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

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.