Myocardial Responses to Chelation

Abstract

The phenomena of displacement and immobilization of calcium ions by chelation is being studied in an increasing number of clinical states. Chelation therapy in hypercalcmmia (Holland et al., 1953;Spencer et al., 1956), calcium deposition in coronary arteries (Meltzer et al., 1960) and peripheral vessels (Clarke et al., 1960) and in skin (Muller et al., 1959), and in the treatment of digitalis toxicity (Cohen et al., 1959) are under scrutiny and therefore careful analysis of the myocardial action of chelating drugs is warranted. In a 28-month study, 125 intravenous infusions of disodium ethylenediaminetetraacetate (disodium edathamil or EDTA) were administered to 58 subjects. Chelation produced four characteristic though occasionally variable responses of ventricular, atrial, and atrio-ventricular (A-V) junctional tissue: (1) suppression of ectopic ventricular beats and ventricular tachycardia, (2) slight slowing of the sino-atrial pacemaker, (3) improvement of A-V nodal conduction in first degree, second degree, and advanced heart block, and (4) increased automaticity of idioventricular pacemakers in complete heart block. Since the slowest effective rate of administration is the safest rate (Spencer et al., 1952), the total quantity of calcium chelated was determined for periods of administration varying from one-half to eleven hours. METHODSThere were 58 subjects, 17 men and 41 women, with a mean age of 65 years. The arrhythmias present were ventricular premature contractions, 18 patients; atrial fibrillation, 11; complete heart block, 7; first-degree heart block, 6; ventricular tachycardia, 4; second degree heart block, 4; advanced heart block, 2; paroxysmal atrial tachycardia with block, 2; atrial flutter, 1; A-V dissociation with a nodal rate above 70, 2; nodal rhythm with ventricular premature contractions and A-V dissociation, 1. Thirty-two patients had a basic sino-atrial pacemaker and 17 were in a state of digitalis intoxication. The disodium EDTA was given in dosages of from 0 5 g. to 4 g. in periods ranging from one-half hour to 11 hours. In three instances 3 g. were administered in 30 minutes but in all other cases the rate of infusion never exceeded 4 g. in 60 minutes. The drug was diluted in either 500 c.c. or 1000 c.c. of 5 per cent glucose in water. The concentration of the drug was maintained below 0 5 per cent unless congestive failure prohibited the use of dilute solutions. Ultrafiltrable serum calciums were determined by the method of Toribara and Terepka (Toribara et al., 1957). Samples deproteinized with trichloracetic acid were used for determining total serum calcium. Ashing with concentrated nitric acid was necessary to obtain complete recovery of chelated calcium.

Effects of Calcium Chelation on Digitalis-Induced Cardiac Arrhythmias

“…It has been possible to reverse the electrocardiographic pattern of digitalis effect (S-T segment and T wave pattern) by EDTA (Page and Real, 1955;Brothers and Kabakow, 1957;Soffer et al, 1961). Our own observations are in agreement with these findings.…”

“…Eliot and Blount (1961) also found EDTA much more reliable in digitalis-induced cardiac arrhythmias than in those of other origin. On the other hand, several reports show that EDTA is equally effective in abolishing ectopic beats not due to digitalis (Cohen et al, 1959;Surawicz et al, 1959;Surawicz, 1960;Soffer et al, 1961;Corday et al, 1962).…”

Ethanol: Modifications of Acute Intoxication by Divalent Cations

“…The finding that verapamil did not have the opposite effect can be rationalized by the fact that this drug has heretofore been used for studies of calcium movement in the heart, and whether or not the drug blocks transmembrane movement centrally is still unknown. Finally, the reduction in ethanol sleeping time by EDTA and EGTA indicates that endogenous calcium is important for the hypnotic effect of this drug, and that the calcium is loosely bound to the membrane or is in the extracellular fluid, since these chelators do not readily cross lipid membranes (21). The finding that lanthanum did not have an effect on sleeping time is surprising, since the drug has been shown to act centrally to enhance the action of morphine (22).…”

Diagnostic de l’intoxication digitalique et son traitement

“…Parmi d'autres thérapeutiques des troubles rythmiques graves de l'intoxication digitalique, les médicaments suivants sont proposés, qui ont chacun des promoteurs convaincus : a) Le Vcrsenate de sodium (Na2EDTA), chélateur du calcium, extrêmement actif, mais auquel on reproche un effet transitoire et des ennuis secondaires prohibitifs à la longue, voire dangereux [135,39,59,62,128,127,22,3]. b) Le Sulfate de magnésie, solution à 20 % : 20 ml i.v.…”