Pulmonary hypertension and pulmonary vascular reactivity in beagles at high altitude

It is unclear whether dogs develop pulmonary hypertension (PH) at high altitude. Beagles from sea level were exposed to an altitude of 3,100 m (PB 525 Torr) for 12-19 mo and compared with age-matched controls remaining at low altitude of 130 m (PB 750 Torr). In beagles taken to high altitude as adults, pulmonary arterial pressures (PAP) at 3,100 m were 21.6 +/- 2.6 vs. 13.2 +/- 1.2 Torr in controls. Likewise, in beagles taken to 3,100 m as puppies 2.5 mo old, PAP was 23.2 +/- 2.1 vs. 13.8 +/- 0.4 Torr in controls. This PH reflected a doubling of pulmonary vascular resistance and showed no progression with time at altitude. Pulmonary vascular reactivity to acute hypoxia was also enhanced at 3,100 m. Inhibition of prostaglandin synthesis did not attenuate the PH or the enhanced reactivity. Once established, the PH was only partially reversed by acute relief of chronic hypoxia, but reversal was virtually complete after return to low altitude. Hence, beagles do develop PH at 3,100 m of a severity comparable to that observed in humans at the same or even higher altitudes.     

Pulmonary vascular disease in a rabbit a high altitude

A male weanling rabbit of the New Zealand White strain, born and living at an altitude of 3800 m in La Paz, Bolivia, developed right ventricular hypertrophy. This was found to be associated with growth of vascular smooth muscle cells in the intima of pulmonary arterioles, and contrasted with muscularization of the walls of pulmonary arterioles, without extension into the intima, found in a healthy, high-altitude control rabbit of the same strain. A low-altitude control showed no such muscularization. It is concluded that alveolar hypoxia, acting directly or through an intermediate agent, is a growth factor for vascular smooth muscle cells in pulmonary arterioles. This is the first report of pulmonary vascular disease due to high altitude in rabbits.     

The lung at high altitude

Men and mammals (excluding the indigenous mountain species) who are born at high altitude, or who ascend to live there for a long period, have to undergo acclimatization which affects virtually every system in the body. Since chronic hypoxia is the most important adverse factor in the mountain environment, the lung plays a major part in the process and shows many alterations in structure and function. However, we remain ignorant about many aspects of acclimatization of the lung to hypoxia especially at the ultrastructural level with respect to those cells whose normal function is not yet established. An account of what is known is given in this paper.     

Hepatic amoebiasis at high altitude

Latent amoebiasis is aggravated at high altitude. Protean manifestations are common. Fever is usually absent. Liver tenderness is not a feature and may have to be specially elicited. Leucocytosis is rare. Bowel symptoms inspite of presence of intestinal ulcerations are usually absent. Response to treatment with emetine or chloroquin is unsatisfactory and relapse rate is high. These points may interest mountaineers and other sojourners to high altitude.     

Pulmonary hypertension and the smooth muscle of the pulmonary arterioles in chickens at high altitude

• 1.1. One-day-old male (m) and female (f) chickens from a population living at 3300m for several generations were raised at 3300 m (HA) and at sea level (SL).
• 2.2. The histology of the pulmonary arterioles was studied in the HA and SL chickens when they were 4 weeks old and the thickness of their muscular coat (MT) determined.
• 3.3. Pulmonary arterial pressure (Ppa), hematocrit (Hct) and the wet and dry weights of the total ventricle, left ventricle, septum and right ventricle (RV) were obtained when the HA and SL birds were 8 weeks old.
• 4.4. Results indicated that chickens have a thick muscular coat in their pulmonary arterioles. MT expressed as a fraction of arteriolar diameter (MT/AD) was 0.113 at SL. Exposure to HA increased this value in the m (0.137, P < 0.01) but not in the f (0.123, P > 0.05).
• 5.5. Ppa, RV and Hct were significantly higher at HA in both sexes. The degree of pulmonary hypertension and right ventricular hypertrophy observed was smaller than that found in earlier generations of these chickens studied several years ago. This probably indicates some degree of adaptation after generations of life at HA.

     

The athlete at high altitude

Track times at moderate altitudes (7000 to 8000 feet) are modified by decreased wind resistance and by systemic disturbances such as mountain sickness, disruption of training, and a decrease of maximum oxygen intake. The optimum period of acclimatization is probably two to three days. This permits adjustment of cerebrospinal fluid acid-base balance, but minimizes disturbances of plasma volume and stroke volume. Further study is needed to establish whether altitude training can improve performance in sea-level competitions.     

