Heart failure after long-term supravalvular aortic constriction in rats

Abstract

Pressure overload in humans follows a chronic and progressive course, often resulting in eventual cardiac decompensation and death. Animal models of heart failure generally fail to mimic the temporal features observed in human disease often covering a major portion of the life span, and findings of short-term studies are of uncertain applicability. The purpose was to determine whether chronic pressure overload introduced gradually in young normotensive rats would lead predictably to heart failure and to characterize specific phenotype features that have been well documented in another model of heart failure. Rats underwent banding of the ascending aorta at 7 weeks of age such that the hemodynamic load increased gradually with ontogenic growth. Two groups of hypertrophied hearts from aortic-banded rats, with and without signs of heart failure, were compared with those of control rats at a mean age of 11 months. Hearts of aorta-banded rats underwent a transition from stable compensated hypertrophy to heart failure that was characterized by augmented hypertrophy, depressed contractile function, elevated fibrosis, increased myocardial stiffness, and marked alterations in the expression of genes encoding contractile, regulatory, and extracellular matrix proteins. Gradual constriction of the rat aorta resulted in heart failure after a variable length of time (3 to 18 months). Despite differences in genotype, the ultimate phenotype associated with the transition to failure in the aorta-banded rat is nearly identical to that observed in the aged spontaneously hypertensive rat (SHR), with a few notable differences. The findings suggest that a common heart failure phenotype follows long-term pressure overload regardless of the underlying etiology.