Pulmonary hypertension in healthy men born and living at high altitudes

Pulmonary Hypertension in Healthy Men Born and Living at High Altitudes DANTE

PE~ALOZA,

RAIL

FRANCISCO SIME, M.D., NATALIO

M.D., F.A.c.c.,

GAMBOA,

JULIO CRUZ,

M.D.,

Lima,

T

HE MAN high

logic

born

changes

to

hy-poxia,

at

exercise.

This

him

and a

on

of

chronic

performing

heavy

acclimatization

is

hypervolemia

pulmonary

the

mechanisms and

function

and

MATERIAL Right

ac-

as

changes

in

enzymatic

ac-

tivity.1-7 Anatomic described tion

and physiologic in the heart

of the

lation

high

between

tion

is

not

yet

studies

have

trophy

and

muscular the

well

resident,

the

diographic

evidence

at high

altitudes.“-l3 has

altitude

dweller.r4

Few been

been

cardiac hand,

In

obtained

living

oxygen

at

at resting and

The

in

conditions

output

acetylcholine

will

more

studies

large

are com-

on the

group The

are

effected

the

pulmonary yet, and the

altitudes.

changes

have

On

of

made a

high

studies

to obtain

we have high

the

of

results

reported

in

by exercise, be

presented

in future papers. From the Cardiovascular Biological Sciences, Lima, RG-8576.

38 healthy

men

were

in villages

born

AND METHODS

catheterization aged

was

performed

17 to 34 years. over

12,000

in

All of them feet

above

sea

from the pulmonary artery, right ventricle and right auricle were then recorded with the zero reference level at the midchest point in the anteroposterior Pulmonary wedge pressure was used as diameter. Brachial arterial an index of left atria1 pressure.t701* pressure was also registered. The measurement of pressures was done using a Statham gauge P23Db and a Twin-Viso Sanborn, Model 60-1300. Mean pressure was obtained by electrical integration. Exjx’red air and arterial and uenous blood samples were obtained simultaneously. The collection of expired air was made in a Tissot calibrated spirometer and its gas content determined in a Haldane-Henderson gas analyzer. The mixed venous blood sample was withdrawn from the pulmonary artery and the arterial blood sample from the brachial artery by arterial cannulation. The analysis of blood gases was performed in a Van Slyke and Neil1 manometric apparatus.

hyper-

in

cardiac

circulation

this article.

pulmonary

mechanism

order

hyper-

and living

altitudes.

concerning

information,

adults

born

has not been clarified

contradictory. plete

high

vectorcar-

ventricular

observed

a

vascula-

and

Mild

at

data

pulmonary

resembling

catheterization the

hypertension previous

lumen

in man

also

performed

other

with

of right

tension

hyper-

arterioles pulmonary

Electrocardiographic

has been found

re-

Anatomic

ventricular

ture.8-10 trophy

the

understood. right

of

but

acclimatiza-

a narrow

pattern

been

circula-

and

pulmonary and

have

pulmonary

changes

shown

wall

fetal

altitude these

changes

and

heart

level and had lived the last eight years in places located over 14,000 feet. These subjects were studied at Morococha at an altitude of 14,900 feet (4,540 meters) with a mean barometric pressure of 446 mm. Hg and an atmospheric ~02 of 80 mm. Hg. A similar investigation was performed in 25 healthy men 17 to 23 years of age who were born and lived permanently in towns near sea level. They were studied in Lima at an altitude of 500 feet (150 meters) with a mean barometric pressure of 753 mm. Hg and an atmospheric ~02 OI 148 mm. Hg. Before a physical examination cardiac catheterization was performed; roentgenograms of the chest, and hematological, electrocardiographic and vectorcardiographic data were obtained. Right heart catheteritatiorPv” was performed in the supine position. The subjects were in the postPressures absorptive state and without medication.

result

such

M.D.,

M.D.

