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  • Effects of subanaesthetic sevoflurane on ventilation. 1: Response to acute and sustained hypercapnia in humans.

    3 July 2018

    We have determined the influence of 0.1 minimum alveolar concentration (MAC) of sevoflurane on ventilation, the acute ventilatory response to a step change in end-tidal carbon dioxide and the ventilatory response to sustained hypercapnia in 10 healthy adult volunteers. Subjects undertook a preliminary 10-min period of breathing air without sevoflurane to determine their normal ventilation and natural end-tidal PCO2. This 10-min period was repeated while breathing 0.1 MAC of sevoflurane. Subjects then undertook two procedures: end-tidal PO2 was maintained at 13.3 kPa and end-tidal PCO2 at 1.3 kPa above the subject's normal value for 30 min of data collection, first with and then without 0.1 MAC of sevoflurane. A dynamic end-tidal forcing system was used to generate these gas profiles. Sevoflurane did not significantly change ventilation: 10.1 (SEM 1.0) litre min-1 without sevoflurane, 9.6 (0.9) litre min-1 with sevoflurane. The response to acute hypercapnia was also unchanged: mean carbon dioxide response slopes were 20.2 (2.7) litre min-1 kPa-1 without sevoflurane and 18.8 (2.7) litre min-1 kPa-1 with sevoflurane. Sustained hypercapnia caused a significant gradual increase in ventilation and tidal volume over time and significant gradual reduction in inspiratory and expiratory times. Sevoflurane did not affect these trends during sustained hypercapnia. These results suggest that 0.1 MAC of sevoflurane does not significantly affect the acute ventilatory response to hypercapnia and does not modify the progressive changes in ventilation and pattern of breathing that occur with sustained hypercapnia.

  • Effects of different levels of end-tidal PO2 on ventilation during isocapnia in humans.

    3 July 2018

    The purpose of this investigation was to examine how the ventilatory decline observed during sustained, eucapnic hypoxia (HVD) is affected by different levels of hypoxia. Six subjects were each studied 3-6 times at each of 5 different levels of isocapnic hypoxia (end-tidal PO2 equal to 45, 50, 55, 65 and 75 Torr) in random order. The following variables were linearly related to saturation: (1) the rapid increase in ventilation at the onset of hypoxia; (2) the decline in ventilation over the period of hypoxia; and (3) the undershoot in ventilation below the pre-hypoxic control values at the relief of hypoxia. The rapid decrease in ventilation at the relief of hypoxia, however, was not linearly related to saturation. The mean time to peak ventilation was 2.13 +/- 0.07 min (+/- SE) at the onset of hypoxia, which was significantly longer (P less than 0.05) than the time to minimum ventilation at the relief of hypoxia of 1.23 +/- 0.18 min. The recovery from the undershoot in ventilation was 95% +/- 3% complete after 5 min, whereas the recovery in sensitivity to hypoxia was only 35% +/- 13% complete after 5 min of euoxia.

  • Ventilation and gas exchange during sustained exercise at normal and raised CO2 in man.

    3 July 2018

    Five subjects underwent each of three protocols for 43 min: (A) at rest; end-tidal PCO2 was held constant at 2-5 Torr above resting values; (B) during 70 Watt bicycle exercise; PETCO2 was uncontrolled; (C) during 70 Watt exercise; PETCO2 was held 2-5 Torr above exercising values. During all protocols, end-tidal PO2 (PETO2) was held at 100 Torr. The first 5 min of each protocol were excluded from data analysis to approach a steady state, and the remaining 38 min analysed to determine whether any trends were present. At rest, ventilation did not change over the 38 min period. However, during hypercapnic exercise (protocol C), ventilation rose significantly by a mean +/- SE of 4.9 +/- 0.8 L/min (P less than 0.01) over the 38 min period. In protocol B, ventilation was lower than in protocol C, but did not change over the 38 min period. However, PETCO2 fell significantly by a mean of 0.65 +/- 0.05 Torr (P less than 0.01). This change in PETCO2 was due to a significant fall in the respiratory quotient (mean = -0.05 +/- 0.01, P less than 0.01) and metabolic CO2 production (mean = -0.06 +/- 0.01 L/min, P less than 0.01). The fall in respiratory quotient implies a change in metabolic substrate during exercise. Furthermore, the results suggest that ventilation is not always matched closely to metabolic CO2 production during exercise.

  • Ventilatory chemoreflexes at rest following a brief period of heavy exercise in man.

