Dynamics of myocardial adaptation to low-flow ischemia and hypoxemia

We investigated whether one or more factors control performance in O2- limited hearts. For this purpose, we measured the dynamics of myocardial adaptation to reduced O2 supply with a specially designed setup, analyzing early changes after reduction in either flow of the perfusion medium or its PO2. For 10 min, 38 isolated rat hearts underwent low-flow ischemia or hypoxemia, matched for O2 supply. Early during ischemia, developed pressure declined at a rate of 311 \ub1 25 mmHg/s; lactate release increased and then leveled off to 3.4 \ub1 0.7 \u3bcmol/min within 2 min. During hypoxemia, pressure dropped initially, as observed during ischemia. However, it then increased before slowly decreasing. Lactate release during hypoxemia peaked at 13.0 \ub1 2.3 \u3bcmol/min after 2 min, leveling off to 3.5 \ub1 1.3 \u3bcmol/min. Glycogen decreased by 52 and 81% in ischemic and hypoxemic hearts, respectively (P < 0.05). Reexposure to ischemia or hypoxemia induced comparable changes in both groups. We conclude that, at the beginning of ischemia, a single factor does limit myocardial performance. This variable, which remains undisturbed for 10 min, is presumably O2 availability. In contrast, 20 s after induction of hypoxemia, glycolytic ATP production can partially override low O2 availability by providing most of the energy needed. During repeated restriction of O2 supply, O2 availability alone limits performance during both ischemia and hypoxemia

Low-frequency positive pressure ventilation with extracorporeal carbon dioxide removal (LFPPV-ECCO2R) : an experimental study

We describe a new form of mechanical pulmonary ventilation, low-frequency positive pressure ventilation with extracorporeal CO2 removal (LEPPV-ECCO2R). In a series of animal studies the rate of mechanical ventilation was 0.66, 1, 2, and 4 min-1 at a tidal volume of 3, 10, and 15 ml kg-1. We were able to maintain normal blood gases and normal lung volumes and lung mechanics even at the lowest ventilator rate with tidal volumes of 10 or 15 ml kg-1. Each experiment lasted 7 hours. Our data suggest a possible new dimension in the management of a difficult patient on mechanical pulmonary ventilation

Environmental health : reflexions of the Brazilian Association of Post-Graduation in Collective Health - ABRASCO

O Brasil, apesar de sua extraordinária biodiversidade e do enorme potencial instalado para desenvolver ações integradas na temática do ambiente, não tem dado, do ponto de vista programático, a prioridade que o tema ambiente merece. A Associação Brasileira de Pós-Graduação em Saúde Coletiva-ABRASCO reconheceu a importância de organizar um Grupo Temático “Saúde e Ambiente” para, de maneira mais organizada, participar da luta pelo desenvolvimento sustentável, através da ação política no campo da saúde coletiva, em busca de ambientes saudáveis e da promoção da saúde. O objetivo principal deste Grupo Temático-GT foi contribuir para que o tema da saúde ambiental seja internalizado no campo da Saúde Coletiva. Método: O Grupo escolheu três eixos para discussão em uma oficina do V Congresso Brasileiro de Epidemiologia, em Curitiba, no ano de 2002. O resultado resultado do debate ocorrido foi apresentado segundo três eixos: identificação do campo teórico-conceitual em Saúde Ambiente; a política de saúde e ambiente; o caminho metodológico. A conclusão foi apresentada no formato de uma agenda do GT para o biênio 2002-2004. _______________________________________________________________________________________ ABSTRACTNot with standing its extraordinary biodiversity and enormous installed potential to develop actions integrated in to the topic of environmental health, Brazil has not given the environmental the priority the subject deserves from the programmatic, point of view. The Brazilian Association of Post-Graduation in Collective Health - ABRASCO recognized the importance of organizing a Thematic Group “Health and Environment” in order to, in a more organized fashion, participate in the struggle for sustainable development, through political action in collective health, oriented to wards health environments and health promotion. The main objective of this Thematic Group was to facilitate the subject of the environmental health to be internalized in to the field of the Collective Health. Method: The theme was debated in a workshop during the V Brazilian Congress of Epidemiology in Curitiba, in 2002. Results were presented according to three axes: 1- Identification of the theoretical-conceptual field in Environmental Health; 2- the politics of health and environment; 3- methodological route. The general conclusion was presented as an agenda for ABRASCO’s Thematic Group in Environmental Health for the biennial 2002-2004

Maximal exercise at extreme altitudes on Mount Everest

Maximal exercise at extreme altitudes was studied during the course of the American Medical Research Expedition to Everest. Measurements were carried out at sea level [inspired O2 partial pressure (PO2) 147 Torr], 6,300 m during air breathing (inspired PO2 64 Torr), 6,300 m during 16% O2 breathing (inspired PO2 49 Torr), and 6,300 m during 14% O2 breathing (inspired PO2 43 Torr). The last PO2 is equivalent to that on the summit of Mt. Everest. All the 6,300 m studies were carried out in a warm well-equipped laboratory on well-acclimatized subjects. Maximal O2 uptake fell dramatically as the inspired PO2 was reduced to very low levels. However, two subjects were able to reach an O2 uptake of 1 l/min at the lowest inspired PO2. Arterial O2 saturations fell markedly and alveolar-arterial PO2 differences increased as the work rate was raised at high altitude, indicating diffusion limitation of O2 transfer. Maximal exercise ventilations exceed 200 l/min at 6,300 m during air breathing but fell considerably at the lowest values of inspired PO2. Alveolar CO2 partial pressure was reduced to 7-8 Torr in one subject at the lowest inspired PO2, and the same value was obtained from alveolar gas samples taken by him at rest on the summit. The results help to explain how man can reach the highest point on earth while breathing ambient air

