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Acute hemodynamic and hormonal response to indoramin in congestive heart failure
Insights
Indoramin effectively reduces cardiac filling pressures and vascular resistance in severe heart failure patients. This alpha-1 antagonist shows promise for managing congestive heart failure symptoms.
Area of Science:
- Pharmacology
- Cardiovascular Medicine
- Clinical Trials
Background:
- Severe chronic congestive heart failure (CHF) presents significant challenges in managing hemodynamic instability.
- Alpha-1 adrenergic antagonists are explored for their potential in cardiovascular therapeutics.
Purpose of the Study:
- To evaluate the acute hemodynamic and hormonal effects of a single dose of indoramin in patients with severe CHF.
- To determine the safety and efficacy of indoramin in this patient population.
Main Methods:
- A single oral dose of indoramin was administered to 11 subjects with severe chronic congestive heart failure.
- Hemodynamic parameters (ventricular filling pressures, stroke index, vascular resistances, heart rate, arterial pressure) and hormonal levels (plasma norepinephrine, plasma renin activity) were monitored for 6 hours.
- Adverse effects were recorded.
Main Results:
- Indoramin administration led to a rapid and sustained reduction in right and left ventricular filling pressures within 1 hour.
- Significant decreases in pulmonary and systemic vascular resistances were observed, accompanied by an increase in stroke index.
- Despite a drop in systemic arterial pressure, heart rate remained unchanged. Plasma renin activity increased, while norepinephrine levels and forearm hemodynamics were unaltered.
- Drowsiness was the primary side effect, reported in 5 out of 11 subjects.
Conclusions:
- Indoramin demonstrates acute effectiveness in reducing ventricular preload and systemic vascular resistance in patients with severe congestive heart failure.
- The findings suggest indoramin's potential as a therapeutic agent for managing acute hemodynamic derangements in CHF.
- Further research is warranted to explore the long-term efficacy and safety profile of indoramin in heart failure management.
Abstract:
Acute hemodynamic and hormonal responses to a single dose of indoramin, an alpha 1-antagonist, were evaluated in 11 subjects with severe chronic congestive heart failure. A hemodynamic effect began within 1 hr of indoramin and persisted during the 6 hr of hemodynamic monitoring. Decreased right and left ventricular filling pressures were associated with increased stroke index and decreased pulmonary and systemic vascular resistances. Heart rate did not increase despite a fall in systemic arterial pressure. Forearm blood flow, forearm venous capacitance, and plasma norepinephrine levels were unchanged, whereas plasma renin activity rose from 12.7 +/- 17.4 to 16.6 +/- 20.4 ng/ml/hr. The only side effect was drowsiness in five of the 11 subjects. Our data demonstrate the acute effectiveness of indoramin in reducing ventricular preload and systemic vascular resistance in heart failure.