systolic time intervals
Springer Online Journal Archives 1860-2000
Chemistry and Pharmacology
Summary An inter-individual, randomized, double-blind study of digitoxin (Dt) and β-acetyl digoxin (D) was performed in 120 healthy male volunteers. Groups of 10 persons each received orally D 0, 0.1, 0.2, 0.3, 0.4, 0.5 or 0.6 mg and Dt 0.04, 0.08, 0.12, or 0.16 mg daily for 7 days; Loading doses were given for the first three days. Plasma levels were measured with an86Rb-erythrocyte assay 24 h after the last dose. ECG, carotid artery pulse and phonocardiogram were recorded prior to (b) and 24 h after (a) the last dose. QTc, amplitude of T-waves in V2 to V6, electromechanical systole (QS2c) and left ventricular ejection time (LVETc) were measured. The differences between a and b (Δ-values) reflect glycoside-induced changes in heart function. The plasma glycoside concentrations depended on dose and ranged from 0 to 2.4 ng/ml for D and from 0 to 42 ng/ml for Dt. QTc, QS2c, and LVETc were significantly shortened by the glycosides and typical parallel, sigmoid, log dose-response curves were obtained for the Δ-values. Dt was 3.8-times as potent as D in diminishing these parameters. The maximal effect of the two glycosides was almost identical at the highest doses: Δ-QTc=−45 ms, Δ-QS2c=−25 ms, Δ-LVETc=−12.5 ms. The latter two parameters showed a plateau of maximum efficacy. Both glycosides caused significant flattening of T-waves, Dt being 7.2-times as potent as D. Significant relationships between plasma concentration and cardiac effects were observed (p〈0.001)−Δ-QTc (D: r=0.7; Dt: r=0.77), Δ-QS2c (D: r=0.7; Dt: r=0.75), and Δ-LVETc (D: r=0.46; Dt: r=0.43); D correlated less well than Dt with the flattening of T (r=0.46; r=0.76, respectively). The most important conclusions were that: Dt was about 4-times as potent as D in influencing cardiac performance; the effects of D and Dt on systolic time intervals reached a plateau at “therapeutic” doses; Dt induced more pronounced flattening of the T-wave than D; and plasma glycoside levels within the “therapeutic” range corresponded to observed effects on the heart.
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