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  • Deep Brain Stimulation for Blood Pressure Control

    3 July 2018

    This chapter focuses on the use of deep brain stimulation (DBS) for controlling blood pressure. Hypertension and orthostatic hypotension refractory to medical treatment present a considerable disease burden, with high associated morbidity and mortality. The periaqueductal gray area (PAG) is an important region for the modulation of pain targeted by DBS electrodes during the treatment of chronic, intractable neuropathic pain. The electrical stimulation of the PAG in animals elicits defence reactions, where dorsal regions are associated with active coping and hypertensive effects and ventral regions with passive coping and hypotensive effects. Thus PAG DBS has been related to hypertensive and chronotropic cardiovascular effects. In a study of 15 chronic neuropathic pain patients (two patients having bilateral implants), blood pressure and heart rate were continuously measured while DBS parameters were altered from 10 to 50 Hz. Cardiovascular responses to stimulation were consistent, as measured on at least three occasions, for any pair of electrode contacts used. Arterial blood pressure reduced significantly overall in seven pairs of electrode contacts in seven patients. Conversely, blood pressure increased significantly in six pairs of contacts in six patients. The demonstration that PAG DBS can increase as well as decrease blood pressure raises the possibility that orthostatic or postural hypotension might be treatable by neurosurgery. © 2009 Elsevier Ltd All rights reserved.

  • Deep brain stimulation for chronic pain

    3 July 2018

    As a clinical intervention, deep brain stimulation (DBS) has provided remarkable therapeutic benefits for otherwise treatment-resistant movement and affective disorders including chronic pain. In this review, we concentrate on the experience of using DBS to treat chronic pain in Oxford. We provide a brief historical background as well as details of our methods for patient selection, surgical techniques and assessment. While the precise mechanisms of action for DBS remain uncertain, we describe how DBS can help for treatment-resistant chronic pain and have great potential to advance our general understanding of the human brain. In particular, we show how DBS can be used in conjunction with methods such as local field potentials and magnetoencephalography to map the underlying mechanisms of normal and abnormal oscillatory synchronization in the brain related to the pleasure of pain relief. © 2010 by Nova Science Publishers, Inc. All rights reserved.

  • The effect of exercise on the development of respiratory depression during sustained isocapnic hypoxia in humans.

    3 July 2018

    The purpose of this study was to examine whether sustained hypoxia during exercise attenuates the degree of decline in hypoxic ventilatory sensitivity which occurs during sustained hypoxia at rest. The acute ventilatory response to hypoxia (AHVR) was used as a measure of the hypoxic ventilatory chemoreflex sensitivity. Seven subjects undertook three protocols. Protocol A was designed to assess the reduction in AHVR as a result of 20 min of isocapnic hypoxia (end-tidal PO2 50 mm Hg) at rest. The first AHVR (control) was measured on exposure to the hypoxia, and the second AHVR (test) measured 6 min after the end of the hypoxic period. Protocols B and C were designed to assess the reduction in AHVR as a result of 20 min of isocapnic hypoxic exercise (70 W). In protocol B, the AHVR (test) was measured at rest, 6 min after the end of 20 min of isocapnic hypoxic (end-tidal PO2 55 mm Hg) exercise. In protocol C, the AHVR (control) as measured at rest, 6 min after the end of 20 min of euoxic (end-tidal PO2 100 mm Hg) isocapnic exercise. There was a 30 +/- 5% decline (mean +/- SEM) in the magnitude of the AHVR after the period of sustained hypoxia at rest. There was an 11 +/- 7% decline in the magnitude of the resting AHVR after the period of sustained hypoxic exercise. The percentage change in AHVR following hypoxic exercise was significantly less than following hypoxia at rest (p < 0.05; paired t test). We conclude that the decline in hypoxic chemoreflex sensitivity which occurs during sustained hypoxia at rest is genuinely attenuated as a result of exercise.

  • Effect of pain and audiovisual stimulation on the depression of acute hypoxic ventilatory response by low-dose halothane in humans.

