title: Practical prevention of cardiac remodeling and atrial fibrillation with full-spectrum antioxidant therapy and ancillary strategies.
abstract: A wealth of research data points to increased oxidative stress as a key driver of the cardiac remodeling triggered by chronic pressure overload, loss of functional myocardial tissue, or atrial fibrillation. Oxidative stress is a mediator of the cardiomyocyte hypertrophy and apoptosis, the cardiac fibrosis, and the deficits in cardiac function which typify this syndrome, and may play a role in initiating and sustaining atrial fibrillation. Nox2- and Nox4-dependent NADPH oxidase activity appears to be a major source of this oxidative stress, and oxidants can induce conformational changes in xanthine dehydrogenase, nitric oxide synthase, and the mitochondrial respiratory chain which increase their capacity to generate superoxide as well. Consistent with these insights, various synthetic antioxidants have been shown to suppress cardiac remodeling in rodents subjected to myocardial infarction, aortic constriction, or rapid atrial pacing. It may prove feasible to achieve comparable benefits in humans through use of a "full-spectrum antioxidant therapy" (FSAT) that features a complementary array of natural antioxidants. Spirulina is a rich source of phycocyanobilin, a derivative and homolog of biliverdin that appears to mimic the potent inhibitory impact of biliverdin and free bilirubin on NADPH oxidase activity. Mega-doses of folate can markedly increase intracellular levels of tetrahydrofolates which have potent and versatile radical-scavenging activities - including efficient quenching of peroxynitrite-derived radicals Supplemental coenzyme Q10, already shown to improve heart function in clinical congestive failure, can provide important antioxidant protection to mitochondria. Phase 2 inducer nutraceuticals such as lipoic acid, administered in conjunction with N-acetylcysteine, have the potential to blunt the impact of oxidative stress by boosting myocardial levels of glutathione. While taurine can function as an antioxidant for myeloperoxidase-derived radicals, its positive inotropic effect on the failing heart seems more likely to reflect an effect on intracellular calcium dynamics. These measures could aid control of cardiac modeling less directly by lowering elevated blood pressure, or by aiding the perfusion of ischemic cardiac regions through an improvement in coronary endothelial function. Since nitric oxide functions physiologically to oppose cardiomyocyte hypertrophy and cardiac fibrosis, and is also a key regulator of blood pressure and endothelial function, cocoa flavanols - which provoke endothelial release of nitric oxide - might usefully complement the antioxidant measures recommended here.
authors.affiliation: NutriGuard Research, 1051 Hermes Ave., Encinitas, CA 92024, USA. mccarty@pantox.com
authors.forename: Mark F
authors.initials: MF
authors.lastname: McCarty
mesh_terms: D000111:Acetylcysteine / Q000378:metabolism; D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use*; D017209:Apoptosis; D001281:Atrial Fibrillation / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D005355:Fibrosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008928:Mitochondria; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D018384:Oxidative Stress / Q000187:drug effects; D030421:Peroxynitrous Acid / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
chemical_list: D000975:Antioxidants; D013481:Superoxides; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D000111:Acetylcysteine