Background: We have demonstrated that sildenafil has a significant inhibitory effect on
hypoxia-induced pulmonary vasoconstriction in healthy subjects (Zhao et al., 2001). However,
the effect of long term treatment by sildenafil on pulmonary hemodynamics of patients with
high altitude pulmonary hypertension (HAPH) has not been studied. Aim: To investigate the
effect of long-term treatment (3 month) by sildenafil on pulmonary hemodynamics in patients
with HAPH. Materials and methods of research: 9 patients with HAPH (8 men and 1 woman) 44-
72 years old (59.77±2.87) were studied in National Center of Cardiology, Bishkek (760 meter
above sea level). Pulmonary artery pressure (PAPm) was measured by right heart catheterization
before and in 3 month of therapy. Sildenafil was given orally in a dose 50 mg thrice a day.
Results: In 3 month after sildenafil therapy the mean PAP significantly decreased from
34.11±6.64 mm Hg to 24.11±7.15 mm Hg (p<0.007) and systolic pulmonary artery pressure
decreased from 53.3±4.55 mm Hg to 39.4±3.53 mm Hg. Whereas cardiac output, systemic blood
pressure, heart rate, SaO2 were not significantly changed. Conclusion: 3 month therapy with
sildenfil in a dose 50 mg trice daily significantly decreases mean and systolic PAP, does not have
the systemic effect and could be recommended for treatment of HAPH.
125.
THE EFFECT OF ALTITUDE AND TIME AT ALTITUDE ON EXERCISE HYPOXIA
AMONG CLIMBERS TAKING ACETAZOLAMIDE. John Lafleur
1
, Dorota Barticzuk
1
, Annie
Collier
1
, Neal Griffin
1
. Lincoln Hospital Dept. Emergency Medicine
1
.
Introduction: Controversy exists regarding how many days and at which altitudes
acetazolamide should be taken. We investigated the optimal altitudes and duration of use of
acetazolamide for maximizing exercise oxygenation among lowlanders going to high altitude.
Methods: The study was conducted in three parts at yearly intervals. For part I six subjects
acclimatized to 4060 meters for six days while taking Acetazolamide 250 Mg TID. Oxygen
saturation was measured daily with a standard oximeter during exercise. On day 7 Acetazolamide
was stopped, then resumed on day 8. Part II of the study followed the same format except that
acclimatization to 4060 meters occurred over 14 days. For Part III of the study seven climbers
acclimatized to 4770 meters over the course of 14 days. Results: In part I cessation of
Acetazolamide after day 7 resulted in a significant drop in exercise oxygenation: 80% on day 7 to
71% (p=0.008) on day 8. On day 9, after resuming Acetazolamide, oxygen saturation went up to
79% (p=0.002). In part II cessation of Acetazolamide after day 14 resulted in a drop in exercise
oxygen saturation from 85% to 83% ( p=0.06). On day 16 after resuming acetazolamide
oxygenation rose to 87% (p=0.03). In part III cessation of Acetazolamide after day 14 resulted in
an increase in oxygen saturation from 74% to 79% ( p=0.03). After resuming Acetazolamide
oxygenation remained unchanged at 80% (p=0.10) on day 16. Conclusion: Up to 4060 meters
acetazolamide protected against exercise hypoxia even after two weeks. After two weeks at
altitudes of 4770 meters acetazolamide may worsen exercise hypoxia. The reasons for this may
relate to the relative contributions of pulmonary shunt and diffusion to exercise hypoxia with
increasing altitude.
126.
HIF-1_ AND OXYGEN SENSING IN THE RAT CAROTID BODY. Sukhamay Lahiri
1
, Arijit
Roy
1
, Santhosh Baby
1
, Jinqing Li
1
, Anil Mokashi
1
. University of Pennsylvania, Philadelphia,
USA
1
.
The study was conducted to test the hypothesis that HIF-1 _ accumulation in the type I cell
(glomus cell) of the carotid body equates to oxygen sensing. HIF-1 _ protein accumulation was
measured by intensity of immunofluorescence. Hypoxic stimulus was provided by bathing the
cells in hypoxic solution, or by chelation of iron or by application of analogue of oxoglutarate,
and glomus cell membrane K+ currents, intracellular calcium concentration and neurotransmitter
release were measured. Also, neural discharge from the in vitro rat carotid body was measured. In
addition mitochondrial inhibitors on glomus cells and carotid body were used to further test the
hypothesis in that HIF-1_ disappearance would amount to loss of chemosensing. Results: Acute
hypoxia inhibited the oxidative modification resulting in HIF-1 _ accumulation and initiated the
