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1. In nine normal subjects, analysis was performed of the number, length and location of apnoeic pauses during 20 min of recovery following voluntary overbreathing (VHV). Based on a definition of apnoea as expiratory time greater than 6 s, apnoeas occurred between mean times of 0-8 and 5-6 min after the end of VHV, the end of this period being associated with a mean PET,cO, value of 36-4 mmHg, which was below the initial mean resting value of 39-8 mmHg. 3. Within this apnoeic period, 80 % of experiments produced apnoeas of less than 10 s duration, 61 % of between 10 and 20 s duration and 42 % of between 20 and 30 s duration. Only one out of nine subjects consistently failed to show apnoeas.4. The range of lengths of individual apnoeas and the number per minute were independent of the length and level of VHV and were not significantly different between the four protocols. 5. The number and length of apnoeas did not change in repeated runs in each subject. We were not able to confirm previous reports that apnoeas occurred more frequently in subjects familiar with the experiment. 6. These results reconciled previous studies showing either apnoea or hyperpnoea following voluntary overbreathing in conscious humans. They showed an initial period of heightened breathing lasting about a minute with few apnoeas, consistent with 'afterdischarge'. Beyond that, apnoeas occurred as an 'all-or-nothing' phenomenon as long as PET,C02 was on average less than 3-4 mmHg below resting PET,co0, The occurrence and length of apnoeas was consistent in individual subjects with no evidence of a learning effect.

We compared respiratory patterning at rest and during steady cycle exercise at work rates of 30, 60, and 90 W in 7 male chronically laryngectomized subjects and 13 normal controls. Breathing was measured with a pneumotachograph and end-tidal PCO2 by mass spectrometer. Inspired air was humidified and enriched to 35% O2. Peak flow, volume, and times for the inspiratory and expiratory half cycles, time for expiratory flow, minute ventilation, and mean inspiratory flow were computer averaged over at least 40 breaths at rest and during the last 2 min of 5-min periods at each work rate. During the transition from rest to exercise and with increasing work rate in both groups, there was an increase in respiratory rate and depth with selective and progressive shortening of expiratory time; these responses were not significantly different between the two groups, but there was a suggestion that respiratory "drive" as quantitated by mean inspiratory flow may limit in the laryngectomized subjects at high work rates. Time for expiratory flow increased on transition from rest to exercise and then decreased in both groups as the work rate increased; it was shorter in the laryngectomy than control group at all levels. In the laryngectomized subjects there was significantly more breath-by-breath scatter in some variables at rest, but there was no difference during exercise. It is concluded that chronic removal of the larynx and upper airways in mildly hyperoxic conscious humans has only subtle and, therefore, functionally insignificant effects on breathing during moderate exercise. Evidence is provided that the upper airways can modulate expiratory flow but not expiratory time during exercise.

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and exclusion criteria, wide dissemination of these criteria across the cardiac/stroke network, and instituting a dedicated LAAO clinic for patient assessment pre-and post-implant. Results Between August 2014 and November 2015, 74 LAAO referrals were reviewed at MDT. LAAO was offered to 52/74 (70.3%) patients, of which 42 (56.8%) underwent the procedure, 8 (10.8%) are awaiting it, while 2 (2.7%) declined consent. A decision was taken to treat 14 (18.9%) patients with a novel oral anticoagulant (NOAC) and to maintain watchful waiting in 5 (6.8%). 3 (4.1%) referrals were felt to be inappropriate.42 patients (mean age 75 ± 9 years, 25 males, median CHA 2 DS 2 VASc score 4, median HAS-BLED score 2) underwent LAAO under GA and TOE guidance. The Amplatzer Cardiac Plug was used in the initial 3 cases and Amplatzer Amulet in the remaining 39. Implant was successful in all cases. Mean procedure time was 93 ± 229 min and mean flouro time was 14 ± 88 min. Periprocedural haemorrhage requiring blood transfusion occurred in 2 (4.8%) cases: no other complications were observed. Patients were discharged on a 6-week course of dual antiplatelet therapy, followed by therapy with a single antiplatelet agent.To date, clinical follow-up is available for 27 patients, while most recent 14 patients are awaiting their first follow up; 1 patient has been lost to follow-up. At mean follow-up of 189 ± 119 days, 25/27 patients (92.6%) are free of haemorrhage or thromboembolic events, 1 patient suffered stroke at 12 months post-LAAO, and 1 patient died 3 weeks after the procedure. 24 patients to date have undergone follow-up imaging, 16 patients are awaiting it, and 1 patient could not tolerate TOE and is awaiting CT. 22 of these 24 (91.6%) patients imaged had good LAA seal with no residual leak, while 2 (8%) had small (<5 mm) leak. 1 patient had evidence of a laminar clot on the device and was started on a NOAC. Conclusions Contemporary LAAO implant is associated with 100% procedural success, a very low rate of complications and a high rate of LAA seal on follow up imaging. At our centre, the CtE process has been a catalyst for change and has led to streamlining processes along the entire patient journey. With good clinician engagement, it should provide informative real-life data on patient outcomes that could be used to make funding decisions for the wider NHS.

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