Ethacrynic Acid Induced Inotropism

Abstract

Ethacrynic acid (ECA) is frequently administered in the presence of acute pulmonary edema. The major mechanisms of improvement in such patients are thought to be an acute reduction of blood volume stemming from the diuresis induced by the drug and drug-induced vasodilation (1, 2). Until recently there has been little direct exploration of the possibility that ECA might also have a direct cardiac effect (3-6). Our own previous work with N-ethyl maleimide (NEM) (7) and P-chloromercuribenzene sulfonic acid (PCMBS) (8), two classical sulfhydryl group inhibitors demonstrated they had positive inotropic properties. Because of the striking hemodynamic response frequently following the administration of ECA and because the compound is known to act by inhibiting sulfhydryl groups (9), ECA was evaluated for possible positive inotropic properties.Methods. Isolated guinea pig left atria were placed in a tissue bath and isometric tension was measured with a strain gauge transducer (Statham, UC3) and recorded with an oscillographic recording system (Sanborn 35 1). Tyrode's solution containing 4 mM K and either 1.8 mM or 0.9 mM Ca was utilized as the bath medium and was bubbled with a 95% O2 and 5% C02 mixture which maintained the pH at approximately 7.3. The bath temperature was maintained at 37". The muscles were paced at 160 beats/min at a voltage 10% above the threshold, utilizing large platinum field electrodes. The preload (diastolic tension) was set at approximately 300 mg in each experiment.Drug solutions were made up daily.

The Action of N-Ethylmaleimide on the Membrane Currents and Contractile Tension in the Bullfrog Atrium

“…Sulfhydryl blocking reagents have been reported to produce a positive inotropic effect in the cardiac muscles (KLEINFELD and STEIN, 1968;FROM, 1970;FROM and PROBSTFIELD, 1971 ;HALBACH, 1975 of a depression of the sodium-carrying system resulting in a decrease in the inward Na current. SMITH (1958) reported that blockade of the sulfhydryl groups in the lobster and frog nerve resulted in a loss of excitability and in the reduction of the resting potential.…”