202  Standardisation  of  Digitalis.  {^"'Maria^i*'" 
all  convincing.  In  view  of  this  fact,  much  work  has  been  done  in 
the  attempt  to  secure  a  satisfactory  method  of  physiological  assay 
for  the  heart  tonics. 
Changes  in  the  blood  pressure  and  heart  rate  of  a  mammal 
following  the  intravenous  administration  of  digitalis  are,  in  all 
probability,  proportional  to  the  therapeutic  value  of  the  drug.  It 
has  been  shown,  however,  that  this  method  of  testing  is  not  suited 
for  accurate  standardization  of  the  drugs  belonging  to  the  digitalis 
group.  The  same  preparation  injected  into  difierent  animals  will 
cause  different  percentage  increase  in  blood-pressure  and  decrease 
in  heart  rate;  while  if  a  standard  be  injected  with  the  purpose  of 
comparing  its  action  with  that  of  the  preparation  to  be  tested,  this 
standard  will  modify  the  results,  secured  by  the  subsequent  injection 
of  the  drug  of  unknown  strength,  owing  to  the  fact  that  the  digitalis 
bodies  are  very  slowly  destroyed  or  eliminated  by  the  animal 
organism. 
The  perfusion  of  the  isolated  mammalian  heart  also  offers  a 
satisfactory  qualitative  test  for  digitalis,  but  the  technic  is  difficult 
and  Sowton  has  shown  that  the  method  is  not  suited  for  quan- 
titative determinations. 
The  methods  now  commonly  advocated  may  be  divided  into: 
I.  Those  upon  frogs. 
A.  Houghton's  12-hour  method. 
B.  Focke's  method. 
C.  One-hour  method. 
II.  Those  upon  mammals. 
A.  Guinea-pig  method. 
B.  Hatcher's  cat  method. 
To  Houghton  belongs  the  credit  of  first  employing  physiolog- 
ical tests  for  the  commercial  standardization  of  the  heart  tonics. 
The  method  which  he  proposed  in  1898  and  which,  with  slight 
modifications,  is  still  employed,  rests  upon  the  determination  of  the 
minimum  lethal  dose  of  the  drug  for  a  frog,  usually  Rana  pipiens. 
A  series  of  frogs  is  injected,  into  the  anterior  lymph  sac,  with  varying 
doses  of  the  preparation  to  be  tested ;  and  at  the  same  time,  another 
series  of  frogs  from  the  same  lot  is  injected  with  a  standard.  At 
the  end  of  12  hours,  the  animals  are  examined.  If  the  variation  of 
dosage  has  been  sufficiently  great,  certain  of  the  animals  are  alive, 
while  certain  others  are  dead.   A  second  series  is  now  injected  with 
