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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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