Acute and Chronic Administration of Disodium Disuccinate Astaxanthin (Cardax) Produces Marked Cardioprotection in Dog Hearts

Mol Cell Biochem. 2005 Apr;272(1-2):221-7. doi: 10.1007/s11010-005-7555-2.

Abstract

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

MeSH terms

  • Animals
  • Cardiotonic Agents / administration & dosage
  • Cardiotonic Agents / pharmacokinetics
  • Cardiotonic Agents / therapeutic use*
  • Dogs
  • Heart / drug effects
  • Myocardial Infarction / prevention & control*
  • Myocardial Reperfusion
  • Myocardial Reperfusion Injury / prevention & control*
  • Succinates / administration & dosage
  • Succinates / pharmacokinetics
  • Succinates / therapeutic use*
  • Xanthophylls
  • beta Carotene / administration & dosage
  • beta Carotene / analogs & derivatives*
  • beta Carotene / blood
  • beta Carotene / pharmacokinetics
  • beta Carotene / therapeutic use

Substances

  • Cardiotonic Agents
  • Succinates
  • Xanthophylls
  • succinic acid mono-(4-(18-(4-(3-carboxypropionyloxy)-2,6,6-trimethyl-3-oxocyclohex-1-enyl)-3,7,12,16-tetramethyloctadeca-1,3,5,7,9,11,13,15,17-nonaenyl)-3,5,5-trimethyl-2-oxocyclohex-3-enyl) ester
  • beta Carotene
  • astaxanthine