    3 July 2018

    1. Ventilatory chemoreflex responses have been studied at rest during the recovery from a brief period of heavy exercise. 2. Six young, healthy male subjects each undertook four experimental studies. In each study measurements were made at rest during recovery from an exhaustive 1-2 min sprint on a bicycle ergometer with a workload of 400 W. Three levels of end-tidal O2 pressure (Po2) were employed. Continuous ventilatory measurements were made during euoxia (end-tidal Po2, 100 Torr), hypoxia (end-tidal Po2, 50 Torr) and hyperoxia (end-tidal Po2, 300 Torr). Arterialized venous blood samples were drawn during each of the measurement periods for the estimation of arterial pH. In two of the studies, end-tidal CO2 pressure (Pco2) was maintained throughout at 1-2 Torr above the eucapnic level that existed prior to exercise (isocapnic post-exercise protocol, IPE). In the other two studies, end-tidal Pco2 was allowed to vary (poikilocapnic post-exercise protocol, PPE). Data from a previously published study on the same subjects involving an infusion of hydrochloric acid were used to provide control data with a varying level of metabolic acidosis, but with no prior exercise. 3. Ventilation-pH slopes in the IPE protocol were no different from control. Ventilation-pH slopes in the PPE protocol were significantly lower than in the IPE and control protocols (P < 0.05, ANOVA). This difference may be due to the progressive change in end-tidal Pco2 in the PPE protocol compared with the constant end-tidal Pco2 in the IPE and control protocols. 4. An arterial pH value of 7.35 was attained 30.4 +/- 2.7 min (mean +/- S.E.M.) after the end of exercise in the IPE protocol and 17.1 +/- 1.4 min after the end of exercise in the PPE protocol. 5. Hypoxic sensitivities at an arterial pH of 7.35 were not significantly different between the IPE, PPE and control protocols (ANOVA). 6. Euoxic ventilation at an arterial pH 7.35 was significantly greater than control for the IPE protocol (P < 0.001, Student's paired t test) and no different from control for the PPE protocol. 7. The results suggest that 30 min after heavy exercise, ventilation remains stimulated by processes other than the post-exercise metabolic acidosis, and that changes in peripheral chemoreflex sensitivity to hypoxia and acid are not implicated in this.

  • Increased hypoxic ventilatory sensitivity during exercise in man: are neural afferents necessary?

    3 July 2018

    1. The acute ventilatory response to 3 min periods of hypoxia (AHR) was examined in nine patients with clinically complete spinal cord transection (T4-T7) during (a) rest and (b) electrically induced leg exercise (EEL). 2. EEL was produced by surface electrode stimulation of the quadriceps muscles so as to cause the legs to extend at the knee against gravity. End-tidal PCO2 was held constant 1-2 mmHg above resting values throughout both protocols. 3. On exercise, the average increase in metabolic CO2 production (VCO2 +/- S.E.M.) was 41 +/- 5 ml min-1. Venous lactate levels did not rise with exercise. 4. Baseline euoxic ventilation did not increase significantly with EEL, but there was a consistent and highly significant increase in the ventilatory response to hypoxia during EEL (mean delta AHR +/- S.E.M. of 1.6 +/- 0.21 min-1). 5. We conclude that an increase in hypoxic sensitivity during exercise can occur in the absence of volitional control of exercise and in the absence of afferent neural input from the limbs.

  • Acute ventilatory responses to hypoxia during voluntary and electrically induced leg exercise in man.

    3 July 2018

    1. The acute ventilatory response to a brief period of hypoxia (AHVR) was measured in six subjects (a) at rest, (b) during electrically induced leg exercise (EEL), (c) during voluntary leg exercise at an external work rate matched to electrical exercise (EV1) and (d) during voluntary leg exercise at an internal work rate (i.e. metabolic rate) matched to electrical exercise (EV2). The end-tidal PO2 during hypoxia was 50 mmHg and the end-tidal PCO2 was held constant at 1-2 mmHg above resting values throughout each of these four protocols. 2. EEL was produced by surface electrode stimulation of the quadriceps muscles so as to cause the legs to extend at the knee and lift a set of weights via a pulley system. During EV1, each subject lifted the same weight through the same height and at the same frequency as during his EEL protocol. During EV2, the weight, the height through which it was lifted and the frequency of voluntary contractions were altered to produce a similar O2 consumption and CO2 production as during EEL. 3. In each subject, end-tidal PCO2 values showed no change between the four protocols, and in three subjects in whom they were measured, arterial PCO2 values were also similar between the protocols. Venous lactate levels did not increase after EEL or EV2. 4. The AHVR during EEL (14.1 +/- 1.42 l min-1; mean +/- S.E.M) was significantly increased (Student's paired t test) compared with rest (7.55 +/- 1.10 l min-1; P < 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

  • An assessment of central-peripheral ventilatory chemoreflex interaction using acid and bicarbonate infusions in humans.

