A pilot investigation into the effects of acute normobaric hypoxia, high altitude exposure and exercise on serum angiotensin-converting enzyme, aldosterone and cortisol

Introduction. Aldosterone decreases at high altitude (HA) but the effect of hypoxia on angiotensin converting-enzyme (ACE), a key step in the renin-angiotensin-aldosterone system, is unclear. Materials and Methods. We investigated the effects of exercise and acute normobaric hypoxia (NH, ~11.0% FiO2) on nine participants and six controls undertaking the same exercise at sea-level (SL). NH exposure lasted 5 hours with 90 min of submaximal treadmill walking. Blood samples for aldosterone, ACE and cortisol were taken throughout exposure and at rest during a trek to HA (5140 m) in eight separate participants. Results. There was no difference in cortisol or aldosterone between groups pre-exercise. Aldosterone rose with exercise to a greater extent at SL than in NH (post-exercise: 700±325 vs 335±238 pmol/L, mean ± SD, p=0.044). Conversely, cortisol rose to a greater extent in NH (post-exercise: 734±165 vs 344±159 nmol/L, mean ± SD, p=0.001). There were no differences in ACE activity. During the trek to HA resting aldosterone and cortisol reduced with no change in ACE. Conclusion. Acute NH subdues the exercise-associated rise in aldosterone but stimulates cortisol, whereas prolonged exposure at HA reduces both resting aldosterone and cortisol. As ACE activity was unchanged in both environments this is not the mechanism underlying the fall in aldosterone

Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial

Background Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects. Methods FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762. Findings Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months. Interpretation Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function. Funding UK Stroke Association and NIHR Health Technology Assessment Programme