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Acute and chronic administration of disodium disuccinate astaxanthin (CardaxTM) produces marked cardioprotection in dog hearts

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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 μM 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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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, USA

    Garrett J. Gross

  2. Hawaii Biotech, Inc., Aiea, HI, USA

    Samuel F. Lockwood

  3. Hawaii Biotech, Inc., 99-193 Aiea Heights Drive, Suite 200, Aiea, HI, 96701, USA

    Samuel F. Lockwood

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  1. Garrett J. Gross
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  2. Samuel F. Lockwood
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Correspondence to Samuel F. Lockwood.

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Gross, G.J., Lockwood, S.F. Acute and chronic administration of disodium disuccinate astaxanthin (CardaxTM) produces marked cardioprotection in dog hearts. Mol Cell Biochem 272, 221–227 (2005). https://doi.org/10.1007/s11010-005-7555-2

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  • DOI: https://doi.org/10.1007/s11010-005-7555-2

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