208 
Standardisation  of  Digitalis. 
(  Am.  Jour.  Phftrm. 
\       May,  1911. 
vantage  certainly  not  possessed  by  the  guinea  method,  for  Nestor 
has  shown  that  with  rabbits,  digitahs  injected  subcutaneously  often 
becomes  encysted  and  is  not  absorbed.  Focke  is  convinced,  from 
many  control  experiments,  that  the  question  of  absorption  does  not 
influence  the  results  secured  by  the  use  of  his  method,  in  which 
the  end  is  reached  in  from  8^  to  lo  minutes. 
The  statements  that  digitalis  always  kills  mammals  by  its  action 
on  the  heart  is  not  generally  admitted.  Edmunds  and  Hale  ^  say : 
"  On  both  mice  and  guinea-pigs,  however,  the  cause  of  death  in 
probably  every  case  is  not  due  to  an  action  upon  the  heart,  but  upon 
the  medulla.  In  every  animal  we  examined  we  found  the  heart 
beating  after  the  respiration  had  stopped  and  it  continued  to  beat  as 
long  as  artificial  respiration  was  maintained.''  Cushny  ^  also  states : 
"  This  stimulation ,  like  that  of  picrotoxin,  seems  almost  entirely 
limited  to  the  medulla  oblongata  in  many  cases.  .  .  .  These  alterations 
are  much  greater  than  those  caused  by  the  interruption  of  the  circu- 
lation, and  are,  therefore,  independent  of  the  action  on  the  heart 
to  which  they  have  been  erroneously  ascribed.  .  .  .  To^  the  same 
cause  is  to  be  attributed  the  rapid,  deep  respiratory  movements  and 
convulsions  which  are  often  observed  in  the  later  stage  of  poisoning 
and  which  are  evidently  not  due  to  cerebral  anaemia,  as  has  been 
supposed,  for  the  brain  at  this  stage  receives  quite  as  much  or  more 
blood  than  it  normally  does." 
In  a  very  thorough  investigation  carried  out  upon  rabbits, 
Nestor  concludes  that  death  from  digitalis  poisoning  is  always 
due  to  the  action  of  the  drug  upon  the  respiration.  He  shows  that 
when  the  symptoms  of  intoxication  are  of  the  most  distressing  kind, 
the  institution  of  artificial  respiration  causes  them  to  disappear. 
He  shows  that  if  a  rabbit  is  given  a  dose  of  digitalis  of  such  size 
that,  uninterfered  with,  it  always  causes  death,  this  animal  can  be 
saved  by  the  maintenance  of  artificial  respiration  for  several  hours. 
He  shows  that  the  amount  of  digitalis  which  always  kills  the  intact 
animal,  when  added  to  the  liquid  circulating  through  the  perfused 
rabbit's  heart,  never  causes  cessation  of  the  cardiac  contractions. 
Finally,  he  removed  the  hearts  of  rabbits  dead  from  digitalis  poison- 
ing and  saw  them  commence  to  beat  normally  when  perfused  with 
Ringer's  solution.  "  D'une  fagon  absolument  constante  les  coeurs 
reprenient  vie  et  battaient  bien.  Ft  ce  n'est  pas  seulement  le  coeur 
du  lapin  qui  pent  se  comporter  de  la  sorte  apre's  I'intoxication 
digitalique,  mais  nous  avons  repete  les  experiences  avec  le  coeur  du 
cohaye,  du  rat,  et  du  pigeon." 
