Grant Amount: $81,918

Dr. Mark A. Oyama, DVM, University of Pennsylvania

January 1, 2008 - August 31, 2012

Sponsor(s): American Cavalier King Charles Spaniel Club Charitable Trust, American Whippet Club, Friends of Norfolk Terrier, Greyhound Club of America, Japanese Chin Club of America, Keeshond Club of America, National American Pit Bull Terrier Association, Norfolk Terrier Club, Saluki Health Research, Inc., Yorkshire Terrier Club of America

Disease(s): Mitral Valve Disease

Abstract

Background: Canine myoxmatous mitral valve disease is very common in older dogs and is similar to the human disorder. Serotonin (5HT) related mechanisms has been found in the certain forms of human heart valve disease, and a beginning study by the investigators has shown heightened 5HT signaling in diseased canine mitral valve interstitial cells (MVIC). Objective: The researchers are investigating the hypothesis that 5HT signaling contributes to the progression of canine myxomatous mitral valve disease. The reseachers seek to 1) further characterize the 5HT signaling pathway in normal and diseased human and canine mitral valve specimens, 2) determine the effects of 5HT-2A receptor antagonism in diseased canine MVIC, 3) perform a dose escalation (Phase I) study of a candidate 5HTR-2A receptor antagonist, ketanserin, in client-owned dogs with myxomatous mitral valve disease, and 4) perform a controlled comparison (Phase II) study in dogs using ketanserin. Ultrasound studies and measurement of neurohormonal markers will assess effects of therapy on progression of mitral valve disease. This study represents a novel translational study that targets a potential underlying pathogenesis of canine mitral valve disease.

Publication(s)

- Oyama, Ma and Levy, Rj (2010) Insights into Serotonin Signaling Mechanisms Associated with Canine Degenerative Mitral Valve Disease. Journal of Veterinary Internal Medicine. 24, 27-36. http://dx.doi.org/10.1111/j.1939-1676.2009.0411.x