8  Resistance  of  Guinea  Pigs  to  Poisoning  {^^"J 
Pharm 
1914. 
in  Indianapolis  and  that  determined  in  Philadelphia ;  and  in  January, 
the  enormous  preponderance  of  108  per  cent,  is  shown  by  the  In- 
dianapolis lethal  dose.  Obviously,  it  is  scarcely  to  be  expected  that 
we  should  secure  very  closely  comparable  results  in  assaying  a  galeni- 
cal if  such  divergence  occurs  in  testing  a  "  pure  principle." 
In  endeavoring  to  account  for  this  disagreement,  the  technic  em- 
ployed should  be  closely  scrutinized.  It  is  a  well-recognized  fact 
that  testing  digitalis  upon  frogs  requires  the  closest  attention  to 
details  and  necessitates  the  avoidance  of  any  disturbing  factors  such 
as  large  variations  in  the  weight  of  the  animals  and,  especially,  ex- 
tremes of  temperature.  From  previous  statements  of  those  who 
have  employed  the  guinea  pig  method,  one  is  led  to  infer  that  such 
extreme  caution  is  not  necessary  when  this  method  is  used,  and  the 
results  of  Vanderkleed  and  Pittenger  seem  to  show  that  weight  and 
age  are  factors  of  little  moment. 
In  all  of  my  experiments,  a  solution  of  ouabain,  I  to  10,000  in  25. 
per  cent,  alcohol,  was  used.  Vanderkleed  and  Pittenger  do  not  state 
whether  alcohol  was  present  in  the  solutions  they  employed,  but  its 
absence  would  explain  the  smaller  dose  determined  by  them  as 
compared  to  the  dose  I  found  necessary  in  August,  because  alcohol 
exerts  a  similar  antagonistic  action  toward  the  absorption  of  subcu- 
taneously-administered  ouabain  as  it  does  toward  digitalis  adminis- 
tered in  this  way.  Some  other  explanation,  however,  is  necessary  to 
account  for  the  difference  between  the  minimum  lethal  dose  deter- 
mined in  Indianapolis  in  January  (.00000052  -(-)  and  that  determined 
in  Philadelphia  for  the  same  month  (.00000025).  The  pigs  used  by 
Vanderkleed  and  Pittenger  were  kept  in  fairly  warm  quarters ;  while 
our  animals  were  subjected  to  considerable  variations  in  temperature, 
the  thermometer  occasionally  registering  as  low  as  500  F.  This,  I 
believe,  has  an  important  bearing  on  the  resistance  of  the  guinea  pigs 
and,  together  with  the  influence  of  the  alcohol  used  in  my  experi- 
ments, may  serve  to  explain  the  difference  in  the  lethal  dose  as 
determined  in  the  winter  months. 
Since  this  earlier  report,  the  minimum  lethal  dose  of  ouabain 
in  25  per  cent,  alcohol  has  been  determined  upon  guinea  pigs  in  a 
number  of  different  months  and  a  comparison  is  of  some  interest. 
In  Table  II  such  a  comparison  is  given. 
These  figures  indicate  that  the  temperature  influences  the  powers 
of  resistance.    During  the  extremely  cold  winter  of  1911-12  the 