Nutritional alterations at high altitude in man

During the French 1980 Mount Pabil (7,102 m) Expedition, a study was made of four altitude-acclimatised climbers (age 36.5 +/- 3.6 years; VO2max 50.5 +/- 3.1 ml X kg-1). Intake of various nutrients, body weight, skinfold thicknesses as indices of body composition, and water and nitrogen balances, were recorded before, and during high altitude exposure, and again after the return to low altitude. There was a significant (35-57%) reduction in total caloric intake at high altitude. Body weight decreased progressively, mainly due to a reduction in body fat. The subjects apparently remained in water balance, while the nitrogen balance was always negative during high altitude exposure. The significant nutritional alterations were mainly observed above 6,000 m. They are discussed with respect to changes in feeding patterns and in hormonal status of the climbers accompanying hypoxia and other stressors proper to high altitude.     

Insulin secretion at high altitude in man

The effect of hypoxia on circulatory levels of insulin, its response to oral glucose administration (100 g) and changes in circadian rhythms of glucose as well as insulin were evaluated in euglycemic males at sea level (SL, 220 m) during their stay at high altitude (3500 m, SJ) and in high altitude natives (HAN).Basal glucose levels were not altered at high altitude but the rise in glucose ( glucose) after glucose load was significantly higher in SJ and HAN (p<0.01) as compared to SL values. An increase (p<0.01) both in basal as well as glucose induced rise in insulin secretion ( insulin) was observed at HA. The rise in insulin in SJ was significantly higher (p<0.01) than in HAN. This elevation in glucose and insulin levels was also evident at different times of the day. The circadian rhythmicity of glucose as well as insulin was altered by the altitude stress. The findings of the study show a rise in insulin level at HA but the hyperglycemia in the face of hyper-insulinism require the presumption of a simultaneous and dispropotionate rise of insulin antagonistic hormones upsetting the effect of insulin on glucose metabolism.Presented at International Conference of Biometeorology held at New Delhi from December 26–30, 1983.     

Glucoregulatory hormones in man at high altitude

Concentrations of glucose, lactic acid, free fatty acid (FFA), insulin, cortisol and growth hormone (GH) in the blood were monitored in 15 euglycaemic men (sojourners, SJ) at sea level (SL) and while at altitudes of 3500 m and 5080 m, in acclimatised low landers (ALL) and in high altitude natives (HAN). In SJ, blood glucose and insulin concentrations showed a significant increase on the 3rd and 7th day after arrival at high altitude (HA), thereafter returning to sea level values and remaining the same during the entire period of their stay at 3500 m. Subsequently, on arrival at higher altitude (5080 m) the glucose concentrations again showed an increase over the preceding values and returned to SL values on day 41 while at 5080 m. A significant increase in cortisol concentrations was seen on day 3 after arrival at HA and the increased levels were maintained until day 21 at 3500 m. The cortisol concentrations on day 30 after arrival at 5080 m came down to SL values and remained unchanged thereafter. No appreciable change in GH and FFA was seen during the sojourn at HA. On the other hand, blood lactic acid concentration decreased significantly. There was no difference between the fasting glucose concentrations in ALL at 3500 m and in HAN at 3500 m and 4200 m compared to values of SJ at SL, whereas ALL at 4200 m had higher glucose values. Concentrations of plasma insulin and GH in ALL and HAN were higher than the values of SJ at SL, whereas cortisol values did not show any difference. These observations indicated that at HA the glucose values were high for the insulin concentration observed and might have been due to increased secretion of GH by the pituitary gland.     

Cell mediated immunity at high altitude

Cell mediated immunity (CMI) was assessed by determining total and differential leucocyte and absolute lymphocyte counts, T and B-rosettes, PHA-blast transformation of lymphocytes, lymphocyte migration index (LMI), and DNCB response in 66 sea-level residents, 45 temporary residents, and 24 natives at high altitude (3,692 m). An accentuated CMI, indicated by increase in PHA-blasts, increased lymphocyte migration index, and intense DNCB response, was present, despite a mild decrease in total leucocytes in temporary residents and in lymphocytes in natives at high altitude. While T-rosettes did not show any change in numbers, B-rosettes were increased in temporary residents, and natives at high altitude. A qualitative change had, therefore, occurred in lymphocytes at high altitude. CMI is equally augmented in temporary residents and natives at high altitude and prevails at a higher plane than at sea-level. Augmentation of CMI at high altitude, therefore, could be used as a therapeutic measure.