Effects of Mild Chronic Hypoxia on the
Pulmonary Circulation in Calves
with Reactive Pulmonary Hypertension
By John H. K. Vogel, M.D., Dan G. McNamara, M.D.,
Grady Hallmon, M.D., Harvey Rosenberg, M.D.,
Gail Jamieson, B.A., and J. D. McCrady, D.V.M.
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ABSTRACT
The effects of the mild hypoxia at an altitude of 5280 ft on the pulmonary
circulation were examined in normal calves and calves with a preexisting
stimulus to maintain a reactive pulmonary vascular bed. In a serial study,
9 calves born at 5280 ft and 9 calves born at sea level underwent left pulmonary
artery (LPA) ligation; 3 calves born at 5280 ft and 8 calves born at sea
level underwent right pulmonary artery (RPA) ligation within 24 to 48 hours
after birth. Progressive pulmonary hypertension and right ventricular heart
failure developed in all calves operated on at 5280 ft but not in those with
LPA ligation performed at sea level until they were transferred to 5280 ft.
In contrast, in some animals with RPA ligation at sea level, progressive
pulmonary hypertension was noted. The increased pulmonary blood flow
consequent to LPA ligation does not result in progressive pulmonary hypertension at sea level but the addition of the mild hypoxia at 5280 ft appears
to provide additional sufficient stimulus to result in progressive pulmonary
hypertension. However, the slightly higher pulmonary blood flow subsequent
to RPA ligation is capable of producing progressive pulmonary hypertension
at sea level. Correlation was found between these results and human patients
with congenital unilateral absence of a pulmonary artery, indicating that,
in subjects with some stimulus to maintain a reactive pulmonary vascular bed,
the mild hypoxia of 5280 ft may exert a significant effect on the pulmonary
circulation.
ADDITIONAL KEY WORDS
unilateral pulmonary artery ligation
heart failure
altitude
vascular reactivity
• In this paper, using observations in calves
with unilateral pulmonary artery ligation, it
will be shown that the mild hypoxia at 5280
ft (Denver, Colorado), as contrasted to sea
level (Houston, Texas), may significantly
alter the pulmonary circulation.
From the Cardiovascular Laboratory, Division of
Cardiology, Department of Medicine, University of
Colorado Medical Center, Denver, Colorado; Texas
Children's Hospital, Houston, Texas; and Department
of Veterinary Physiology, Texas A & M, College Station, Texas.
This work was supported in part by the American
Heart Association Grant 63G 158, The Idaho Heart
Association, and U.S. Public Health Service Grant
5TI HE-08999-03 from the National Heart Institute
Accepted for publication September 22, 1967.
Circulation Research, Vol. XXI, November
1967
Methods
Left pulmonary artery (LPA) ligation was
performed in 9 calves born at 5280 ft within 24
hr after birth. Six normal calves were followed
from birth, and in 4, a thoracotomy without
pulmonary artery ligation was performed.
Left pulmonary artery ligation was performed
in 9 calves born at sea level within 24 to 48 hr
after birth. Eight normal calves were followed
from birth.
Right pulmonary artery ligation was performed
in 3 1-day-old calves born at 5280 ft, 6 l-day-old
calves born at sea level, and in 2 calves at sea
level at 1 week of age. Surgery was performed
using halothane*-nitrous oxide-oxygen inhalation
anesthesia (1).
"Kindly supplied as Fluthane by Ayerst Laboratories.
661
662
VOGEL, McNAMARA, HALLMAN, ROSENBERG, JAMIESON, McCRADY
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Serial right heart catherterizations were performed percutaneously via an external jugular
vein using either PE 160 tubing or a 6 F smooth
bore catheter (2). Systemic arterial blood and
pressures were obtained by needle puncture of the
descending aorta through the last intercostal
space on the left, using a 6-inch 18 gauge thinwalled needle (3). All studies were performed
without sedation with the animals standing. Pressures were obtained using a P23 db Statham
strain gauge and recorded photographically
(Electronics for Medicine). Mean pressures were
obtained electronically. The zero point was taken
to be at the level of the shoulder. Oxygen contents and capacities of blood samples were obtained by the method of Van Slyke and Neill
(4). Blood pH was determined by the micro
technique of Siggaard-Andersen et al. (5), and
oxygen and carbon dioxide tensions were measured directly by Radiometer microelectrodes at
body temperature.
