Acute and chronic administration of disodium disuccinate astaxanthin (CardaxTM) produces marked cardioprotection in dog hearts |
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Authors: | Garrett J. Gross Samuel F. Lockwood |
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Affiliation: | (1) Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, USA;(2) Hawaii Biotech, Inc., Aiea, HI, USA;(3) Hawaii Biotech, Inc., 99-193 Aiea Heights Drive, Suite 200, Aiea, HI 96701, USA |
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Abstract: | Previous results from our laboratory have shown that a novel carotenoid derivative (disodium disuccinate astaxanthin; CardaxTM) produced dose-related reductions in myocardial infarct size (IS) in Sprague–Dawley rats when it was administered at any of three doses (25, 50 and 75 mg/kg, iv) on four consecutive days, followed by the acute infarct size study on day 5. Maximum salvage occurred at the highest dose (75 mg/kg) tested, and was shown as a 56% reduction in IS. In the present follow-up study, we used a more relevant large animal model, the dog, and looked at the effect of administering CardaxTM iv either acutely 2 h prior to occlusion (N = 8) or for 4 days at 50 mg/kg iv as previously done in the rat model (N = 6). The results were compared to a saline vehicle-treated group (N = 10). In all groups, dogs were subjected to 60 min of left anterior descending (LAD) coronary artery occlusion and 3 h of reperfusion. IS was determined using a triphenyltetrazolium chloride (TTZ) histochemical stain and was expressed as a percent of the area at risk (IS/AAR). IS/AAR was 20.9 ± 1.6 % (mean ± S.E.M.) in controls and was reduced to 11.0± 1.7% (47.3% salvage; p < 0.01) in dogs treated only once iv at 2 h prior to occlusion, and 6.6± 2.8% (68.4% salvage; p < 0.001) in dogs treated for 4 days. In the chronic treatment group, two of the three dogs with plasma concentrations of non-esterified astaxanthin above 1 M had 0% IS/AAR (100% cardioprotection). These results suggest that CardaxTM has marked cardioprotective properties in both rodents and canines. Thus, CardaxTM may be a novel and powerful new means to prevent myocardial injury and/or necrosis associated with elective and/or urgent cardiac surgical interventions such as coronary angioplasty and stenting, as well as coronary artery bypass surgery (CABG). |
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Keywords: | disodium disuccinate astaxanthin astaxanthin CardaxTM carotenoids cardioprotection myocardial salvage infarct size canine infarct model |
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