Canine chronic valvular heart disease : how does myxomatous degeneration of the mitral valve ultimately lead to congestive heart failure?

Canine chronic valvular heart disease (CVHD) is a degenerative disease, primarily affecting the mitral valve apparatus. The disease is common, accounting for about 75% of cardiovascular diseases in the dog. Myxomatous degeneration of the valve causes valvular insufficiency, and regurgitation of blood into the atrium. This is well compensated, often over years, and does not at onset cause outward symptoms in the dog. However, as valvular degeneration continues, and the regurgitant fraction of the total stroke volume grows, a point of decompensation may be reached. In this literature review I discuss the compensatory changes that occur in CVHD, intrinsic and extrinsic, that allow for the maintenance of a satisfactory mean arterial pressure despite the reduction in forward stroke volume, and also, how they eventually fail. Extrinsically, there is activation of the sympathetic nervous system as well as the renin-angiotensin system. A large part of the thesis focuses on the far reaching consequences of circulatory renin-angiotensin activation. The antidiuretic and antinatriuretic effects of angiotensin II and the hormones it activates, namely aldosterone and vasopressin, lead to an increase in blood volume, aiding in blood pressure upkeep. The natriuretic peptide system acts to counterbalance the effects of renin-angiotensin system activation. Intrinsically, the heart compensates by recruitment of the Frank-Starling mechanism, as well as through eccentric hypertrophy. Eccentric hypertrophy involves the cardiac renin-angiotensin system and also bradykinin, with generally opposing effects. In CVHD, congestive heart failure occurs foremost by increase of the regurgitant fraction, that at first leads to atrial enlargement, then to increased atrial pressures, and eventually pulmonary edema. The function of this thesis is twofold. It can act as a reference for the compensatory changes that occur particularly in CVHD. It also attempts to explain general molecular mechanisms of interactions between the hormones and autacoids involved and their receptors. This is a necessary starting point for possible medical modulation of the disease. Also, mechanisms are similar regardless of receptor location, thus the thesis has general applicability, especially with regards to the renin-angiotensin system. The information presented may also benefit the medical community, as humans are afflicted with a very similar disease.