Physiological and Biological Responses to Short-Term Intermittent Hypobaric Hypoxia Exposure: From Sports and Mountain Medicine to New Biomedical Applications.

In recent years, the altitude acclimatization responses elicited by short-term intermittent exposure to hypoxia have been subject to renewed attention. The main goal of short-term intermittent hypobaric hypoxia exposure programs was originally to improve the aerobic capacity of athletes or to accelerate the altitude acclimatization response in alpinists, since such programs induce an increase in erythrocyte mass. Several model programs of intermittent exposure to hypoxia have presented efficiency with respect to this goal, without any of the inconveniences or negative consequences associated with permanent stays at moderate or high altitudes. Artificial intermittent exposure to normobaric hypoxia systems have seen a rapid rise in popularity among recreational and professional athletes, not only due to their unbeatable cost/efficiency ratio, but also because they help prevent common inconveniences associated with high-altitude stays such as social isolation, nutritional limitations, and other minor health and comfort-related annoyances. Today, intermittent exposure to hypobaric hypoxia is known to elicit other physiological response types in several organs and body systems. These responses range from alterations in the ventilatory pattern to modulation of the mitochondrial function. The central role played by hypoxia-inducible factor (HIF) in activating a signaling molecular cascade after hypoxia exposure is well known. Among these targets, several growth factors that upregulate the capillary bed by inducing angiogenesis and promoting oxidative metabolism merit special attention. Applying intermittent hypobaric hypoxia to promote the action of some molecules, such as angiogenic factors, could improve repair and recovery in many tissue types. This article uses a comprehensive approach to examine data obtained in recent years. We consider evidence collected from different tissues, including myocardial capillarization, skeletal muscle fiber types and fiber size changes induced by intermittent hypoxia exposure, and discuss the evidence that points to beneficial interventions in applied fields such as sport science. Short-term intermittent hypoxia may not only be useful for healthy people, but could also be considered a promising tool to be applied, with due caution, to some pathophysiological states.

Combined intermittent hypobaric hypoxia and muscle electro-stimulation: a method to increase circulating progenitor cell concentration?

BACKGROUND: Our goal was to test whether short-term intermittent hypobaric hypoxia (IHH) at a level well tolerated by healthy humans could, in combination with muscle electro-stimulation (ME), mobilize circulating progenitor cells (CPC) and increase their concentration in peripheral circulation. METHODS: Nine healthy male subjects were subjected, as the active group (HME), to a protocol involving IHH plus ME. IHH exposure consisted of four, three-hour sessions at a barometric pressure of 540 hPa (equivalent to an altitude of 5000 m). These sessions took place on four consecutive days. ME was applied in two separate 20-minute periods during each IHH session. Blood samples were obtained from an antecubital vein on three consecutive days immediately before the experiment, and then 24 h, 48 h, 4 days, 7 days and 14 days after the last day of hypoxic exposure. Four months later a control study was carried out involving seven of the original subjects (CG), who underwent the same protocol of blood samples but without receiving any special stimulus. RESULTS: In comparison with the CG the HME group showed only a non-significant increase in the number of CPC CD34+ cells on the fourth day after the combined IHH and ME treatment. CONCLUSION: CPC levels oscillated across the study period and provide no firm evidence to support an increased CPC count after IHH plus ME, although it is not possible to know if this slight increase observed is physiologically relevant. Further studies are required to understand CPC dynamics and the physiology and physiopathology of the hypoxic stimulus.

Age and sex differences in perioperative myocardial infarction after cardiac surgery.

We investigate age and sex differences in acute myocardial infarction (AMI) after cardiac surgery in a prospective study of 2038 consecutive patients undergoing cardiac surgery with cardiopulmonary bypass. An age of ≥ 70 years implied changes in the type of AMI from the ST-segment elevation myocardial infarction (STEMI) to non-ST-segment elevation myocardial infarction (non-STEMI). Men were more likely than women to suffer from AMI after cardiac surgery (11.8% vs. 5.6%), as a result of the higher frequency of STEMI (6% of men vs. 1.8% of women; P < 0.001) in both age groups. A troponin-I (Tn-I) peak was significantly higher in patients ≥ 70 years old. In-hospital mortality was higher in patients ≥ 70 (7.3%) than in those < 70 years old (3.3%), because of the increased mortality observed in men with non-AMI (2.1% vs. 6.3%) and women with STEMI (0% vs. 28.6%) and non-STEMI (0% vs. 36.8%, P < 0.05). Old age was associated with a higher frequency of non-STEMI, Tn-I peak, mortality and length of stay in the intensive care unit (ICU). Regardless of age, men more often suffer from AMI (particularly STEMI). AMI in women had a notable impact on excess mortality and ICU stay observed in patients ≥ 70 years of age. Clinical and Tn-I peak differences are expected in relation to age and gender after AMI post-cardiac surgery.

Combined intermittent hypoxia and surface muscle electrostimulation as a method to increase peripheral blood progenitor cell concentration.