Peru

at

physio-

natural

environment

and

adaptive

polycythemia, the

permanently-

anatomic

allow

an

rest

several

living

shows

that

climatization

of

and

altitudes

BANCHERO,

M.D. and EMILIO MARTICORENA,

Laboratory of the High Altitudes Research Institute, Peruvian University of Medical and This investigation was supported by U. S. Public Health Service research grant Per6

150

THE AMERICAN JOURNAL OF CARDIOLOGY

Pulmonary

Hypertension

This procedure supplied the samples necessary for the calculation of oxygen uptake, arteriovenous oxygen difference, and cardiac output by application of the Fick principle. Cardiac index, pulmonary total resistance, pulmonary vascular resistance, total systemic resistance and the work of both ventricles were also calculated. The data were statistically analyzed, and Fisher’s t-test was used in order to estimate the significance of the differences between the mean values obtained at high altitudes and those at sea level; p values were obtained from t tables, and the 2 per cent level of confidence was accepted as significant.lg RESULTS

The data obtained from subjects studied at high altitudes and at sea level are shown in Table I. The comparative analysis between these two groups appears in Table II. CLINICAL

STUDY

In contrast to sea level inhabitants, the man living in high altitudes exhibited a reddish skin, broad thorax and lesser height and body surface area, all anthropologic features peculiar The roentgen examination to these people.20 of the chest frequently revealed slight enlargement of the right ventricle and pulmonary artery, and slight accentuation of the pulmonary vascular markings, particularly in the hilar regions. Heart rate did not show significant differences between the two groups studied. The electrocardiogram and vectorcardiogram showed in natives of high altitudes the signs of right ventricular preponderance previously described.12J3 The mean value of arterial hemoglobin oxygen saturation was 78.4 f 0.78 per cent at high altitudes, in contrast to 95.7 f 0.44 per cent obtained at sea level (p < 0.001). At high altitudes the mean values of hemoglobin and the hematocrit were 19.5 f 0.31 gm.% and 59.1 f 1.18 per cent, respectively, compared to 14.7 f 0.18 gm.($ (p < 0.001) and 44.1 f 0.55 per cent (p < 0.001) obtained at sea level.

in Men at High Altitudes

151

mm. Hg for inhabitants at sea level. Right ventricular systolic, diastolic I, diastolic II and mean pressures averaged 42 f 1.8, - 3.5 i 0.31, 3.6 f 0.34, and 18 f 0.7 mm. Hg at high altitudes compared with 26 f 0.6, - 1.6 f 0.14, 3.4 f 0.25, and 9 f 0.3 mm. Hg, obtained at sea level. Significant differences were found between mean values of systolic and mean pressures (p < 0.001). Right atria1 mean pressure and pulmonary wedge mean pressure averaged 2.6 f 0.27 and 5.4 i 0.32 mm. Hg at high altitudes, and 2.6 f 0.26 and 6.2 f 0.34 mm. Hg at sea level. Differences between mean pressures were not statistically significant. Some of the pressure tracings from the right ventricle showed the anacrotic shape described by Shanahan et a1.21 in cases with pulmonary arteriolar hypertension. Cardiac index mean values were 3.71 f 0.272 and 3.97 f 0.218 L./min./M2. at high altitude and at sea level, respectively. The difference between the mean values was not statistically significant. Total and vascular pulmonary mean resistances were 401 f 38.1 and 332 f 35.9 dynes sec. cm.-5 in high altitude natives compared with 159 f 10.4 and 69 f 5.7 dynes sec. cm.-5 obtained at sea level. Differences between mean values were highly significant (p < 0.001). Right ventricular work mean value was 1.49 f 0.117 and 0.55 f 0.050 kg.M./min./M2. at high altitude and at sea level, respectively. Thedifference between mean values was statistically significant (p < 0.001). The systemic arterial mean pressures were 118 f 1.4 systolic, 73 f 1.2 diastolic with a mean of 95 f 1.2 mm. Hg for residents in high altitudes as compared with 127 f 1.7, 70 f 1.3 and 94 f 1.6 mm. Hg obtained at sea level. Difference between systolic mean pressures was statistically significant (p < 0.001). Total systemic resistance and left ventricular work showed similar values at sea level and at high altitudes. DISCUSSION

HEMODYNAMIC

STUDY

Mean values for systolic, diastolic and mean pressures in the pulmonary artery were 41 f 2.1, 15 f 1.2 and 28 f 1.7 mm. Hg in those living in high altitudes and 22 f 0.7,6 f 0.5 and 12 f 0.4 mm. Hg in those at sea level. The difference between the mean values was highly signifiExtreme values of systolic cant (p < 0.001). pulmonary pressures were 21 and 72 mm. Hg for natives in high altitudes, and 16 and 29 FEBRUARY 1963

lnfuence of Hypoxia on the Heart and Pulmonary Circulation: Previous studies performed in this field dealt generally with the effects of acute that hypoxia.22-30 There is general agreement induced acute hypoxia produces in animals as well as in man increases in the pulmonary arterial pressure, heart rate and cardiac output. Thi: rise in pulmonary pressure would result in an increase in pulmonary vascular which in turn would be related resistance,

TABLE

I

Physiologic Data Blood Age

Heart

(yr.1

Rate

B.S.A.

