332  Notes  on  ''Physiological  Testing"      { AmjJu01^1Sf8arm* 
according  to  species,  sex,  seasons,  whether  summer  or  winter,  and 
also  with  the  temperature  at  which  they  are  kept,  that  I  think  frogs 
unsatisfactory.  Then  again,  large  amounts  of  inorganic  salts  present 
in  the  extracts  would  act  injuriously  on  frogs.  Many  of  the  ob- 
servers forget  the  original  investigations  of  Schmiedeberg,  who 
found  that  only  so-called  Rana  temporaria  showed  the  characteristic 
systolic  stoppage  of  the  heart  from  digitalis  in  a  typical  manner. 
Masi  noted  that  digitalin  arrested  the  frog  heart  in  systole,  while 
digitonine  caused  diastolic  arrest  of  the  heart;  and  further,  that  if 
the  frogs  were  immersed  in  0-75  per  cent,  saline  solution  at  3201, 
digitaline  would  then  cause  diastolic  stoppage,  and  Ziegenbein  has 
found  that  while  small  doses  of  digitoxin  cause  systolic  arrest  of  the 
heart,  often  large  doses  do  not. 
In  one  experiment  performed  in  summer,  Focke  noted  that  the 
ventricle  at  times  stopped  in  diastole  and,  therefore,  urged  that  the 
temperature  of  the  room,  in  which  such  experiments  are  carried  out, 
should  be  within  certain  limits.2 
Dr.  Reed,  of  Philadelphia,  has  made  an  important  advance  by 
using  guinea  pigs,  animals  which  are  more  resistant  to  injury.  He 
apparently  uses  a  dose  of  06  to  1  c.c.  of  the  tincture  per  240  grammes 
of  guinea  pig  as  his  standard. 
While  these  methods  are  all  very  desirable,  the  mere  determining 
of  the  toxicity  of  the  preparation  does  not  to  my  mind  determine 
its  medicinal  value.  For  example,  it  has  been  well  recognized  that 
the  reported  active  principles  readily  decompose  into  digitoxiresin, 
toxiresin,  etc.,  which  are  very  toxic  bodies.  If  we  had  a  slightly 
larger  amount  than  normal  of  decomposition  products,  we  would  have 
an  extremely  high  toxicity,  but  this  would  not  necessarily  mean  a 
high  medicinal  action. 
Sowton3  has  improved  the  method  of  testing  such  preparations 
by  using  the  mammalian  heart.  He  perfuses  rabbit  hearts  isolated 
by  the  Langendorff  method  with  tincture  of  digitalis  I  to  200, 
1  Masi,  G.  B.  Sull  Azione  fisiol.  della  Digitalina.  Riforma  Med.,  Vol.  6, 
pt.  1,  p.  741.  1890.  Data  on  our  American  frogs  can  be  found  in  Mary  Dicker- 
son's  Frog  Book,  while  details  as  to  the  European  species  may  be  seen  in  G. 
A.  Boulenger's  '*  The  Tailless  Batrachians  of  Europe."    Ray  Soc,  1897. 
2  Focke,  C.  Weiteres  z.  physiol.  Priifung  d.  Digitalisblatter.  Arch.  d.  Pharm. 
Vol.  245,  p.  646,  1907. 
3  Sowton,  S.  C.  M.  Some  Experiences  in  the  Testing  of  Tincture  of  Digitalis. 
Brit.  Med.  Journ.,  1908,  Vol.  I,  p.  310. 
