Congestive heart failure: where homeostasis begets dyshomeostasis.
Congestive heart failure: where homeostasis begets dyshomeostasis.
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DOI：
10.1097/fjc.0b013e3181ed064f
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发表时间：
2010-09
影响因子：
3
通讯作者：
Weber KT
中科院分区：
文献类型：
--
作者：
Kamalov G;Bhattacharya SK;Weber KT
尽管目前的护理标准旨在控制体内平衡的神经激素激活，但最近因充血性心力衰竭（CHF）住院的每5名患者中就有1名将在出院后30天内因其症状和体征复发而再次入院。鉴于最近的病理生理学的见解，现在是有利的，重新审视CHF的互补和不断发展的管理策略。CHF是一种进行性全身性疾病。其特点包括：不同组织中的氧化应激;循环促炎细胞因子的免疫刺激状态;软组织的消耗;以及骨的吸收。它的起源是植根于稳态机制出了差错，产生失调。例如，Ca 2+和Mg 2+的显著排泄损失伴随着肾素-血管紧张素-醛固酮系统（RAAS）激活，引起离子化低钙血症和低镁血症，导致继发性甲状旁腺功能亢进（SHPT），随之发生骨吸收和非创伤性骨折的倾向。甲状旁腺激素（PTH）占矛盾的细胞内Ca 2+超载在不同的组织和随之而来的全身诱导氧化应激。在心肌细胞和线粒体中，这些事件协调了线粒体膜通透性转换孔（mPTP）的打开，随后这些细胞器的基于细胞毒性的破坏，并导致心肌细胞坏死和心肌瘢痕形成。与Ca 2+和Mg 2+稳态异常同时发生的是低锌血症和低硒血症，这会损害基于金属酶的抗氧化防御，而维生素D缺乏症则会威胁预防SHPT所需的Ca 2+储存。细胞内Ca 2+和Zn 2+（分别代表促氧化剂和抗氧化剂）的内在偶联稳态失调是调节线粒体氧化还原状态不可或缺的;它可以通过Zn 2+补充剂解偶联，有利于抗氧化防御。因此，应考虑补充使用营养品，以消除涉及宏量和微量营养素的平衡失调反应。不断发展的策略，包括干扰其Ca 2+摄取或作为选择性抗氧化剂或mPTP抑制剂的靶向干预措施，也可能在CHF的整体管理中有效。
Despite today’s standard of care, aimed at containing homeostatic neurohormonal activation, 1 in every 5 patients recently hospitalized with congestive heart failure (CHF) will be readmitted within 30 days of discharge because of a recurrence of their symptoms and signs. In light of recent pathophysiologic insights, it is now propitious to revisit CHF with a view toward complementary and evolving management strategies. CHF is a progressive systemic illness. Its features include: oxidative stress in diverse tissues; an immunostimulatory state with circulating proinflammatory cytokines; a wasting of soft tissues; and a resorption of bone. Its origins are rooted in homeostatic mechanisms gone awry to beget dyshomeostasis. For example, marked excretory losses of Ca2+ and Mg2+ accompany renin-angiotensin-aldosterone system (RAAS) activation, causing ionized hypocalcemia and hypomagnesemia that lead to secondary hyperparathyroidism (SHPT) with consequent bone resorption and a propensity to atraumatic fractures. Parathyroid hormone (PTH) accounts for paradoxical intracellular Ca2+ overloading in diverse tissues and consequent systemic induction of oxidative stress. In cardiac myocytes and mitochondria these events orchestrate opening of the mitochondrial membrane permeability transition pore (mPTP) with an ensuing osmotic-based destruction of these organelles and resultant cardiomyocyte necrosis with myocardial scarring. Contemporaneous with Ca2+ and Mg2+ dyshomeostasis is hypozincemia and hyposelenemia, which compromise metalloenzyme-based antioxidant defenses while hypovitaminosis D threatens Ca2+ stores needed to prevent SHPT. An intrinsically coupled dyshomeostasis of intracellular Ca2+ and Zn2+, representing prooxidant and antioxidant, respectively, is integral to regulating mitochondrial redox state; it can be uncoupled by a Zn2+ supplement in favor of antioxidant defenses. Hence, the complementary use of nutriceuticals to nullify dyshomeostatic responses involving macro- and micronutrients should be considered. Evolving strategies with mitochondria-targeted interventions interfering with their uptake of Ca2+ or serving as selective antioxidant or mPTP inhibitor may also prove efficacious in the overall management of CHF.