Influence of acute normobaric hypoxia on physiological variables and lactate turn point determination in trained men.

The goal of this study is to evaluate the response of physiological variables to acute normobaric hypoxia compared to normoxia and its influence on the lactate turn point determination according to the three-phase model of energy supply (Phase I: metabolically balanced at muscular level; Phase II: metabolically balanced at systemic level; Phase III: not metabolically balanced) during maximal incremental exercise. Ten physically active (VO2max 3.9 [0.49] l·min(-1)), healthy men (mean age [SD]: 25.3 [4.6] yrs.), participated in the study. All participants performed two maximal cycle ergometric exercise tests under normoxic as well as hypoxic conditions (FiO2 = 14%). Blood lactate concentration, heart rate, gas exchange data, and power output at maximum and the first and the second lactate turn point (LTP1, LTP2), the heart rate turn point (HRTP) and the first and the second ventilatory turn point (VETP1, VETP2) were determined. Since in normobaric hypoxia absolute power output (P) was reduced at all reference points (max: 314 / 274 W; LTP2: 218 / 184 W; LTP1: 110 / 96 W), as well as VO2max (max: 3.90 / 3.23 l·min(-1); LTP2: 2.90 / 2.43 l·min(-1); LTP1: 1.66 / 1.52 l·min(-1)), percentages of Pmax at LTP1, LTP2, HRTP and VETP1, VETP2 were almost identical for hypoxic as well as normoxic conditions. Heart rate was significantly reduced at Pmax in hypoxia (max: 190 / 185 bpm), but no significant differences were found at submaximal control points. Blood lactate concentration was not different at maximum, and all reference points in both conditions. Respiratory exchange ratio (RER) (max: 1.28 / 1.08; LTP2: 1.13 / 0.98) and ventilatory equivalents for O2 (max: 43.4 / 34.0; LTP2: 32.1 / 25.4) and CO2 (max: 34.1 / 31.6; LTP2: 29.1 / 26.1) were significantly higher at some reference points in hypoxia. Significant correlations were found between LTP1 and VETP1 (r = 0.778; p < 0.01), LTP2 and HRTP (r = 0.828; p < 0.01) and VETP2 (r = 0.948; p < 0.01) for power output for both conditions. We conclude that the lactate turn point determination according to the three-phase-model of energy supply is valid in normobaric, normoxic as well as hypoxic conditions. The turn points for La, HR, and VE were reproducible among both conditions, but shifted left to lower workloads. The lactate turn point determination may therefore be used for the prescription of exercise performance in both environments. Key PointsThe lactate turn point concept can be used for performance testing in normoxic and hypoxic conditionsThe better the performance of the athletes the higher is the effect of hypoxiaThe HRTP and LTP2 are strongly correlated that allows a simple performance testing using heart rate measures only.

Oxidative stress and free radicals in COPD--implications and relevance for treatment.

Oxidative stress occurs when free radicals and other reactive species overwhelm the availability of antioxidants. Reactive oxygen species (ROS), reactive nitrogen species, and their counterpart antioxidant agents are essential for physiological signaling and host defense, as well as for the evolution and persistence of inflammation. When their normal steady state is disturbed, imbalances between oxidants and antioxidants may provoke pathological reactions causing a range of nonrespiratory and respiratory diseases, particularly chronic obstructive pulmonary disease (COPD). In the respiratory system, ROS may be either exogenous from more or less inhalative gaseous or particulate agents such as air pollutants, cigarette smoke, ambient high-altitude hypoxia, and some occupational dusts, or endogenously generated in the context of defense mechanisms against such infectious pathogens as bacteria, viruses, or fungi. ROS may also damage body tissues depending on the amount and duration of exposure and may further act as triggers for enzymatically generated ROS released from respiratory, immune, and inflammatory cells. This paper focuses on the general relevance of free radicals for the development and progression of both COPD and pulmonary emphysema as well as novel perspectives on therapeutic options. Unfortunately, current treatment options do not suffice to prevent chronic airway inflammation and are not yet able to substantially alter the course of COPD. Effective therapeutic antioxidant measures are urgently needed to control and mitigate local as well as systemic oxygen bursts in COPD and other respiratory diseases. In addition to current therapeutic prospects and aspects of genomic medicine, trending research topics in COPD are presented.

