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

Previous results from our laboratory have shown that a novel carotenoid derivative ( disodium disuccinate astaxanthin; Cardax(TM)) 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 Cardax(TM) 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 mu M had 0% IS/AAR (100% cardioprotection). These results suggest that Cardax(TM) has marked cardioprotective properties in both rodents and canines. Thus, Cardax(TM) 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).