B’ood Hb.

Hct.

CM*.)

(%I

R.A.

(%)

‘F’(I

Right

Mean

-

18 21 25 23 22 27 26 18 18 22 23 25 27 21 33 28 18 34 20 22 19 20 22 18 24 23 23 19 21 21 23 20 20 19 20 20 18 24

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 ia 19 20 21 22 23 24 25

26 27 28 29 30 31 32 33 34 35 36 37 38

22 0.6 3.5

Meall zt S.E. zt SD.

-

--

75 68 60 75 1 00 62 65 83 85 53 83 75 88 80 60 71 68 79 70 88 88 75 71 53 74 62 72 76 70 57 55 60 48 52 57 53 50 75 69 19 11.8

64 0 53 2 54 4 57 6 63 7 63.2 77.4 59.8 70 7 56 0 64.0 54 4 55 9 50.3 58 1 57 8 48 8 58 4 52 9 57 1 54.0 so 0 56.4 50 8 68.3 58 8 52 0 56 4 54 3 56.7 64.7

80.5 a3 5 a0 2 66.0 72 2 84 0 87 0 82.6 73.3 80 4 81.9 79 1 81 3 74 0 71 8 70.2 80.8 75 3 73.4 83.1 76.5 75.6 80.6 81 2 a3 74.3 79.0 83 2 80 6 80 1 87 9 77.0 72 0 78.8 72.9 75.1 79.5 80.5

59.1 1 18 7 20

19 5 0 31 I 97

78.4 0.78 4.81

1 54 3.010 0.076

a 8 0 0 0 0

-

-

-xzzFzk S.E. f S.D.

20 21 21 21 20 21 21 19 21 21 20 21 20 21 19 17 21 22 23 21 23 22 21 21 19 21 0.6 1.2

-_ -

_.

-

74 75 68 72 54 56 75 65 65 63 68 65 70 78 78 75 56 54 88 78 60 63 75 65 75

Venrricle MeaIl

D,/D?

Hg)

Pulmonary s

Artery

P.W.P.

D

MeaIl

13 7 21 32 20 10 8 34 32 20 6 14 32 21 5 15 14 11 10 8 12 6 13 7 11 9 15 12 20 11 7 16 18 18 10 13 11 20

24 23 32 50 34 18 26 56 43 34 15 26 62 31 25 29 23 24 30 13 27 20 20 20 21 20 26 21 32 20 18 31 38 31 23 31 24 36

15 12 76

28 1.7 10 5

Meall

41 44 42

-2/5 -6/2 - 3/6

19 18 23

46 37 49 80 43 40 32 35 76 47 42 48 37 36

-c/z oi3 - 7/2 -a/4 -4/o -3;4 --2/z - 3/3 -4/5 -5/5 -5/3 -o/3 -l/7 -3/10

;5’ 18 17 34 16 17 13 15 31 19 19 20 18 18

5 5 0 3 1 0 3 2 1 0 2 3 3

2k 37 34 35 35 40 33 39 15 38 34 37 42 64 46 35 42

-_;/5 -3/5 -3/3 -4/z -4/3 -3/l -4;7 -Z/5 -5/2 -2/I -5/Z -S/2 - 5/5 -4/5 -5/3 -4/l -4/5

34 48

o/6 -4/3

11 16 15 15 17 14 15 16 13 16 12 13 20 26 20 15 19 15 22

40 44 40 70 48 35 46 72 60 47 21 36 a4 47 38 36 33 36 44 21 37 28 29 31 3s 28 36 30 36 30 30 42 58 46 35 42 32 48

