MODELS OF CARDIOPULMONARY FUNCTION IN CALVES 
J. A. Will, G. E. BIsgard, A. V. Ruiz' and R. F. Grover" 
The bovine calf develops marked pulmonary hyper- 
tension when chronically exposed to high altitude. This 
chronic hypoxic pulmonary vasoconstriction is readily 
reversible by the administration of oxygen, and there- 
fore, this striking vascular reactivity has been used by 
us as an in vivo animal screening system to test the 
efficacy of pulmonary vasoactive drugs in the presence 
and absence of chronic hypoxia. 
In addition, calves fail to hyperventilate when chron- 
ically exposed to a PaOa of 50 mmHg. While the 
mechanism can not be defined at this time, certain fea- 
tures such as cerebrospinal fluid alkalosis, depressed 
central respiratory center or peripheral chemoreceptor 
activity, or a diminished response to acute hypoxia can 
apparently be ruled out. These differences between 
calves and man provide an interesting model for study 
of the comparative physiology of the regulation of res- 
piration. 
Excision of the carotid bodies in calves results in 
marked hypoventilation, an increase in PaCOa, a de- 
crease in PaOs, the development of pulmonary hyper- 
tension at a moderate altitude and provides a model of 
chronic respiratory acidosis and cor pulmonale without 
the presence of airway disease. 
The large accessible lung surface and the tendency to 
develop pulmonary hypertension make the calf useful 
in the study of regional ventilation and perfusion. Un- 
like man, the lung perfusion of the calf is apparently 
not entirely dependent upon gravity for its distribution 
and is therefore a useful model to study the relationship 
between ventilation and perfusion under a variety of 
conditions. If the differences between calves and man in 
their response to chronic hypoxia are recognized, bo- 
vine calves are useful as models of chronic hypoxic pul- 
monary hypertension, for the screening of vasoactive 
drugs, of hypoventilation and chronic pulmonary aci- 
dosis without airway disease, and for the study of 
mechanisms which relate local pulmonary perfusion to 
ventilation. 
• Department of Veterinary Science, College of Agricultural and 
Life Sciences and the Cardiovascular Research Laboratory of the 
Department of Medicine, Medical School at the University of Wis- 
consin, Madison, Wisconsin. 
** Cardiovascular-Pulmonary Research Laboratory, University of 
Colorado Medical Center, Denver, Colorado. 
INTRODUCTION*** 
While chronic airway hypoxia causes sus- 
tained pulmonary vasoconstriction in many ani- 
mals including goats^ and llamas,^ this re- 
sponse is most marked in the bovine calf. In 
1963, Grover and his associates' reported their 
detailed observations of this phenomenon in 
Hereford steers exposed to chronic atmospheric 
hypoxia at high altitude. They concluded that 
hypoxic pulmonary vasoconstriction is the pri- 
mary cause of the right heart failure syndrome 
occurring in cattle at high altitude and popu- 
larly known as "brisket disease." Studies by 
other investigators have confirmed these 
results.* This pulmonary vasoconstriction is re- 
versible when the hypoxic stimulus is removed 
by oxygen inhalation or moving the animal 
to a lower altitude. Complete reversal of pul- 
monary hypertension may occur in less than 
two days (unpublished observations). 
PULMONARY DRUG TESTING 
This reversible pulmonary vasoconstriction 
makes the calf with hypoxic pulmonary hyper- 
tension a useful model for testing drugs with 
potential pulmonary vasodilator activity. Re- 
cently we took a group of calves from sea level 
to 3,400 m altitude at Climax, Colorado. At this 
altitude, PaO^ was reduced to 50 mmHg. After 
two weeks, these calves had an average mean 
pulmonary artery pressure of 62 mmHg or 2V2 
times normal. The well known pulmonary vaso- 
dilator aminophylline produced transient relief 
of this pulmonary hypertension (Figure 1). 
Next we tested glucagon, since a recent report^ 
indicated that this drug could lower pulmonary 
*** These studies were supported by the College of Agricultural 
and Life Sciences, University of Wisconsin, U.S. Public Health 
Service Grant HE-13154, U.S.P.H.S. Special Fellowship HE 39684 
and McNeil Laboratories, Inc., Fort Washington, Pennsylvania. 
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