22 
CARDIAC MODELS 
The cat — primarily a favorite of the neuro- 
logical related researchers — was used mostly 
in studies of shock in the nervous system and, 
to some extent, histamine research. 
The mouse was used primarily for work with 
anaphylactic shock and burns. The mouse is 
inexpensive, but its small size makes surgical 
procedures difficult. 
In recent years, primates have come into gen- 
eral use in many types of shock research by 
virtue of their phylogenic relationship to man. 
They have the disadvantages of being fre- 
quently disease-ridden, particularly with tuber- 
culosis; they are apt to be mean and difficult; 
their vessels are friable; and their anatomy is 
relatively small. 
The major problem with animal research in 
shock is that all animals differ in various re- 
spects from man. For instance, the dog has an 
unusually receptive gastrointestinal tract to 
changes in shock, and the rabbit is particularly 
susceptible to bacterial toxins. One of the most 
important, but perhaps least recognized differ- 
ence, is the coagulability differences between 
man and dog. Dog blood clots more easily than 
human blood. This has been the occasion for 
misunderstandings, particularly in the field of 
open heart surgery, as well as in the field of 
shock research. In spite of these differences, 
most of the advances made in study of shock 
have been accomplished on animals — most 
prominently in the dog. 
One of the most interesting and definitive 
studies carried out in dogs involves the dissemi- 
nated intravascular coagulation and its relation- 
ship with shock of various types. With regard 
to hemorrhagic shock, the first observation on 
hypercoagulability and clotting, as contributed 
to by acute hemorrhage, was performed on hu- 
mans by Hewson ^ in the early 18th century. In 
the process of producing severe hemorrhage 
during the therapeutic procedure of blood let- 
ting, he noted that that which was taken away 
last was first coagulated. In other words, hemor- 
rhage produced a hastening of coagulation. 
Definitive studies of this phenomena were 
started at Walter Reed Army Institute of Re- 
search in I960.* The decrease in clotting time of 
the blood after severe hemorrhage was corre- 
lated with the onset of a severe acidosis due to 
lactiacidemia secondary to cellular anoxia. This 
may or may not be due to the inactivation of en- 
dogenous heparin by acidosis (Figure 1). It 
was found that severe hemorrhage reduced the 
clotting time in dogs to a small fraction of the 
normal. It was also found that if the shock thus 
produced by the hemorrhage was prolonged, the 
clotting time would suddenly become indefinitely 
prolonged and the blood become completely in- 
coagulable (Figure 2). It was also shown that 
if the blood became incoagulable the animals 
would die even if all of their blood were im- 
mediately returned. If this phenomena did not 
occur, the dogs would survive. 
These experiments were done using the Wig- 
gers reservoir system, although it was necessary 
to avoid the use of heparin used by Wiggers in 
order to study the coagulation mechanism. The 
blood was kept fluid by means of an ion ab- 
sorbing resin column. Wiggers ^ and many oth- 
ers have shown that dogs invariably die if their 
blood pressure is reduced to approximately 40 
mm of mercury over a period of 1-3 hours. This 
conception has continued down to the present 
time. However, at Walter Reed, experiments in 
1962 6 showed that this phenomena of irreversi- 
bility was not associated in any way with the 
intensity or the duration of the hemorrhagic 
shock period, but in fact was associated with 
the use of the Wiggers reservoir. While in the 
reservoir the blood in some way became toxic 
to a dog in hemorrhagic shock even though it 
was his own blood. Investigations to explain 
this mystery showed that if one substituted a 
polyethylene bag, for the open reservoir, elimi- 
nated all contacts of the extracorporeal blood 
with air, metal, glass, or any substance with 
the exception of the plastic, and avoided the 
flow of blood over the plastic more than one 
time, dogs could survive for periods up to 24 
hours in hemorrhagic shock with 35 mm of mer- 
cury with a very low mortality rate (Figure 3). 
The hypercoagulable circulating blood in the 
animal did not clot in the circulation unless 
clotting was initiated by some other factor. This 
could be by the contact of the blood with a for- 
eign surface, including air, glass, metal, etc. If 
the extracorporeal blood was altered, the hyper- 
coagulable stagnant flow in the animal resulted 
in disseminated intravascular coagulation with 