Exercise-induced norepinephrine decreases circulating hematopoietic stem and progenitor cell colony-forming capacity.

A recent study showed that ergometry increased circulating hematopoietic stem and progenitor cell (CPC) numbers, but reduced hematopoietic colony forming capacity/functionality under normoxia and normobaric hypoxia. Herein we investigated whether an exercise-induced elevated plasma free/bound norepinephrine (NE) concentration could be responsible for directly influencing CPC functionality. Venous blood was taken from ten healthy male subjects (25.3+/-4.4 yrs) before and 4 times after ergometry under normoxia and normobaric hypoxia (FiO2<0.15). The circulating hematopoietic stem and progenitor cell numbers were correlated with free/bound NE, free/bound epinephrine (EPI), cortisol (Co) and interleukin-6 (IL-6). Additionally, the influence of exercise-induced NE and blood lactate (La) on CPC functionality was analyzed in a randomly selected group of subjects (n = 6) in vitro under normoxia by secondary colony-forming unit granulocyte macrophage assays. Concentrations of free NE, EPI, Co and IL-6 were significantly increased post-exercise under normoxia/hypoxia. Ergometry-induced free NE concentrations found in vivo showed a significant impairment of CPC functionality in vitro under normoxia. Thus, ergometry-induced free NE was thought to trigger CPC mobilization 10 minutes post-exercise, but as previously shown impairs CPC proliferative capacity/functionality at the same time. The obtained results suggest that an ergometry-induced free NE concentration has a direct negative effect on CPC functionality. Cortisol may further influence CPC dynamics and functionality.

Impact of mental and physical stress on blood pressure and pulse pressure under normobaric versus hypoxic conditions.

OBJECTIVE: Hypobaric hypoxia, physical and psychosocial stress may influence key cardiovascular parameters including blood pressure (BP) and pulse pressure (PP). We investigated the effects of mild hypobaric hypoxia exposure on BP and PP reactivity to mental and physical stress and to passive elevation by cable car. METHODS: 36 healthy volunteers participated in a defined test procedure consisting of a period of rest 1, mental stress task (KLT-R), period of rest 2, combined mental (KLT-R) and physical task (bicycle ergometry) and a last period of rest both at Graz, Austria (353 m asl) and at the top station Dachstein (2700 m asl). Beat-to-beat heart rate and BP were analysed both during the test procedures at Graz and at Dachstein and during passive 1000 m elevation by cable car (from 1702 m to 2700 m). RESULTS: A significant interaction of kind of stress (mental vs. combined mental and physical) and study location (Graz vs. Dachstein) was found in the systolic BP (p = .007) and PP (p = .002) changes indicating that during the combined mental and physical stress task sBP was significantly higher under hypoxic conditions whereas sBP and PP were similar during mental stress both under normobaric normoxia (Graz) and under hypobaric hypoxia (Dachstein). During the passive ascent in cable car less trivialization (psychological coping strategy) was associated with an increase in PP (p = .004). CONCLUSION: Our data show that combined mental and physical stress causes a significant higher raise in sBP and PP under hypoxic conditions whereas isolated mental stress did not affect sBP and PP under hypoxic conditions. PP-reaction to ascent in healthy subjects is not uniform. BP reactions to ascent that represents an accumulation of physical (mild hypobaric hypoxia) and psychological stressors depend on predetermined psychological traits (stress coping strategies). Thus divergent cardiovascular reactions can be explained by applying the multidimensional aspects of the biopsychosocial concept.

Exercise increases the frequency of circulating hematopoietic progenitor cells, but reduces hematopoietic colony-forming capacity.

