Critical Life Functions: Can Placebo Replace Oxygen? Benedetti Fabrizio,Barbiani Diletta,Camerone Eleonora International review of neurobiology A crucial question in placebo research is related to which conditions and physiological functions are affected by placebos. Here we present evidence that critical life functions, like ventilation, oxygenation, circulation, and perfusion, can be sensitive to placebo treatments in some circumstances. Indeed, we have investigated the role of placebo effects at an altitude of 3500m, where oxygen pressure is 64% compared to the sea level. In these extreme conditions, hypoxia triggers several compensatory responses, such as hyperventilation, increased cardiac output, and increased brain perfusion. A conditioned placebo procedure was found to mimic the effects of oxygen on these compensatory responses, and these effects are still present at altitudes as high as 4500 and 5500m, where oxygen pressure is only 57% and 50%, respectively, compared to the sea level. Thus, placebo effects also take place for those functions that are critical for life and whereby oxygen is the key element. 10.1016/bs.irn.2018.01.009

Nutrition and energetics of exercise at altitude. Theory and possible practical implications. Kayser B Sports medicine (Auckland, N.Z.) Altitude exposure may lead to considerable weight loss. Most reports, showing weight losses of 3% in 8 days at 4300m and up to 15% after 3 months at 5300 to 8000m, appear to indicate that this weight loss is a function of both absolute altitude and the duration of exposure. Based on the available scientific evidence to date, it is concluded that altitude weight loss is because of an initial loss of water and subsequent loss of fat and muscle mass due to malnutrition. Up to 5500m, malabsorption of macronutrients does not occur. Up to altitudes around 5000m, weight loss from a reduction of fat and muscle appears to be avoidable by maintaining adequate dietary intake. Primary anorexia, lack of comfort and palatable food, detraining, and possibly direct effects of hypoxia on protein metabolism seem inevitably to lead to weight loss during longer exposures at higher altitudes. To minimise losses, it is advisable to acclimatise properly, reduce the length of stay at extreme altitude as much as possible and maintain a high and varied nutrient intake. With sojourns at intermediate altitude for training purposes, adequate energy intake should be maintained taking into account the decrease in aerobic training intensity and the increase in basal metabolic rate that ensue from the hypoxic environment. 10.2165/00007256-199417050-00004

Cortisol awakening response and emotion at extreme altitudes on Mount Kangchenjunga. Aguilar Raúl,Martínez Carlos,Alvero-Cruz José R International journal of psychophysiology : official journal of the International Organization of Psychophysiology The cortisol awakening response (CAR) was examined over a 45days stay at extreme altitudes (above of about 5500m) on Mount Kangchenjunga. The CAR refers to a peak cortisol response during the waking period that is superimposed to the diurnal rhythmicity in cortisol secretion, whose function has been proposed to be the anticipation of demands of the upcoming day (the CAR anticipation hypothesis). According to this hypothesis, we distinguished between resting days on which the expedition team engaged in routine activities in the base camp, and ascent days on which it planned to climb up a very demanding track. We were also interested in examining the association of testosterone with emotional anticipation, given the role of this steroid hormone in reward-related processes in challenge situations. Results showed that the climber group had a bigger CAR on ascent days, relative to the Sherpa group at the same altitude and the non-climber group at sea level. Several methodological issues, however, made it difficult to interpret these group differences in terms of the CAR anticipation hypothesis (e.g. a seemingly influential covariate was awakening time). Although based on tentative results, correlational and regression analyses controlling for awakening time coherently showed that the CAR was associated with anticipation of a hard day and feelings of fear, and testosterone was associated with feelings of energy and positive affect. Whether or not the anticipation of a hard day played a key role in regulation of the CAR, the observation of an intact CAR in the climber group under hypobaric hypoxia conditions would require in-depth reflection from the perspective of human adaptive evolution. 10.1016/j.ijpsycho.2017.12.007

Cardio-pulmonary interactions at high altitude. Pulmonary hypertension as a common denominator. Maggiorini Marco Advances in experimental medicine and biology The purpose of this review is to find the evidence that a disproportionate pulmonary vasoconstriction persisting for days, weeks and years during residence at high altitude is the common pathophysiologic mechanism of high altitude pulmonary edema (HAPE), subacute mountain sickness and chronic mountain sickness. A recent finding in early HAPE suggests that transmission of excessively elevated pulmonary artery pressure to the pulmonary capillaries leading to alveolar hemorrhage as the pathophysiologic mechanism of HAPE. The elevated incidence of HAPE in Indian soldiers led the Indian Army to extend the acclimatization period from a few days to 5 weeks. Using this protocol, HAPE was prevented, but after several weeks of residence at an altitude of 6000m dyspnea, anasarca and pleuro-pericardial effusion developed. Clinical examination revealed severe congestive right heart failure. This condition has been previously described in long-term high altitude residents of the Himalaya and the Andes. In rats, smooth muscle cells appear in normally non-muscular arterioles within days of simulated altitude. Rapid remodeling of the small precapillary arteries may prevent HAPE but increase pulmonary vascular resistance leading to pulmonary hypertension in long-term high altitude residents. Symptoms and signs of HAPE, subacute mountain sickness and chronic mountain sickness reverse completely after residents are transfered to low altitude. In conclusion, these findings strongly suggest that pulmonary hypertension at high altitude, which could be named "high altitude pulmonary hypertension", is the principal and common pathogenic factor of all three cardio-pulmonary manifestations of high altitude illness. Accordingly, subacute mountain sickness and chronic mountain sickness could be renamed in "acute-" and "chronic right heart failure of high altitude", respectively. 10.1007/978-1-4419-8997-0_13

Changes in atrial natriuretic peptide and brain natriuretic peptide associated with hypobaric hypoxia-induced pulmonary hypertension in rats. Nakanishi K,Tajima F,Itoh H,Nakata Y,Osada H,Hama N,Nakagawa O,Nakao K,Kawai T,Takishima K,Aurues T,Ikeda T Virchows Archiv : an international journal of pathology Experimental pulmonary hypertension induced in a hypobaric hypoxic environment (HHE) is characterized by structural remodeling of the heart and pulmonary arteries. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) both have diuretic, natriuretic, and hypotensive effects, and both are involved in cardiovascular homeostasis as cardiac hormones. To study the effects of HHE on the natriuretic peptide synthesis system, 170 male Wistar rats were housed in a chamber at the equivalent of the 5500-m altitude level for 1-12 weeks. After 1 week of HHE, pulmonary arterial pressure was significantly raised, and the ratio of left ventricle plus septum over right ventricle of the heart showed a significant decrease (compared with those of ground-level control rats). In both ventricular tissues, the expression of ANP messenger (m)RNA and BNP mRNA increased after exposure to HHE. The amounts of ANP and BNP had decreased significantly in right atrial tissue at 12 weeks of HHE (compared with those of the controls), whereas in ventricular tissues at the same time point, both levels had increased significantly. In in situ hybridization and immunohistochemical studies, the staining of the mRNAs for ANP and BNP and of ANP and BNP themselves was more intense in both ventricular tissues after exposure to HHE than before (i.e., in the controls). The results suggest that, in response to HHE, the changes in ventricular synthesis are similar for ANP and BNP. These changes may play a role in modulating pulmonary hypertension in HHE. However, under our conditions, pulmonary hypertension increased progressively throughout the HHE period.