2.6 0.27 1.69

42 1.8 11 0

18 0 7 4.7

41 2.1 134

1 2 3 3 4 5 4 3 4 1 3 5 3 2 0 3 2 1 3 1 2 1 3 4 3

2x 24 27 28 22 26 22 25 22 23 28 30 1X 30 28 30 26 24 26 26 35 23 25 25 25

7 B 9 9 10 9 9 8 10 8 9 13 7 9 a 13 9 7 9 10 12 7 10 11 10

23 23 22 22 22 21 18 21 21 18 22 24 16 28 18 29 ia 17 20 18 27 21 25 25 23

-1

_

-35/36 o 31 1.87

0 34 2 07

8 4 6 4 5 6 5 8 2 4 8 6 8 5 2 5 9 8 .. . 6 a 4 5 a 4 6 6 5 3 9 3 3 3 5 4 6 5 3 54 0.32 1.96

-

-

-

14 9 13 7 15 0 15 9 14 3 15 6 14 2 13 5 15 6 14 5 13 8 14 6 16 0 15 8 15 0 14 5 16 7 15 0 13.9 13 3 14 5

6 92 8 96 4 96 9 97 8 93 7 96 1 95 5 92 8 99 0 97 9 95 4 95.6 92.2 94 8 97 4 94 9 96.6 9R.O 98.2 95.9

46’0

13 7

95.1

1.61 0.014 0.076

44.1 0.55 2.59

> 14 7 0.18 0.88

I

s

6 5 3 1 3 6 3 5 2 3 4 3 2 3 2 3 3 5 2 4 1 1 2 2

I

45 5 40.6 43 5 47.5 43.3 43 8 44 5 42.6 44 5 45 2 40 3 42.6 47 0 4x.1 45.0 42 9 48 5 45 0 42 9 47 0 39 6

1

._

I

1.77 1.72 1.65 1 61 .65 57 58 1.70 1.60 1.60 1.53 1.59 1 79 1.68 1.59 50 1.63 .57 1.59 1.60 1.73 1.54 1.61 1.50 1.57

1 1 i

68 1.; I 8.7 I

-

20 5 18 9 22 a 23 6 17.9 20 3 21 0 18 17.8 18 0 19 0 22.1 21 2 24 3 19.8 22.8 18 9 20 5 18.0 I9 7 17 4 18 G 18 9 15 7 19.6 17 7 19 3 17.R 16 7 19 8 16 9 22 3 19 3 17 4 17 5 17.8 19.1 20.6

58 54 78 73 58 64

_ 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 I8 19 20 21 22 23 24 25

-

7

1.60 1.43 1.59 1.53 1.51 1.58 1.55 1.48 1.47 1 59 1.45 1.61 1.46 1 43 1.63 1.75 1.57 1.55 1.60 1.53 1.49 1.61 1.60 1.61 I.43 1 .‘+!J 1.68 1.56 1.47 1 51 1.44 1 51 1.72 1 55 1.50 1.50 1.64 1.56

Pressures

(mm.

Arter. Hb.0,

-

B.S.A. - body surface area; R.A. = right auricle; pulmonary wedge pressure; Hb. = hemoglobin.

91

__

.

.

95.7 0.44 2.07

--

S = systolic

2.6 0.26 1.31

--

26 0.6 3.4

-2/l -2/z - 3/2 -Z/3 -l/4 -l/4 -l/5 -z/3 - 1:/4 - 2,/3 -2.‘5 -l/7 - 212 --3/2 -3;Z -l/4 -l/3 -t/3 -l/3 -Z/4 -l/4 -z/3 -l/4 -l/4 -l/4 -1.6 0.14 0.70

3.4 0.25 1.25

9 0.3 1.5

2 6 4 6 9 6 4 4 5 4 4 9 5 6 3 8 5 5 6 10 7 8 12 7

22 0.7 3.4

6 0.5 2.3

8 11 12 13 14 14 11 10 13 11 12 15 9 15 10 17 10 10 11 12 15 9 13 15 12 12 0.4 2.2

6 7 7 7 8 8 6 4 9 7 7 10 4 6 4 6 8 4 5 5 8 4 6 4 6 6.2 0.34 1.71

pressure;

DL/D2

= diastolic

pressures;

Mean

= mean pressure

and P.W.P.

_

TABLE I,continued

Systemic

Artery

Cm. s

D

Pulmonary VaXUlZlr Resistance (dyn. sec. cm. -6)

Total Pulmonary Resistance (dyn. sec. -1)

Total Systemic Resistance (dyn. sec. cm. -6)

Right Vent. Work (kg.M./ min./?@.)

Mean

Left Vent. Work (kg.M/min./ M’.)

02 Cons. S.T.P.D. (cc./min.)

A-V Oxygen Differe”Ce

Cardiac Index (L./min./ Mz.)