Circulating hematopoietic progenitor cells (CPCs) may be triggered by physical exercise and/or normobaric hypoxia from the bone marrow. The aim of the study was to investigate the influence of physical exercise and normobaric hypoxia on CPC number and functionality in the peripheral blood as well as the involvement of oxidative stress parameters as possibly active agents. Ten healthy male subjects (25.3±4.4 years) underwent a standardized cycle incremental exercise test protocol (40 W+20 W/min) under either normoxic (FiO2 ∼0.21) or hypoxic conditions (FiO2<0.15, equals 3,500 m, 3 h xposure) within a time span of at least 1 week. Blood was drawn from the cubital vein before and 10, 30, 60, and 120 min after exercise. The number of CPCs in the peripheral blood was analyzed by flow cytometry (CD34/CD45-positive cells). The functionality of cells present was addressed by secondary colony-forming unit-granulocyte macrophage (CFU-GM) assays. To determine a possible correlation between the mobilization of CPCs and reactive oxygen species, parameters for oxidative stress such as malondialdehyde (MDA) and myeloperoxidase (MPO) were obtained. Data showed a significant increase of CPC release under normoxic as well as hypoxic conditions after 10 min of recovery (P<0.01). Most interestingly, although CD34+/CD45dim cells increased in number, the proliferative capacity of CPCs decreased significantly 10 min after cessation of exercise (P<0.05). A positive correlation between CPCs and MDA/MPO levels turned out to be significant for both normoxic and hypoxic conditions (P<0.05/P<0.01). Hypoxia did not provoke an additional effect. Although the CPC frequency increased, the functionality of CPCs decreased significantly after exercise, possibly due to the influence of increased oxidative stress levels.

Influence of Intramuscular Application of Autologous Conditioned Plasma on Systemic Circulating IGF-1.

Platelet-rich plasma (PRP) to increase levels of platelets and growth factors has been used for the treatment of sports injuries suggesting to improve healing and regeneration. This method offers some potential especially for elite athletes. However, the insulin like growth factor-1 (IGF-1) is prohibited by the World Anti Doping Agency and, in addition, there may be a possible link between increased levels of IGF-1 and cancer risk. Aim of the study was to evaluate a systemic increase of IGF-1 after local intramuscular administration of PRP in young healthy moderately trained male subjects. Blood samples were drawn and PRP preparation was performed by means of centrifugation. Enriched plasma was injected into the gluteus muscle. Venous blood was collected and serum prepared before as well as after 0.5, 3 and 24 hours after PRP administration. IGF-1 analysis was performed applying an ELISA test kit. No significant systemic increase of mean IGF-1 was found after the PRP injection. Only one subject showed an increase after 24 h, but all IGF-1 values were found within reference limits. We conclude that a single intramuscular application of PRP does not significantly increase systemic IGF-1 levels. Therefore, a single application of PRP is safe with respect to systemic IGF-1 response and cancer risk and this should be allowed for treatment of muscle injuries in elite athletes. Key pointsThere is no increase of systemic IGF-1 levels after a single local intramuscular administration of PRP.Professional athletes and non-athletes alike can benefit from such a treatment option for muscle injuries and related sports injuries without an increased risk of cancer.More studies are warranted to provide definitive evidence to guide surgeon's decision making regarding the appropriate use for PRP products.

[Arterial hypertension due to altitude]. / Arterielle Hypertonie unter Höheneinfluss.

The behavior of blood pressure under hypoxic conditions depends on individual factors, altitude and duration of stay at altitude. While most humans are normotensive at higher altitudes, a few will react with moderate hypertension or hypotension. Excessive elevation of arterial blood pressure is not even to be expected below 4,000 m. Rather, several weeks' stay at higher altitude will decrease systolic and diastolic blood pressure at rest as well as during physical exertion. A high-altitude treatment for rehabilitation purposes at moderate altitude may be recommended for patients with cardio-circulatory disorders. Improvements can last several months even after returning to accustomed altitudes. Furthermore, endurance-trained hypertensive patients with pharmacologically controlled arterial blood pressure might be able to participate in mountain treks without additional health risk.

EEG, ECG and oxygen concentration changes from sea level to a simulated altitude of 4000m and back to sea level.

