Four elderly female patients in sinus rhythm and with mild congestive cardiac failure were treated with digoxin and studied over a 6-month period. There were significant linear correlations between serum digoxin concentrations and several quantitative electrocardiographic (ECG) parameters. T-wave amplitude was the most important ECG variable. ECG changes reverted to baseline values when digoxin was discontinued. These findings suggest that quantitative ECG changes are potentially useful in clinical and research situations involving digitalis glycosides.

No abstract

The influence of age on tissue distribution of digoxin in mice and guinea pigs and uptake by mouse heart slices was investigated. 4 h after a single dose of ³H-digoxin, tissue:plasma ratios were significantly greater in very young animals and declined with increasing age. A similar relationship was apparent for packed red blood cell:plasma concentration ratios in mice. Uptake of ³H-digoxin by heart tissue slices was also higher for 21-day-old mice than 200-day-old mice. These data seem to correlate with the larger volume of distribution of digoxin observed in the young. Tissue digoxin relative to plasma concentration seems higher in the young, although they appear less sensitive to the effects of cardiac glycosides.

We studied platelet alpha-adrenergic receptor concentration and function in 19 subjects with simple obesity participating in a double-blind, controlled clinical trial of diet and anorexiants (phentermine, fenfluramine, or a combination of the two) or placebo. From wk 1 to wk 8, weight loss for the group as a whole was 4.9 +/- 0.7 kg (mean +/- SE). Concomitant with this weight loss, the platelet alpha-adrenergic receptor concentration rose from 85.7 +/- 5.8 to 113 +/- 5.8 fmol/mg protein. This increase moved the values for the obese subjects toward or beyond values in lean controls (100 +/- 10.5 fmol/mg protein). The response in the different treatment groups was similar. The receptor concentration increase was accompanied by a corresponding increase in alpha-adrenergic receptor-mediated platelet aggregation. For individual subjects the extent of weight loss over time generally correlated with percent receptor change. Altered adrenergic sensitivity occurring in obese subjects who are losing weight may have important implications in relation to external (therapeutic or inadvertent) administration of catecholamines.

The influence of age on activity of cardiac Mg²⁺-ATPase and Na⁺, K⁺-ATPase from guinea pigs was studied. Tissue homogenates and Nal-washed membranes were prepared from the heart tissue of 10- to 12-day-old or > 12-month-old male guinea pigs. Tissue homogenates from the young animals had significantly greater enzyme activities than those from the older. Na⁺, K⁺-ATPase activity in young tissue preparations was less inhibited by ouabain than in older tissue preparations. These differences may be related to the observations that young animals and humans are less sensitive to cardiac glycosides than adults.