The Failing SHHF Rat Heart
The SHHF/Mccfa cp (SHHF) rat is a reliable genetic model of congestive heart failure secondary to essential hypertension. These animals are closely related to the SHR (spontaneously hypertensive rat), but unlike the SHR, all animals, male and female, develop fatal congestive heart failure, most in the second year of life. SHHF rats are now being widely used by the pharmaceutical industry to evaluate potential therapeutic agents for preventing the maladaptive ultrastructural and biochemical remodeling associated with cardiac hypertrophy and the progression to failure. SHHF rats have also proved to be useful for mechanistic studies of the contractile and signaling abnormalities associated with heart failure. The failing SHHF rat heart is hypertrophied, dilated, fibrotic, and exhibits a pronounced decline in fractional shortening in vivo as measured by M-mode echocardiography. The response to ß-adrenoceptor stimulation is markedly blunted; there is evidence to suggest a decline in excitation-contraction coupling gain; and there is a decline in maximal Ca2+ activated force per cross sectional area. Isolated perfused failing SHHF hearts exhibit a predisposition to develop mechanical alternans, a negative force-frequency response and altered electromechanical restitution. Comparable abnormalities are seen in human heart failure, making the SHHF rat an ideal small animal model for investigating the natural history of cardiac hypertrophy, the transition to failure, and the unique properties of the failing myocardium.
Key wordsHeart failure SHR rat hypertension cardiac hypertrophy adrenoceptor calcium
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