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Biomedical subjects

S J Semple

Publications and source records attributed to S J Semple.

At least 73 records · Page 4Linked to original sources

The effect of small changes in arterial carbon dioxide tension on carotid chemoreceptor activity in the cat.

The hypothesis that the fluctuations in carotid chemoreceptor discharge represent more than a simple proportional response to respiratory oscillations of Pa, CO2 has been examined. Simultaneous recordings of the activity in few- or multi-fibre chemoreceptor preparations of the cut carotid sinus nerve and oscillations of carotid arterial pH have been made in four anaesthetized cats which were paralysed and artificially ventilated at constant frequency. Chemoreceptor activity was averaged over a minimum of twenty consecutive pH cycles and the amplitude of the fluctuations in discharge frequency determined. Using the mean Pa, CO2 obtained from blood-gas analysis and the slope of the relationship between log Pa, CO2 and pH obtained in each cat, the amplitude of the pH oscillations was converted to Pa, CO2 amplitude. This amplitude relative to the mean Pa, CO2 has been compared with the amplitude of the corresponding fluctuation in the chemoreceptor discharge frequency recorded from the carotid sinus nerve (e.s.n.d. amplitude) relative to its mean level. Whereas the Pa, CO2 amplitude was always less than 8% of the mean Pa, CO2, the c.s.n.d. amplitude ranged from 40 to 186% of the mean discharge frequency. C.s.n.d. amplitude was divided by the corresponding Pa, CO2 amplitude to give an index of the sensitivity of the chemoreceptors to Pa, CO2. This sensitivity has been compared with that determined from the mean discharge frequency produced in response to changes in mean Pa, CO2 comparable in magnitude to the Pa, CO2 amplitude. The former sensitivity was usually at least 3 times greater than the latter. Examination of the fluctuations in chemoreceptor discharge frequency in relation to the corresponding pH oscillations revealed that whereas the minimum discharge frequency coincided with the alkaline peak of the pH oscillation (trough of the Pa, CO2 oscillation), the maximum discharge frequency did not invariably coincide with the acid trough of the pH oscillation (peak of the Pa, CO2 oscillation). On 30% of occasions, the maximum discharge frequency was associated with the region of maximum rate of fall of pH (maximum rate of rise of Pa, CO2). It was concluded that fluctuations in the discharge of carotid chemoreceptors cannot be accounted for on the basis of a simple proportional relationship to Pa, CO2. They contain a large rate of change component.

Action Potentials↗

Is the voluntary control of exercise in man necessary for the ventilatory response?

The ventilatory response to electrically induced exercise (EEL) was studied in eighteen normal subjects and compared with the response to performing the same exercise voluntarily (EV). EEL was produced by surface electrode stimulation of the quadriceps and hamstring muscles so as to cause a pushing movement at 1 HZ against a spring load; this produced no pain or discomfort. Matching of EV to EEL was achieved by subjects copying a tension signal recorded during EEL and displayed on a storage oscilloscope. There were no differences between the resting states measured before either form of exercise. The ventilatory response (change in ventilation as a ratio of the change in CO2 elimination) was similar in the two types of exercise. The increases in ventilation and CO2 elimination were greater with EEL. Small but significant increases in the gas exchange ratio and serum lactate were found for EEL but not for EV, suggesting an increase in anaerobic metabolism in EEL. End-tidal PCO2 showed little change in either form of exercise. In some runs end-tidal PCO2 rose, but insufficiently to account for the ventilatory response as judged by the response to inhaled CO2. In two subjects arterial blood samples showed small and inconsistent changes in both Pa,CO2 and PaO2 for EV and EEL. pH and base excess changes also were consistent with more anaerobiosis with EEL compared to EV. The first ten breaths of exercise were used to study the on transient. In EV, expiratory duration shortened and ventilation increased significantly on the first breath but CO2 elimination did not increase until the second breath; in EEL, these variables did not change significantly until the second breath. For the remainder of the on transient the pattern of the ventilatory response was similar for EV and EEL. By the end of the on transient both EV and EEL had reached approximately 80% of their final steady-state values. These results suggest that a normal ventilatory response can occur in the absence of a drive to exercise from the cortex.

Adult↗

The role of spinal cord transmission in the ventilatory response to exercise in man.