Cardiac Output (L./min.)

(vol. %)

af High Alrifudrs

135 100 125 115 105 122 125 132 121 111 112 107 126 125 117 106 104 118 133 120 122 123 112 113 109 113 130 120 116 126 111 130 128 118 108 119 109 121

85 65 83 70 75 75 75 82 79 66 74 71 74 74 75 69 76 85 81 80 75 66 68 66 64 60 80 79 74 79 60 80 64 73 58 73 64 84

118 14 88

73 12 73

105 80 105 92 87 95 100 105 88 90 88 93 98 97 94 88 94 94 99 110 94 94 86 82 90 89 102 105 98 106 94 108 91 100 81 100 86 102 95 12 7.7

-

395 295 516 920 378

264 250 419 846 323

1730 1025 1694 1693 969

0 7R 1.13 1.30 1.99 2.10

4.35 4.70 4.47 3.54 5.57

221 224 209 179 252

4 56 3.79 4 22 4 13 3.51

4 85 6 24 4.95 4 34 7 17

3.03 4.36 3.12 2 R4 4.74

263 1447 530 409 210 412 712 276 363 402 407 319 329 190 355 234 244 300 297 279 257 282 347

213 1241 506 349 98 317 620 232 334 332 248 213 117 250 198 183 195 241 209 198 214 336

1012 2714 1085 lOi 1235 1476 1125 864 1365 1219 1667 1249 1086 1608 1235 1097 1051 1232 1274 1241 1009 1408 1064

1.68 1 53 2 60 1.86 0.62 1.03 4.10 2.52 1.11 1.23 0.83 1.58 1.83 0 46 1.52 1.16 1.06 0.85 1.25 0.83 1.45 1.15 2.08

6.;4 2 99 5 27 5.09 4 68 3.95 6 36 8.28 4.31 3.93 3.66 4.95 6.14 5 38 5.21 5.43 4 75 3.65 4 81 4 64 6 69 5.48 6 69

27’7 38 268 248 264 217 285 321 254 250 233 273 283 250 285 262 256 245 246 205 278 250 251

3 5; 4 47 4 13 3 73 4 64 4 30 4.10 3.58 4 61 4.33 5.17 4.54 3 89 4 57 4 69 3.83 3 91 4 61 4 36 3.57 3.44 4 20 3 41

7.89 3 09 6 48 6.64 5 69 5.04 6.96 8.97 5 50 5.77 4.51 6 01 7.28 5.47 6 08 6 85 6 54 5.32 5 64 5 73 8.08 5.96 7.36

5.09 2.09 4 42 4 18 3 93 3 13 4 77 6 27 3 38 3 29 2 87 3.88 4 55 3 57 4 08 4 25 4 09 3 30 3 95 3 85 4 81 3 82 5 01

308 388 445 289 317 574 313 417

2!Il’ 351 421 242 275 463 261 382

16’1’1’ 1353 1065 933 1116 1853 1122 118f

0.84 1.69 2 05 2.38 1.28 1.19 1.13 2.95

4 13 6 24 4.90 7.53 4.22 3.92 4.34 6 16

273 228 248 252 239 223 265 259

5.85 3 58 3.64 2.94 4 12 5.18 4 33 9 75

4.66 6.38 6.83 8.57 5.80 4.31 6 12 6.90

332 35 9 212 6

1298 58.7 352 3

1.49 0 117 0 706

5 09 0.198 1 194

247 54 32 7

4.14 0 096 0 584

6 11 0.208 1.252

401 38 1 228 6

_-

I

-

115 108 135 125 125 135 132 120 130 125 135 135

65 53 75 75 75 75 72 60 80 70 65 75

90 75 105 87 95 103 100 85 100 95 87 105

140 130 120 125 125 125 135 145 120 125

75 75 67 60 75 70 75 75 70 65

105 100 95 85 100 90 100 100 95 90

120

70

60’

