Chronic Mountain Sickness Patients Research Articles

Pulmonary Pressure and Cardiac Function in Chronic Mountain Sickness Patients

Chronic mountain sickness (CMS) is characterized by a loss of adaptation to hypoxia in high-altitude (HA) dwellers. Chronic hypoxemia, excessive erythrocytosis and frequently pulmonary hypertension (PH), which may lead to cardiac failure, develop in patients. We sought to assess the determinants of cardiac function in CMS patients with hypoxia-induced PH. Fifteen healthy men living at sea level (SL) were compared to 15 healthy men living at HA and 55 patients with CMS from Cerro de Pasco, Peru (altitude, 4,300 m). Pulmonary pressures and cardiac function were estimated by echocardiography. None of the subjects had overt cardiac failure symptoms. CMS patients exhibited elevated mean pulmonary pressures as assessed by high-tricuspid pressure gradients (CMS patients, 34 +/- 10 mm Hg; HA subjects, 25 +/- 4 mm Hg [p = 0.002]; and SL subjects, 19 +/- 3 mm Hg [p < 0.001]). They also showed right ventricular (RV) dilation (mean end-diastolic RV area: CMS patients, 17 +/- 2 cm(2); HA subjects, 13 +/- 2 cm(2); SL subjects, 12 +/- 2 cm(2); p < 0.001) but did not display impaired systolic ventricular function. However, the RV Tei index was increased in CMS and HA subjects (CMS patients, 0.56 +/- 0.15; HA subjects, 0.52 +/- 0.12; SL subjects, 0.21 +/- 0.12; p < 0.001). Despite obvious pulmonary arterial hypertension and right heart dilation, CMS patients did not show any symptom or echocardiographic parameter of heart failure. ClinicalTrials.gov. Identifier: NCT00424970.

Chronic hypoxia in Andeans; are there lessons for neurology at sea level?

Hypoxia is implicated in aging and neurodegenerative diseases. We posited that changes in gene expression induced by ambient hypoxia at altitude may be neuroprotective to natives of these regions. We studied 30 men. Twenty natives of Cerro de Pasco (CP), altitude 4338 m were examined in CP; then transported within 6 h to Lima (150 m-sea level) and examined 1 h after arrival. They were assessed by a Chronic Mountain Sickness-score (CMS-sc) in CP, 10 were normal Andeans and 10 had chronic mountain sickness (CMS), a sudden inexplicable loss of adaptation to their native environment. RNA was extracted from venous blood white cells. The Andeans were compared to 10 normal US men living at 1500 m using RT-PCR. We focused on the cyto-neuro-protective genes, Ataxia telangiectasia mutated (ATM), heme-oxygenase-1 (HMOX 1), heat shock protein-70 (HSP-70), heat shock protein-90 (HSP-90), and the neuroprotective enzyme, nicotinamide mononucleotide adenylyl transferase 1 (Nnmat 1). CMS patients had significantly higher levels of gene expression (HMOX-1, HSP-70, ATM) than Andean controls in CP. HSP-90 and Nmnat 1, however, were higher in Andean controls in all locations. Significant reductions of all gene products, within an hour of arriving in normoxia in Lima, were found. In Andean controls, the gene products in Lima fell to levels approaching US controls. Correlation and regression methods showed men with high expression of all gene products had an average CMS-sc = 19.8; those with low expression a normal score (9.4, P = 0.02). ATM expression was related to age ( P < 0.001). The natural experiment that unfolds in the mountainous regions of the world provides opportunities to study neuroprotection in intact humans.

Cerebrovascular responses to hypoxia and hypocapnia in high‐altitude dwellers

Cerebral blood flow is known to increase in response to hypoxia and to decrease with hypocapnia. It is not known, however, whether these responses are altered in high-altitude dwellers who are not only chronically hypoxic and hypocapnic, but also polycythaemic. Here we examined cerebral blood flow responses to hypoxia and hypocapnia, separately and together, in Andean high-altitude dwellers, including some with chronic mountain sickness (CMS), which is characterized by excessive polycythaemia. Studies were carried out at high altitude (Cerro de Pasco (CP), Peru; barometric pressure (P(B)) 450 mmHg) and repeated, following relief of the hypoxia, on the day following arrival at sea level (Lima, Peru; P(B) 755 mmHg). We compared these results with those from eight sea-level residents studied at sea level. In nine high-altitude normal subjects (HA) and nine CMS patients, we recorded middle cerebral artery mean blood flow velocity (MCAVm) using transcranial Doppler ultrasonography, and expressed responses as changes from baseline. MCAVm responses to hypoxia were determined by changing end-tidal partial pressure of oxygen (P(ET,O2)) from 100 to 50 mmHg, with end-tidal partial pressure of carbon dioxide clamped. MCAVm responses to hypocapnia were studied by voluntary hyperventilation with (P(ET,O2)) clamped at 100 and 50 mmHg. There were no significant differences between the cerebrovascular responses of the two groups to any of the interventions at either location. In both groups, the MCAVm responses to hypoxia were significantly greater at Lima than at CP (HA, 12.1 +/- 1.3 and 6.1 +/- 1.0%; CMS, 12.5 +/- 0.8 and 5.6 +/- 1.2%; P < 0.01 both groups). The responses at Lima were similar to those in the sea-level subjects (13.6 +/- 2.3%). The responses to normoxic hypocapnia in the altitude subjects were also similar at both locations and greater than those in sea-level residents. During hypoxia, both high-altitude groups showed responses to hypocapnia that were significantly smaller at Lima than at CP (HA, 2.17 +/- 0.23 and 3.29 +/- 0.34% mmHg(-1), P < 0.05; CMS, 1.87 +/- 0.16 and 3.23 +/- 0.24% mmHg(-1); P < 0.01). The similarity of the results from the two groups of altitude dwellers suggests that haematocrit is unlikely to greatly affect cerebrovascular reactivity to hypoxia and hypocapnia. The smaller vasodilatation to hypoxia and larger vasoconstriction to hypoxic hypocapnia at high altitude suggest that cerebrovascular responses may be impaired at the high altitude, i.e. a maladaptation. The changes in the responses within less than 24 h at sea level indicate that this impairment is rapidly reversible.

