268 
PULMONARY MODELS 
sec min 
Figure 1.— The effects of a 3 mg total dose (TD) of 
glucagon as compared to aminophylline when in- 
jected IV into calves with chronic hypoxic pulmo- 
nary hypertension, n = 5. 
vascular resistance. We found that glucagon 
produced a prolonged reduction of the high pul- 
monary vascular resistance in our calves (Fig- 
ure 1). We have tested other vasodilators in 
this same animal model. 
Since marked pulmonary vasoconstriction oc- 
curs in the bovine calf in response to the stimu- 
lus of airw^ay hypoxia, this high degree of vaso- 
reactivity can be used to test drugs vi^hich are 
potential pulmonary vasoconstrictors. Ami- 
norex (MenociF), which is pharmacologically 
similar to amphetamine, was suspected of hav- 
ing pulmonary hypertensive properties. How- 
ever, when Byrne-Quinn and Grover" tested 
aminorex in the calf, pulmonary vasoconstric- 
tion did not occur. 
REGIONAL DISTRIBUTION OF PULMONARY 
BLOOD FLOW 
Pulmonary hypertension should alter the re- 
gional distribution of lung perfusion. We have 
recently completed one phase of a study of this 
phenomenon using the calf as a model.^ Most 
investigators have implicated gravity as the 
main determinant of the distribution of pul- 
monary blood flow in erect man and animals. 
Theoretically then, the moderate increase in 
pulmonary arterial perfusion pressure which 
occurs in man and animals residing at high alti- 
tude should increase blood flow to the upper 
lung zone, thus improving the uniformity of 
ventilation-perfusion ratios and gas exchange. 
This would then be the adaptive "advantage" of 
pulmonary hypertension at high altitude. In 
this project we have begun to test the hypoth- 
esis that pulmonary hypertension improves gas 
exchange at high altitude. The calf was chosen 
for this study because its size provides rela- 
tively large accessible lung fields and because 
the calf readily develops pulmonary hyperten- 
sion at altitude. Ventilation and perfusion dis- 
tribution were measured using steady state 
breathing and infusion techniques with 133 
Xenon. Probes for detection of gamma emission 
were placed vertically over the upper, middle, 
and lower zones of the right lung with the calf 
in a normal standing position. 
In normal calves studied at sea level, perfu- 
sion per unit of lung volume (Q) was greater at 
the top lung than at the bottom (Figure 2). 
Likewise, ventilation per unit of lung volume 
(V) decreased from the dorsal to the ventral re- 
gions of the lung. However, these regional dif- 
ferences were not matched, with the result that 
regional V/Q decreased dorso-ventrally. The 
gradients are in the opposite direction to those 
observed in normal man, and hence do not re- 
flect the influence of gravity observed in erect 
man. When these calves breathed 100% oxygen 
at sea level, Q increased in the ventral regions 
of the lung, thus reversing the initial gradient 
in lung perfusion. This observation implies that 
in the normal calf, selective pulmonary vasocon- 
striction in the dependent lower zones of the 
lung accounts for the unusual regional distribu- 
tion of Q in this species. Acute hypoxia (15% 
Oo or 8% Oo) did not alter the normal perfu- 
sion gradient (Figure 3) , 
When these calves were exposed to chronic 
hypoxia at 3,400 m altitude for two to four 
weeks, mean pulmonary artery pressure in- 
creased to 2 to 3 times normal. The regional dis- 
tribution of both Q and V became more 
uniform, as did regional V/Q. These effects of 
pulmonary hypertension support our hypothesis. 
After four weeks at high altitude, the acute ad- 
ministration of gas mixtures either high or low 
in oxygen concentration caused little alteration 
