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Development of mild aortic valve stenosis in a rabbit model of hypertension.

Cuniberti LA, Stutzbach PG, Guevara E, Yannarelli GG, Laguens RP, Favaloro RR

Lipid and Atherosclerosis Research Laboratory, Department of Pathology, Favaloro University, Buenos Aires, Argentina. cuniberti@favaloro.edu.ar

OBJECTIVES: This study was designed to investigate the association between hypertension and aortic valve stenosis (AVS) in a rabbit model. BACKGROUND: Degenerative AVS is a prevalent disease in elderly persons. Its molecular mechanisms remain unclear, in part because of the absence of experimental models. Epidemiologic data suggest a link between hypertension and AVS. However, there has been no evidence of a cause-effect relationship. METHODS: New Zealand White rabbits were divided into two groups: 1) animals (n = 20) instrumented according to one-kidney/one-clip hypertensive model; and 2) control animals (n = 10) sham operated. Echocardiography (S12 MHz) was used to assess aortic valve (AV) morphology and function as well as left ventricular mass at baseline and after two and four months of hypertension. RESULTS: Blood pressure and left ventricular mass increase were highly significant in the animal model but not in controls at two months, without noticeable AV function abnormalities. After 4 months, however, 14 hypertensive survived animals showed a 14.6% reduction of AV area (0.240 +/- 0.063 cm2 vs. 0.205 +/- 0.060 cm2, p < 0.05), a 19.6% increase of AV thickness (0.056 +/- 0.011 cm vs. 0.067 +/- 0.010 cm, p < 0.001), a 40.4% increase of transvalvular mean gradient (5.35 +/- 2.26 mm Hg vs. 7.51 +/- 3.73 mm Hg, p < 0.05) and a 63.6% increase of transvalvular maximal gradient (10.56 +/- 3.68 mm Hg vs. 17.28 +/- 10.95 mm Hg, p < 0.05). Control animals did not show significant changes. CONCLUSIONS: We report a novel experimental model of AVS in rabbits that may prove useful in studying the progression of the disease and the efficacy of new treatments. The present findings support the hypothesis of a causal link between hypertension and AVS.

Published 5 June 2006 in J Am Coll Cardiol, 47(11): 2303-9.
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