204  Standardization  of  Digitalis.  {'^■"■^^"^9^1*™' 
Githens  ^  is  firmly  convinced  of  the  superiority,  as  experimental 
animals,  of  guinea-pigs  over  frogs.  The  latter  are  markedly  in- 
fluenced "  by  external  surroundings,  temperature,  amount  of  moist- 
ure present  in  the  cage,  relation  of  time  of  feeding  to  time  of 
injection,  etc.  The  species  of  frog  also  makes  a  difference,  and, 
according  to  many  authors,  the  time  of  year."  The  guinea-pig,  on 
the  contrary,  "  show^s  no  such  variation."  The  use  of  a  standard 
preparation  for  comparison  with  the  preparation  to  be  tested  is 
unsafe,  because  the  standard  is  "  dependent  on  the  keeping  prop- 
erties of  a  stock  galenical,  and  these  are  exceedingly  uncertain  in 
many  drugs." 
Finally,  the  committee  on  pharmacological  assay,  of  the  Philadel- 
phia branch  of  the  American  Pharmaceutical  Association,^'^  advocates 
the  adoption  of  the  guinea-pig  method  as  the  official  method  of 
assay  for  digitahs.  Frogs,  they  state,  vary  according  to  species, 
season  of  year,  and  locality.  "  Guinea-pigs,  on  the  other  hand,  are 
obtainable  in  all  parts  of  the  world  .  .  ,  their  susceptibility  to 
digitalis,  so  far  as  is  knozmi,  does  not  vary  under  ordinary  con- 
ditions. Temperature,  food,  season,  weight,  and  sex  do  not  in- 
fluence their  reaction."  The  members  of  the  committee  are  con- 
vinced that  the  use  of  a  standard  preparation  is  unsafe,  because  this 
standard  may  vary  in  strength  and  cause  error  in  testing  the 
preparation  of  unknown  strength. 
Granting  that  the  guinea-pig  is  a  better  experimental  animal 
than  the  frog,  do  the  methods  present  any  differences  ?  In  speaking 
of  the  frog  methods.  Reed  says :  "  It  is,  after  all,  only  a  toxic 
effect,  and  the  fact  that  the  frog  dies  with  its  heart  in  systole  is 
not  any  more  characteristic  than  the  mammalian  heart  in  diastole. 
In  either  case,  the  animal  dies,  and  the  cause  of  its  death  is  the 
action  of  digitalis  on  the  heart."  Crawford  ^  also  considers  both 
frog  and  guinea-pig  methods  to  rest  upon  the  determination  of  the 
m.  1.  d.  Githens  ^  discusses  the  matter  rather  fully.  "  The 
physiologic  action  of  these  drugs,  on  which  their  therapeutic  value 
depends,  is  mainly  a  stimulation  of  the  heart,  shown  by  more 
forcible  contraction  of  its  walls.  The  drugs  kill  either  by  inducing  a 
state  of  constant  contraction  (death  in  systole)  or  by  overworking 
the  heart  muscle  to  such  an  extent  that  it  gives  way  to  a  more  or 
less  sudden  exhaustion  with  relaxation  (death  in  diastole).  In 
either  case  the  effect  is  primarily  due  to  stimulation  of  the  heart,  and 
thus  varies  in  accord  Avith  the  physiologic  or  therapeutic  activity. 
