Cardioprotection and myocardial salvage by a disodium disuccinate astaxanthin derivative (Cardax).
Cardioprotection in humans by carotenoids has been inferred from observational and epidemiologic studies, however, direct studies of cardioprotection and myocardial salvage by carotenoids are lacking. In the current study, intravenous (I.V.) pre-treatment with a novel carotenoid derivative (disodium disuccinate astaxanthin; Cardax) was evaluated as a myocardial salvage agent in a Sprague-Dawley rat infarct model. Animals were dosed once per day I.V. by tail vein injection for 4 days at one of 3 doses (25, 50, and 75 mg/kg) prior to the infarct study carried out on day 5. The results were compared with control animals treated with saline vehicle. Thirty (30) minutes of occlusion of the left anterior descending (LAD) coronary artery was followed by 2 hours of reperfusion prior to sacrifice, a regimen which resulted in a mean infarct size (IS) as a percent (%) of the area at risk (AAR) of 59 +/- 3%. Area at risk was quantified by Patent blue dye injection, and infarct size (IS) was determined by triphenyltetrazolium chloride (TTC) staining. Cardax at 50 and 75 mg/kg for 4 days resulted in a significant mean reduction in IS/AAR to 35 +/- 3% (41% salvage) and 26 +/- 2% (56% salvage), respectively. Infarct size and myocardial salvage were significantly, and linearly, correlated with plasma levels of non-esterified, free astaxanthin at the end of reperfusion. These results suggest that parenteral Cardax may find utility in those clinical applications where pre-treatment of patients at risk for myocardial infarction is performed.
Gross
Garrett J
GJ
Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Lockwood
Samuel F
SF
D000704:Analysis of Variance; D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D017202:Myocardial Ischemia / Q000473:pathology*; D015425:Myocardial Reperfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013386:Succinates / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000627:therapeutic use*; D013778:Tetrazolium Salts; D024341:Xanthophylls; D019207:beta Carotene / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000627:therapeutic use*
D002316:Cardiotonic Agents; D013386:Succinates; D013778:Tetrazolium Salts; D024341:Xanthophylls; C476770: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; D019207:beta Carotene; C009591:triphenyltetrazolium