    3 July 2018

    1. The object of this study was to investigate the effect of central chemoreceptor stimulation on the ventilatory responses to peripheral chemoreceptor stimulation. 2. The level of central chemoreceptor stimulation was varied by performing experiments at two different levels of end-tidal CO2 pressure (PCO2). Variations in peripheral chemoreceptor stimulus were achieved by varying arterial pH (at constant end-tidal PCO2) and by varying end-tidal O2 pressure (PO2). 3. Two protocols were each performed on six human subjects. In one protocol ventilatory measurements were made during eucapnia, when the arterial pH was lowered from 7.4 to 7.3. The variation in pH was achieved by the progressive infusion of acid (0.1 M HCl). In the other protocol ventilatory measurements were made during hypercapnia, when the arterial pH was increased from 7.3 to 7.4. The variation in pH was achieved by the progressive infusion of 1.26% NaHCO3. In each protocol ventilatory responses were measured during euoxia (end-tidal PO2, 100 Torr), hypoxia (end-tidal PO2, 50 Torr) and hyperoxia (end-tidal PO2, 300 Torr), with end-tidal PCO2 held constant. 4. The increase in ventilatory sensitivity to arterial pH induced by hypoxia (50 Torr) was not significantly different between protocols (acid protocol, -104 +/- 31 l min-1 (pH unit)-1 vs. bicarbonate protocol, -60 +/- 44 l min-1 (pH unit)-1; mean +/- S.E.M.; not significant (n.s.)). The ventilatory sensitivity to hypoxia at an arterial pH of 7.35 was not significantly different between protocols (acid protocol, 14.7 +/- 3.3 l min-1 vs. bicarbonate protocol, 15.6 +/- 2.4 l min-1; mean +/- S.E.M.; n.s.). The results provide no evidence to suggest that peripheral chemoreflex ventilatory responses are modulated by central chemoreceptor stimulation.

  • On the origin of oscillopsia during pedunculopontine stimulation.

    3 July 2018

    We report a case of induced oscillopsia caused by deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN). Recent reports have described involuntary oscillopsia during DBS of the PPN that patients have described as trembling vision. Here we substantiate this observation using infra-red eye tracking. It has been suggested that this phenomenon might be used as an indicator of accurate targeting of the PPN with DBS. Our observations suggest that this phenomenon may not be related to a constricted anatomical structure and therefore such practise may be unwise. Scrutiny has led us to believe that the oscillopsia in our patient is not caused by direct stimulation of the oculomotor nerve as suggested in a previous report, but by stimulation of fibres in the uncinate fasciculus of the cerebellum and the superior cerebellar peduncle, which in turn stimulate the saccadic pre-motor neurones in the brainstem.

  • Driving oscillatory activity in the human cortex enhances motor performance

    3 July 2018

    Voluntary movement is accompanied by changes in the degree to which neurons in the brain synchronize their activity within discrete frequency ranges. Two patterns of movement-related oscillatory activity stand out in human cortical motor areas. Activity in the beta frequency (15-30 Hz) band is prominent during tonic contractions but is attenuated prior to and during voluntary movement [1]. Without such attenuation, movement may be slowed, leading to the suggestion that beta activity promotes postural and tonic contraction, possibly at a cost to the generation of new movements [2, 3]. In contrast, activity in the gamma (60-90 Hz) band increases during movement [4]. The direction of change suggests that gamma activity might facilitate motor processing. In correspondence with this, increased frontal gamma activity is related with reduced reaction times [5]. Yet the possibility remains that these functional correlations reflect an epiphenomenal rather than causal relationship. Here we provide strong evidence that oscillatory activities at the cortical level are mechanistically involved in determining motor behavior and can even improve performance. By driving cortical oscillations using noninvasive electrical stimulation, we show opposing effects at beta and gamma frequencies and interactions with motor task that reveal the potential quantitative importance of oscillations in motor behavior. © 2012 Elsevier Ltd.

  • Lakhal-Littleton Group

    10 July 2016

    Iron Homeostasis- Mechanisms and importance in systems (patho)physiology

  • Mann Group

    10 July 2016

    Laboratory of Oscillations & Plasticity

  • McMenamin Group

    16 September 2013

  • Miesenboeck Group

    10 July 2016

    Optical Control of Neurons; Neuronal Control of Behaviour

  • Morris Group

    16 September 2013

    Ultrastructural immunocytochemistry

  • Noble Group

    16 September 2013

    University of Oxford Innovative Systems Biology Project Sponsored by Tsumura

  • Oliver Group

    10 July 2016

    Investigating novel gene function in neurodegeneration and behaviour

  • Parekh Group

    16 September 2013

    Intracellular calcium signalling in health and disease

  • Parker Group

    10 July 2016

    Neural systems and circuits for visual perception

  • Paterson Group

    10 July 2016

    Gene Transfer of Nitric Oxide Synthase into Cardiac Nerves Modulates Neurotransmission