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Merits of Non-Invasive Rat Models of Left Ventricular Heart Failure
Citation:
Carll, A. P., M. Willis, D. P. Costa, AND A. FARRAJ. Merits of Non-Invasive Rat Models of Left Ventricular Heart Failure. Cardiovascular Toxicology. Humana Press Incorporated, Totowa, NJ, 11(2):91-112, (2011).
Impact/Purpose:
The EPA is charged with protecting sensitive human populations from the adverse effects of ennvironmental contaminants. This manuscnipt provides a thorough review of non-invasive rat models of heart failure and will help guide the Agency in conductmg animal studies on the impacts of pollution exposure in particularly sensitive individuals- those with pre-existing heart failure.
Description:
Heart failure (HF) is defined primarily by the impairment of cardiac function and consequent inability of the heart to supply tissues with ample oxygen. To study HF etiology, investigators have applied many different techniques to elicit this condition in animals, with varying degrees of success at mimicking the pathophysiology of human HF. While surgically invasive techniques are the most prevalent for rat HF models, they often bear several shortcomings, including high mortality rates and crude approximations of the pathophysiology, etiology, and progression of HF. There are a number of non-invasive methods of HF induction that avoid many of these pitfalls. Thus, it is appropriate to evaluate the merits of non-invasive methodologies for HF induction based on technical simplicity, reliability, survivability, and comparability to the pathophysiologic and pathogenic characteristics of HF found in humans and in invasive models. This review focuses particularly on the physiological impairment and primary pathogenic mechanisms common to genetic strains (spontaneously hypertensive and spontaneously hypertensive heart failure), pharmacological models of toxic cardiomyopathy (doxorubicin and isoproterenol), and dietary salt models that have been shown to induce left ventricular HF in the rat. Additional non-invasive techniques that may potentially enable the development of new HF models are also discussed.
