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Nutrition and Disease

Antioxidant Status in Dogs with Idiopathic Dilated Cardiomyopathy1,2
Lisa M. Freeman,3 Don J. Brown and John E. Rush
Department of Medicine, Tufts University School of Veterinary Medicine, North Grafton, MA 01536 EXPANDED ABSTRACT

KEY WORDS:

antioxidant

dilated cardiomyopathy

glutathione peroxidase

dogs

Free radicals, metabolites of oxygen metabolism, are produced under normal conditions, but their rate of production does not exceed the capacity of the body to catabolize them. It is only when the natural defenses are overwhelmed that free radical damage occurs. Therefore, the host’s endogenous antioxidant system plays a major role in the prevention or limitation of myocardial damage. Endogenous antioxidants include enzymatic antioxidants (e.g., superoxide dismutase or glutathione peroxidase), free radical scavengers (e.g., vitamins A, C or E) and metal chelators. Antioxidants also can be derived exogenously through the diet or through the use of supplements. Free radical-induced injury has been implicated in the development of a number of cardiac diseases, including coronary artery disease, myocardial infarction and some forms of cardiomyopathy in people and laboratory animals (Kaul et al. 1993). Free radicals not only have cytotoxic effects on the myocardium, but also act as negative inotropes (Prasad et al. 1993). Altered antioxidant status has been identified in an aortic banding model of congestive heart failure, with elevated levels during cardiac hypertrophy and decreased levels in failure (Dhalla and Singal 1994, Gupta and Singal 1989). Similar changes have been seen in other human diseases such as inflammatory bowel disease and human immunodeficiency virus (Delmas-Beauvieux et al. 1996, Hoffenberg et al. 1997). Elevated mean vitamin A concentration was found in cats with dilated cardiomyopathy compared with healthy controls (Fox et al. 1993). Whether these alterations contribute to disease progression or reflect a compensatory response to increased free radical stress is unclear at present. The purpose of this pilot study was to determine antioxidant status in dogs with idiopathic dilated cardiomyopathy (IDCM)4 compared with healthy controls.

1 Presented as part of the Waltham International Symposium on Pet Nutrition and Health in the 21st Century, Orlando, FL, May 26 –29, 1997. Guest editors for the symposium publication were Ivan Burger, Waltham Centre for Pet Nutrition, Leicestershire, UK and D’Ann Finley, University of California, Davis. 2 Supported in part by Hill’s Pet Nutrition. 3 To whom correspondence should be addressed. 4 Abbreviations used: ACEI, angiotensin converting-enzyme inhibitor; IDCM, idiopathic dilated cardiomyopathy; NYHA, New York Heart Association.

Materials and methods. Antioxidant status in canine IDCM. All dogs were client-owned animals. A diagnosis of IDCM was based on the presence of left atrial enlargement and a fractional shortening 28% ( 22% in Doberman pinschers) on 2-D and M-mode echocardiography. Controls were ageand weight-matched to the IDCM dogs. Dogs with major concurrent diseases, such as cancer, chronic renal failure and hepatic failure were excluded from the study. Owners signed a consent form before enrolling their dogs in the study. The study was approved by the Tufts University Animal Care and Use Committee. Blood (10 mL) was collected in EDTA, centrifuged and separated within 20 min. Fasting levels of vitamins A (retinol), C (ascorbic acid) and E ( -tocopherol) were measured in plasma; glutathione peroxidase and superoxide dismutase were measured in washed erythrocytes. Vitamins A, C and E were determined by reverse-phase HPLC, and glutathione peroxidase was analyzed using a Cobas Fara II centrifugal analyzer (Roche Diagnostics Systems, Nutley, NJ). Superoxide dismutase was determined by a commercial spectrophotometric assay (SOD-525, Bioxytech, Cedex, France). Dietary vitamins A and E were calculated based on manufacturer’s data (IU/kg diet on a dry matter basis) for dogs eating commercial dog foods. One dog, which ate a homemade diet, was excluded from determinations of dietary vitamins. Mean antioxidant concentrations between the IDCM and control groups were compared using Student’s t test; Pearson correlation was used to identify potential correlations between disease severity and antioxidant concentrations. Results were considered significant when the two-tailed P- value was 0.05. Results. Twelve dogs with IDCM and 11 healthy controls were enrolled in the study. Mean age of the IDCM dogs was 8.9 2.5 y compared with 7.9 1.9 y in the control group (P 0.21). Body weight also was not different between the groups (46.0 18.3 kg for the IDCM group vs. 40.2 6.9 kg for the controls; P 0.57). All control dogs and 11 of the 12 IDCM dogs ate commercial dry diets; one IDCM dog ate a homemade diet. In the IDCM group, one dog was classified as New York Heart Association (NYHA) Class I, four were NYHA Class II, five were NYHA Class III, and two were NYHA Class IV. An arrhythmia was detected in 11 of 12 IDCM dogs (and 0 of 11 controls). The arrhythmia was atrial

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0022-3166/98 $3.00 © 1998 American Society for Nutritional Sciences. J. Nutr. 128: 2768S–2770S, 1998.