Six of the 9 calves with left pulmonary artery
ligation performed at 5280 ft remained there
throughout the study. Three calves with left
pulmonary artery ligation were taken to sea
level at varying periods, and 1 of these was subsequently returned to 5280 ft. Of the 6 normal
calves, the 4 with thoracotomy remained at
5280 ft and the other 2 were taken to sea level.
Seven of 9 calves with left pulmonary artery
ligation performed at sea level were taken to
5280 ft at various ages and 2 remained at sea
level. Two normal calves were taken to 5280
ft. Two calves born at sea level whose right
pulmonary artery was ligated were moved from
sea level to 5280 ft.
Results
The results of the calf studies are shown
in Tables 1 and 2 and summarized in Table
3. Data are given from the last study in each
calf. In addition, if the animal was transported to a different altitude, data are listed
just before moving to and shortly after arrival at the new altitude.
NORMAL CALVES
Denver
Two normal calves (no. 1, 2) from 5280
ft were taken to sea level at 63 and 64 days
of age; they continued to have normal pulmonary arterial pressures (25 to 30 mm Hg)
even after 998 days at sea level. The 4 calves
that had a thoracotomy without ligation (no.
3-6) were followed at 5280 ft from 51 to 90
days; they had normal pulmonary arterial
pressures (20 to 29 mm Hg).
Houston
Two normal calves born at sea level and
brought to 5280 ft at 50 days of age had
normal pulmonary arterial pressures (26 to
27 mm Hg) after 202 days (no. 7, 8). Six
normal calves remaining at sea level had retained normal pulmonary arterial pressures
(20 to 32 mm Hg) after 228 to 448 days
(no. 9-14).
CALVES WITH LPA LIGATED
Denver
Five of the 6 calves with left pulmonary
artery ligation that remained at 5280 ft (no.
15-19) died from 56 to 154 days after birth
with progressive pulmonary hypertension
(mean pulmonary arterial pressures from 71
to 130 mm Hg) and right ventricular failure
(mean right atrial pressures from 15 to 35
mm Hg). One calf (no. 20) died at 104 days
of age with septicemia.
Two calves born at 5280 ft, whose LPA
was ligated, were taken to sea level 63 and 66
days after surgery. They (no. 21, 22) are
living and well after 2 yr at sea level with
normal mean pulmonary arterial pressures of
30 mm Hg.
One calf with LPA ligation (no. 23) at
5280 ft that developed severe pulmonary hypertension (mean pulmonary arterial pressure
130 mm Hg) 156 days after surgery was
treated with chronic administration of intravenous acetylcholine and oxygen by mask
(6). This therapy reduced mean pulmonary
arterial pressure to 33 mm Hg. Following
therapy, over a 7-week period, it again developed severe pulmonary hypertension
(mean pressure of 120 mm Hg) and heart
failure; at 224 days of age it was taken to
sea level. One hour after arrival at sea level,
mean pulmonary arterial pressure was 77 mm
Hg; after 16 hr, 38, and after 40 hr, 35 (6).
The pressure remained low, 36 mm Hg, after
888 days at sea level. However, 27 days after
returning to 5280 ft, mean pulmonary arterial
pressure had risen to 90 mm Hg.