127 1.7 R4

70 13 6.4

94 1.6 7.8

-_ -

3 23 4 23 3 97 5 53 3 87 2 88 3 73 4 42 --__ 3 71 0.272 1 636

0 43

5.26

248

3.25

7.64

4 32

1359 1096 1758 1328

0 0 0 0

48 57 38 51

5.37 4 64 3 40 5 55

283 301 173 144

4:58 4 75 4 01 2.32

6 17 6.34 4 32 6 20

3.74 3 94 2 63 3.95

bl’ 69 56 59 53 64 83 67 88 23 64 83 90 93

703 1734 1776 1279 1121

6’5; 3 93 3.45 4 19 6 76

Ii89 1116 761 972 1281 1244 1280 1729

0.57 0 37 0 38 0 46 0.68 0.30 0.86 0.65 1 34 0 49 0 51 0 42 0 62 0.65

246 198 222 254 281 253 237 242 267 276 339 258 237 271

2 55 4.30 5.20 4.65 3 76 4 09 3 08 3 38 2 68 3 95 5 44 4 47 3 80 4 50

9 66 4 61 4 27 5 45 7 49 6.19 7.71 7 16 9.97 6 99 6 24 5.78 6.24 6.02

5 6; 2 88 2.67 3 56 4.71 3 46 4 59 4 50 6 65 4 28 3.96 3.63 3 90 3.48

11;

1533

0 42

3.5;

247

5.2;

4.69

2 91

1247 69 9 304.7

0 55 0 050 0 225

5 19 0 703 1 322

249 96 42.9

4 00 0 202 0 905

6 45 0 345 1 544

3 9: Il.218 0.976

84

21

941

155 164 259 180

52’ 63 111 77

83 225 206 176 160 116 155 112 136 114 128 152 154 199 221.

159 10 4 46 9

--

6 6 R 4 5 4 5 4

58 14 59 91 40 42 32 i4

: 69 5.7 25.3

154

Peiialoza

et al.

TABLE

II

Comparison of Data Obtained at High Altitudes and at Sea Level Blood B.S.A.

Hct.

(Ml.1

(%I

Art&al Hb. 01

Blood Hb. (pm.

I,)

(%I

Heart Rate

R.A.

Right

hf

s

Ventricle

D

Pulmonary

S

D

M

15 7.6

28 10.5

1.54 0.076

59.1 7.20

19.5 1 97

78.4 4.81

69 11.8

I

2.6 1.69

I

42 11 .o

3.6 2.07

18 4.7

41 13.4

Mean

1 .bl 0.076

44.1 2.59

14.7 0.88

95.7 2.07

68 8.7

I

2.6 1.31

!

26 3.4

3.4 1.25

9 1.5

22 3.4



<0.80 0 26

)1

>0.90 0.04

/


/
S.D.

f


R.A. P.W.P. P.T.R.

= right auricle = pulmonary wedge pressure = pulmonary total resistance

to

vasoconstriction

at

10 15 95 001

P.V.R. T S.R. R.V.W. L.V.W.

the

= = = =


<0.60 0 57

pulmonary vascular resistance total systemic resistance right ventricular work left ventricular work

precapillary

leVe1.23,24,26-30

Some observations have also been made in animals and men taken to high altitudes and Guinea exposing them to prolonged hypoxia. pigs developed right ventricular hypertrophy after eight weeks in a low pressure chamber at a simulated altitude of 18,000 feeL31 Some authors have reported right ventricular hypertrophy and pulmonary hypertension, without increased cardiac output, in steers transported for some months to altitudes of 10,000 and 12,700 feet. Vasoconstriction of the pulmonary vasculature was demonstrated in these animals when partial decline of the pulmonary hypertension was obtained after oxygen inhalation. The maintenance of a lesser degree of pulmonary hypertension was ascribed to the development of structural changes in the pulmonary vasculature.32-34 Rotta et al.r4 observed the development of mild pulmonary hypertension, without changes in the cardiac output, in normal men at sea level after one year of continuous In subjects taken from residence at 14,900 feet. sea level to high altitudes for a period of one year, Pen’aloza and Echevarr$a35 have observed progressive changes in the electrocardiogram suggesting development of right ventricular hypertrophy. In addition, a transitory rise in heart rate has been noticed during the first week after arrival in high altitude.36

Artery

M

MCZI f SD.

f

Pressures

M s D SD.