The ventilatory response to electrically induced exercise was studied in thirteen patients with traumatic spinal cord transection at or about the level of T6. The steady-state and on-transient responses to this exercise were compared with those obtained in eighteen normal subjects (Adams, Garlick, Guz, Murphy & Semple, 1984). Exercise was produced by surface electrode stimulation of the quadriceps and hamstring muscles so as to produce a pushing movement at 1 HZ against a spring load. At rest there was no significant difference between normals and patients, except that the patients had a lower CO2 elimination (VCO2) and end-tidal PCO2 (PET,CO2) and a higher heart rate. On exercise the mean rise in VCO2 for the patients was 172 ml min-1 (S.D. 72), and for the normals was 287 ml min-1 (S.D. 143). The corresponding mean changes in ventilation (VI) were 4.4 l min-1 (S.D. 2.2) and 7.6 l min-1 (S.D. 3.2). However, the ventilatory equivalent for CO2 (delta VI/delta VCO2) in the steady state was not significantly different between patients (26.0, S.D. 5.9) and normals (28.5, S.D. 7.4). In the steady state there was a mean rise in PET,CO2 of 0.9 mmHg (S.D. 1.4) in the normals, and 3.2 mmHg (S.D. 2.7) in the patients, but there was overlap between the two groups. In many experimental runs in both groups, PET,CO2 did not rise, and sometimes fell. Where PCO2 did rise, the ventilatory response to exercise could not be accounted for on the basis of the ventilatory sensitivity to CO2 inhalation. From arterial sampling in three of the patients it was found that when PET,CO2 rose, the corresponding change in Pa,CO2 was less. During the on transient, there was a significant rise in both VCO2 and VI by the second breath in both groups. At the end of the on transient the normal subjects had achieved 84% (S.D. 40) of the steady-state increase in VCO2 and 88% (S.D. 24) of the increase in VI. The corresponding values for the patients were 67% (S.D. 17) and 77% (S.D. 16) respectively; these differences between normals and patients are significant. The increase of VI during the on transient in the patients was achieved almost entirely by an increase in tidal volume whereas in normals, an increase in respiratory rate was a more important component. We conclude therefore that in man, spinal cord transection with a presumed loss of muscle afferents allows a ventilatory response to electrically induced exercise that cannot be explained by classical chemoreception.(ABSTRACT TRUNCATED AT 400 WORDS)

Carbon Dioxide↗

Effect of 3-hydroxybutyrate in obese subjects on very-low-energy diets and during therapeutic starvation.

Sodium DL-3-hydroxybutyrate was administered to obese subjects (more than 150% ideal body-weight) who were either receiving a 2 . 5 MJ (600 kcal) diet containing 34 g protein on one day with a total fast (water and vitamins only) on the next day, for 21 days, or were undergoing therapeutic starvation for 14 days. Both intravenous and oral hydroxybutyrate significantly reduced net body protein loss as measured by total urinary nitrogen and 3-methylhistidine excretion. Hydroxybutyrate administration did not significantly affect the rate of weight-loss but seemed to increase the fat/lean ratio of the tissue loss. The subjects experienced no untoward effects and none complained of hunger while receiving 3-hydroxybutyrate.

3-Hydroxybutyric Acid↗

Effect of intravenous 3-hydroxybutyrate on postoperative nitrogen balance.

Thirty-two patients routinely admitted for cholecystectomy were allocated randomly to receive a post-operative fluid regimen containing either 18 g/d of sodium DL-3-hydroxybutyrate, or isoenergetic glucose, each for 3 d. The difference in the post-operative mean daily urinary nitrogen excretion between the control (median 8.3 g/d) and the 3-OH-butyrate groups (median 8.3 g/d) was not statistically significant, nor was there any difference when allowances were made for patient's surface area or for changes in blood urea during the course of the study.

Adult↗

The role of spinal cord transmission in the ventilatory response to electrically induced exercise in the anaesthetized dog.

