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BACKGROUND: Activation of the renin-angiotensin-aldosterone system (RAAS) occurs as a compensatory response to decreased cardiac output. Vasoconstriction and sodium and water retention that result from the hormonal changes in response to heart failure are beneficial initially, but eventually become detrimental and contribute to progression and clinical signs of heart failure. Atrial natriuretic peptide (ANP) inhibits and counteracts the RAAS. Serum thyroid hormones are decreased by many nonthyroidal illnesses including congestive heart failure. Because thyroid hormones are necessary for normal depolarization of the heart and myocardial function, altered thyroid hormone concentrations may be detrimental in dogs with heart failure.

SUMMARY: Three groups of 15 dogs each were evaluated in this study. Dogs with dilated cardiomyopathy and clinical and radiographic evidence of congestive heart failure comprised one group. Another group consisted of dogs with dilated cardiomyopathy based on finding decreased fractional shortening on echocardiography but without clinical findings of congestive heart failure. The third group consisted of 15 normal age-, breed-, and sex-matched dogs. Echocardiography, electrocardiography, and thoracic radiographs were performed in all dogs. Blood was collected for measurement of N-terminal proANP (released in equimolar amount to the active C-terminal hormone and is more stable in vitro), plasma renin activity, angiotensin converting enzyme activity (ACE), aldosterone, endogenous canine thyroid-stimulating hormone (cTSH), total thyroxine (T4), and free T4 (fT4) by chemiluminescent enzyme immunometric assay (not equilibrium dialysis), urea nitrogen, and total protein. Urine and plasma creatinine, sodium, potassium, and osmolality were also measured. Dogs with cardiomyopathy and heart failure had significantly increased left atrial size, decreased aortic size, and increased heart rate compared with control dogs and dogs with cardiomyopathy without heart failure. Atrial fibrillation was present in four dogs with heart failure and five dogs with cardiomyopathy without heart failure. Dogs with clinical signs of heart failure had significantly increased plasma renin activity, plasma aldosterone concentration, ANP, and urinary aldosterone:creatinine ratio compared with control dogs and dogs with cardiomyopathy but no clinical signs of heart failure. Plasma ANP concentrations increased with increased heart rate, left atrial size, left ventricle size, and fractional shortening. There was positive correlation between plasma renin activity, plasma aldosterone concentration, and urinary aldosterone:creatinine ratio consistent with activation of the RAAS. There was no significant difference in ACE activity between the three groups. Serum T4 and cTSH concentrations were not different among the groups of dogs. However, fT4 concentration was significantly decreased in dogs with cardiomyopathy and clinical signs of heart failure. Plasma renin activity, aldosterone, and urinary aldosterone:creatinine ratio were inversely correlated with decreased fT4 concentration. Dogs with clinical signs had significantly decreased plasma protein and urine:plasma creatinine ratio compared to the other groups of dogs. The authors concluded that activation of the RAAS is present in dogs with dilated cardiomyopathy and clinical signs of heart failure.

CLINICAL IMPACT: The compensatory mechanisms that maintain tissue perfusion in dogs with impaired cardiac function, in particular activation of the RAAS, contribute to progression of heart failure in later stages of the disease. Use of ACE inhibitors such as enalapril prior to the onset of clinical signs of heart failure has been recommended based on finding elevated renin activity and aldosterone concentrations in some dogs with mitral valve insufficiency. Other studies of dogs with dilated cardiomyopathy have shown results similar to the current study, with elevations of renin activity and aldosterone primarily occurring only when signs of heart failure were present. A recent prospective evaluation of the effects of ACE inhibitors on progression of cardiac disease in dogs with early mitral valve insufficiency failed to show any effect of enalapril administration in reducing the occurrence of congestive heart failure. The finding of low serum fT4 concentrations in the presence of normal T4 and cTSH may be the result of the fT4 assay used. Although hypothyroidism does cause decreased myocardial contractility in dogs, it has not been shown to cause dilated cardiomyopathy.

Front Page : Library : Effects of Dilated Cardiomyopath...