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Toxicologic Pathology
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The Relative Protective Effects of Moderate Dietary Restriction versus Dietary Modification on Spontaneous Cardiomyopathy in Male Sprague-Dawley Rats

Masayuki Kemi

Department of Safety Assessment, Banyu Pharmaceutical Co, Menuma, Japan,

Kevin P. Keenan

Department of Safety Assessment, Merck Research Laboratories, West Point, Pennsylvania 19486, USA

Carol Mccoy

Department of Safety Assessment, Merck Research Laboratories, West Point, Pennsylvania 19486, USA

Chao-Min Hoe

Biometrics, Merck Research Laboratories, West Point, Pennsylvania 19486, USA

Keith A. Soper

Biometrics, Merck Research Laboratories, West Point, Pennsylvania 19486, USA

Gordon C. Ballam

Purina Mills Inc, St Louis, Missouri 63116, USA

Matthew J. Van Zwieten

Department of Safety Assessment, Merck Research Laboratories, West Point, Pennsylvania 19486, USA

The relative protective effects of modifying dietary protein, fat, fiber, and energy content vs moderate food or dietary restriction (DR) on spontaneous cardiomyopathy of Charles River male Sprague-Dawley (SD) rats was evaluated at 1 and 2 years. For 2 years, SD rats were fed Purina Rodent Chow 5002 (21.4% protein, 5.7% fat, 4.1% fiber, 3.1 kcal/g) or a modified rodent chow 5002-9 (13.6% protein, 4.6% fat, 15.7% crude fiber, 2.4 kcal/g) ad libitum (AL) or by moderate DR at approximately 65% of the caloric intake of the AL group fed the 5002 diet. Serum lipids, carcass composition, and organ weights were evaluated and hearts were qualitatively and quantitatively examined microscopically for male SD rats at 1 and 2 years. Cardiomyopathy was characterized by the colocalization of myocardial degeneration, the development of subepicardial, perivascular, subendocardial, and interstitial fibrosis, and mononuclear inflammatory cell infiltration that increased by incidence and severity in an age-dependent manner from 1 to 2 years. SD rats fed the 5002 diet AL had the greatest heart weights and the most severe cardiomyopathy, with the highest myocardial fibrotic index. These parameters were relatively decreased in the AL 5002-9 diet, the DR 5002 diet, and the DR 5002-9 diet rats at 1 and 2 years. Regardless of the type of diet fed, both AL groups had the most severe cardiomyopathy by 2 years. Moderate DR allowed isocaloric comparisons of the relative effects of modified diets on survival, obesity, and heart disease. Only slight improvements in the severity and progression of spontaneous cardiomyopathy were seen by modification of the protein, fiber, fat, and energy content of the diet if fed AL. However, moderate DR with either diet was more effective than changing the diet composition in preventing and controlling the progression of cardiomyopathy in male SD rats.

Key Words: Cardiomyopathy • myocardial fibrosis • dietary restriction • caloric restriction • dietary fiber • dietary protein • aging • Sprague-Dawley rats

Toxicologic Pathology, Vol. 28, No. 2, 285-296 (2000)
DOI: 10.1177/019262330002800208


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