n6  Standardisation  of  Digitalis  Bodies.  {AmMar°cUh'iP9i3rm' 
of  a  batch  of  these  animals  to  either  of  the  "  standard  "  drugs,  or 
even  to  both  of  them,  does  not  necessarily  give  any  index  of  their 
reactivity  toward  other  members  of  the  digitalis  series.  It  does  not 
even  suffice  for  the  testing  of  digitalis  itself  to  standardize  the 
frogs  against  digitoxin,  for  it  is  generally  believed  that  digitalis 
owes  its  activity  to  other  glucosides  in  addition  to  its  digitoxin 
content,  and  that  the  relative  amounts  of  the  several  glucosides 
present  is  not  constant,  or  the  same  for  any  two  samples. 
The  necessity  for  the  similar  standardization  of  the  guineapig 
prior  to  each  series  of  assays  has  been  urged  by  Haskell,  but  it  is 
obvious  from  the  enormous  seasonal  variations  found  to  exist  in 
these  animals  that  no  standard  reaction  can  be  obtained,  and  ab- 
sorption plays  a  part  here  as  well  as  in  the  case  of  frogs. 
The  method  of  assay  should  be  one  which  tests  that  action  of  the 
drug  upon  which  its  therapeutic  use  depends.  One  method  does 
this  as  well  as  another,  for  each  depends  upon  the  production  of 
death  through  the  action  of  the  drug  upon  the  heart.  Upon  this 
point  several  have  raised  objections  to  the  so-called  general  toxic 
methods  on  the  cat  and  guineapig.  These  objections  are  not  valid 
for  it  can  be  shown  that  death  by  either  of  these  methods  is  due  to 
paralysis  of  the  heart.  Reed  and  Vanderkleed  and  Githens  and 
Vanderkleed  hold  this  to  be  true  for  the  guineapig  method,  and  the 
action  in  the  cat  method  has  been  shown  to  be  upon  the  heart,  a  point 
confirmed  by  the  observations  of  Eckler  already  cited.  The  tracing 
reproduced  on  page  109  illustrates  the  truth  of  this  statement,  and 
we  have  taken  a  very  large  number  of  such  tracings,  all  of  which 
give  the  same  evidence,  namely,  that  death  is  primarily  due  to  cardiac 
paralysis,  though  in  some  rare  instances  the  heart  becomes  so  weak 
just  prior  to  its  cessation  that  the  circulation  is  insufficient  to 
maintain  a  completely  normal  state  of  the  respiratory  center,  and 
these  animals  show  dyspnea  and  sometimes,  even,  temporary  stop- 
page of  respiration.  A  further  fact  which  shows  that  death  in  the 
cat  is  not  due  to  the  action  of  the  drug  on  the  respiratory  center 
is  that  artificial  respiration  does  not  alter  the  dose  which  is  re- 
quired to  cause  death,  an  observation  frequently  made  by  us  and 
one  which  is  strikingly  shown  by  the  experiments  which  Eckler 
made.  He  found  that  at  most  the  induction  of  artificial  respiration 
permitted  the  injection  of  an  additional  c.c.  of  the  ouabain  solution, 
truly  an  insignificant  amount  (0.01  mg.)  for  a  cat  of  several 
kilos.  It  might  also  be  mentioned  that  drugs  which  act  directly 
and  chiefly  on  the  respiratory  center  to  produce  death  cannot  be 
