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Clinical and hemodynamic experience with enalapril in congestive heart failure
Insights
Enalapril effectively treats congestive heart failure (CHF) by improving hemodynamics and exercise capacity. Long-term, twice-daily oral administration of this ACE inhibitor offers sustained benefits for CHF patients.
Area of Science:
- Cardiology
- Pharmacology
Background:
- The renin-angiotensin system is often overactive in congestive heart failure (CHF).
- This activation leads to vasoconstriction and fluid retention, worsening CHF symptoms.
Purpose of the Study:
- To assess the efficacy of enalapril, a novel converting enzyme inhibitor, in patients with CHF.
- To evaluate both short-term hemodynamic and hormonal effects, and long-term clinical outcomes with enalapril therapy.
Main Methods:
- Single-dose oral and intravenous administration of enalapril to measure immediate responses.
- One-month oral enalapril therapy to assess changes in exercise duration and invasive hemodynamics compared to baseline.
- Monitoring of hemodynamic parameters (systemic vascular resistance, cardiac output) and hormonal responses.
Main Results:
- Both oral and intravenous enalapril reduced systemic vascular resistance and increased cardiac output after single doses.
- Intravenous enalapril showed faster onset of action (15-30 minutes) compared to oral enalapril (3-4 hours) due to pro-drug conversion.
- Long-term oral enalapril therapy improved CHF symptoms, exercise tolerance, and sustained hemodynamic improvements.
Conclusions:
- Enalapril is an effective treatment for chronic congestive heart failure.
- Optimal short-term management might involve combined intravenous and oral enalapril, though responses were comparable.
- Twice-daily oral administration is recommended for effective long-term therapy in CHF.
Abstract:
The renin-angiotension system is activated in many patients with congestive heart failure (CHF), resulting in angiotensin-mediated vasoconstriction and aldosterone-mediated sodium and water retention. To evaluate the effectiveness of enalapril, a new converting enzyme inhibitor, enalapril was administered to patients either orally or intravenously in a single dose, and hemodynamic and hormonal responses were measured. Patients were then placed on oral enalapril therapy for 1 month, and treadmill exercise duration and invasive hemodynamics were compared with baseline pretreatment data. With single-dose administration, both oral and intravenous enalapril reduced systemic vascular resistance and increased cardiac output. However, the effects of oral enalapril were not manifest for 3 to 4 hours, because oral enalapril is a pro-drug form that requires hepatic deesterification. In contrast, intravenous enalapril resulted in significant hemodynamic and hormonal changes 15 to 30 minutes after administration. During long-term therapy, enalapril was associated with improved symptomatology, increase of treadmill exercise duration and sustained hemodynamic improvement. Enalapril was effective therapy for chronic CHF. Optimal short-term response may require coadministration of both intravenous and oral preparations of enalapril; however, the magnitude of the short-term response was comparable for both preparations. Long-term therapy is most effective when the drug is administered as a twice-daily regimen.