Circulation Research, Vol. XXI, November 1967
MILD HYPOXIA AND THE PULMONARY
Houston
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Eight calves that were born at sea level
and then had a LPA ligation were studied
at sea level from 60 to 1414 days following
the ligation (no. 24-31); the mean pulmonary
arterial pressures ranged from 24 to 40 mm
Hg. Five of these were brought to 5280 ft
shortly after surgery, between 50 and 110
days of age (no. 28-32). Three (no. 28, 31,
32) died with severe pulmonary hypertension and heart failure after 43, 80, and 794
days at 5280 ft. The other 2 (no. 29, 30)
had moderate to severe pulmonary hypertension and were hyperreactive to 10% oxygen,
i.e., with 10% oxygen there were excessive
rises in mean pulmonary arterial pressure of
53 and 65 mm Hg, as compared to 21 mm Hg
in normal calves (2).
Two animals (no. 25, 27) were transported
to 5280 ft after prolonged exposures (694
and 1414 days) at sea level. In the calf (no.
27) transported to 5280 ft after 694 days at
sea level, mean pulmonary arterial pressure
rose from 40 mm Hg at sea level to 103 after
141 days at 5280 ft; at this time the animal
was in failure with a right atrial pressure of
31 mm Hg. In the older calf (no. 25), mean
pulmonary arterial pressure rose from 38 mm
Hg after 1414 days at sea level to 56 after 26
days at 5280 ft.
CALVES WITH RPA LIGATED
Denver
All three calves at 5280 ft with the right
pulmonary artery ligated developed severe
pulmonary hypertension (mean pulmonary arterial pressures from 82 to 124 mm Hg) and
heart failure (mean right atrial pressures
from 19 to 26 mm Hg). They died 36 to 60
days after birth (no. 33-35).
Houston
The RPA was ligated within 24 hr in 6
calves (no. 36-41) born at sea level. Two developed pulmonary hypertension and heart failure, and died (no. 37, 38); and 2 developed
severe pulmonary hypertension and died suddenly (no. 36, 39). Two calves (no. 40, 41)
failed to develop pulmonary hypertension after 688 and 752 days at sea level, and were
Circulation Research, Vol. XXI, November 1967
663
CIRCULATION
subsequently transported to 5280 ft. There,
over a 277-day period, no. 41 developed severe
pulmonary hypertension and heart failure.
Calf no. 40 had a mean pulmonary arterial
pressure of 94 mm Hg after only 27 days at
5280 ft and died in failure after 81 days with
a mean pulmonary arterial pressure of 140 mm
Hg. Two calves, born at sea level, whose RPA
was ligated at 1 week of age, retained normal
pulmonary arterial pressures up to 139 days
of age (no. 42, 43).
The ratio of the weight of the free wall
of the right ventricle (RV) to total ventricular
weight (T), RV/T, is shown in Table 1.
As expected, the ratio is considerably higher
in the animals with pulmonary hypertension
than in those with normal pulmonary arterial
pressures.
Discussion
In normal calves (2), steers (7), and man
(8), there is little difference in pulmonary
arterial pressure between sea level and 5280
ft. However, in the animal with some stimulus
to maintain a reactive pulmonary vascular
bed, the mild hypoxia at 5280 ft can have a
significant effect on the pulmonary circulation as compared to sea level. Thus, left pulmonary artery ligation in the newborn calf
at sea level, which resulted in slightly less
than a doubling of blood flow into the right
lung, was an insufficient stimulus to produce
progressive pulmonary hypertension. Although resting pressures were slightly higher
than in normal animals, ranging from 24 to
40 mm Hg as compared to 20 to 32 in normals,
studies lasting more than 3 years at sea level
failed to show progressive pulmonary hypertension. In contrast, significant changes in the
pulmonary circulation were noted in 7 calves
with LPA ligation taken to 5280 ft; 4 of the
calves died in heart failure (no. 27, 28, 31, 32)
and the remaining 3 calves developed moderate to severe pulmonary hypertension (no. 25,
29,30).
In contrast to sea-level calves with the
LPA ligated previous studies (2) as well as
the present series have shown that LPA ligation at 5280 ft frequently results in progres-
664
VOGEL, McNAMARA, HALLMAN, ROSENBERG, JAMIESON, McCRADY
TABLE 1
Denver
Blood
Mean pressures (mm Hg)
Days
Calf
no.
