24 
CARDIAC MODELS 
SILICONE CLOTTING TIME 
CONTROL GROUP 
< X CONTROLLED HYPOTENSION »« » 
BLEED TRANSFUSION 
+ DIED 
O SURVIVED 
Figure 2. — Silicone clotting times of dogs subjected to 
hemorrhagic shock. Bleeding produced a decrease in 
clotting time. Those dogs that later showed a pro- 
longed clotting time (over 35 minutes) died (as noted 
by the crosses) ; those which did not, survived (as 
noted by the circles). Two typical animals are shown 
by the lines. 
These factors were subsequently investigated 
in a series of experiments.'' I'll describe tissue 
trauma and hemolysis first. It was found that 
if a dog was anesthetized and mallet trauma 
applied to one thigh, and the animal then sub- 
jected to an otherwise nonfatal hemorrhagic 
shock, it would survive. However, if 48 hours 
were allowed to elapse between the trauma and 
the hemorrhage the animal would die. This phe- 
nomena was seen to be correlated with the ap- 
pearance of a hemoglobin or hemoglobin-like 
pigment which appeared in the blood stream 
with a peak level of 48 hours, post-trauma 
(Figure 4). It was, therefore, decided to see the 
effect of a minute amount of hemolysis on the 
non-fatal hemorrhagic shock. Accordingly, 20 
cc of the animal's own blood was withdrawn, 
hemolized by freezing, and returned to the ani- 
mal. This produced a level of hemoglobin in the 
blood approximately equal to the trauma 48 
hours after it was applied. Immediately follow- 
ing the administration of the animal's own 
hemolized blood, the dog was subjected to a non- 
fatal hemorrhagic shock. The animal died with 
the coincidental production of an incoagulabil- 
ity. At autopsy, it was found to have suffered 
the typical changes of DIG including focal in- 
farction. In addition to these studies, it was 
found that this fatal DIG could be prevented 
either by pre-treatment with heparin or by 
treating the animal during shock with fibrino- 
lysin, which apparently dissolved the intravas- 
cular clots (Figure 5).'-* 
Studies on the effect of bacterial toxins i° 
showed that all types of toxins produced 
changes typical of DIG. Even a minute dose of 
E. coli indotoxin produced an immediate in- 
coagulapathy of the blood with the immediate 
disappearance of platelets. A fall in fibrinogen 
and other clotting factors increased over a 
period of a few hours and produced death. It 
was found that this phenomena could not be 
prevented with heparin which was somewhat 
surprising, and several studies involving the 
use of heparin were initiated.^^ It was found 
that heparin had no influence on the aggrega- 
tion of platelets, which was the first phenomena 
FIBRINOGEN 
GROUP A-l GROUP fl-2 GROUP 6 GROUP C 
J 300 
H3 
300 
--i^ 
ja7 
^64 
. 436 
42 0 
46. 7 
48 0 
''^^^'^^^''^"^^^^30 0 
il3 
P^oiiJ ser. 
* h^/i ♦ 
300 £96 
Foil 36%Mo.i 
♦ iia!'* 1 1 * 
J47 
264 
Foil 
"53''- 0-/.MO.- 
INITIAL AFTER INITIAL AFTER INITIAL AFTER INITIAL AFTER 
SHOCK SHOCK SHOCK SHOCK 
Figure 3. — Fibrinogens of groups of dogs subjected to 
hemorrhagic shock. Group Al was subjected to hemor- 
rhagic shock by the Wiggers reservoir technique, 
with a blood pressure of 40 for four hours. Fibrinogen 
fell from 313 mgVo to 172 mg%. The corrected fibri- 
nogen levels were calculated using the hematocrit as 
a measure of dilution. This left a significant fibri- 
nogen fall. This utilization of fibrinogen was corre- 
lated with a high mortality rate (96%). Group A2 
was treated similarly but heparinized. This prevented 
mortality and fibrinogen fall. Group B did not use 
the Wiggers reservoir but a plastic bag with preven- 
tion of exposure of blood to air or glass. Note an 
insignificant fall in fibrinogen and a small mortality. 
Group C did not have any blood returned at the end 
of the shock period. Note that fibrinogen did not fall 
significantly and there was no mortality. 
