy chain and β-myosin heavy chain in MI-induced heart failure were not influenced by prazosin treatment. Conclusions:It is suggested that the activation of α-AR system may be associated with cardiac remodeling and heart failure and the reverse cardiac remodeling by α-AR blockade may improve cardiac performance by attenuating defects in SR Ca 2+ -pump.

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Section: +contrasting

confidence: 88%

Section: +mentioning

confidence: 72%

Section: Introductionmentioning

confidence: 97%

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Reversal of Cardiac Remodeling and Subcellular Defects by Prazosin in Heart Failure Due to Myocardial Infarction

Babick¹,

Elimban²,

Dhalla³

2012

J Clinic Experiment Cardiol

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“…The magnitude of increase in ejection fraction produced by minoxidil may be greater than that produced by other vasodilators. 13 14 Minoxidil may have direct inotropic effects. '5 In addition, the observed increase in heart rate in our patients suggests reflex sympathetic stimulation, and the increased pulmonary wedge pressure during minoxidil treatment may indicate a positive inotropic effect resulting from increased preload.…”

Section: Discussionmentioning

confidence: 99%

Minoxidil in patients with chronic left heart failure: contrasting hemodynamic and clinical effects in a controlled trial.

Franciosa¹,

Jordan²,

Wilen³

et al. 1984

Circulation

120

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Minoxidil, a potent predominant arterial dilator, improves hemodynamics over the short term in patients with heart failure. In random double-blind fashion 17 patients with chronic left heart failure were given minoxidil (nine patients) or placebo (eight patients) in addition to digoxin and diuretics for 3 months. Cardiac index and heart rate increased and mean arterial pressure and systemic vascular resistance fell within 4 hr of minoxidil administration. Right heart and pulmonary arterial pressures were unchanged over the short term but rose after long-term minoxidil. After 3 months of minoxidil treatment, systemic vascular resistance was still reduced ( failure who had been symptomatic for at least 3 months despite treatment with digitalis and diuretics were selected for study. The diagnosis of congestive heart failure was based on a histo-y of symptoms on exertion and the presence of a ventricular gallop sound, jugular venous distention, pulmonary rales, or otherwise unexplained peripheral edema. In addition, all patients were required to have at least one of the following during the month preceding enrollment into the study: (1) cardiothoracic ratio on standard chest x-ray of greater than 0.55, (2) left ventricular ejection fraction less than 40% by radionuclide angiography, (3) echocardiographic left ventricular end-diastolic dimension greater than 2.7 cm/m2, or (4) resting cardiac index by carbon dioxide rebreathing below 2.5 liters/min/m2.The cause of congestive heart failure was coronary artery 63

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“…'6 16 The principal goal of this investigation was to examine the effects, time course and mechanism of action of prazosin on the coronary circulation and left ventricle in conscious dogs. A single dose of prazosin caused sustained reductions (> 12 hours) in mean arterial pressure and coronary vascular resistance associated with sustained decreases in indicators of afterload (mean arterial and LV systolic pressures) and LV preload (LV end-diastolic diameter and pressure).…”

Section: Discussionmentioning

confidence: 99%

Effects of prazosin on coronary and left ventricular dynamics in conscious dogs.

Macho

Vatner²

1982

Circulation

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SUMMARY The left ventricular (LV) and coronary vascular effects of prazosin, a drug that reduces peripheral vascular resistance by blocking postsynaptic a receptors, were examined in conscious dogs. Prazosin, 0.07 mg/kg/mmn i.v. for 7 minutes, induced sustained hypotensive effects for more than 12 hours. The peak effects occurred 3045 minutes after administration. Prazosin increased heart rate by 28 ± 9%, did not change mean coronary blood flow significantly, decreased mean arterial pressure by 15 i 4%, LV enddiastolic diameter by 10 + 2%, LV end-systolic diameter by 8 ± 2%, late diastolic coronary resistance by 22 :7%, and---LV dP/dt by 9 i 4%. These effects of prazosin were not altered substantially by maintaining heart rate constant with electrical pacing or by pretreatment with ,B-adrenergic blockade. However, after chronic reserpine treatment, prazosin did not reduce either mean arterial pressure or late diastolic coronary resistance. The a-blocking properties of the drug were established when prazosin attenuated pressor responses to phenylephrine, norepiphrhrine and bilateral carotid occlusion. Thus, in conscious dogs with heart rate constant, prazosin, by blocking a-adrenergic receptors, induces prolonged coronary vasodilation associated with reductions in the major determinants of myocardial oxygen consumption, e.g., arterial and LV pressures, LV end-diastolic diameter and LV dP/dt. However, the coronary vasodilation was not intense enough to increase coronary blood flow above control levels.PRAZOSIN, a quinazoline derivative, reduces peripheral vascular resistance, an action that is clinically beneficial, particularly in the treatment of hypertension and congestive cardiac failure.' 7 However, its effects on the coronary circulation have not been established. The goal of this investigation was to determine the coronary vascular effects and mechanism of action of this drug in conscious dogs without the mitigating effects of anesthesia and recent surgery.8 Because the control of the coronary circulation is linked tightly to changes in cardiac function, the effects of prazosin on left'ventricular (LV) pressures, dimensions and contractility were also examined. If the drug merely reduced preload and afterload, and consequently myocardial oxygen consumption, then coronary vascular resistance should increase because it is inversely related to myocardial oxygen consumption. However, if prazosin also elicited reflex increases in heart rate and myocardial contractility or a direct effect on the coronary vasculature, it would oppose the secondary effects due to reductions in myocardial oxygen demand. To separate direct and indirect effects of the drug on the coronary circulation, prazosin was administered in the presence and absence of constant heart rate, f-adrenergic blockade and catecholamine depletion with chronic reserpine treatment. Finally, to test the efficacy of the drug in blocking a-adrenergic receptors, the pressor effects of phenylephrine, norepinephrine and bilateral carotid occlusion were assessed ...

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Improved exercise ejection fraction with long-term prazosin therapy in patients with heart failure

Cited by 79 publications

References 25 publications

Reversal of Cardiac Remodeling and Subcellular Defects by Prazosin in Heart Failure Due to Myocardial Infarction

Reversal of Cardiac Remodeling and Subcellular Defects by Prazosin in Heart Failure Due to Myocardial Infarction

Minoxidil in patients with chronic left heart failure: contrasting hemodynamic and clinical effects in a controlled trial.

Effects of prazosin on coronary and left ventricular dynamics in conscious dogs.

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