In order to describe how high altitude affects the body during a one night stay at 4000m experiments were performed in a hypobaric chamber and compared to a study on Dachstein (mountain in Austria, 2700m). Ten subjects had to perform a reaction time task at different altitudes. The EEG and ECG were recorded simultaneously. Additionally, the oxygen saturation of the blood was measured at different altitudes and the subjects filled out a Lake Louise questionnaire that describes the degree of altitude mountain sickness (AMS). After elevation from 134m to 4000m in the hypobaric chamber heart-rate increased from 68.9bpm to 81.6bpm, RMSSD (root mean square of squared differences of adjacent heart beat intervals) decreased from 54.3ms to 33.3ms, the LF/HF ratio increased from 2.5 to 3.9 and oxygen saturation decreased to 82.7% after 11h at 4000m altitude. The Lake Louise Score (LSS) reached 3.4 after one night at 4000m. EEG beta activity between 14Hz and 18Hz was attenuated at 4000m and also after return to 134m. The results indicate that the subjects were not able to adapt to 4000m within 12h in the hypobaric chamber. Even after 1h after the return to 134m all parameters are still affected from the night at 4000m altitude. ECG and EEG changes are in line with results obtained at 2700m height at Dachstein.

Successful outcome after intravenous gasoline injection.

INTRODUCTION: Gasoline, ingested intentionally or accidentally, is toxic. The majority of reported cases of gasoline intoxication involve oral ingestion or inhalation. Data are scarce on complications and outcomes following hydrocarbon poisoning by intravenous injection. CASE REPORT: Following a suicide attempt by intravenous self-injection of 10 ml of gasoline, a 26-year-old medical student was admitted to the intensive care unit (ICU) with hemoptysis, symptoms of acute respiratory failure, chest pain, and severe abdominal cramps. Gas exchange was severely impaired and a chest x-ray indicated chemical pneumonitis. Initial treatment consisted of mechanical ventilation, supportive hyperventilation, administration of nitrogen oxide (NO), and prednisone. Unfortunately, the patient developed multi-organ dysfunction syndrome (MODS) complicated by life-threatening severe vasoplegia within 24 hours after gasoline injection. High doses of vasopressors along with massive amounts of parenteral fluids were necessary. Despite fluid replacement, renal function worsened and required hemofiltration on 5 sequential days. After 12 days of intensive care management, the patient recovered completely and was discharged to a psychiatric care facility. DISCUSSION: Intravenous gasoline injection causes major injury to the lungs, the organ bearing the first capillary bed encountered. Treatment of gasoline poisoning is symptomatic because no specific antidote is available. Early and aggressive supportive care may be conducive to a favorable outcome with minimal residual pulmonary sequelae.

[Lung cavities, mycetomas and hemoptysis]. / Pulmonale Hohlraumbildungen, Myzetome und Hämoptysen.

Pulmonary mycetomas, or fungus balls, consist of spherical masses of mycelia and hyphae, fibrin and granulocytes that grow and partly fill cavitary lesions without invading tissue. They are usually caused by molds of the Aspergillus species, rarely by Mucor or yeast fungi such as Candida species, that colonize damaged lung tissue. Hemoptysis is the most frequent symptom. Since systemic and local administration of antifungal agents is of uncertain efficacy, resectional surgery should be the treatment of choice in cases of severe hemoptysis, if lung function is not severely compromised. As pulmonary resection in the form of lobectomy or pneumonectomy is associated with raised mortality, cavernostomy and cavernoplasty may be options for high-risk patients.

[Invasive candidiasis in the critically ill, patient non-neutropenic]. / Invasive Candidiasis beim nicht-neutropenischen kritisch kranken Patienten.

Invasive candidiasis can occur in immunosuppressed patients as well as in critically ill, non-immunocompromised patients and is associated with high mortality (20-40 %). Intestinal Candida colonisation is an important source for invasive candidiasis. Risk factors for the development of invasive candidiasis include presence of an intravascular device, organ dysfunction, impaired mucosal or skin barrier function, therapy with antacids or corticosteroids, prolonged stay at the ICU, total parenteral nutrition and prolonged antibiotic therapy. Among patients with invasive candidiasis, antifungal treatment should be started without delay. Antifungal prophylaxis is currently not recommended in critically ill, non-immunocompromised patients.

Oxidative stress caused by acute and chronic exposition to altitude.

