ANIMAL RESEARCH IN SHOCK 
R. M. Hardaway, III* 
With exception of clinical observations made during 
World War II and the Korean conflict, essentially all 
shock research prior to 1964 was carried out utilizing 
animals. This was necessitated by the fact that acute, 
severe injuries in civilian practice occur at irregular 
and infrequent intervals not conducive to organized 
study, and because of the resources required merely to 
treat the patient, much less to study him. Beginning in 
1964 several clinical shock study units were organized, 
and considerable research was done utilizing clinical 
patients. Animal studies continued and greater use was 
made of primates. 
Much fundamental work was accomplished utilizing 
dogs, and the bulk of the information on shock has re- 
sulted therefrom. The work encompassed hemodynamic 
effects, hormones, cardiac, respiratory, and blood coagu- 
lation studies, bacterial toxins, hemorrhage, trauma, etc. 
The role of the various treatments including intravenous 
fluids and drugs were explored primarily with animals. 
Great care must be taken in interpolating between 
animals and man, however, and some misleading con- 
clusions were made. Brief summaries are made of 
studies in pathophysiology and treatment of shock in 
animals which resulted in important new concepts in the 
treatment of clinical shock. 
INTRODUCTION 
The first scientific investigations in the field 
of shock v^^ere made in 1890 by Crile ^ utilizing 
animals. Important scientific observations in 
the field of shock in humans were made by U.S. 
Army medical officers in World War I, and 
several hypotheses developed. Following World 
War I, however, research in shock was essen- 
tially confined to work with animals. This was 
primarily the result of the following conditions : 
1. The occurrence of clinical shock in humans 
was relatively uncommon and unpredict- 
able in civilian medical practice. 
2. When clinical shock did occur, the entire 
capabilities and resources of the treat- 
ment center were devoted to treatment 
only, leaving none for research. 
•Brigadier General, Medical Corps Commanding General, William 
Beaumont General Hospital, El Paso, Texas 79920 
3. Clinical research was more difficult than 
laboratory research. Adequate controls 
were nearly impossible, whereas in lab- 
oratory research most variables could be 
controlled. 
4. The cost of animal research was small 
compared with that involved in clinical 
research. Very little money was available 
for any type of research until after World 
War II. 
METHOD 
The animals used in shock research were nu- 
merous. Possibly the most important and com- 
monly used animal was the dog. The dog had a 
number of advantages : it was a relatively large 
animal with a large blood volume and more or 
less human-sized vessels and organs, and its 
anatomy and behavior were amenable to labora- 
tory conditions. A classic hemorrhagic shock 
model, utilizing the dog, was developed by Wig- 
gers,2 which, together with its modifications, 
has become a standard in the field. The dog also 
has been used to study hemodynamic altera- 
tions, concepts of irreversibility, influence of 
steroids, and other aspects of shock. 
Another animal frequently used in shock 
studies was the rat, which had the advantage 
of being inexpensive and available in great 
numbers. The rat was used most commonly in 
studies of traumatic shock, hemorrhagic shock,' 
concepts of host resistance and tolerance, RES 
blockade, microcirculatory changes, and bio- 
chemical shifts in the blood. More recently with 
the development of fine surgical techniques, the 
rat has become particularly adapted for work 
with hemorrhagic shock. 
The rabbit has been used primarily for work 
with endotoxin, generalized Shwartzman reac- 
tion, and other toxins. 
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