A™'ctoberr,  ww"1'}   Cardie  Stimulants  and  Depressants.  455 
but  for  the  fact  that  organs  isolated  from  the  body  and  kept  under 
artificial  conditions  are  .very  susceptible  to  slight  alterations  in  their 
surroundings, — so  much  so,  that  if  four  strips  are  cut  from  the 
same  heart  and  are  kept  under  apparently  identical  conditions, 
they  may  show  great  differences  among  themselves,  and  although 
the  effect  of  the  addition  of  a  given  drug  to  the  solution  might 
easily  be  seen  in  the  alteration  of  the  rhythm,  the  differences 
between  the  reaction  of  different  strips  would  be  greater  than 
that  between  different  specimens  of  the  same  drug.  In  work  of 
this  sort  which  I  have  done,  I  found  that  the  difference  in  the 
effect  of  a  given  quantity  of  a  drug  and  twice  this  amount  was  not 
very  marked,  although  there  was  generally  a  fairly  marked  differ- 
ence between  a  given  amount  and  four  times  as  much.  A  method 
which  gives  results  showing  a  variation  of  50  per  cent,  in  one 
direction  or  the  other  can  of  course  not  be  depended  on  for 
quantitative  standardization. 
The  second  method,  the  effect  on  the  blood-pressure,  has  also 
something  in  its  favor,  inasmuch  as  the  stimulating  effect  of  these 
drugs  on  the  heart  is  in  more  or  less  direct  proportion  to  the 
effect  on  the  blood-pressure.  If  the  effect  of  drugs  on  the  blood- 
pressure  is  studied,  it  will  be  found  that  the  rise  following  an 
injection  is  not  in  proportion  to  the  dose  given.  A  small  dose 
will  cause  a  perceptible  rise,  but  twice  this  dose  will  not  cause  twice 
this  rise.  In  fact,  we  find  that  a  certain  dose  brings  about  almost 
a  maximal  rise  and  that  increasing  the  dose  will  merely  increase 
toxic  phenomena,  so  that  the  pressure  will  fall  more  rapidly  than 
after  the  smaller  dose.  The  effects  of  large  and  small  doses  are 
thus  distinguished  with  difficulty  and  the  same  is,  pari  passu,  true 
of  equal  doses  of  strong  and  weak  preparations.  It  is  evident  from 
these  facts  that  if  we  choose  as  our  standard  dose  the  smallest 
amount  which  will  bring  about  a  maximum  rise,  a  drug  mrr' 
stronger  than  our  standard  will  cause  much  the  same  rise  and 
will,  through  its  toxic  action,  cause  the  pressure  to  fall  sooner  than 
would  a  weaker  preparation,  and  thus  a  strong  preparation  will 
appear  weak  instead  of  strong. 
To  avoid  this  tendency  to  toxic  action  it  will  be  necessary 
to  give  a  dose,  of  the  preparation  to  be  tested,  so  small  that  there 
is  no  danger  of  overstepping  the  bounds  of  normal  physioloei^ 
action,  however  strong  the  specimen  in  hand.  The  use  of  so  sm^ll 
a  dose  betrays  us  unfortunately  from  the  Scylla  of  toxic  action 