BACKGROUND: Our goal was to determine whether short-term intermittent hypoxia exposure, at a level well tolerated by healthy humans and previously shown by our group to increase EPO and erythropoiesis, could mobilize hematopoietic stem cells (HSC) and increase their presence in peripheral circulation. METHODS: Four healthy male subjects were subjected to three different protocols: one with only a hypoxic stimulus (OH), another with a hypoxic stimulus plus muscle electrostimulation (HME) and the third with only muscle electrostimulation (OME). Intermittent hypobaric hypoxia exposure consisted of only three sessions of three hours at barometric pressure 540 hPa (equivalent to an altitude of 5000 m) for three consecutive days, whereas muscular electrostimulation was performed in two separate periods of 25 min in each session. Blood samples were obtained from an antecubital vein on three consecutive days immediately before the experiment and 24 h, 48 h, 4 days and 7 days after the last day of hypoxic exposure. RESULTS: There was a clear increase in the number of circulating CD34+ cells after combined hypobaric hypoxia and muscular electrostimulation. This response was not observed after the isolated application of the same stimuli. CONCLUSION: Our results open a new application field for hypobaric systems as a way to increase efficiency in peripheral HSC collection.

Are there sex-based differences in serum troponin I after cardiac surgery?

OBJECTIVE: To determine whether there are sex-based differences in serum troponin I (TnI) after cardiac surgery with cardiopulmonary bypass. DESIGN: Prospective, observational, cohort study. SETTING: Tertiary cardiac surgery intensive care unit (ICU) at a university hospital. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serum TnI was measured in samples obtained at ICU admission and 6, 12, 24, and 48 hours later. A total of 761 consecutive patients were studied (444 men and 317 women). The characteristics and results of the different sex subgroups were as follows:A) Coronary bypass: 165 men and 38 women. Age, Parsonnet score, Acute Physiology and Chronic Health Evaluation III score, prevalence of renal failure, intra-aortic balloon use, and the lengths of cardiopulmonary bypass, mechanical ventilation, and ICU stay were similar in the two groups. Body mass index, red-cell transfusion needs, and use of noradrenaline were significantly higher in women, whereas dobutamine requirements were higher in men. Mortality: 3 men (1.6%) vs. 0 women (p = not significant).The TnI peak was slightly, but significantly, higher in men (6.2 +/- 4.9 vs. 4.5 +/- 2.6 microg/L. p < 0.05).B) Valve surgery: 279 men and 279 women. Some significant differences were found: Women were older than men and had higher Parsonnet score and transfusion needs. The other recorded variables were similar. Mitral prosthesis: 62 men and 125 women (p < 0.05). Mitral valvuloplasty: 24 men, 7 women (p < 0.05). Aortic prosthesis: 162 men, 103 women (p < 0.05). Mitral and aortic prosthesis: 31 men and 44 women (p < 0.05). TnI peaks were similar for both sexes in each valve subgroup. Mortality: 3 men (1%) vs. 11 women (3.4%) (p < 0.05).The TnI peak did not reach any significant differences between sexes (men 7.9 +/- 6.0 vs. 8.5 +/- 6.5 microg/L in women. p = not significant). CONCLUSION: No clinically relevant sex-based differences were found in the TnI peaks after cardiac surgery.

Diabetic retinopathy at high altitude.

The objective of this study was to determine whether altitude hypoxia favors the development of diabetic retinopathy (DR) in healthy type 1 diabetic climbers with tight glycemia control. The retinas of 7 type 1 diabetic climbers with a history of stays at high altitude were studied through nonmydriatic chamber retinography (Ffo-CNM). The retinographies were performed before and after a 7,143 m peak expedition. One of the subjects presented evidence of DR prior to the ascent, in addition to a microhemorrhage afterward; the rest of the retinographies were normal. Fine glycemia management and adequate acclimatization are not the only cautions for diabetics going to altitude; an ophthalmologic exam beforehand is also recommended.

Effects of sildenafil on the human response to acute hypoxia and exercise.

We examined the effects of the 5-phosphodiesterase (5-PDE) inhibitor sildenafil on pulmonary arterial pressure and some oxygen transport and cardiopulmonary parameters in humans during exposure to hypobaric hypoxia at rest and after exercise. In a double-blind study, 100 mg sildenafil or placebo was administered orally to 14 healthy volunteers 45 min before exposure to 5,000 m of simulated altitude. Arterial oxygen saturation (SaO2), heart rate (HR), tidal volume (VT), respiratory rate (RR), left ventricular ejection fraction (EF), and pulmonary arterial pressure (PAP) were measured first at rest in normoxia, at rest and immediately after exercise during hypoxia, and after exercise in normoxia. The increase in systolic PAP produced by hypoxia was significantly decreased by sildenafil at rest from 40.9 +/- 2.6 to 34.9 +/- 3.0 mmHg (-14.8%; p = 0.0046); after exercise, from 49.0 +/- 3.9 to 42.9 +/- 2.6 mmHg (-12.6%; p = 0.003). No significant changes were found in normoxia either at rest or after exercise. Measurements of the effect of sildenafil on exercise capacity during hypoxia did not provide conclusive data: a slight increase in SaO2 was observed with exercise during hypoxia, and sildenafil did not cause significant changes in ventilatory parameters under any condition. Sildenafil diminishes the pulmonary hypertension induced by acute exposure to hypobaric hypoxia at rest and after exercise. Further studies are needed to determine the benefit from this treatment and to further understand the effects of sildenafil on exercise capacity at altitude.