﻿136 
  

  

  Dr. 
  H. 
  H. 
  Dale. 
  

  

  been 
  applied. 
  If 
  the 
  shock 
  is 
  due 
  to 
  changes 
  set 
  up 
  in 
  the 
  blood, 
  the 
  

   optimum 
  conditions 
  should 
  be 
  provided 
  by 
  the 
  simultaneous 
  injection 
  into 
  

   the 
  blood 
  of 
  the 
  two 
  necessary 
  factors. 
  

  

  I 
  would 
  not 
  be 
  understood 
  to 
  deny 
  the 
  possibility 
  that 
  liberation 
  of 
  toxic 
  

   substances 
  may 
  play 
  some 
  part 
  in 
  the 
  anaphylactic 
  shock, 
  or 
  that 
  in 
  some 
  

   species, 
  in 
  which 
  the 
  phenomena 
  have 
  been 
  less 
  completely 
  analysed, 
  it 
  may 
  

   play 
  a 
  larger 
  share 
  in 
  the 
  effect 
  than 
  in 
  the 
  guinea-pig. 
  But 
  I 
  do 
  not 
  think 
  

   that 
  the 
  evidence, 
  in 
  favour 
  of 
  the 
  earlier 
  and 
  simpler 
  view 
  of 
  the 
  nature 
  of 
  

   anaphylaxis 
  in 
  this 
  species, 
  has 
  been 
  in 
  any 
  way 
  weakened 
  by 
  the 
  immense 
  

   amount 
  of 
  industry 
  and 
  ingenuity 
  devoted 
  to 
  the 
  search 
  for 
  an 
  anaphylatoxin. 
  

   In 
  support 
  of 
  the 
  earlier 
  conception, 
  which 
  makes 
  anaphylaxis 
  depend 
  upon 
  a 
  

   location 
  of 
  the 
  antibody 
  in 
  the 
  cells 
  of 
  vital 
  organs, 
  I 
  propose 
  now 
  to 
  put 
  

   before 
  you 
  some 
  evidence 
  of 
  a 
  more 
  direct 
  nature, 
  derived 
  from 
  my 
  own 
  

   experiments. 
  

  

  I 
  may 
  remind 
  you 
  that 
  the 
  most 
  characteristic 
  feature 
  of 
  the 
  anaphylactic 
  

   shock 
  in 
  the 
  guinea-pig 
  is 
  the 
  contraction 
  of 
  the 
  plain 
  muscle 
  surrounding 
  

   the 
  bronchioles, 
  causing 
  asphyxiation. 
  It 
  was 
  early 
  shown 
  by 
  Auer 
  and 
  

   Lewis 
  (loc. 
  cit.) 
  that 
  this 
  was 
  independent 
  of 
  the 
  nerve 
  supply, 
  and 
  due 
  to 
  a 
  

   direct 
  action 
  on 
  the 
  muscle 
  fibres. 
  The 
  only 
  question 
  remaining, 
  therefore, 
  was 
  

   whether 
  the 
  muscle 
  fibres 
  were 
  themselves 
  sensitive 
  to 
  the 
  antigen, 
  or 
  

   whether 
  the 
  antigen 
  acted 
  by 
  causing 
  the 
  production 
  of 
  some 
  toxic 
  

   substance 
  in 
  the 
  blood 
  or 
  in 
  some 
  other 
  organ, 
  which 
  then 
  acted 
  on 
  the 
  

   plain 
  muscle. 
  I 
  found 
  that, 
  if 
  the 
  lungs 
  of 
  the 
  anaphylactic 
  guinea-pig 
  

   were 
  removed 
  from 
  the 
  body 
  and 
  their 
  blood-vessels 
  perfused 
  clear 
  of 
  blood 
  

   by 
  Ringer's 
  saline 
  solution, 
  while 
  the 
  lungs 
  were 
  rhythmically 
  inflated 
  by 
  a 
  

   pump, 
  addition 
  of 
  a 
  trace 
  of 
  the 
  specific 
  antigen 
  to 
  the 
  perfused 
  fluid 
  caused 
  

   an 
  immediate 
  constriction 
  of 
  the 
  bronchioles, 
  so 
  intense 
  that 
  air 
  could 
  not 
  be 
  

   forced 
  past 
  the 
  obstruction. 
  The 
  effect 
  was 
  perfectly 
  specific, 
  and 
  it 
  seemed 
  

   clear 
  that 
  the 
  action 
  of 
  the 
  antigen 
  on 
  the 
  plain 
  muscle 
  of 
  the 
  bronchioles 
  

   was 
  direct, 
  and 
  independent 
  of 
  other 
  organs 
  and 
  of 
  the 
  presence 
  of 
  the 
  

   blood. 
  Other 
  kinds 
  of 
  plain 
  muscle, 
  more 
  convenient 
  for 
  observation 
  when 
  

   isolated 
  from 
  the 
  body, 
  such 
  as 
  a 
  horn 
  of 
  the 
  uterus 
  suspended 
  in 
  Einger's 
  

   solution, 
  gave 
  quite 
  similar 
  results. 
  While 
  my 
  own 
  experiments 
  were 
  in 
  

   progress, 
  Schultz,* 
  of 
  Washington, 
  published 
  experiments 
  demonstrating 
  the 
  

   reaction 
  to 
  the 
  antigen 
  of 
  isolated 
  intestinal 
  plain 
  muscle 
  from 
  anaphylactic 
  

   guinea-pigs. 
  Using 
  the 
  horn 
  of 
  the 
  uterus 
  of 
  a 
  young 
  virgin 
  guinea-pig 
  as 
  

   an 
  easily 
  isolated 
  and 
  reactive 
  sample 
  of 
  plain 
  muscle, 
  I 
  was 
  able 
  to 
  

  

  * 
  ' 
  Journ. 
  Pharmacol, 
  and 
  Exp. 
  Therap.,' 
  vol. 
  1, 
  p. 
  549 
  (1910); 
  vol. 
  2, 
  p. 
  221 
  (1910) 
  ; 
  

   ' 
  Hyg. 
  Lab. 
  Bull.,' 
  No. 
  80, 
  Washington, 
  1912. 
  

  

  