Short-term effects of ecadotril in dogs with induced congestive heart failure

Objective-To evaluate short-term hemodynamic effects of ecadotril in a mode l of congestive heart failure in dogs. Animals-6 conscious adult male dogs. Procedures-Instruments were placed in dogs to measure left ventricular, aor tic, and atrial blood pressures. Heart failure was induced by repeated coro nary 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 excreti on were measured before and 30, 90, and 150 minutes, and 10 and 21 hours af ter 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 appar ent. Urinary sodium excretion significantly increased in response to the lo w and high doses of ecadotril but not in response to the 10 mg/kg dose. Lef t ventricular end diastolic pressure (LVEDP) consistently decreased in dose - and time-dependent manner. Maximal group-averaged reductions in LVEDP wer e 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 chang e in urine flow. Conclusions and Clinical Relevance-Orally administered ecadotril reduced le ft ventricular filling pressures in these dogs by a mechanism that does not require a substantial diuretic effect, Ecadotril may be effective for alle viating clinical signs in dogs with left-sided heart failure and may be par ticularly beneficial for use in dogs that are refractory to traditional diu retic therapy.