6 2.3

<05.41 001

= = = =

12 22

<07.32 001

mean pressure systolic pressure diastolic pressure standard deviatmn

There are few studies concerning the effects of chronic hypoxia upon the heart and pulmonary circulation. In healthy men, born and living permanently in an environment of hypoxia, the electrocardiogram and the vectorcardiogram indicate the presence of right ventricular in agreement with anatomic hypertrophy,12,i3 studies.8tg Cardiac catheterization has been performed previously in a few natives of high altitudes by Rotta et a1.14 These authors observed mild pulmonary hypertension, slightly higher than in temporary residents, and ascribed it to hypervolemia and polycythemia. Mild pulmonary hypertension in adults of high altitudes has been confirmed in our studies, which have also elucidated that the increased pulmonary resistance occurs at the precapillary level. This pulmonary hypertension is slightly modified, at resting conditions, by injecting acetylcholine3’ or administering oxygen,14a37 which suggests structural changes of the pulmonary vascular tree. Our results concerning the pulmonary wedge pressure, cardiac output and heart rate showed no significant differences between the data obtained at sea level and at high altitude. The changes occurring in the heart and pulmonary circulation in man living permanently at high altitudes are not quite comparable with the changes described in the temporary residents at high altitudes, nor with those THE

AMERICAN

JOURNAL

OF

CARDIOLOGY

Pulmonary Hypertension in Men at High Altitudes TABLE

II,

P.T.R.

(mm. Hg) P.W.P.

Systemic

s

continued

P.V.R.

T.&R.

R.V.W.

L.V.W. Cardiac Index (L./min./M’.)

Artery (dynes

M

155

D

M

sec.

cm.?)

(kg.M./min./Mz.)

Altiludr

5.4 I 96

118 8.8

73 7.3

95 7.7

401 228.6

332 212.6

6.2 1.71

127 8.4

70 6.4

94 7.8

159 46.9

69 25.3

1.54 <0.20

0.16 >0.90

1.80
4.04


4.65
5.49


obtained experimentally by acute hypoxia. This means that when studying the effects of hypoxia upon the heart and pulmonary circulation, it is important to bear in mind not only the degree of hypoxia but also the time of exposure to it. Probable Mechanism of Pulmonary Hypertension at High Altitudes: The-data obtained indicate that the pulmonary hypertension in high altitude dwellers is related to an increased pulmonary vascular resistance, since both cardiac output and pulmonary wedge pressure are within normal limits. In these subjects AriasStella and Saldafialo have found thickening of the muscular layer in small pulmonary arteries and muscularization of the pulmonary arterioles, resembling somewhat the fetal pulmonary vascular tree. These structural changes are associated with widespread narrowing of the lumen in small pulmonary arteries and arterioles, and it explains the increased pulmonary vascular resistance in the high altitude subject. Arteriolar vasoconstriction does not play a significant role since the pulmonary hypertension of inhabitants in high altitudes decreases slightly following the injection of acetylcholine or the inhalation of a gas mixture having 35 per cent oxygen (alveolar pO2 = 100 mm. Hg) .14J7 Hypervolemia and polycythemia appear to be also of minor importance in determining pulmonary hypertension at high FEBRUARY

1963

1.298 352.3

1.49 0.706

5.09 1.194

3.71 1.636

1247 304.7

0.55 0.225

5.19 1.322

3.97 0.976

0.80 <0.50

5.79


0.28 <0.80

0.65 <0.60

Some observations support this statealtitudes. ment. When a native of high altitude is taken down to sea level, pulmonary hypertension diminishes slowly while hypervolemia and polycythemia disappear in a short period of time.37 On the other hand, as far as we know, in patients having polycythemia vera neither pulmonary hypertension nor right ventricular hypertrophy has been found. The Role of Pulmonary Hypertension in the Acclimatization Process to High Altitudes: Little is known about the role of pulmonary hypertension in the mechanism of acclimatization in people born and living at high altitudes. Apparently the pulmonary hypertension would not accomplish an important part in the complex mechanism of acclimatization. On the contrary, it was initially assumed that pulmonary hypertension was a consequence of the hypervolemia and polycythemia.14 If the vascular structure is taken into consideration as a main factor accounting for pulmonary hypertension, the question arises as to the meaning of the persistence of such a fetal-like pattern on the mechanism of acclimatization. It is possible that there is no relation between both phenomena and that the environment of chronic hypoxia in which these people live after birth accounts for the maintenance of the vascular pattern that normally disappears during the first months of life.

