title: Left ventricular remodeling in preclinical experimental mitral regurgitation of dogs.
abstract: Dogs with experimental mitral regurgitation (MR) provide insights into the left ventricular remodeling in preclinical MR. The early preclinical left ventricular (LV) changes after mitral regurgitation represent progressive dysfunctional remodeling, in that no compensatory response returns the functional stroke volume (SV) to normal even as total SV increases. The gradual disease progression leads to mitral annulus stretch and enlargement of the regurgitant orifice, further increasing the regurgitant volume. Remodeling with loss of collagen weave and extracellular matrix (ECM) is accompanied by stretching and hypertrophy of the cross-sectional area and length of the cardiomyocyte. Isolated ventricular cardiomyocytes demonstrate dysfunction based on decreased cell shortening and reduced intracellular calcium transients before chamber enlargement or decreases in contractility in the whole heart can be clinically appreciated. The genetic response to increased end-diastolic pressure is down-regulation of genes associated with support of the collagen and ECM and up-regulation of genes associated with matrix remodeling. Experiments have not demonstrated any beneficial effects on remodeling from treatments that decrease afterload via blocking the renin-angiotensin system (RAS). Beta-1 receptor blockade and chymase inhibition have altered the progression of the LV remodeling and have supported cardiomyocyte function. The geometry of the LV during the remodeling provides insight into the importance of regional differences in responses to wall stress.
authors.affiliation: College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA. dilloar@auburn.edu
authors.forename: A Ray
authors.initials: AR
authors.lastname: Dillon
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Dell'Italia
authors.forename: Michael
authors.initials: M
authors.lastname: Tillson
authors.forename: Cheryl
authors.initials: C
authors.lastname: Killingsworth
authors.forename: Thomas
authors.initials: T
authors.lastname: Denney
authors.forename: John
authors.initials: J
authors.lastname: Hathcock
authors.forename: Logan
authors.initials: L
authors.lastname: Botzman
mesh_terms: D000818:Animals; D004283:Dog Diseases / Q000209:etiology / Q000473:pathology*; D004285:Dogs; D008944:Mitral Valve Insufficiency / Q000150:complications / Q000473:pathology / Q000662:veterinary*; D020257:Ventricular Remodeling / Q000502:physiology*