Houston
Heart
failure
RA
PA
Aorta
C0VO2
Sao»
PaOs
faCOa
(ml/100 ml) (% Sat) (mmHg) (mmHg)
pHa
RV/T
Denver Calves—Normal
1
64
2
63
0
224
998
0
224
418
0
0
0
0
0
0
4
1
26
35
25
20
24
30
125
5.80
94.1
75
43
7.392
119
90
3.94
4.80
95.6
91.4
85
64
40
46
7.450
7.381
91.3
91.0
89.0
92.0
64
60
45
43
7.392
7.351
4.06
5.55
93.0
92.6
66
71
51
44
7.390
7.399
26.0*
3.99
5.39
82.2
93.8
95.0
99.0
51
65
54
47
7.390
7.421
25.2*
44
49
62
39
7.351
Denver Calves—Normal (Thoracotomy)
76
51
0
0
5
75
0
6
90
0
3
4
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0
0
0
0
2
4
5
3
20
26
29
28
103
106
110
115
6.02
4.78
25.9*
Houston Calves—Normali
7
8
9
10
11
12
13
14
0
1
202
0
1
202
0
0
0
0
0
0
50
50
0
0
0
0
0
365
228
259
365
396
488
0
0
0
0
0
0
0
4
4
21
27
110
4
4
3
25
26
22
32
27
22
20
26
116
135
160
145
137
151
165
2
7
90.0
95.0
Denver Calves—LPA Ligated
15
16
17
18
19
20
21
98
154
56
70
67
104
60
22
55
23
224
0
0
0
0
0
0
0
224
998
0
224
418
0
2
888
27
0
+
+
+
+
+
0
0
0
0
0
0
0
+
0
0
0
19
35
15
28
15
7
87
113
71
84
108
130
69
31
7.57
42.9
52.5
55.3
52.5
78.8
74
62
7.64
73.7
122
90
6.21
5.84
94.0
93.8
111
118
5.26
5.10
96.4
84.9
94
34
7.480
7.335
135
112
103
183
7.65
5.20
3.65
6.48
89.1
95.6
95.6
89.3
58
90
86
59
40
42
38
35
7.465
7.453
7.460
7.468
85
40
30
7.430
7.455
40.6
36
4
9
2
9
30
27
28
30
122
38
36
90
28.5t
.
Houston Calves—LPA Ligated
24
25
26
27
0
430
0
1414
26
0
0
130
695
0
0
0
0
0
3
37
38
56
24
40
169
131
112
102
188
38.0*
3.98
7.49
95.5
87.0
72
Circulation Research, Vol. XXI, November
1967
MILD HYPOXIA AND THE PULMONARY CIRCULATION
665
TABLE 1 (cont.)
Mean pressures (mm Hg)
Days
Calf
no.
