1. The forearm perfusion technique was used to study the effect of intra-arterial injections of ethanol with or without digoxin on the metabolism and electrolyte flux of forearm tissues in normal male volunteers.

2. In six subjects infusion of ethanol alone (2·9 mg/min over 30 min) resulted in no alterations of forearm blood flow, O2 consumption, carbohydrate metabolism, or flux of potassium and calcium. Although there was no change in extraction of [14C]oleic acid, a significant net output of oleic and total free fatty acids was observed from both deep venous and superficial venous systems.

3. In six subjects the intra-arterial infusion of [3H]digoxin (0·09 μg/min with ethanol, 2·9 mg/min over 30 min) resulted in no alteration of forearm blood flow. During the steady state achieved after 5–8 min of perfusion, 50·3% of the calculated local arterial plasma digoxin concentration of 2·73 μg/l was extracted by the deep venous system with a significant increase in glucose extraction. The respiratory quotient and fractional utilization of O2 by glucose increased. No change in extraction of [14C]oleic acid from arterial blood was observed. However, the net output of oleic and total free acids from both deep and superficial venous systems was insignificant in comparison with that observed in the ethanol control subjects. The changes in K+ flux were similar to those noted in the ethanol group. In the post-digoxin period there was a significantly increased uptake of Ca2+ by forearm tissues.

4. This is the first demonstration of the stimulatory effects of digoxin on glucose metabolism, the antilipolytic effects of this drug and its effect on Ca2+ fluxes in vivo in man.

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