Hemodynamically induced heart lesions in the dog after the administration of cardio-active substances

Authors' reply

“…Moreover, and importantly, pimobendan treatment was associated with specific mitral valve lesions, eg, acute focal hemorrhages and endothelial papillary hyperplasia. These pathological findings could not be due to the spontaneous MVD per se and are in accordance with data previously published 2–4 and also results provided by Boehringer Ingelheim using (as here) 6 Beagle dogs per group 5…”

“…Our concerns regarding the safety of pimobendan were initially triggered by two clinical cases in which cardiac lesions had been induced in dogs by pimobendan at dosages close to those recommended 1 . Pimobendan‐induced cardiac lesions in healthy dogs had already been described in the literature 2–5 . Moreover, toxicological studies 3 concluded that the dog “appears to be an especially sensitive species” to pimobendan with regard to the development of atrioventricular, endocardial and myocardial lesions as a consequence of exaggerated inotropic activity.…”

Cardiac Valvular Pathology: Comparative Pathology and Animal Models of Acquired Cardiac Valvular Diseases

“…Vasoactive pharmaceuticals have been associated with hemodynamically induced heart lesions, including valve injury, in dogs. Experimental positive inotropic substances, particularly those with additional vasodilatory properties, have been associated with acute mitral valve injury (Schneider 1990). At toxicologic doses for periods of weeks to months, dogs displayed mitral valvular injury such as focal swellings of granulation tissue, hemorrhage, myxomatous interstitial change, and fibrosis at the base of the mitral valve and along the valve closure margins (Schneider 1990).…”