In this article, current views on cellular and molecular biology (biochemical) mechanisms are discussed under the aspect of altitude exposition. The Andean, Tibetan, and Ethiopian patterns of adaptation to high-altitude hypoxia are known [Beal et al. (2002) Proc Natl Acad Sci USA 99: 17215-17218]. The phylogenetic tree of the human species suggests that there are genetic differences in adaptation patterns to chronic hypoxic hypoxia. Five defense mechanisms are well established for lowlanders who are exposed to acute hypoxic hypoxia. Consequences of the cellular decrease in ATP are the formation of hypoxanthine and xanthine, which are the substrates for the massive formation of superoxide anion radicals and hydrogen peroxide via the oxidase activity of the xanthine oxidoreductase reaction. Under severe hypoxia, about 51 % of the total inhaled oxygen is used to form superoxide anion radicals in rat liver [Gerber et al. (1989) Adv Exp Med Biol 253B, Plenum Press, New York, 497-504]. The reactivity and selectivity of the superoxide anion radical are modified by specific interactions and electron exchange. It is commonly accepted that the superoxide anion radical in aqueous solutions has a lifetime in the millisecond range. However, electron spin resonance spectroscopy studies in a KO2/H2O/iron ion system revealed for the first time a stabilization of a part of the initially added superoxide anion radicals lasting up to hours at room temperature [Földes-Papp (1992) Gen Physiol Biophys 11: 3-38]. Superoxide anion radicals adsorbed on an oxidic iron hydrate phase in aqueous systems might function as a strong oxidant similar to that species which has been suggested to be a complex between oxygen and different valence states of iron in the initiation of lipid peroxidation by ferrous iron. There were serious doubts about the identity of alkoxy radicals. For the first time, alkoxy radicals were directly demonstrated in solution by electron spin resonance spectroscopy [Földes-Papp et al. (1991) Adv Synth Catal 333: 293-301]. The redox status in mammalian cells is mainly determined by the antioxidant glutathione, which is a key player in maintaining the intracellular redox equilibrium and in the metabolic regulation of the cellular defense against oxidative stress. As reactive oxygen species occupy an essential role in membrane damage, the idea of membrane-bound enzymatic defense mechanisms gets a new dimension [Földes-Papp et al. (1981) Acta Biol Med Ger 40: 1129-1132; Földes-Papp and Maretzki (1982) Acta Biol Med Ger 41: 1003-1008]. The steady-state between antioxidants and pro-oxidants affects the gene expression via hypoxia-induced transcription activities. The transcription factor hypoxia-inducible factor 1 (HIF-1) is a global regulator of oxygen homeostasis. As discussed in this article, hypoxia or 'oxidative stress' is accompanied by appropriate molecular adaptation mechanisms at the enzymatic or epigenetic level (enzymatic and non-enzymatic radical inhibitors, posttranslational modifications) and at the genetic level (transcription, translation).

[Aspects and necessity of moderate-altitude research]. / Alpinmedizinische forschung in mittlerer Höhe: Aspekte und Notwendigkeit.

Alpinism in all its variations is a leading factor in tourism. Within a few decades, alpine sports, even at high altitudes, have become available to a wide range of people. Now, more people than ever before are hiking, trekking, climbing and skiing at moderate and high altitudes. Annually, 40 million people spend time in the Alps and 100 million visit high altitudes worldwide. However, alpine excursions may entail health problems and many aspects of impaired adaptation to altitude remain unstudied. High-altitude research has mainly been associated with expeditions, with moderate altitudes receiving far less attention, though most tourism takes place at that level. The overwhelming numbers of alpine tourists mean that there is urgent need for high- and moderate-altitude medical research, which would also be within the realm of political responsibility in mountainous countries. Research in mountain medicine and dissemination of relevant findings can show how to improve and conserve performance in healthy individuals and could point the way toward new, safe approaches in the rehabilitation of patients with chronic diseases. It is imperative that mountain medicine continues to develop on a scientific basis.

Effects of cable car ascent to 2700 meters on mean EEG frequency and event-related desynchronization (ERD).