Denver
Houston
5
28
29
30
31
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32
141
0
2
43
0
2
170
0
2
170
0
2
794
0
1
80
Heart
failure
106
106
PA
Aorta
4
31
46
103
40
152
96
6.14
6.38
89.2
80.0
57
20
90
101
5.52
7.45
80.9
89.5
8
112
40
53
52
46
70
48
56
119
10
85
137
4.78
6.31
85.0
85.2
57
53
37
47
45
38
102
128
7.17
5.16
85.3
82.2
55
95
5.53
10.70
5.51
+
0
0
+
0
0
0
0
0
7
0
60
50
Blood
PaOs
PaCCh
(mmHg) (mmHg)
RA
0
110
CavO»
Satt>
(ml/100 m!) (% Sat)
0
0
3
+
55
4
26
+
28
98
0
0
108
pHa
RV/T
51
48
48
41
39
46
33
36
47
46
44
46
46
7.406
7.438
7.442
7.438
7.400
7.470
7.450
7.402
7.449
7.432
7.402
88.1
85.2
53
48
41
30
7.439
7.475
46.0
90.5
82.4
54
57
46
44
7.382
7.291
45.5
79.1
72.0
92.0
42
62
45
31
7.384
7.330
47.9
44.8
53.2
9.89
43.3
43.9
Denver Calves—RPA Ligated
33
34
35
60
57
36
0
0
0
+
+
+
105
124
82
26
19
20
107
84
65
9.09
5.24
9.79
Houston Calves—RPA Ligated
36
37
38
39
40
41
0
0
0
0
0
27
81
0
55
100
95
140
752
688
5
42§
43§
277
0
0
106
139
5
0
+
+
0
0
0
+
0
0
+
7
47
6
39
70
88
62
102
70
35
94
140
35
31
97
84
0
113
132
174
181
128
114
54.2*
54.0
38.0
? *
3.55
6.87
9.02
94.0
97.5
84.0
76
64
56
40
34
48
7.450
7.425
7.350
44.6
4.85
6.28
83.7
86.4
57
52
52
44
7.373
7.380
42.0
28
30
0
RA = right atrial; PA = pulmonary arterial; Cavo2 = arteriovenous oxygen difference, Sao., = arterial oxygen
saturation; Pao2 = arterial oxygen tension; Paco., = arterial carbon dioxide tension; pHa = arterial pH; RV/T =
(right ventricular weight/total ventricular weight) X 100.
•Killed.
tVentricular fibrillation during cardiac catheterization.
tDied suddenly.
§Operation at 1 week of age.
sive pulmonary hypertension. Of 6 animals
remaining at 5280 ft, 6 have died, 5 in heart
failure (no. 15-19). Three calves with the
LPA ligated remained healthy when taken to
sea level with only slight elevations of pulmonary arterial pressure. Studies in 1 of these
calves (no. 23) clearly illustrated the reOrculalion Retearch. Vol. XXI,
November
1967
versibility of his pulmonary hypertension
both with pharmacologic therapy at 5280 ft
and by going to sea level. Moreover, 27 days
after this calf was returned to 5280 ft, after
888 days at sea level, mean pulmonary arterial
pressure had risen to 90 mm Hg from a sealevel value of 36.
666
VOGEL, McNAMARA, HALLMAN, ROSENBERG, JAMIESON, McCRAOY
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A similar series of events has been reported
in a normal 19-yr-old girl in whom there was
a reduction in pulmonary arterial pressure
after moving to sea level from Leadville, Colorado (10,150 ft), followed by a rise in pressure after returning to Leadville after 18
months at sea level (9). Peiialoza and associates have also reported reversibility of
hypoxic pulmonary hypertension in residents
of Morococha, Peru (14,900 ft) after moving
to Lima, Peru (500 ft) (10). Similarly, Kuida
and associates have demonstrated reversibility of hypoxic pulmonary hypertension in
calves with brisket disease upon going to lower altitude (11). In contrast to our studies,
however, they did not observe recurrent hypertension when their animals were returned
to high altitude.
Thus, our results suggest that whereas the
increased pulmonary blood flow consequent
to left pulmonary artery ligation is an insufficient stimulus to result in progressive pulmonary hypertension when performed at sea
level, the addition of the mild hypoxia present
at 5280 ft provides sufficient additional stimulus to result in progressive pulmonary hypertension. Moreover, the pulmonary hypertension is reversible upon going to sea level
and may recur with repeat exposure to
5280 ft.
The degree of hypoxia is illustrated in
Table 2. In normal calves at sea level, mean
arterial oxygen saturation was 94.9% and arterial oxygen tension 85.0 mm Hg as compared to 90.8% and 63.7 mm Hg at 5280 ft.
To evaluate the effects of surgery without ligation, observations were made in 4 Denver
animals following thoracotomy only. In these
animals arterial oxygen saturation and tension were similar to the unoperated normals
being 91.1% and 66.5 mm Hg. However, following LPA ligation arterial oxygen tension
was significantly lower than in normal calves
being 57.5 mm Hg, thus suggesting that
physiologically some of the animals were
higher than 5280 ft in terms of oxygenation.
