HYPOXIC-INDUCED BOVINE PULMONARY HYPERTENSION 
A. F. Alexander, C. S. Card, R. S. Jaenke, J. L. Hicks and D. H. Will* 
Hypoxic induced pulmonary hypertension has been 
indirectly recognized for years in the bovine species 
through the existence of a syndrome known as High 
Mountain or Brisket Disease, characterized by the de- 
velopment of pulmonary hypertension and resultant 
congestive heart failure. To study the possibility of her- 
itable factors in resistance and susceptibility to hypoxic 
induced pulmonary hypertension, two groups of cattle 
were established based on the degree of pulmonary hy- 
pertension occurring at high altitude and on the pres- 
ence or absence of high mountain disease in their his- 
tory. Offspring of the susceptible parentage have shown 
a consistently greater pulmonary hypertension and vas- 
cular resistance to both acute and chronic hypoxia than 
have the progeny of the resistant group. The reasons 
for the differences in response remain unclear, although 
some evidence implicates a greater degree of airway hy- 
poxia in the more susceptible animals. Ultrastructural 
studies of hypertensive pulmonary arterioles suggest 
changes in the metabolic activity of medial smooth 
muscle cells. 
INTRODUCTION** 
Pulmonary hypertension occurs in man and 
animals in association with many diseases and 
conditions. One etiologic factor of pulmonary 
hypertension is inhalation hypoxia. In the past 
decade hypoxic induced pulmonary hyperten- 
sion has become a well known entity in cattle. It 
had been indirectly recognized in that species 
for years by the existence of a clinical syndrome 
called High Mountain or Brisket Disease.^ 
When exposed to chronic or long term hypoxia 
cattle distinguish themselves from most other 
species by developing more severe levels of pul- 
monary hypertension. Bovine high mountain 
disease, characterized by the development of se- 
vere pulmonary hypertension and resultant 
congestive right heart failure,^ has been recog- 
nized in the mountainous areas of Colorado 
* Departments of Pathology and Physiology-Biophysics College of 
Veterinary Medicine and Biomedical Sciences Colorado State Uni- 
versity, Fort Collins, Colorado 80521. 
•♦ Supported by Grant HE 08759 from the National Heart and 
Lung Institute, National Institutes of Health, Bethesda, Maryland. 
since the end of the 19th century. The first re- 
port pertaining to the disease was by Glover 
and Newsom in 1915.^ The spontaneous disease 
is reported from the Rocky Mountains of North 
America, the Andes Mountains of South Amer- 
ica, and the mountainous elevations of East Af- 
rica. 
The syndrome develops most frequently in 
animals resident in altitudes above approxi- 
mately 7,000 feet. However, uncomplicated 
cases have been recognized at elevations of ap- 
proximately 5,000 feet, and the pulmonary hy- 
pertensive effect of mild chronic hypoxia in 
calves has been confirmed.* The overall inci- 
dence of the disease is estimated to be between 
0.5 to 2% in native cattle residing above 7,000 
feet, with a direct relationship existing between 
resident altitude and incidence. All ages and 
both sexes are aifected. In Colorado and Wyo- 
ming, a higher incidence is seen in animals 
under one year of age, and in animals newly im- 
ported to the high altitudes from low elevations. 
This epidemiological pattern is also observed in 
the Andes and East Africa. In contrast, at alti- 
tudes of approximately 5,000 feet in Montana, 
the incidence is noted to be higher in adult cat- 
tle. In Colorado, there is a definite seasonal var- 
iation in the incidence of the natural disease in 
native cattle, with the occurrence being highest 
in the fall and winter, especially following peri- 
ods of inclement weather. 
Clinical signs in an affected animal are those 
of congestive heart failure and include subcuta- 
neous edema, especially in the ventral, pectoral 
and cervical areas, distention and pulsation of 
the jugular vein, ascites, and frequently a pro- 
fuse fluid diarrhea. The animals tend to show 
labored breathing, and upon forced exertion 
may collapse and die. The removal of affected 
animals to lower elevation results in sponta- 
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