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Short-term effects of ecadotril in dogs with induced congestive heart failure
N B Olivier1, S M Kutas, S Beals
1Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing 48824, USA.
Insights
Ecadotril effectively reduced left ventricular filling pressures in dogs with heart failure. This effect occurred without significant diuretic action, suggesting potential benefits for refractory cases.
Area of Science:
- Cardiovascular Pharmacology
- Veterinary Cardiology
Background:
- Congestive heart failure (CHF) in dogs often involves elevated left ventricular filling pressures.
- Diuretic therapy is a cornerstone for managing CHF, but some cases become refractory.
Purpose of the Study:
- To assess the short-term hemodynamic effects of orally administered ecadotril in a canine model of congestive heart failure.
- To investigate the relationship between ecadotril dosage, hemodynamic changes, and diuretic effects.
Main Methods:
- Six adult male dogs with induced congestive heart failure were studied.
- Ecadotril was administered orally at doses of 3, 10, and 30 mg/kg, with hemodynamic parameters and urinary output monitored.
- Left ventricular end-diastolic pressure (LVEDP), mean arterial pressure, and heart rate were measured.
Main Results:
- Ecadotril significantly reduced LVEDP in a dose- and time-dependent manner (maximal reductions of 5.2, 8.1, and 10 mm Hg).
- Urinary sodium excretion increased with low and high doses but not the middle dose.
- No significant changes were observed in urine flow, heart rate, or mean arterial pressure.
Conclusions:
- Orally administered ecadotril effectively reduced left ventricular filling pressures in dogs with heart failure.
- The mechanism of action does not appear to be primarily diuretic.
- Ecadotril shows promise for treating canine left-sided heart failure, especially in diuretic-refractory patients.
Objective:
To evaluate short-term hemodynamic effects of ecadotril in a model of congestive heart failure in dogs.
Animals:
6 conscious adult male dogs.
Procedures:
Instruments were placed in dogs to measure left ventricular, aortic, and atrial blood pressures. Heart failure was induced by repeated coronary embolization with latex microspheres. Four times, and in random order, dogs were given vehicle or active drug (3, 10, or 30 mg/kg of body weight) orally. Hemodynamic variables, urine flow, and urinary electrolyte excretion were measured before and 30, 90, and 150 minutes, and 10 and 21 hours after drug administration.
Results:
Changes in urine flow, heart rate, mean arterial pressure, or peak positive and negative rate of change in ventricular pressure were not apparent. Urinary sodium excretion significantly increased in response to the low and high doses of ecadotril but not in response to the 10 mg/kg dose. Left ventricular end diastolic pressure (LVEDP) consistently decreased in dose- and time-dependent manner. Maximal group-averaged reductions in LVEDP were 5.2, 8.1, and 10 mm Hg for the low, middle, and high doses, respectively. The magnitude of the decrease in LVEDP was not related to cumulative change in urine flow.
Conclusions And Clinical Relevance:
Orally administered ecadotril reduced left ventricular filling pressures in these dogs by a mechanism that does not require a substantial diuretic effect. Ecadotril may be effective for alleviating clinical signs in dogs with left-sided heart failure and may be particularly beneficial for use in dogs that are refractory to traditional diuretic therapy.