Short-term effects of ecadotril in dogs with induced congestive heart failure.
OBJECTIVE
To evaluate short-term hemodynamic effects of ecadotril in a model of congestive heart failure in dogs.


METHODS
6 conscious adult male dogs.


METHODS
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
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.
Olivier
N B
NB
Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing 48824, USA.
Kutas
S M
SM
Beals
S
S
Hanson
B
B
Windram
S
S
D000818:Animals; D006152:Cyclic GMP / Q000652:urine; D004283:Dog Diseases / Q000188:drug therapy* / Q000503:physiopathology; D004285:Dogs; D004562:Electrocardiography / Q000662:veterinary; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology / Q000662:veterinary*; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D008863:Microspheres; D011188:Potassium / Q000652:urine; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D012964:Sodium / Q000652:urine; D015244:Thiorphan / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D011480:Protease Inhibitors; C049331:racecadotril; D012964:Sodium; D015244:Thiorphan; D006152:Cyclic GMP; D011188:Potassium