J. A. WILL, G. E. BISGARD, A. V. RUIZ AND R. F. GROVER 
271 
nary artery pressure was mildly but significant- 
ly elevated when these observations were made. 
Therefore, in the absence of hyperventilation 
PaOo is lower and the hypoxic stimulus is 
consequently greater. 
From the data we now have, it is impossible 
to determine the mechanism for the failure of 
calves to hyperventilate at high altitude. We 
have, however, found some clues by the elimina- 
tion of certain possibilities. Cerebrospinal fluid 
(CSF) pH was measured and found to be un- 
changed between the high altitude and post-alti- 
tude studies although other parameters had re- 
turned to sea level control values; therefore 
CSF alkalosis can apparently be excluded as the 
cause of relative hypoventilation. Central res- 
piratory center and peripheral chemoreceptor 
activity were evaluated by the ventilatory re- 
sponse to the intravenous infusion of doxapram 
and cyanide. The responses to these drugs 
at altitude were similar to sea level (Figure 6) 
and not reduced. In addition, the response 
to acute hypoxia is retained at altitude and 
C 1-2d 2w 6w 4w C 1-2d 2w 6w 4w 
SL A A A SL SL A A A SL 
Figure 6. — Ventilatory responses to IV injections of 
KCN and doxapram. 
80 
60 
20 
• — ■ Hereford 
— Holstein 
C 2 4 6 wks 
Figure 7. — The development of pulmonary hyperten- 
sion in two different breeds of calves. The 2, 4, and 6 
week levels at altitude are statistically different from 
the sea level control studies (C) in each case; one 
star P < 0.05, 2 stars P < 0.01, 3 stars P < 0.001. 
PpA is shown in mmHg. 
leads to the speculation that the mechanisms 
involved in the ventilatory responses to acute 
and to chronic hypoxia may be different. 
We have also found that Holstein calves de- 
velop more severe pulmonary hypertension than 
Hereford calves when taken from sea level to 
3,400 m (Figure 7). Preliminary data suggests 
that Holstein calves may be hypoventilating 
more than the Hereford calves at high altitude. 
Chronically hypoxic calves, then, are good mod- 
els to use for the study of pulmonary hyperten- 
sion in the absence of lung disease. The relative 
hypoventilation most certainly contributes to 
the development of pulmonary hypertension at 
high altitude. 
SUMMARY 
1. The bovine calf at high altitude is a good 
model of chronic hypoxic pulmonary hyperten- 
sion that is readily reversible by the adminis- 
tration of oxygen or an appropriate pulmonary 
vasodilating drug. 
2. Calves fail to hyperventilate when chroni- 
cally confronted with a PaOo of 50 mmHg. This 
response is apparently not the result of cere- 
brospinal fluid alkalosis, depressed central res- 
piratory center or peripheral chemoreceptor 
