Cation interdependency in acute stressor states.

Acute stressor states are inextricably linked to neurohormonal activation which includes the adrenergic nervous system. Consequent elevations in circulating epinephrine and norepinephrine unmask an interdependency that exists between K+, Mg2+ and Ca2+. Catecholamines, for example, regulate the large number of Mg2+-dependent Na/K ATPase pumps present in skeletal muscle. A hyperadrenergic state accounts for a sudden translocation of K+ into muscle and rapid appearance of hypokalemia. In the myocardium, catecholamines promote Mg2+ efflux from cardiomyocytes, whereas intracellular Ca2+ influx and overloading account for the induction of oxidative stress and necrosis of these cells with leakage of their contents, including troponins. Accordingly, acute stressor states can be accompanied by nonischemic elevations in serum troponins, together with the concordant appearance of hypokalemia, hypomagnesemia and ionized hypocalcemia, causing a delay in myocardial repolarization and electrocardiographic QTc prolongation raising the propensity for arrhythmias, including atrial fibrillation and polymorphic ventricular tachycardia. In this review, we focus on the interdependency between K+, Mg2+ and Ca2+ which are clinically relevant to acute stressor states.

Supplemental vitamin D and calcium in the management of African Americans with heart failure having hypovitaminosis D.

INTRODUCTION: A dyshomeostasis of macro- and micronutrients, including vitamin D and oxidative stress, are common pathophysiologic features in patients with congestive heart failure (CHF). In African Americans (AA) with CHF, reductions in plasma 25(OH)D are of moderate-to-marked severity (<20 ng/mL) and may be accompanied by ionized hypocalcemia with compensatory increases in serum parathyroid hormone (PTH). The management of hypovitaminosis D in AA with CHF has not been established. METHODS: Herein, a 14-week regimen: an initial 8 weeks of oral ergocalciferol (50,000 IU once weekly); followed by a 6-week maintenance phase of cholecalciferol (1400 IU daily); and a CaCO3 (1000 mg daily) supplement given throughout was designed and tested. Fourteen AA patients having a dilated (idiopathic) cardiomyopathy with reduced ejection fraction (EF, <35%) were enrolled: all completed the initial 8-week course; and 12 complied with the full 14 weeks. At baseline, 8 and/or 14 weeks, serum 25(OH)D and PTH; serum 8-isoprostane, a biomarker of lipid peroxidation, and echocardiographic EF were monitored. RESULTS: Reduced 25(OH)D at entry (14.4 ± 1.3 ng/mL) was improved (P < 0.05) in all patients at 8 weeks (30.7 ± 3.2 ng/mL) and sustained (P < 0.05) at 14 weeks (30.9 ± 2.8 ng/mL). Serum PTH, abnormally increased in 5 patients at baseline (104.8 ± 8.2 pg/mL), was reduced at 8 and 14 weeks (74.4 ± 18.3 and 73.8 ± 13.0 pg/mL, respectively). Plasma 8-isoprostane at entry (136.1 ± 8.8 pg/mL) was reduced at 14 weeks (117.8 ± 7.8 pg/mL; P < 0.05), whereas baseline EF (24.3 ± 1.7%) was improved (31.3 ± 4.3%; P < 0.05). CONCLUSIONS: Thus, the 14-week course of supplemental vitamin D and CaCO3 led to healthy 25(OH)D levels in AA with heart failure having vitamin D deficiency of moderate-to-marked severity. Albeit a small patient population, the findings suggest that this regimen may attenuate the accompanying secondary hyperparathyroidism and oxidative stress and improve ventricular function.

A dyshomeostasis of electrolytes and trace elements in acute stressor states: impact on the heart.

Acute stressor states are associated with a homeostatic activation of the hypothalamic-pituitary-adrenal axis. A hyperadrenergic state follows and leads to a dyshomeostasis of several intra- and extracellular cations, including K, Mg, and Ca. Prolongation of myocardial repolarization and corrected QT interval (QTc) of the ECG are useful biomarkers of hypokalemia and/or hypomagnesemia and should be monitored to address the adequacy of cation replacement. A dyshomeostasis of several trace elements, including Zn and Se, are also found in critically-ill patients to compromise metalloenzyme-based antioxidant defenses. Collectively, dyshomeostasis of these electrolytes and trace elements have deleterious consequences on the myocardium: atrial and ventricular arrhythmias; induction of oxidative stress with reduced antioxidant defenses; and adverse myocardial remodeling, including cardiomyocytes lost to necrosis and replaced by fibrous tissue. To minimize such consequences during hyperadrenergic states, systematic surveillance of electrolytes and trace elements, together with QTc, are warranted. Plasma K and Mg should be maintained at > or =4.0 mEq/L and > or =2.0 mg/dL, respectively (the 4 and 2 rule).