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

    26 December 2017

    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.

    16 February 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.

    6 March 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 April 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.

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

    3 April 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.

    2 February 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.

    15 March 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 April 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?

    16 March 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.

    25 December 2017

    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)

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