454  Cardiac  Stimulants  and  Depressants,  j 
Am.  Jour.  Phartn, 
October,  1910. 
amount  required  to  produce  certain  effects.  In  the  text-books  on 
therapeutics  we  find  a  distinction  drawn  between  the  effects  of 
"  small  "  and  of  "  large  "  or  "  toxic  "  doses  on  the  various  animals 
used  for  experimental  purposes,  but  very  rarely  do  we  find  any 
exact  statement  as  to  what  amount  of  the  drug  per  gramme  of 
animal  constitutes  such  a  dose. 
For  this  reason  it  has  seemed  interesting  as  well  as  important 
to  determine  the  exact  amount  of  various  drugs  which  was  re- 
quired to  produce  definite  effects  in  laboratory  animals  and  to 
determine  also  which  method  of  testing  was  best  suited  to  each 
drug. 
Commercially  this  study  is  of  importance  on  account  of  the 
desire  of  manufacturers  of  these  drugs  and  their  products  to  put 
on  the  market  preparations  of  definite  physiologic  strength,  from 
drugs  the  chemical  study  of  which  is  not  a  criterion  of  activity. 
My  studies  have  been  largely  limited  to  such  drugs  for  this  reason. 
The  drugs  whose  standardization  I  will  consider  are  apocynum, 
aconite,  convallaria,  digitalis,  gelsemium,  squill,  strophanthus,  and 
veratrum.  These  drugs  fall  into  two  groups :  those  which  raise 
blood-pressure,  the  so-called  digitalis  series,  apocynum,  convallaria, 
digitalis,  squill,  and  strophanthus ;  and  those  which  lower  blood- 
pressure,  aconite,  gelsemium,  and  veratrum. 
We  will  consider,  first,  the  drugs  of  the  digitalis  series.  Three 
methods  are  available  for  the  purpose  of  quantitative  determination 
of  their  activity. 
1.  The  effect  on  the  isolated  heart  of  the  frog  or  turtle. 
2.  The  effect  on  the  blood-pressure. 
3.  The  amount  required  to  cause  death. 
As  the  effect  on  the  heart  is  that  which  makes  these  drugs 
useful  in  practical  medicine,  it  is  often  stated  that  the  best  method 
of  testing  them  is  directly  on  the  heart.  The  effect  on  this  organ 
can  be  studied  to  the  exclusion  of  all  other  factors  by  the  following 
method :  The  heart  of  a  frog  or  turtle  will  continue  to  beat,  if  it  is 
placed  in  a  solution  of  proper  salts,  after  its  removal  from  the 
body.  If  the  heart  is  cut  into  longitudinal  strips,  each  of  these 
will  continue  to  beat  under  proper  conditions,  and  may  live  for 
two  or  even  three  days  after  removal  from  the  body.  It  would 
seem  that  by  adding  the  drug  to  be  tested  to  the  liquid  in  which 
the  strips  are  suspended,  the  effect  of  this  on  the  heart  itself 
might  be  determined  with  great  accuracy.    This  would  be  true 
