Electrolytes in Human Tissue. Iii. A Comparison of Normal Hearts With Hearts Showing Congestive Heart Failure 1

Wilkins, Walter E.; Cullen, Glenn E.

doi:10.1172/jci100557

Cited by 41 publications

(1 citation statement)

References 3 publications

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“…During the 1930s, there was considerable interest in determining whether abnormal K + homeostasis in heart and skeletal muscle was an important underlying factor in chronic disease. K + c and Na + c were measured in hearts from persons deceased due to heart failure, pulmonary disease, or traumatic injuries (Wilkins and Cullen 1933 ; Calhoun et al 1930a ; Harrison et al 1930 ). Cardiac K + c from patients with heart failure was abnormally low, with the authors suggesting that K + loss is one of the predisposing factors to cardiac fatigue and failure (Calhoun et al 1930a ).…”

Section: Early Work On Muscle K + and Na ...mentioning

confidence: 99%

A century of exercise physiology: effects of muscle contraction and exercise on skeletal muscle Na+,K+-ATPase, Na+ and K+ ions, and on plasma K+ concentration—historical developments

McKenna,

Renaud,

Ørtenblad

et al. 2024

Eur J Appl Physiol

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This historical review traces key discoveries regarding K+ and Na+ ions in skeletal muscle at rest and with exercise, including contents and concentrations, Na+,K+-ATPase (NKA) and exercise effects on plasma [K+] in humans. Following initial measures in 1896 of muscle contents in various species, including humans, electrical stimulation of animal muscle showed K+ loss and gains in Na+, Cl− and H20, then subsequently bidirectional muscle K+ and Na+ fluxes. After NKA discovery in 1957, methods were developed to quantify muscle NKA activity via rates of ATP hydrolysis, Na+/K+ radioisotope fluxes, [3H]-ouabain binding and phosphatase activity. Since then, it became clear that NKA plays a central role in Na+/K+ homeostasis and that NKA content and activity are regulated by muscle contractions and numerous hormones. During intense exercise in humans, muscle intracellular [K+] falls by 21 mM (range − 13 to − 39 mM), interstitial [K+] increases to 12–13 mM, and plasma [K+] rises to 6–8 mM, whilst post-exercise plasma [K+] falls rapidly, reflecting increased muscle NKA activity. Contractions were shown to increase NKA activity in proportion to activation frequency in animal intact muscle preparations. In human muscle, [3H]-ouabain-binding content fully quantifies NKA content, whilst the method mainly detects α2 isoforms in rats. Acute or chronic exercise affects human muscle K+, NKA content, activity, isoforms and phospholemman (FXYD1). Numerous hormones, pharmacological and dietary interventions, altered acid–base or redox states, exercise training and physical inactivity modulate plasma [K+] during exercise. Finally, historical research approaches largely excluded female participants and typically used very small sample sizes.

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Section: Early Work On Muscle K + and Na ...mentioning

confidence: 99%

A century of exercise physiology: effects of muscle contraction and exercise on skeletal muscle Na+,K+-ATPase, Na+ and K+ ions, and on plasma K+ concentration—historical developments

McKenna,

Renaud,

Ørtenblad

et al. 2024

Eur J Appl Physiol

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Further Studies on Human Cardiac and Voluntary Muscle

Mangun¹

1941

Arch Intern Med (Chic)

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The Effects of Induced Hypocalcemia on Myocardial Irritability and Conductivity

Kabakow¹

1958

AMA Arch Intern Med

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The role of calcium and potassium in myocardial irritability and contractility has been well studied. More recently the interrelationship between these ions and digitalis has been explored.The concept of synergism between, or additive effect of, calcium and digitalis has been debated for many years.1-4 The use of potassium salts orally and parenterally in the treatment of digitalis intoxication is well established.5,6 It is known, in addition, that low serum calcium levels potentiate the cardiac toxicity of hyperkalemia.7Digitalis is known to cause egress of potassium from the myocardial cell.8 It is this relative intracellular potassium depletion which may, in part, be responsible for the commonly observed electrocardiographic effects of digitalis.9 Calcium ions at the cell membrane exert a stabilizing influence, making more difficult the active reentry of potassium.10 This results in the same net effect. It seemed reasonable to expect that lowering the concentration of calcium ions at the cell membrane might facilitate entry of potassium back into the cell.The following study was undertaken pri¬ marily to ascertain whether the commonly observed electrocardiographic manifesta¬ tions of digitalis, varying from ST and changes to evidence of marked myocardial hyperirritability, could be influenced by an induced transient hypocalcémie state. Materials and MethodsThe chelating agent disodium ethylenediaminetetraacetate (Na· EDTA) was employed in this study to produce a transient hypocalcemia. This agent binds the available systemic calcium which is excreted in the urine as the calcium chelate. The duration and extent of the effective hypocalcemia is a function of the quantity and rapidity of ad¬ ministration of the Na2 EDTA, the route of ad¬ ministration, and the ability of the calcium stores of the subject to replace the chelated calcium.Twenty-six patients received a total of 27 intra¬ venous infusions of 4 gm. of Na2 EDTA in 250 cc.of 5% dextrose and water over a four-hour period. Electrocardiograms were taken prior to the infu¬ sions and after one, two, three, and four hours.In most cases, venous blood was drawn prior to and after the infusion and analyzed for calcium and potassium. The serum calcium was determined by the Kramer-Tisdall method,11 and the potas¬ sium, by the use of the Beckman Model 1400 Flame Photometer.The deviation of the ST segment is expressed in millimeters above or below the T-P segment (isoelectric line), where the latter is at the same horizontal level for two or more successive cycles and where no artifacts are present in the QRST complex. Amplitude of waves is expressed in millimeters measured from the top of the iso¬ electric line to the summit of an upright or from the bottom to the nadir of an inverted T.Twenty patients demonstrated cardiac arrythmias suggestive of altered myocardial excitability. Five patients, three of whom were taking main¬ tenance doses of a digitalis preparation, demon¬ strated marked ST depressions and T-wave inversions. One patient had no evidence of myo¬ card...

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Electrolytes in Human Tissue. Iii. A Comparison of Normal Hearts With Hearts Showing Congestive Heart Failure 1

Cited by 41 publications

References 3 publications

A century of exercise physiology: effects of muscle contraction and exercise on skeletal muscle Na+,K+-ATPase, Na+ and K+ ions, and on plasma K+ concentration—historical developments

A century of exercise physiology: effects of muscle contraction and exercise on skeletal muscle Na+,K+-ATPase, Na+ and K+ ions, and on plasma K+ concentration—historical developments

Further Studies on Human Cardiac and Voluntary Muscle

The Effects of Induced Hypocalcemia on Myocardial Irritability and Conductivity

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