^"•iugusrr9To: }         Methods  for  Digitalis  Assay.  535 
The  frogs  are  injected  in  the  abdominal  lymph  sac  with  dilutions 
of  the  preparation,  using  such  dilutions  as  to  make  a  total  dose  less 
than  I  Cc.  The  frogs  consistently  dying  with  this  dose  are  ex- 
amined to  observe  the  position  of  the  heart  which  must  be  in  systole, 
the  same  as  by  the  one-hour  method. 
This  has  all  the  merits  of  the  U.  S.  P.  Method  with  the  added 
advantage  that  in  case  of  slow  absorption  the  longer  time  limit 
permits,  in  most  cases,  total  absorption.  A  further  advantage  lies 
in  the  fact  that  the  frogs  are  not  handled  roughly,  as  in  pithing  a:nd 
laying  bare  the  heart,  a  procedure  which  may  tend  to  influence  the 
results  adversely. 
A  third  advantage  is  in  the  certainty  of  the  end-point — death — 
as  against  the  frequent  occurrence  of  a  heart  at  the  end  of  the  one- 
hour  period  not  being  positively  stopped  in  systole. 
Dr.  Edmunds,  of  the  Department  of  Pharmacology  of  the  Uni- 
versity of  Michigan,'  and  Dr.  Worth  Hale,  Assistant  Dean  of  the 
College  of  Medicine  of  Harvard  University,  were  called  to  Wash- 
ington to  carry  out  such  experiments  as  would  determine,  if  possible, 
which  of  the  methods  is  most  practicable  and  reliable  for  the  assay 
of  digitalis.  Their  results  and  conclusions  appear  in  Hygienic 
Laboratory  Bulletin  No.  48.^^ 
Regarding  Focke's  Method,  which  is  used  mostly  in  Germany, 
they  say:  "However  even  with  these  precautions  we  believe  that 
this  method  allows  of  greater  variations  and  inaccuracies  than  any 
other  method  we  employed." 
Attempts  to  apply  a  test  by  which  the  increase  in  blood  pressure 
is  used  as  the  measurable  reaction  led  to  the  following  conclusion: 
"The  blood  pressure  method  upon  cats  and  dogs  commends  itself 
on  account  of  the  close  relation  it  sustains  to  the  use  of  the  drug  in 
clinical  practice.  The  objections  consist  in  the  difficulty  of  pro- 
curing these  animals  at  times,  and  also  the  necessity  of  carrying  out 
repeated  tests  to  confirm  the  results  which  a  study  of  our  tables 
show  will  vary  greatly." 
As  regards  the  M.  L.  D.  and  M.  S.  D.  Frog  Heart  Methods, 
they  found  it  impossible  to  choose  with  any  degree  of  accuracy. 
"Between  these  two  methods  as  far  as  can  be  judged  in  the  light  of 
our  present  knowledge  it  is  largely  a  question  of  personal  preference 
or  convenience." 
Cushny^^  ("Pharmacology  and  Therapeutics")  comparing  the 
action  of  digitalis  on  frogs  and  mammals,    says:    "The  effects 
