Pulmonary hypertension in high-altitude chronic hypoxia: response to nifedipine

Abstract

The vasoconstrictive effect of hypoxia upon pulmonary artery vessels is well known in most mammalian species, including humans. A pure form of hypoxic pulmonary artery hypertension can be seen in high-altitude residents. A loss of adaptation to chronic hypoxia, known as chronic mountain sickness (CMS), is observed in 5-10% of people sojourning above 3,000 m and is characterized by excessive polycythaemia (H-Hb), pulmonary hypertension and nonspecific neurological symptoms [1]. Ongoing pulmonary vasoconstriction leads to increased vascular resistance and pulmonary artery pressure (Ppa), which are probable maladaptive responses to high altitude since they result in minimal improvement in ventilation-perfusion matching and increased workload for the right ventricle.In addition to vasoconstriction, chronic alveolar hypoxia is associated with structural changes in the media of terminal portions of pulmonary arterioles [2], such as smooth muscle cell proliferation, thickening of the media, proliferation and turgescence of endothelial cells. Recently, this vascular remodelling has been found in only a few residents at high altitude [3], but it is admitted that sustained hypoxia is able to increase muscularization of the small pulmonary vessels and to increase even further the pulmonary vascular resistance.A reduction in Ppa, under hypoxic conditions, has been obtained by the calcium channel-blocker nifedipine in healthy humans exposed to acute normobaric hypoxia [4] or in subjects suffering from high-altitude pulmonary oedema in hypobaric hypoxia [5]. In other aetiologies of pulmonary hypertension, such as primary pulmonary hypertension [6] or secondary to obstructive pulmonary disease [7,8], nifedipine and felodipine were efficient in decreasing Ppa. Calcium antagonists have also been shown to be efficient in experimental hypoxic pulmonary vasoconstriction [9,10].Reversal of hypoxic pulmonary hypertension with calcium channel-blockers has not been evaluated in a population chronically exposed to high altitude. Venesection has been used to treat CMS, but no modification of pulmonary haemodynamics has been reported.The objectives of this study were to assess pulmonary hypertension in native residents at high-altitude by echocardiography, to analyse the relationship between Ppa and H-Hb, and to study the effect of acute administration of nifedipine on pulmonary pressure. In the presence of reversible vascular changes in altitude-induced pulmonary hypertension, a nifedipine-induced vasodilatation could be anticipated. Materials and methods SubjectsThirty males and one females, native residents of La Paz (3,500-4,100 m), Bolivia, were included in this nonrandomized study. Asymptomatic subjects were recruited Systolic pulmonary arterial pressure (Ppa) was studied by Doppler echocardiography, at rest and after sublingual nifedipine, in 31 asymptomatic residents at 3,600 m. Individuals were separated into two groups according to resting Ppa: a group with low Ppa (ð4.7 kPa, n=17) and a group with high Ppa (>4.7 kPa, n=14). Ind...

High-altitude pulmonary hypertension: a pathophysiological entity to different diseases

“…Figure 4 summarises haemoglobin and mean PAP pairs published in Han Chinese [14], and South Americans without [18] and with CMS [20]. The figure shows that for the pooled data (n=47), there is a significant correlation of the second order between haemoglobin and PAP (r=0.64, pv0.001), but that, as previously reported [20,53], this relationship is lost in patients with CMS (r=0.25, p=0.62). Furthermore, the figure illustrates that at a comparable mean PAP of y40 mmHg (mean ¡ SD: Han Chinese 40 ¡ 11 versus South Americans 45 ¡ 18, p=0.87), haemoglobin concentration is lower in Han Chinese (mean ¡ SD 20.3 ¡ 1.9 g?dL -1 , range [17][18][19][20][21][22] than in the natives of the Andes (mean ¡ SD 24.6 ¡ 2.1 g?dL -1 , range 20-27; pv0.01, MannWhitney U-test).…”

Right Ventricle and High Altitude

“…The magnitude of pulmonary hypertension increases with the altitude level and the degree of exercise. There is reversal of pulmonary hypertension after prolonged residence at sea level or treatment with vasodilators [ 33 ]. Chronic mountain sickness develops when the capacity for altitude adaptation is lost [ 34 , 35 ].…”

The Heart and Pulmonary Circulation at High Altitudes

“…Calcium-channel blockers such as nifedipine, already used for treatment and prevention of high-altitude pulmonary edema, have also been tested on CMS, which resulted in transient and partial reduction of PH. 91 Selective pulmonary vasodilators, currently used for idiopathic pulmonary arterial hypertension, are being tested for long-term treatment of high-altitude PH. Sildenafil, a phosphodiesterase-5 inhibitor, has been tested in symptomatic highlanders with PH, and after several months improvement in pulmonary hemodynamics and exercise tolerance was observed.…”