1. The ventilatory response to electrically induced ;exercise' was studied in six chloralose-anaesthetized dogs. The on-transient and steady-state responses to ;exercise' were compared in the same dogs before and after spinal cord transection at T8/9 (dermatome level T6/7) on fifteen occasions.2. Phasic hind limb ;exercise' was induced for periods of 4 min by passing current (2 Hz modulated 50 Hz sine wave) between two needles inserted through the hamstring muscles. The maximum current used was 30 mA. This was below the level previously found to produce an artifactual stimulation of breathing with the cord intact.3. Cord transection produced no significant change in either the resting values of ventilation ( V(I)) and CO(2) production ( V(CO) (2)) or the ventilatory equivalent for CO(2) during ;exercise' ( big up tri, open V(I)/ big up tri, open V(CO) (2)).4. During the steady state of exercise P(a, CO) (2) was on average significantly lower than at rest with the cord intact (mean big up tri, openP(a, CO) (2), - 2.1 mmHg; range - 5.7 to + 1), and higher, though not significantly, with the cord cut (mean P(a, CO) (2), + 1.2 mmHg; range - 1.5 to + 4.3). However, even in the absence of spinal cord transmission, the ventilatory response to exercise could not be accounted for on the basis of CO(2) sensitivity; the big up tri, open V(I)/ big up tri, openP(a,CO) (2) obtained with exercise (apparent sensitivity) was significantly greater than that obtained with CO(2) inhalation (true sensitivity) both before and after cord section.5. V(I) and V(CO) (2) increased more slowly with the cord cut than with the cord intact. This was thought to be due to a slower increase in venous return in the absence of sympathetic innervation of the lower half of the body following cord transection.6. Similar experiments were performed during muscle paralysis (following gallamine triethiodide). Ventilation was maintained with a respirator controlled by phrenic nerve activity. These experiments showed an increase in ventilation, independent of muscle contraction, which was only present when the cord was intact and which was confined to the on-transient. Only in the absence of spinal cord transmission could there be certainty that the dynamics of the ventilatory response to electrically induced ;exercise' was free of artifact.7. It was concluded that spinal cord transmission is not necessary for the steady-state ventilatory response to electrically induced exercise of the hind limbs.8. The dog with spinal cord transection provides a suitable model for the study of the chemical control of breathing during electrically induced exercise.

Anesthesia, General↗

The ph oscillations in arterial blood during exercise; a potential signal for the ventilatory response in the dog.

1. The effect of electrically induced ;exercise' on the respiratory oscillation of arterial pH was studied in chloralose-anaesthetized dogs with spinal cord transection at T8/9 (dermatome level T6/7).2. Respiratory oscillations of arterial pH (presumed to be due to oscillations of arterial P(CO2)) were sensed with a fast-responding electrode in one carotid artery. Breath-by-breath estimates of the maximum rate of change of pH of the downstroke of the pH oscillation (dpH/dt downward arrowmax) were obtained by differentiating the pH signal.3. Consistent with the findings of the previous paper (Cross et al. 1982), the ventilatory response to exercise could not be explained on the basis of sensitivity to CO(2); the Delta V(I)/DeltaP(a, CO2) was significantly greater for ;exercise' than for CO(2) inhalation.4. On average, the amplitude of the pH oscillations decreased during ;exercise'. The change in the phase relationship (varphi) between respiratory and pH cycles, although significant from the second breath onwards, was not thought to be responsible for the increased ventilation V(I); the direction of the change was opposite to that previously found to increase V(I).5. Inspiratory duration (t(i)), expiratory duration (t(e)), V(I) and the dpH/dt downward arrowmax changed significantly by the third breath of ;exercise'. A significantly linear relationship was obtained between t(e) and dpH/dt downward arrowmax during the on-transient (first ten breaths) of ;exercise'. This relationship was maintained throughout ;exercise'. V(I) and dpH/dt downward arrowmax were also linearly related during the on-transient, although the same relationship did not hold true throughout ;exercise'.6. The dpH/dt downward arrowmax was related to CO(2) production ( V(CO2)) lending support to the prediction that the slope of the downstroke of the pH oscillation is a function of V(CO2).7. It was concluded that the dpH/dt downward arrowmax (dpCO(2)/dt upward arrowmax) is a potential humoral signal in ;exercise' and could account totally for the shortening of t(e). Since there was a late rise in V(I) (due to an increase in tidal volume V(T)) in the absence of a change in dpH/dt downward arrowmax, it was considered unlikely that the dpH/dt downward arrowmax was the only humoral signal present during ;exercise'.