Atrial natriuretic peptide and red cell 2,3-diphosphoglycerate in patients with chronic mountain sickness

Individuals with chronic mountain sickness (CMS) show severe hypoxemia, excessive polycythemia, and marked pulmonary hypertension. The pathophysiologic mechanisms of CMS are still not completely understood. We determined plasma atrial natriuretic peptide (ANP), red cell 2,3-diphosphoglycerate (2,3-DPG), hematocrit, hemoglobin, and arterialized ear lobe blood gas values in 13 patients with CMS (9 Hans, 4 Tibetans) and 18 control Han Chinese men of similar age, height, and weight who had been living at 4300 m on the Tibetan plateau of Qinghai Province, China, for approximately 14 years. A significantly higher level of ANP was found in the CMS patients compared to the non-CMS patients (113.4+/-5.5 pg/mL vs 87.6+/-4.7 pg/mL, P < .01), and the levels of ANP correlated positively with the hemoglobin concentration (r = 0.8282, P < .01). The 2,3-DPG levels in the CMS patients were significantly increased compared to the non-CMS subjects (5.23+/-0.16 mmol/L vs 4.40+/-0.12 mmol/L, P < .01), and the 2,3-DPG concentrations in the CMS patients were negatively correlated with their PaO2 values (r = -0.7898, P < .01). The CMS patients had significantly higher PaCO2 levels, lower pH values, lower PaO2 levels, and greater alveolar-arterial oxygen differences (PAO2 - PaO2) compared to the non-CMS subjects. These findings suggest that overproduction of ANP and 2,3-DPG at high altitudes may play an important role in the pathophysiology of chronic mountain sickness.

Breathing and brain blood flow during sleep in patients with chronic mountain sickness

Chronic mountain sickness (CMS) patients have lower arterial O2 saturation (SaO2) during sleep compared with healthy high-altitude residents, but whether nocturnal arterial O2 content (CaO2) and brain O2 delivery are reduced is unknown. We measured SaO2, CaO2, sleep-disordered breathing (SDB), and internal carotid artery flow velocity in 8 CMS patients, 8 age-matched healthy CMS controls, 11 healthy younger-aged Han, and 11 healthy younger-aged Tibetan male residents of Lhasa, Tibet (3,658 m). CMS patients spent a greater portion of the night in SDB (total no. of episodes of apnea, hypopnea, and hypoventilation) than did the CMS controls, young Han, or young Tibetans (15% vs. 5, 1, and 1%, respectively; P < 0.05) because of more frequent apnea and hypoventilation episodes and longer duration of all types of episodes. SDB and unexplained arterial O2 desaturation caused nocturnal SaO2 to be lower and more variable in CMS patients than in CMS controls or in younger-aged Han or Tibetan men. Average CaO2 was similar, but the CMS patients spent 29%, whereas the other groups spent < 4%, of the night at values < 18 ml O2/100 ml whole blood. Internal carotid artery flow velocity during wakefulness was similar in CMS patients and CMS controls despite higher end-tidal PcO2 values in the CMS patients. When contiguous sleep stages are compared, flow velocity rose from stage 2 to rapid-eye-movement sleep in both groups. Whereas flow velocity remained elevated from awake to rapid-eye-movement sleep in the CMS controls, it fell in the CMS patients. During episodes of SDB, internal carotid flow velocity increased in CMS controls but did not change in the CMS patients such that values were lower in the CMS patients than in CMS controls at the end and after SDB episodes. We concluded that SDB and episodes of unexplained desaturation lowered nocturnal SaO2 and CaO2, which, together with a lack of compensatory increase in internal carotid artery flow velocity, likely decreased brain O2 delivery in CMS patients during a considerable portion of the night.

Chronic Mountain Sickness-Phobrang Type

Clinical0 features of 27 cases of Chronic Mountain Sickness (CMS) from the Himalayas are reported. They are compared with 75 native highlanders (NH). All CMS patients were immigrants to high altitude. Mean duration of stay at high altitude was seven years. Mean values for haematocrit and haemoglobin were 80% and 23 G% respectively for the CMS group and 40% and 17.9 G% respectively for the native highlande group. Mean QRS axis in the former was +118 and in the latter +76. Incidence and quantum of protienuria were significantly higher in the CMS group. Cardiac catheteri -sation studies done in eight CMS cases showed elevated Pulmonary Artery (PA) pressures even after a mean of 14.2 days at sea level. The disease which has four diagnostic elements-hypoxemia and polycythemia, pulmonary hypertension, right ventricular enlargement and nephropathy with dense proteinuria-is a variant of 'Monge's Disease' and a name CMS Phobrang Type is suggested, along with a new approach to clinical classification which may help in diagnosis before cor pulmonale sets in. Limited therapeutic trials conducted at highaltitude seem to indicate that yogic deep breathing exercises, low-dose aspirin and diamox may be beneficial in the prevention and therapy of CMS Phobrang Type at high altitude.