Congestive heart failure

Where homeostasis begets dyshomeostasis

Research output: Contribution to journalReview article

28 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)320-328
Number of pages9
JournalJournal of Cardiovascular Pharmacology
Volume56
Issue number3
DOIs
StatePublished - Sep 1 2010

Fingerprint

Homeostasis
Heart Failure
Antioxidants
Secondary Hyperparathyroidism
Bone Resorption
Cardiac Myocytes
Mitochondria
Oxidative Stress
Hypocalcemia
Micronutrients
Standard of Care
Renin-Angiotensin System
Dietary Supplements
Parathyroid Hormone
Organelles
Signs and Symptoms
Oxidation-Reduction
Cicatrix
Reactive Oxygen Species
Necrosis

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Congestive heart failure : Where homeostasis begets dyshomeostasis. / Kamalov, German; Bhattacharya, Syamal; Weber, Karl.

In: Journal of Cardiovascular Pharmacology, Vol. 56, No. 3, 01.09.2010, p. 320-328.

Research output: Contribution to journalReview article

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