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That the hypoxia is capable of determining the development of anatomic changes in the pulmonary vasculature has been observed in steers taken for several weeks to an altitude of 12,700 feet.38 Grover and co-workers34 believe that the pulmonary hypertension would favor a more effective perfusion of all the pulmonary areas, “thus increasing the effective area of the bloodalveolar gas interface. Perfusion of the entire lung would increase the oxygen diffusing capacity of the lung and should decrease the A-a gradient at high altitude.” These changes, according to the authors, would concur to provide a more effective arterial blood oxygenation. This hypothesis, we believe, is applicable to the man of high altitudes in whom, besides a low PO:, A-a gradient, an extensive capillary bed of the lungs and hyperventilation have been described.4Bs According to Hurtado et a1.4 the hyperventilation would favor a more emcient ventilation of all lung areas. In this way, hyperventilation and pulmonary hypertension would result as factors which concur to increase the arterial blood oxygenation in the dweller of high altitudes. That hyperventilation serves for this purpose is known, but the role played by pulmonary hypertension in improving the perfusion of the entire lung needs to be demonstrated. SUMMARY

Right heart catheterization studies were performed in 38 healthy men 17 to 34 years of age born and living at high altitudes. In order to obtain comparative data, a similar investigation was made in 25 healthy men born and living at sea level. Previously, a physical examination was performed, and roentgenograms of the chest, hematological, electrocardiographic and vectorcardiographic data were obtained. Mild pulmonary hypertension and a moderate increase of the pulmonary vascular resistance and right ventricular work were found in men living permanently at high altitudes. Pulmonary wedge pressure, cardiac output and heart rate did not show significant differences from the data obtained at sea level. The changes occurring in the heart and pulmonary circulation in men living permanently at high altitudes are not quite comparable with the changes described in temporary residents at high altitudes, nor with those experimentally obtained by acute hypoxia.

This means that when studying the effects of hypoxia upon the heart and pulmonary circulation, it is important to bear in mind not only the degree of hypoxia but also the time of exposure to it. The augmented pulmonary vascular resistance in the high altitude dweller is related to the anatomic changes in the small pulmonary arteries and arterioles which have been described by other investigators. Functional factors such as vasoconstriction, hypervolemia and polycythemia do not play an important role in the mechanism of the pulmonary hypertension at high altitudes. The role of the pulmonary hypertension in the complex mechanism of acclimatization to life at high altitude is not well understood. Apparently pulmonary hypertension would not accomplish a useful part in this mechanism. It is possible, however, that pulmonary hypertension, in association with other factors such as hyperventilation and an extensive capillary bed of the lungs, does play a role in improving the arterial oxygenation in men living at high altitude. REFERENCES 1. MONGE, M. C., Enfermedad de 10s Andes. Estudio fisiol6gico. An. Fat. med. Lima, 11: 1, 1928. 2. HURTADO,A., MERINO, C. and DELGADO,E. Influence of anoxemia on the hemopoietic activity. A.M.A. Arch. Znt. Med., 75: 284, 1945. 3. HURTADO,A. and ASTE-SALAZAR,H. Arterial blood gases and acid-base balance at sea level and at high altitudes. J. Appl. Physiol., 1 : 304, 1948. 4. HURTADO,A. et al. Mechanisms of natural acclimatization. Studies on the native resident of Morococha, Peru, at an altitude of 14,900 feet. Report to the U.S.A.F. School of Aviation Medicine, 1956. 5. REYNAFARJE, C., LOZANO, R. and VALDIVIESO, J. The polycythemia of high altitudes: iron metabolism and related aspects. Blood, 14: 433, 1959. 6. REYNAFARJE, B. Estudios de quimica tisular en la hipoxia. Simposios y conferencias, XXI Congreso International de Ciencias Fisiolbgicas, Buenos Aires, 1959. 7. HURTADO, A. Some clinical aspects of life at high altitudes. Ann. Znt. Med., 53: 247, 1960. 8. C~IPOS, J. and IGLESIAS,B. Observaciones andtomo patolbgicas en 49 personas normales nativas y residentes en la altura (3,700-5,000 mts.) muertas en accidente. Rev. Latinoam. anat. pa&., 1 : 109, 1957. 9. ARIAS-STELLA, J. and RECAVARREN,S. Right ventricular hypertrophy in native children living at altitudes. Am. J. Path., 41: 55, 1962. 10. ARIAS-STELLA,J. and SALDARA,M. The muscular pulmonary arteries in people native to high altitude. Fifth Annual Conference on Research in Emphysema, Aspen, Colo., 1962. 11. ROTTA, A. Physiologic conditions of the heart in the THE

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