    3 July 2018

    BACKGROUND: The effects of different low-dose volatile agents in blunting the acute hypoxic ventilatory response (AHVR) are variable. Arousal (due to audiovisual stimulation) may prevent isoflurane-induced blunting of AHVR. The purpose of this study was to assess whether this was also the case for halothane. The authors also assessed the effects of pain on the interaction of halothane and AHVR. METHODS: Step decreases in end-tidal partial pressure of oxygen using dynamic end-tidal forcing were performed from normoxia to hypoxia (50 mmHg) in 10 healthy volunteers, with end-tidal partial pressure of carbon dioxide held 1-2 mmHg above normal, in six protocols: (1) control conditions (darkened, quiet room, eyes closed) without halothane and (2) with 0.1 minimum alveolar concentration (MAC) halothane; (3) audiovisual stimulation (bright room, loud television) without halothane and (4) with 0.1 MAC halothane; (5) pain (electrical stimulation of skin over the tibia to produce a visual analog pain score of 5-6 out of 10) without halothane and (6) with 0.1 MAC halothane. The Bispectral Index of the electroencephalogram was also monitored. RESULTS: Halothane did not affect normoxic minute ventilation in any arousal state but significantly reduced the magnitude of AHVR by 50% regardless of the background arousal state (P < 0.001). Bispectral Index values were reduced by halothane only in the absence of arousal (P < 0.003). Both pain and audiovisual stimulation modestly increased normoxic minute ventilation (P < 0.002) and AHVR (P < 0.003). CONCLUSIONS: Audiovisual stimulation does not prevent the blunting of AHVR by low-dose halothane. This result with halothane differs from previous results with isoflurane. Therefore, different anesthetics interact in different ways with arousal states. This finding raises the possibility that different anesthetics might differentially affect the hypoxic chemoreflex loop or that they might act in the brain at sites separate from the chemoreflex loop, differently to influence the wakefulness drive to ventilation.

  • The ventilatory effects of sustained isocapnic hypoxia during exercise in humans.

    3 July 2018

    To investigate how the ventilatory response to isocapnic hypoxia is modified by steady-state exercise, five subjects were studied at rest and performing 70 W bicycle exercise. At rest, isocapnic hypoxia (end-tidal PO2 50 Torr) for 25 min resulted in a biphasic response: an initial increase in ventilation was followed by a subsequent decline (HVD). During exercise, an end-tidal PO2 of 55-60 Torr was used. The magnitude of the initial ventilatory response to isocapnic hypoxia was increased from a mean +/ SE of 1.43 +/- 0.323 L/min per % arterial desaturation at rest to 2.41 +/- 0.424 L/min per % during exercise (P less than 0.05), but the magnitude of the HVD was reduced from 0.851 +/- 0.149 L/min per % at rest to 0.497 +/- 0.082 L/min per % during exercise (P less than 0.05). The ratio of HVD to the acute hypoxia response was reduced from 0.696 +/- 0.124 at rest to 0.202 +/- 0.029 during exercise (P less than 0.01). We conclude that while exercise augments the ventilatory sensitivity to hypoxia, it also has a direct effect on the mechanisms by which sustained hypoxia depresses peripheral chemosensitivity.

  • Statistical properties of breath-to-breath variations in ventilation at constant PETCO2 and PETO2 in humans.

    3 July 2018

    The purpose of this study was to provide a statistical description of the breath-to-breath variations in ventilation during steady breathing in both rest and during light exercise, with the end-tidal gases controlled by using an end-tidal forcing system. Sixty data sets were studied, only one of which was white (i.e., did not show autocorrelation). Three simple autoregressive moving average (ARMA) models, i.e., AR1, AR2, and AR1MA1, and one simple state-space model were fitted to the data and resulted in white residuals in 15, 31, 46, and 48 out of 60 occasions, respectively. Evolutionary spectral analysis revealed that only 13 data sets had a constant power spectrum, although 50 were uniformly modulated. An autoregressive estimate of variance could be used to "demodulate" the data in most cases, but the results were not significantly affected by fitting the model to the demodulated data. The results indicate that 1) both simple ARMA models and a simple state-space model can describe the autocorrelation present; 2) variations in spectral power were present in the data that cannot be described by these models; and 3) these variations were often due to a uniform modulation and did not significantly affect the coefficients for the models. For these kinds of data, a heteroscedastic form of state-space model provides an attractive theoretical structure for the noise processes.