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P 0.6 2280 159. These results contradict those found using a rodent model of cardiac hypertrophy.47.92 0. There was a trend for higher concentrations of plasma vitamin A and vitamin C in the IDCM group as well. digoxin and a -blocker (n 6).009. further study of these changes is warranted.1 7.60. Erythrocyte glutathione perioxidase concentrations were measured in only 21 of 23 dogs due to technical difficulties (11 dogs with IDCM and 10 controls). Fig. digoxin and diltiazem (n 3). For example. erythrocyte superoxide dismutase or dietary vitamin A. P 0. both when severity was measured by NYHA Class (r 0. cm Left ventricular internal dimension in systole. U/g Hb 1 FIGURE 1 Comparison of disease severity [based on end-systolic volume index (ESVI)] and glutathione peroxidase (GPX) concentrations in dogs with idiopathic dilated cardiomyopathy (n 11) and controls (n 10).4 1. The elevations also may be secondary to medications used in the therapy of IDCM. but it is likely related to the disease model because at least two human studies demonstrated elevated antioxidant concentrations in inflammatory bowel disease and human immunodeficiency virus (Delmas.8 412 14.6 175 86 18. There was no difference between groups in plasma vitamin E or erythrocyte superoxide dismutase. are a primary or secondary occurrence is currently unknown. cm Aorta. Circulating antioxidant levels are shown in Table 2.1 470 19. Whether these alterations. Discussion.4 2071 138.07). a reduced-sodium cardiac diet is more likely to be prescribed. these alterations in antioxidant status may play a role in the development or progression of disease.11. but these did not reach significance (P 0. (Left ventricular internal dimension in systole)3/body surface area.15 49. *ESVI (left ventricular internal dimension in systole)3/body surface area. Mean Left atrium.4 U/g Hb. These diets tend to contain high levels of vitamin A. respectively).org by on October 23. furosemide.05). There was a significant correlation between disease severity and erythrocyte glutathione peroxidase.47 23. P 0.7 0.8 U/g Hb) compared with controls (138. Medication regimens included an angiotensin-converting enzyme inhibitor (ACEI) and a -blocker (n 3). although there was no correlation between dietary vitamin A and circulating vitamin A. mol/L Vitamin C. 1). cm End-diastolic volume index. There was no difference between groups in dietary vitamin E levels (343 222 IU/kg for IDCM dogs vs. Hoffenberg et al 1997). Either way. Mean echocardiographic measurements in the IDCM group are shown in Table 1. plasma vitamin E. % 1 2 SD 0.07 50.12 and P 0. New TABLE 2 Mean circulating antioxidant concentrations in dogs with idiopathic dilated cardiomyopathy (IDCM) and controls1 IDCM (n 12) Vitamin A. P 0. 275 124 IU/kg for controls. Additional studies will be necessary to determine whether circulating levels of antioxidants accurately reflect tissue concentrations. 2006 . 1. similar to those in our study. P 0. There was a trend for higher levels of dietary vitamin A in the IDCM group (32488 11481 IU/kg) compared with the controls (22775 3005 IU/kg. The cause for this discrepancy is unknown. in which reduced levels of antioxidants were found in animals with congestive heart failure (Gupta and Singal 1989). there are known to be some differ- Downloaded from jn. and ACEI.ANTIOXIDANT STATUS IN CANINE IDCM 2769S TABLE 1 Mean echocardiographic measurements in dogs with idiopathic dilated cardiomyopathy (n 12).1 34.nutrition. P 0. On the other hand.11 0.52.5 SD. The most likely cause for these weak relationships is that as cardiac disease becomes more severe.49.4 Pvalue 0.2 mL/m2 Fractional shortening.8 Values are mean York Heart Association Class was associated with plasma vitamin C (r 0. cm Left ventricular internal dimension in diastole.27 0. Mean erythrocyte glutathione peroxidase concentration was significantly higher in IDCM dogs (159.12 0.4 14.4 0.1 mL/m2 End-systolic volume index. furosemide. mol/L Superoxide dismutase.48). This study also identified trends for higher dietary intakes of vitamin A in dogs with IDCM and a correlation between dietary vitamin A and disease severity.7 16. Class also was correlated with dietary vitamin A (r 0.01).5 2. The results of this pilot study suggest that alterations in some aspects of the endogenous antioxidant system exist in dogs with IDCM.0 43. especially for circulating glutathione peroxidase and vitamin C.3 3.1 (Left ventricular internal dimension in diastole)3/body surface area. P 0.9 0.02).01 4. fibrillation in six dogs and ventricular premature complexes in five dogs. There was no significant correlation between disease severity and plasma vitamin A.02) and when severity was measured by endsystolic volume index (r 0.9 118 54 6. Controls (n 11) 3. Elevations in antioxidant levels may be a marker of a compensatory response to increased oxidant stress. U/g Hb Glutathione peroxidase.5 19. ACEI. Disease severity (NYHA Class) was related to circulating antioxidants.38 18. mol/L Vitamin E.Beauvieux et al 1996.7 4.9 5.

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