Changes in labial capillary density on ascent to and descent from high altitude

Present knowledge of how the microcirculation is altered by prolonged exposure to hypoxia at high altitude is incomplete and modification of existing analytical techniques may improve our knowledge considerably. We set out to use a novel simplified method of measuring in vivo capillary density during an expedition to high altitude using a CytoCam incident dark field imaging video-microscope. The simplified method of data capture involved recording one-second images of the mucosal surface of the inner lip to reveal data about microvasculature density in ten individuals. This was done on ascent to, and descent from, high altitude. Analysis was conducted offline by two independent investigators blinded to the participant identity, testing conditions and the imaging site. Additionally we monitored haemoglobin concentration and haematocrit data to see if we could support or refute mechanisms of altered density relating to vessel recruitment. Repeated sets of paired values were compared using Kruskall Wallis Analysis of Variance tests, whilst comparisons of values between sites was by related samples Wilcoxon Signed Rank Test. Correlation between different variables was performed using Spearman’s rank correlation coefficient, and concordance between analysing investigators using intra-class correlation coefficient. There was a significant increase in capillary density from London on ascent to high altitude; median capillaries per field of view area increased from 22.8 to 25.3 (p=0.021). There was a further increase in vessel density during the six weeks spent at altitude (25.3 to 32.5, p=0.017). Moreover, vessel density remained high on descent to Kathmandu (31.0 capillaries per field of view area), despite a significant decrease in haemoglobin concentration and haematocrit. Using a simplified technique, we have demonstrated an increase in capillary density on early and sustained exposure to hypobaric hypoxia at thigh altitude, and that this remains elevated on descent to normoxia. The technique is simple, reliable and reproducible

AltitudeOmics: Red Blood Cell metabolic adaptation to high altitude hypoxia

Red blood cells (RBCs) are key players in systemic oxygen transport. RBCs respond to in vitro hypoxia  through  the so-called  oxygen-dependent  metabolic  regulation,  which  involves  the competitive  binding  of  deoxyhemoglobin  and  glycolytic  enzymes  to  the  N-terminal  cytosolic domain  of  band  3.  This  mechanism  promotes  the  accumulation  of  2,3-DPG,  stabilizing  the deoxygenated state of hemoglobin, and cytosol acidification, triggering oxygen off-loading through the  Bohr  effect.  Despite  in  vitro  studies,  in  vivo adaptations  to  hypoxia  have  not  yet  been completely elucidated. Within  the  framework  of  the AltitudeOmics  study,  erythrocytes  were  collected  from  21 healthy volunteers at sea level, after exposure to high altitude (5260m) for 1, 7 and 16days, and following  reascent  after  7days  at 1525m.  UHPLC-MS  metabolomics  results  were  correlated  to physiological and athletic performance parameters. Immediate  metabolic  adaptations  were  noted as early as a few hours from ascending  to >5000m, and maintained for 16 days at high altitude.  Consistent with the mechanisms elucidated in vitro, hypoxia promoted glycolysis and deregulated the pentose phosphate pathway, as well purine catabolism, glutathione homeostasis, arginine/nitric oxide and sulphur/H2S metabolism. Metabolic adaptations were preserved one week after descent, consistently with improved physical performances in comparison to the first ascendance, suggesting a mechanism of metabolic memory

Phosphodiesterase-5 Inhibition Mimics Intermittent Reoxygenation and Improves Cardioprotection in the Hypoxic Myocardium

Although chronic hypoxia is a claimed myocardial risk factor reducing tolerance to ischemia/reperfusion (I/R), intermittent reoxygenation has beneficial effects and enhances heart tolerance to I/R. Aim of the study: To test the hypothesis that, by mimicking intermittent reoxygenation, selective inhibition of phosphodiesterase-5 activity improves ischemia tolerance during hypoxia. Adult male Sprague-Dawley rats were exposed to hypoxia for 15 days (10% O2) and treated with placebo, sildenafil (1.4 mg/kg/day, i. p.), intermittent reoxygenation (1 h/day exposure to room air) or both. Controls were normoxic hearts. To assess tolerance to I/R all hearts were subjected to 30-min regional ischemia by left anterior descending coronary artery ligation followed by 3 h-reperfusion. Whereas hypoxia depressed tolerance to I/R, both sildenafil and intermittent reoxygenation reduced the infarct size without exhibiting cumulative effects. The changes in myocardial cGMP, apoptosis (DNA fragmentation), caspase-3 activity (alternative marker for cardiomyocyte apoptosis), eNOS phosphorylation and Akt activity paralleled the changes in cardioprotection. However, the level of plasma nitrates and nitrites was higher in the sildenafil+intermittent reoxygenation than sildenafil and intermittent reoxygenation groups, whereas total eNOS and Akt proteins were unchanged throughout. Conclusions: Sildenafil administration has the potential to mimic the cardioprotective effects led by intermittent reoxygenation, thereby opening the possibility to treat patients unable to be reoxygenated through a pharmacological modulation of NO-dependent mechanisms