Chronic hypoxia increases blood pressure and noradrenaline spillover in healthy humans

Chronic hypoxia is associated with elevated sympathetic activity and hypertension in patients with chronic pulmonary obstructive disease. However, the effect of chronic hypoxia on systemic and regional sympathetic activity in healthy humans remains unknown. To determine if chronic hypoxia in healthy humans is associated with hyperactivity of the sympathetic system, we measured intra-arterial blood pressure, arterial blood gases, systemic and skeletal muscle noradrenaline (norepinephrine) spillover and vascular conductances in nine Danish lowlanders at sea level and after 9 weeks of exposure at 5260 m. Mean blood pressure was 28% higher at altitude ( P < 0.01) due to increases in both systolic (18% higher, P < 0.05) and diastolic (41% higher, P < 0.001) blood pressures. Cardiac output and leg blood flow were not altered by chronic hypoxia, but systemic vascular conductance was reduced by 30 % ( P < 0.05). Plasma arterial noradrenaline (NA) and adrenaline concentrations were 3.7- and 2.4-fold higher at altitude, respectively ( P < 0.05). The elevation of plasma arterial NA concentration was caused by a 3.8-fold higher whole-body NA release ( P < 0.001) since whole-body noradrenaline clearance was similar in both conditions. Leg NA spillover was increased similarly (× 3.2, P < 0.05). These changes occurred despite the fact that systemic O₂ delivery was greater after altitude acclimatisation than at sea level, due to 37 % higher blood haemoglobin concentration. In summary, this study shows that chronic hypoxia causes marked activation of the sympathetic nervous system in healthy humans and increased systemic arterial pressure, despite normalisation of the arterial O₂ content with acclimatisation.     

Case Report: Giant choledochal cyst

We report an adult female with a rare giant choledochal cyst. The patient presented following a normal pregnancy with the classical triad of an abdominal mass associated with jaundice and right upper quadrant abdominal pain. The cyst was excised using an intramural technique and biliary reconstruction achieved with a Roux-en-Y hepaticojejunostomy. Our patient has remained well with no evidence of malignancy over a 12 year review period. The aetiology and current management of this condition are discussed.     

Determination of optimal cryoprotectants and procedures for their addition and removal from human spermatozoa

The objective was to test the hypothesis that the optimal cryoprotective agent for cryopreservation of human spermatozoa would be a solute for which cells have the highest plasma membrane permeability, resulting in the least amount of volume excursion during its addition and removal. To test this hypothesis, theoretical simulations were performed using membrane permeability coefficients to predict optimal procedures for the addition and removal of a cryoprotectant. Simulations were performed using data from four different cryoprotectants: (i) glycerol, (ii) dimethyl sulphoxide, (iii) propylene glycol and (iv) ethylene glycol. Thermodynamic formulations were applied to determine approaches for the addition and removal of 1 M and 2 M final concentrations of cryoprotectant, allowing the spermatozoa to maintain a cell volume within their osmotic tolerance limits. Based on these data, ethylene glycol was predicted to be optimal for minimizing volume excursions among the solutes evaluated. These predictions were then experimentally tested using glycerol as the control cryoprotectant and ethylene glycol as the experimental cryoprotectant. The results indicate that there was a higher (P < 0.05) recovery of motile spermatozoa after cryopreservation when using 1 M ethylene glycol than with 1 M glycerol, supporting the hypothesis that use of the cryoprotectant for which the cell has the highest permeability will result in higher cell survival.      

Oxygen tension and content in the regulation of limb blood flow

During submaximal exercise, muscle blood flow increases when arterial oxygen content (CaO2) is reduced. The increase in blood flow is brought about by elevating cardiac output (CO) and enhancing leg vascular conductance. Conversely, increased CaO2 elicits lower limb blood flow (LBF) and CO. During maximal exercise, the influence of CaO2 on muscle blood flow is modulated depending on the amount of muscle mass recruited. When a small muscle mass is activated and the pumping capacity of the heart is not limited, changes in CaO2 barely influence the level of blood flow attained at peak exercise. However, when a large muscle mass is engaged in the exercise, as occurs for example during cycling and running, muscle blood flow is decreased if maximal CO is reduced, as happens during exercise in severe hypoxia. In contrast, maximal muscle blood flow and CO are maintained at peak exercise when CaO2 is increased. As such, exercise intensity, muscle mass and CaO2 appear to be the critical factors determining muscle blood flow during exercise.