By contrast, at sea level there was no significant difference in arterial oxygen satura-
tions or tensions between normal calves and
calves with LPA ligation.
In contrast to LPA ligation, the results of
RPA ligation, which more than doubles blood
flow into the left lung, indicate that this
procedure may result in progressive pulmonary hypertension at sea level, even though
Pao2 is significantly higher than at 5280 ft.
These results indicate the importance of the
magnitude of the flow. The calf with a RPA
ligated has been particularly useful as a
model for studying heart failure (unpublished observations).
Of particular interest was that in 2 sealevel calves that underwent RPA ligation at
1 week of age, pulmonary arterial pressure
remained normal. Further studies will be
necessary to determine whether the early responses in these 2 animals are the result of
less reactive pulmonary vascular beds, or a
slight delay in surgery. That the timing plays
an important role is suggested by past studies
which have shown that unilateral pulmonary
Blood Gas Studies
TABLE 2
Arterial O2 saturation Arterial O« tension
(%)
(mm Hg)
Normal Calves
Denver
Denver
(thoracotomy)
Houston
(a) 90.8 ±4.2
±1.1
(b) 91.1 ±1.2
± .6
(c) 94.9 ±3.2
±1.4
(g) 63.7 ± 6.2
±1.7
(h) 66.5 ± 5.7
±1.0
85.0
LPA Ligated
Denver
Houston
(d) 88.7 ±4.1
± .7
(e) 95.8 ± .4
± .2
(i) 57.5 ± 6.1
±1.2
(j) 85.0 ± 9.1
±3.89
RPA Ligated
Denver
Houston
(f) 89.0 ±3.1
±1.1
94.0
(k) 53.6 ± 4.2
±1.5
76.0
Mean values are given ± the standard deviation
followed by ± the standard error of the mean. All
values were obtained from calves listed in Table 1
prior to onset of failure.
Significant differences (P < 0.01) = a:c, a:e, d:e,
g:i, g:k, g:j. Not significant P > . 0 5 = a:b, a:d, a:f,
c:e, i:k.
Circulation Research, Vol. XXI, November 1967
MILD HYPOXIA AND THE PULMONARY CIRCULATION
667
TABLE 3
Outcome
Number
Normal Calves
Denver
Sent to Houston
Stayed in Denver
Houston
Sent to Denver
Stayed in Houston
6
2
4
Normal PAP
Normal PAP
2
6
Normal PAP
Normal PAP
3
6
Near Normal PAP
5 died with CHF
7
2
4 died with CHF
3 have t PAP
Normal to mild t PAP
3
All died with CHF
2
Both died with CHF
2 died with CHF
2 have t PAP
2 have normal PAP
8
LPA Ligated
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Performed in Denver
Sent to Houston
Stayed in Denver
Performed in Houston
Sent to Denver
9
9
Stayed in Houston
RPA Ligated
Performed in Denver
Stayed in Denver
Performed in Houston
Sent to Denver
Stayed in Houston
3
8
6
CHF = congestive heart failure; PAP = mean pulmonary arterial pressure.
artery ligation in adult dogs does not result
in pulmonary hypertension, whereas it does
when performed in the newborn puppy (12,
13). However, marked reactivity of the pulmonary vascular bed has been shown in
adult cows with chronic exposure to hypoxia
(14). Moreover, the results of our study have
shown that 3 years after ligation, pulmonary
arterial pressure still may increase markedly.
Thus, timing of the stimulus in cows may be
less critical than in man or dogs. However,
that individual reactivity is important (even
in calves who basically have hyperreactive
pulmonary vascular beds) is apparent from
the widely varying rates at which pulmonary
hypertension developed at 5280 ft.
