NutriGuard Research, 1051 Hermes Ave., Encinitas, CA 92024, USA.
Med Hypotheses. 2010 Aug;75(2):141-7. doi: 10.1016/j.mehy.2009.12.025. Epub 2010 Jan 18.
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.
大量研究数据表明，氧化应激增加是慢性压力超负荷、功能性心肌组织丧失或心房颤动引发心肌重构的关键驱动因素。氧化应激是心肌细胞肥大和凋亡、心脏纤维化以及这种综合征典型的心脏功能缺陷的介质，并且可能在引发和维持心房颤动中发挥作用。Nox2 和 Nox4 依赖性 NADPH 氧化酶活性似乎是这种氧化应激的主要来源，氧化剂可以诱导黄嘌呤脱氢酶、一氧化氮合酶和线粒体呼吸链构象变化，从而增加它们生成超氧化物的能力。有鉴于此，各种合成抗氧化剂已被证明可抑制心肌梗死、主动脉缩窄或快速心房起搏的啮齿动物的心脏重构。通过使用具有互补天然抗氧化剂的“全谱抗氧化疗法”（FSAT），在人类中实现类似的益处可能是可行的。螺旋藻是藻蓝蛋白的丰富来源，藻蓝蛋白是胆红素的衍生物和同源物，似乎模拟胆红素和游离胆红素对 NADPH 氧化酶活性的强烈抑制作用。大剂量叶酸可显著增加四氢叶酸的细胞内水平，四氢叶酸具有强大且多功能的自由基清除活性，包括有效猝灭过氧亚硝酸盐衍生的自由基。已显示可改善临床充血性心力衰竭患者心脏功能的辅酶 Q10 补充剂可为线粒体提供重要的抗氧化保护。阶段 2 诱导的营养保健品，如硫辛酸，与 N-乙酰半胱氨酸联合使用，通过增加心肌中的谷胱甘肽水平，有可能减轻氧化应激的影响。虽然牛磺酸可以作为髓过氧化物酶衍生自由基的抗氧化剂，但它对衰竭心脏的正性肌力作用似乎更可能反映对细胞内钙动力学的影响。这些措施可以通过降低升高的血压或通过改善冠状动脉内皮功能来辅助缺血性心脏区域的灌注，从而间接地帮助控制心脏建模。由于一氧化氮在生理上起作用以拮抗心肌细胞肥大和心脏纤维化，并且也是血压和内皮功能的关键调节剂，可可黄烷醇 - 可引发内皮释放一氧化氮 - 可能有助于补充这里推荐的抗氧化措施。
