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Congestive heart failure: where homeostasis begets dyshomeostasis.

Abstract：

:Despite today's standard of care, aimed at preventing homeostatic neurohormonal activation, one in every five 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 pathophysiological 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 activation, causing ionized hypocalcemia and hypomagnesemia that lead to secondary hyperparathyroidism with consequent bone resorption and a propensity to atraumatic fractures. Parathyroid hormone 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 permeability transition pore 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, whereas hypovitaminosis D threatens Ca2+ stores needed to prevent secondary hyperparathyroidism. An intrinsically coupled dyshomeostasis of intracellular Ca2+ and Zn2+, representing pro-oxidant and antioxidant, respectively, is integral to regulating the 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 mitochondrial permeability transition pore inhibitor may also prove efficacious in the overall management of CHF.

journal_name

J Cardiovasc Pharmacol

journal_title

Journal of cardiovascular pharmacology

authors

Kamalov G,Bhattacharya SK,Weber KT

doi

10.1097/FJC.0b013e3181ed064f

subject

Has Abstract

pub_date

2010-09-01 00:00:00

pages

320-8

issue

eissn

0160-2446

issn

1533-4023

journal_volume

pub_type

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Congestive heart failure: where homeostasis begets dyshomeostasis.