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A RAT MODEL OF HEART FAILURE INDUCED BY ISOPROTERENOL AND A HIGH SALT DIET
Citation:
Carll, A. P., N. HAYKAL-COATES, D. W. WINSETT, M. S. HAZARI, J. E. RICHARDS, D. L. COSTA, AND A. FARRAJ. A RAT MODEL OF HEART FAILURE INDUCED BY ISOPROTERENOL AND A HIGH SALT DIET . Presented at American Thoracic Society 2008 International Conference, Toronto, ON, CANADA, May 16 - 21, 2008.
Impact/Purpose:
Biochemical effects of salt-fortified diets on a rat model of isoproterenol (ISO)-accelerated heart failure (HF) were examined. Salt diet alone induces biochemictry more semblant to HF than ISO +/- salt.
Description:
Rat models of heart failure (HF) show varied pathology and time to disease outcome, dependent on induction method. We found that subchronic (4wk) isoproterenol (ISO) infusion in Spontaneously Hypertensive Heart Failure (SHHF) rats caused cardiac injury with minimal hypertrophy. Others have shown that dietary salt loading induces HF in spontaneously hypertensive (SH) rats without acute injury. We hypothesized ISO and salt combined would induce injury and more overt HF in SHHF rats than either treatment alone. Rats (male, 90d) were infused for 4 weeks with ISO (2.5mg/kg/d s.c.) or saline via osmotic pump. At 2 weeks of infusion, rats were fed high-salt diets (4, 6, or 8%) for 6 weeks. ISO elicited significant changes in breathing parameters at 9d. There were no significant differences in breathing parameters at the end of the exposure regimen (8 wk). Relative to naïve and ISO-infused rats fed a normal diet, saline-infused rats fed an 8% salt diet had increased bronchoalveolar indicators of lung injury (micro-albumin, protein, lactate dehydrogenase, n-acetyl-B-D-glucosaminidase). Rats fed 8% salt +/- ISO showed trends toward neutrophilic lung inflammation, while only the 8% salt-alone group had increased lung lymphocytes. The 8% salt-alone group had significantly greater heart mass, plasma B-type natriuretic peptide, and plasma IL-6 than rats fed a normal diet, and significantly greater urine pro atrial natriuretic peptide than ISO rats. All ISO treated groups had ischemic myocardial lesions with little cardiomegaly. The data suggest that the 8% salt diet alone induces biochemical changes more consistent with HF than ISO treatment either with or without 8% salt diet.