It is well known that exposure to high altitude (HA) leas to hypoxic pulmonary hypertension.
More than 5 years prospective evaluation of pulmonary hemodynamics in healthy men working at
HA on 4 week shifts has not been studied. The aim of the present study was long-term follow up
of pulmonary circulation dynamics in employees of an open-pit gold mine situated at altitude of
3700 to 4200m. Doppler echocardiographic estimation of pulmonary circulation in 84 men
working at mine site aged 27 to 58 years (mean 40,9±1,8) was studied in 1998 and 2003. Their
average time of work at the mine was 2±1,0 yr in 1998. Cardiac and pulmonary diseases were
excluded by clinical examination, X-ray, ECG, lung function test. Results are represented in
table.
Year
Working
period, yrs
Mean PAP,
mmHg
RVD, cm
RVAWT,
cm
CO,
l/min
1998
2.03±1.0
18.5±4.0
1.52±0.6
0.34±0.04
5.6±1.1
2003
7.00±1.1
23.4±3.5
1.91±0.3
0.36±0.05
5.7±1.0
P
<0.001
<0.001
<0.001
ns
ns
Legend: PAP-pulmonary artery pressure, RVD - right ventricular dimension, RWAWT - right
ventricular anterior wall thickness, CO - cardiac output. Thus, more than 5 years chronic
intermittent exposure to high altitude leads to significant increase of pulmonary artery pressure
and slight dilatation of right ventricle. More pronounced increase of PAP was correlated with
body mass index (26) and forced vital capacity (< 86%).
151.
PARTIAL GENETIC CHARACTERIZATION OF DIFFERENCES IN HYPOXIC EXERCISE
TOLERANCE IN MICE. Dale McCall
1
, Dargan Frierson
1
, James Blum
1
, Stephen Kinsey
1
. U.
North Carolina-Wilmington
1
.
Mice from inbred mouse strains BALB/c (C) and C57BL/6 (B) and their F1 hybrid were
exposed for 8 weeks to either normoxia (N) or hypoxia (H; 380 Torr = 1/2 atm) before hypoxic
exercise tolerance (Behavior Genetics 27:181-190) was measured. The genetic basis of
differences in hypoxic exercise was investigated as follows: Gastrocnemius muscle total RNA
was extracted from each of the 3 genetic backgrounds in normoxia and hypoxia (N= 37) and used
in a cDNA microarray analysis of expression levels in 5000 genes. Proper quality control and
normalization issues were investigated prior to applying a mixed models analysis of the array data
with appropriate adjustment for multiple testing. Of ~ 300 genes the expressions of which were
significantly different, 49 could be attributed to interactions between genotypes and treatments.
Specific contrasts were built to investigate the difference between F1(H) and all other genotypes
and treatments. Among the genes most significantly upregulated in the F1(H) sample was
superoxide dismutase 1 (Sod-1). This result represents the intersection with our previously
published reports that: (1) the expression of two genes predominates in the difference in exercise
tolerance. A feature important to that analysis, and to the present one, was the existence of a
strong epistatic (i.e., nonadditive) interaction of the two genes that produced in the "F1-like"
double heterozygote in hypoxia--but not in normoxia--a "super mouse" with mean exercise
tolerance more than 4 S.D. units above the high parent (B) mean; and (2) that the chromosomal
location of one of the two major genes is in a region of mouse chromosome 16 that contains Sod-
1 with very high probability (LOD = 5.4). Confirmation of Sod-1's role is underway, as is a
functional cluster analysis of genes.
152.
ARE PERIODIC BREATHING AND ACUTE MOUNTAIN SICKNESS DEPENDENT UPON
THE HYPOXIC VENTILATORY RESPONSE?. Jim Milledge
1
, Giorgos Tsianos
2
, Paul
Richards
3
, Philippa Seal
4
, Juliette Leverment
5
, Mary Morrell6, Annabel H Nickol7, David J
Collier8. Northwick Park Hospital, UK
1
, Glasgow
2
, Royal Free, London, UK
3
, Bristol, UK
4
,
Southampton, UK
5
, Imperial College, London, UK6, Osler Chest Unit, Oxford, UK7, Dept Clin
Pharmacology, Barts, London, UK8.