An experiment of nature, illustrating the
difference between LPA and RPA ligation at
sea level, exists in human patients with congenital unilateral absence of a pulmonary artery. In a reevaluation of our review (12) of
the above subject, we found that no signifiCirculation Research, Vol. XXI, November
1967
cant pulmonary hypertension was present in
14 subjects with isolated, unilateral absence
of the left pulmonary artery. However, of 18
subjects with isolated absence of the right
pulmonary artery, 5 were dead 4 days to 14
months after birth with evidence of severe
pulmonary hypertension, and 1 of the 13 living subjects had severe pulmonary hypertension. All had resided at or near sea level
at altitudes of 10 to 1080 ft. In contrast, as in
the Denver calves with LPA ligation, in a recent report moderate pulmonary hypertension was noted in 1 subject with isolated absence of the left pulmonary artery who had
resided at Bogota, Columbia (altitude 8660
ft) (15).
Other studies in humans also have suggested that mild hypoxia may significantly
alter the pulmonary circulation in the subject with a reactive pulmonary vascular bed.
Thus, in a comparison of two groups of infants with ventricular septal defects studied
668
VOGEL, McNAMARA, HALLMAN, ROSENBERG, JAMIESON, McCRADY
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in Houston and Denver, we observed that
whereas pulmonary arterial pressures were
similar, pulmonary blood flow was significantly lower at 5280 ft, presumably due to. the
mild hypoxia (15a). Of interest is that this
"hypoxic banding" of the small pulmonary
arteries has greatly reduced the need for surgical banding of the main pulmonary artery for
control of heart failure in infants with ventricular septal defects living at higher altitudes. This may represent a beneficial effect
of mild hypoxia. Moreover, in a recent survey
of patients with chronic obstructive lung disease and cor pulmonale, the mortality rate
was significantly higher in subjects living
above 4000 ft being 74% as compared to 55%
in sea-level subjects (16). In these subjects
the mild hypoxia is obviously detrimental in
contrast to the infant with a ventricular septal
defect. Also, as in calf no. 23, we have observed a significant decrease in pulmonary
arterial pressure at sea level in an infant with
congenital mitral stenosis and a ligated patent
ductus arteriosus 48 hr after leaving 5280 ft
(unpublished observations). Of importance is
that the mild hypoxia and acidemia occurring
during sleep may significantly increase pulmonary arterial pressure in the subject with reactive pulmonary hypertension, sustained by
either chronic hypoxia or intracardiac shunts
(17).
Recently, the effectiveness of a slight increase in alveolar oxygen tension, achieved
by continuous chronic administration of oxygen at low flow rates, in lowering pulmonary
arterial pressure in a subject with chronic
bronchitis was reported (18). Of further interest, in our calves chronic exposure to
hypoxia resulted in a decreased cardiac output as evidenced by widening of the arteriovenous oxygen differences. Similarly, in man
a reduction in cardiac output with exposure
to the chronic hypoxia of high altitude has
been reported (19).
Acknowledgments
The authors are indebted to Drs. Bruce Paton, Jens
Rosenkrantz, Harry Page, Louis Vasquez, Hugh Overy,
and Hank Brammell for help in the performance of
the animal studies in Denver; to Dr. Nick Booth of
Colorado State University at Fort Collins who pro-
vided housing, assistance, and recording equipment
for studying two of the older calves brought from
sea level; and Dr. Archibald Alexander for assistance
with the autopsies of these two animals; to Eva Toyos
and Chris Mueller for blood gas analysis; to Mr.
Daniel Cameron and Mr. Harry Mills, Supervisors of
the animal chamber where the studies were performed; and to M. Leek for typing the manuscript.
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Effects of Mild Chronic Hypoxia on the Pulmonary Circulation in Calves with Reactive
Pulmonary Hypertension
JOHN H. K. VOGEL, DAN G. McNAMARA, GRADY HALLMAN, HARVEY ROSENBERG,
GAIL JAMIESON and J. D. McCRADY
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Circ Res. 1967;21:661-669
doi: 10.1161/01.RES.21.5.661
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