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The Journal of Nutrition Vol. 128 No. 12 December 1998,
pp. 2768S-2770S
Department of Medicine, Tufts University School of Veterinary Medicine, North Grafton, MA 01536 USA
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 The purpose of this pilot study was to determine antioxidant status in dogs with idiopathic dilated cardiomyopathy (IDCM)4 compared with healthy controls.
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 age- and 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.
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 fibrillation in six dogs and ventricular premature complexes in five dogs. Medication regimens included an angiotensin-converting enzyme inhibitor (ACEI) and a Discussion.
The results of this pilot study suggest that alterations in some aspects of the endogenous antioxidant system exist in dogs with IDCM, especially for circulating glutathione peroxidase and vitamin C. These results contradict those found using a rodent model of cardiac hypertrophy, in which reduced levels of antioxidants were found in animals with congestive heart failure (Gupta and Singal 1989
INTRODUCTION
Introduction
References
). 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.
-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.
View this table:
Table 1.
Mean echocardiographic measurements in dogs with idiopathic dilated cardiomyopathy (n = 12).
View this table:
Table 2.
Mean circulating antioxidant concentrations in dogs with idiopathic dilated cardiomyopathy (IDCM) and controls1
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Fig 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); *ESVI = (left ventricular internal dimension in systole)3/body surface area.
-blocker (n = 3); ACEI, furosemide, digoxin and a -blocker (n = 6); and ACEI, furosemide, digoxin and diltiazem (n = 3). Mean echocardiographic measurements in the IDCM group are shown in Table 1.
). The cause for this discrepancy is unknown, 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- Beauvieux et al 1996, Hoffenberg et al 1997). Whether these alterations, similar to those in our study, are a primary or secondary occurrence is currently unknown. Elevations in antioxidant levels may be a marker of a compensatory response to increased oxidant stress. The elevations also may be secondary to medications used in the therapy of IDCM. On the other hand, these alterations in antioxidant status may play a role in the development or progression of disease. Either way, further study of these changes is warranted.
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LITERATURE CITED |
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Introduction
References
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-carotene.
Am. J. Clin. Nutr.
1996;
64:101-107
-tocopherol, retinol, selenium, and total triglycerides and cholesterol concentrations in cats with cardiac disease and in healthy cats. Am. J. Vet. Res. 54: 563-569.
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