198 
PULMONARY MODELS 
tive stimulus is reduced oxygen tension in the 
distal airways or alveoli. Quite logically then, in 
hypoxic environments, variations in ventilation 
might be expected to produce individual differ- 
ences in the pulmonary pressor response. Re- 
sults appear to indicate that differences in ven- 
tilation may account for the different levels of 
pulmonary hypertension seen in the tv^o genetic 
groups. Although we have not carried out venti- 
latory studies in these animals since they have 
not yet been adequately trained for this proce- 
dure, the evidence which indicates that ventila- 
tion is probably different for the two groups is 
the consistently lower arterial PO2 and pH and 
higher arterial PCO2 in the susceptible versus 
the resistant cattle (Figure 7) . 
We have also examined the effects of hypoxia 
on other systems in these animals. One system 
which could be expected to participate in the 
adaptation to hypoxia is blood oxygen trans- 
port. Closely related to this is the erythropoietic 
system. Interest in blood oxygen transport in 
hypoxic environments has increased in recent 
years with the discovery that in man, at least, 
residence high altitude or chronic hypoxia in- 
creases the level of 2,3 diphosphoglycerate 
(DPG) in the erythrocytes and reduces the af- 
finity of hemoglobin for oxygen, i.e., shifts the 
oxyhemoglobin dissociation curve to the 
right."'^^ These same parameters were stud- 
ied in the two genetic groups of cattle. The two 
original female parent groups were the first to 
50 ■ 
40 - 
I 5S(5qnd9mo) q 
1 30 - ^ 
o*^ 5R(5and9ino) 
^20 - 
.5 
r • o opto 5,000' 
^ '0 " Jk ^^ cloMd 15,000 
' 1 1 1 I I I I 
0 10 20 30 40 50 60 70 
Artwiol PO^. mm Hq. 
Figure 7. — Arterial PCO2 and PO2 at 5,000 feet and 
after 2 hours at 15,000 feet in susceptible and resist- 
ant calves. 
be examined for differences in the positions of 
their oxyhemoglobin dissociation curves.^*' This 
was done, however, one year after they had 
been selected at high altitude and moved to the 
lower altitude of 5,000 feet. The results showed 
that the resistant females had a dissociation 
curve significantly more to the right. 
More detailed studies of blood oxygen trans- 
port have been carried out on the five resistant 
and five susceptible third year offspring.^"^ No 
significant differences were found between the 
two groups in the position of their dissociation 
curves or levels of 2,3 DPG either at the labora- 
tory altitude of 5,000 feet or after an 18 day ex- 
posure to a chamber altitude of 15,000 feet. 
However, associated studies showed that the 
DPG levels were significantly higher in cattle 
permanently residing at 10,000 feet as com- 
pared with their counterparts at 1,200 feet, 
even though the oxygen dissociation curve of 
the permanent high altitude residents was sig- 
nificantly more to the left. 
Further indication of a greater hypoxic state 
in the susceptible cattle was found in studies of 
erythropoiesis and hemoglobin. These were con- 
ducted on both the resistant and susceptible 
groups during chronic exposure to natural alti- 
tude of 10,000 feet and during both acute and 
chronic exposure to simulated altitude of 15,000 
feet. Although no significant differences be- 
tween the groups were noted in erythropoietin 
levels, the development of a greater red cell 
mass and longer retention of fetal hemoglobins 
in the susceptible group^^ may indicate a 
greater hypoxic stimulus in these animals. 
The hallmark of the hypoxic stimulus is the 
development of pulmonary hypertension. In pul- 
monary hypertension induced by acute hypoxia 
and possibly in the moderate pulmonary hyper- 
tension of chronic hypoxia, the pulmonary vas- 
cular bed appears to remain labile and rapid re- 
turn to normo-tensive pressures can be induced 
by the administration of oxygen.^ In contrast, 
in the severe level of chronic hypoxic induced 
pulmonary hypertension, the vascular bed ap- 
pears somewhat more fixed and the administra- 
tion of oxygen fails to result in immediate 
return to normotensive levels. The intrisic rea- 
sons for the differences, if any, in these vessels 
remain unknown. 
