Senescence-related changes in the responsiveness to ouabain of canine Purkinje fibers

K Hewett, Y Vulliemoz and MR Rosen

Clinical studies have suggested that old adults are more susceptible to the toxic effects of digitalis than young adults. To test whether this reflects an age-related change in responsiveness to digitalis of cardiac fibers, standard microelectrode techniques were used to study the effects of ouabain (O) on Purkinje fibers (PF) from 5- and 10-year- old beagles. PF driven at cycle length = 600 msec were superfused with O, 2 x 10(-7) M, containing 3% [3H]O for 25 min. PF-O uptake was the same at both ages. Control maximum diastolic potential, action potential amplitude, upstroke velocity (Vmax) and duration to 50% repolarization (APD50) did not differ significantly between the two age groups. However, the effects of O on action potential characteristics and on delayed after depolarizations in PF from the 10 year old PF were significantly greater than that on the 5 year old PF. Additional experiments were done in which we superfused PF from adult and old animals with O for long periods to determine the time-response relationships for ouabain effects on maximum diastolic potential, action potential amplitude, Vmax and APD50. The rate of change was 2 to 3 times greater in the 10 than the 5 year old PF. After 55 min of O, only 2 of 7 10-year-old PF remained excitable, compared with 6 of 6 5- year-old PF. In conclusion, PF from old dogs show greater responsiveness to the toxic effects of O than those of younger adults, explaining in part the clinical observation of increased digitalis toxicity with age.

Volume 223, Issue 1, pp. 153-156, 10/01/1982
Copyright © 1982 by American Society for Pharmacology and Experimental Therapeutics