Enhancement of phrenic nerve activity by digoxin: an effect dependent upon intact ninth and tenth cranial nerves

Digitalis increases phrenic nerve activity and causes hyperventilation. To determine whether this effect on respiration is caused by central drug actions on brainstem respiratory neurons or by peripheral drug actions which increase excitatory afferent drive to central respiratory neurons, digoxin was administered intravenously to cats with or without intact IXth and Xth cranial nerves. Digoxin caused marked increases in phrenic nerve activity in cats with intact afferent cranial nerves, but it had no effect in cats with severed afferent nerves. This suggested that effects of digoxin on respiration depend upon afferent input to respiratory neurons. However, digoxin may have had subliminal effects on central neurons which increased phrenic activity only in the presence of excitatory input. To test this possibility, effects of intravenously administered digoxin were observed on centrally evoked submaximal responses in the phrenic nerve. Subarrhythmic, arrhythmic or lethal doses of digoxin had no effect on excitatory phrenic responses evoked from the pons. Thus, effects of digoxin on phrenic nerve activity appeared to be due primarily to drug actions on peripheral neural sites which had excitatory influences on respiration.