  • Total oxygen uptake with two maximal breathing techniques and the tidal volume breathing technique: a physiologic study of preoxygenation.

    3 July 2018

    BACKGROUND: Three common methods for preoxygenation are 3 min of tidal breathing, four deep breaths taken within 30 s (4DB), and eight deep breaths taken within 60 s (8DB). This report compares these three techniques in healthy volunteers. METHODS: Five healthy subjects breathed through a mouthpiece and wore a nose clip; oxygen was delivered at 180 l/min via a low-resistance T-piece. Each subject repeated each of the three oxygenation techniques four times. The end-tidal fraction of oxygen was measured, and the oxygen uptake at the mouth was measured breath by breath. The additional difference between oxygen uptake at the mouth during the period of breathing oxygen (as compared with that during air breathing) was taken to represent the total oxygen sequestrated into body stores. RESULTS: The mean +/- SD maximum end-tidal fraction of oxygen after the 4DB method was 0.83 +/- 0.09, which was significantly less than either after the 3-min method (0.92 +/- 0.01; P < 0.04) or after the 8DB method (0.91 +/- 0.04; P < 0.03). The mean additional oxygen taken up during oxygenation with the 4DB method was 1.67 +/- 0.45 l, which was significantly lower than with the 3-min method (2.23 +/- 0.85 l; P < 0.04) or with the 8DB method (2.53 +/- 0.74 l; P < 0.01). There were no significant differences for these variables between the 3-min and 8DB methods. CONCLUSIONS: For the physiologic measurements that were made, both the 3-min and the 8DB method are superior to the 4DB method. The 3-min and 8DB methods seem to be equally effective.

  • Effects of subanaesthetic sevoflurane on ventilation. 2: Response to acute and sustained hypoxia in humans.

    3 July 2018

    We have determined the influence of 0.1 minimum alveolar concentration (MAC) of sevoflurane on the acute ventilatory response to hypoxia (AHVR), hypoxic ventilatory decline (HVD) and the magnitude of the rapid decline in ventilation on relief of sustained hypoxia (the off-response) in eight healthy adult volunteers. The following design was used with and without 0.1 MAC of sevoflurane: end-tidal PO2 was maintained at 13.3 kPa for 5 min, at 7.9 kPa for 20 min and at 13.3 kPa for 5 min. End-tidal PCO2 was held constant throughout at 1.3 kPa above the subject's normal value. A dynamic end-tidal forcing system was used to generate these gas changes. Sevoflurane reduced AHVR from 14.5 (SEM 1.2) to 11.6 (1.6) litre min-1, and the off-response at cessation of hypoxia from 7.1 (1.1) to 6.3 (1.4) litre min-1. The magnitude of HVD was slightly increased by sevoflurane from 8.2 (1.1) to 10.6 (2.8) litre min-1. None of these changes was significant (ANOVA). These results suggest that 0.1 MAC of sevoflurane had very little effect on the AHVR, and that it did not markedly alter the processes underlying HVD during sustained hypoxia.

  • Dorrington Group

    10 July 2016

    Human physiology: the pulmonary circulation, age, iron, and exercise

  • El Andaloussi Group

    16 September 2013

    Development of delivery vectors for therapeutic nucleic acids and proteins

  • Ellory Group

    10 July 2016

    Alterations in membrane transport in response to environment and disease

  • Evans Group

    10 July 2016

    Role of triacylglycerol-rich lipoproteins in substrate supply and metabolic signalling

  • Glitsch Group

    2 April 2014

    Proton dependence of intracellular calcium signalling in the cerebellum in health and disease - role of extracellular pH sensing receptors and ion channels.

  • Goberdhan Group

    10 July 2016

    Growth Regulation and Cancer: mTORC1, Exosomes and Cellular Amino Acid Sensing

  • Goodwin Group

    10 July 2016

    Genetic Dissection of Sexual Behaviour

  • Heather Group

    10 July 2016

    Abnormal metabolism in type 2 diabetes, and how this affects the heart

  • King Group

    10 July 2016

    Neural coding and plasticity in the auditory system

  • Krug Group

    10 July 2016

    Visual Perception and Decision-Making