In the Eastern Alps, the Dachstein massif with a height of almost 3000 m is an ideal location for investigating the effects of changes in altitude on the human body. A cable car allows an ascent within a few minutes to 2700 m, where the partial pressure of oxygen is about 550 mm of mercury compared to 760 mm at sea level. Ten healthy subjects performed a reaction time task at an altitude of 990 m and 2700 m. The subjects were instructed to perform a right hand index finger movement as fast as possible after a green light had flashed. The green light flashed 50 times. Simultaneously to the task, the electroencephalogram (EEG) was recorded. The event-related desynchronization (ERD) analysis of the EEG data showed that changes in alpha ERD values are not significant, but event-related synchronization (ERS) values in the beta band decrease significantly from around 50 % to 10 %. Furthermore, the mean frequency of the beta band increased from 16.68 Hz to 16.81 Hz (p = 0.0019) with the ascent. The suppressed post-movement beta ERS at an altitude of 2700 m may therefore be interpreted as a result of an increased cortical excitability level when compared with the reference altitude of 990 m above sea level.

[Performance testing in mountaineering]. / Leistungsdiagnostik im Bergsport.

Laboratory ergometry to exhaustion allows cardiopulmonal risk assessment for the prevention of health problems related to mountaineering. Moreover, exercise testing evaluates functional status, so permitting individualized training programs and evaluation of training effects. Additionally, mountaineering-specific performance diagnosis allows individual as well as group-specific determination of exercise performance related to field conditions. Laboratory tests are standardized, easy to perform and cost effective. Treadmill ergometry with constant walking speed and increasing inclination is suggested to be predictive for mountaineering performance. On the other hand, the validity for the specific conditions for mountaineering is questionable. Standardized laboratory exercise tests combined with sport-specific exercise tests provide rough information on the ability to sustain real-situation strain. To compare individual exercise performance, published data tables obtained from field tests may be used. It must, however, be mentioned that high-altitude-adaptation is independent of exercise performance evaluated separately.

Effects of a fast cable car ascent to an altitude of 2700 meters on EEG and ECG.

In the Eastern Alps, the Dachstein massif with a height of almost 3000 m is an ideal location for investigating the effects of changes in altitude on the human body. Within a few minutes, a cable car facilitates an ascent from 1702 to 2700 m above sea level, where the partial pressure of oxygen is about 550 mmHg (as compared to 760 mmHg at sea level). In this study, 10 healthy subjects performed a reaction time task at 990 m and 2700 m in altitude. The subjects were instructed to perform a right hand index finger movement as fast as possible after a green light flashed (repeated 50 times). The corresponding electrocardiogram (ECG) and the electroencephalogram (EEG) were recorded. From the ECG heart rate and heart rate variability measures in the time and frequency domain were calculated. An event-related desynchronization/synchronization (ERD/ERS) analysis was performed with the EEG data. Finally, the EEG activity and the ECG parameters were correlated. The study showed that with the fast ascent to 2700 m the heart rate increased and the heart rate variability measures decreased. The correlation analysis indicated a close relationship between the EEG activity and the heart rate and heart rate variability. Furthermore it was shown for the first time that the beta ERS in the 14-18 Hz frequency range (post-movement beta ERS) was significantly reduced at high altitude. Very interesting also is the loss of correlation between EEG activity and cardiovascular measures during finger movement at high altitude. The suppressed post-movement beta ERS at the altitude of 2700 m may be interpreted as results of an increased cortical excitability level when compared with the reference altitude at 990 m above sea level.

Clinical applicability of mass spectrometry for inhaled carbon compounds and the characterization of trace element patterns in body fluids.

So far, chemists, molecular biologists and biochemists have reaped the greatest benefits from mass spectrometry (Aebersold et al., 2003). This type of analysis could, however, be useful in many fields. Mass spectrometry is on its way to the doctor's office (Pusch et al., 2003; Földes-Papp et al., 2002; Henry 1999). The article is focused on laser-activated microprobe mass analysis (LAMMA) and inductively coupled argon plasma mass spectrometry (ICP-MS). Potential applications of the two types of mass spectrometry are demonstrated in clinical medicine. It is the first comprehensive review on qualitative characterization of carbonaceous compounds in lung tissue samples in situ and quantitative trace element determination in body fluids.