Animals↗

Ventilatory response to inhaled and infused CO2: relationship to the oscillating signal.

The purpose of this study was to determine the relationship between the respiratory oscillations of CO2 and the ventilatory response to CO2. Cats anaesthetized with chloralose and urethane were given CO2 either by exchange transfusion into the inferior vena cava or by inhalation. Changes of amplitude of the respiratory oscillations of CO2 (amp PCO2) were assessed from measurements of the amplitude of the arterial pH oscillations (amp pH). For short periods of CO2 loading (2-8 min), the ventilatory response to CO2 was greater for venous than for airway loading; this difference was statistically significant at low and intermediate loads but not at high loads. The dependence of the respiratory response to the route of administration of CO2 could not be related to amp PCO2. For long periods of CO2 loading (20 min or more) there was no marked change of minute ventilation when the route of administration was changed from airway to venous route, despite an increase of amp pH at both low and intermediate loads. We suggest that the dependence of ventilatory response to CO2 on the route of administration observed in this study was mainly due to a longer period required to attain steady state conditions for CO2 inhalation, and that the respiratory oscillations of CO2 do not affect the ventilatory response to CO2.

Animals↗

Dependence of phrenic motoneurone output on the oscillatory component of arterial blood gas composition.

1. The hypothesis that respiratory oscillations of arterial blood gas composition influence ventilation has been examined. 2. Phrenic motoneurone output recorded in the C5 root of the left phrenic nerve and the respiratory oscillations of arterial pH in the right common carotid artery were measured in vagotomized anaesthetized dogs which had been paralysed and artificially ventilated. 3. The effect of a change in tidal volume for one or two breaths on phrenic motoneurone output was measured with the inspiratory pump set at a constant frequency similar to, and in phase with, the animal's own respiratory frequency. A reduction of tidal volume to zero or an increase by 30% led to a corresponding change of mean carotid artery pH level. The changes of carotid artery pH resulted in a change of phrenic motoneurone output, predominantly of expiratory time (Te) but to a lesser extent of inspiratory time (T1) and also peak amplitude of 'integrated' phrenic motoneurone output (Phr). Denervation of the carotid bifurcation blocked this response. 4. The onset of movement of the inspiratory pump was triggered by the onset of phrenic motoneurone output. When a time delay was interposed between them, the phase relationship between respiratory oscillations of arterial pH and phrenic motoneurone output altered. The dominant effect was to alter Te; smaller and less consistent changes of Phr and T1 were observed. 5. When the inspiratory pump was maintained at a constant frequency but independent of and slightly different from the animal's own respiratory frequency (as judged by phrenic motoneurone output), the phase relationship between phrenic motoneurone output and the respiratory oscillations of pH changed breath by breath over a sequence of 100-200 breaths, without change of the mean level of arterial blood gas composition. Te varied by up to 30% about its mean value depending on the phase relationship. Ti and Phr were also dependent on the phase relationship but varied to a lesser extent. The changes were comparable to the results obtained in paragraph 4. 6. It was concluded that phrenic motoneurone output is dependent in part on its relationship to the respiratory oscillations of arterial blood gas composition. 7. Information concerning a transient ventilatory disturbance is stored in the arterial blood in the form of an altered pattern of the respiratory oscillations of blood gas composition; this in turn can change breathing by an effect on the carotid bodies.

Action Potentials↗

Breathlessness.

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Dyspnea↗

Hypercapnia during oxygen therapy in acute exacerbations of chronic respiratory failure. Hypothesis revisited.

A modification is proposed to the well-known hypothesis which explains the development of progressive carbon-dioxide retention in patients with acute exacerbations of chronic respiratory failure when they are given supplementary oxygen to breathe. It is suggested that, in these patients, increased production of lactic acid by the brain, due to profound hypoxia, leads to a central hypoxic drive to breathing which is absent in remission when the arterial oxygen tension is higher. Evidence from the literature in support of this modification is sought by comparing the respiratory response to oxygen of patients in an acute exacerbation of respiratory failure with the response of patients in a chronic stable state. Three patients are described in whom the response to oxygen during an acute infective episode was very different from their response when in remission.

Acute Disease↗