Merits of Non-Invasive Rat Models of Left Ventricular Heart Failure

Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, 27599 USA.
Cardiovascular toxicology (Impact Factor: 1.72). 06/2011; 11(2):91-112. DOI: 10.1007/s12012-011-9103-5
Source: PubMed


Heart failure (HF) is characterized as a limitation to cardiac output that prevents the heart from supplying tissues with adequate oxygen and predisposes individuals to pulmonary edema. Impaired cardiac function is secondary to either decreased contractility reducing ejection (systolic failure), diminished ventricular compliance preventing filling (diastolic failure), or both. To study HF etiology, many different techniques have been developed to elicit this condition in experimental animals, with varying degrees of success. Among rats, surgically induced HF models are the most prevalent, but they bear several shortcomings, including high mortality rates and limited recapitulation of the pathophysiology, etiology, and progression of human HF. Alternatively, a number of non-invasive HF induction methods avoid many of these pitfalls, and their merits in technical simplicity, reliability, survivability, and comparability to the pathophysiologic and pathogenic characteristics of HF are reviewed herein. In particular, this review focuses on the 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, all of which 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.

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Available from: Alex P Carll,
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    • "The signaling mechanisms associated with β-AR overactivation have been studied in using isoproterenol (ISO)-treated animals [3]. It was demonstrated that ISO treatment induces myocardial oxidative stress [4] and synthesis of proinflammatory cytokines [5], [6]; these mechanisms were also involved in long-term β-AR stimulation-induced cardiac damage, such as cardiac hypertrophy, necrosis and fibrosis. "
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    • "At 15 months of age, 16 rats were implanted with radiotelemeters (model TA11CTA-F40; Data Sciences International, St Paul, MN) for the purpose of recording ECG, heart rate (HR), core body temperature, and activity wirelessly as previously described (Lamb et al., 2012). Lean male SHHF rats acquire cardiac hypertrophy by 3 months of age and transition into dilated cardiomyopathy and heart failure at 18 months of age (Carll et al., 2011b). All studies conformed to the guidelines of the U.S. EPA Institutional Animal Care and Use Committee. "
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    • "Telemeter implantation was performed by surgeons at Charles River Laboratory in adherence with preoperative, anesthetic, and surgical procedures described previously (Carll et al., 2010). Lean male SHHFs acquire cardiac hypertrophy by 3 months of age and transition into dilated cardiomyopathy and heart failure (HF) at 18 months of age as a consequence of hypertension and hyperleptinemia (Carll et al., 2011b). Rats were shipped after a 10-day recovery period to our Association for Assessment and Accreditation of Laboratory Animal Care International-approved animal facility, housed individually in 42-× 21-× 20-cm Plexiglas cages with pine-shave bedding in a room (22°C ± 1°C, 50% ± 5% relative humidity, 12-h light:dark cycle 0600:1800 h), and provided standard Purina rat chow (5001; Brentwood, MO) and water ad libitum. "
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