Hypercapnia In Man Research Articles

A respiratory response to the activation of the muscle metaboreflex during concurrent hypercapnia in man

In this study, we aimed to assess the ventilatory and cardiovascular responses to the combined activation of the muscle metaboreflex and the ventilatory chemoreflex, achieved by postexercise circulatory occlusion (PECO) and euoxic hypercapnia (end-tidal partial pressure of CO2 7 mmHg above normal), respectively. Eleven healthy subjects (4 women and 7 men; 29 +/- 4.4 years old; mean +/- S.D.) undertook the following four trials, in random order: 2 min of isometric handgrip exercise followed by 2 min of PECO with hypercapnia; 2 min of isometric handgrip exercise followed by 2 min of PECO while breathing room air; 4 min of rest with hypercapnia; and 4 min of rest while breathing room air. Ventilation was significantly increased during exercise in both the hypercapnic (+3.17 +/- 0.82 l min(-1)) and the room air breathing trials (+2.90 +/- 0.26 l min(-1); all P < 0.05). During PECO, ventilation returned to pre-exercise levels when breathing room air (+0.52 +/- 0.37 l min(-1); P > 0.05), but it remained elevated during hypercapnia (+3.77 +/- 0.23 l min(-1); P < 0.05). The results indicate that the muscle metaboreflex stimulates ventilation with concurrent chemoreflex activation. These findings have implications for disease states where effort intolerance and breathlessness are linked.

Variability of cardiovascular responses to hypercapnia in Man

This study attempted to assess the presence of missed opportunity for tetanus toxoid immunization using a Community and Family Survey (CFS) data collected in the five densely populated zones of the SNNPR. The study established the existence of a true missed opportunity for tetanus toxoid immunization among antenatal clients after examining the data for possible sources of biases. A bivariate and multivariate analysis using logistic regression model suggested the absence of both recall and life long protection biases in the data. Accordingly, 11.6% of the women represented a true missed opportunity for tetanus toxoid immunization in the study area. The level of missed opportunity was found to be about 13% in the rural area as compared to only 4% in the urban parts of the study area. Missed opportunity was also high among those women who initiated antenatal visit in their third trimester of pregnancy and those women who had only one visit in the whole course of pregnancy. In the light of the findings, in-depth operational studies are recommended to better understand the reasons behind missed opportunity for tetanus immunization in the study area. (Ethiopian Journal of Health Development, 2000, 14(2): 135-142)

Influence of body position on pressure and airflow generation during hypoxia and hypercapnia in man.

1. Inspiratory oesophageal pressure and ventilatory responses to hyperoxic, progressive hypercapnic rebreathing (HCVR) and isocapnic, progressive hypoxic rebreathing (HVR) were studied in five normal males in both supine and upright seated positions. 2. No significant differences were found in the ventilatory response to hypercapnia between the supine and upright position. The slopes of the relationship between minute ventilation (VI) and the increase of end tidal PCO2 (delta P(ET), CO2) were 3.27 +/- 0.23 and 2.76 +/- 0.24 1 min-1 mmHg-1 supine and upright, respectively. However, the change in oesophageal pressure from the end expiratory level observed during quiet breathing to that at peak inspiration (delta P(oes), I) in relationship to delta P(ET),CO2 was greater supine than upright (1.23 +/- 0.07 versus 0.79 +/- 0.11 cmH2O mmHg-1, P < 0.01). 3. In contrast, during hypoxia-stimulated breathing the slope of the minute ventilation versus oxyhaemoglobin saturation curve (VI-Sa,O2) was flatter supine than upright (1.00 +/- 0.03 versus 1.75 +/- 0.05 l min-1 (percentage fall in Sa,O2)-1, P < 0.0001), but delta P(oes), I in relation to Sa,O2 during hypoxic rebreathing was similar supine and upright (0.38 +/- 0.03 versus 0.40 +/- 0.04 cmH2O (percentage fall in Sa,O2)-1, respectively. 4. It is concluded that body position does not affect the ventilatory response to progressive hyperoxic hypercapnia but does affect the relationship between delta P(oes), I and delta P(ET),CO2. In contrast, body position affects the ventilatory response to isocapnic progressive hypoxia, but does not affect the relationship between delta P(oes), I and Sa,O2.

Metabolic acidosis and breathlessness during exercise and hypercapnia in man.

1. A previous study showed that when combined with exercise in normal subjects, hypercapnic and hypoxic ventilatory stimuli did not have a specific effect on the intensity of the sensation of breathlessness in addition to their stimulation of ventilation. The aim of the present study was to assess the significance of another reflex ventilatory stimulus, metabolic acidosis, in the genesis of this sensation. 2. Six subjects performed progressive exercise tests (mean workload, 103 W; range, 88-125 W) with normal acid-base status. Following NH4Cl-induced metabolic acidosis (mean change in base excess, -3.6 mmol l-1; range, -0.3 to -6.8 mmol l-1) exercise was repeated (mean workload, 91 W; range, 53-116 W) such that the combined ventilatory stimulation resulted in levels of ventilation (mean maximum, 65 l min-1) 'matched' to those resulting from exercise alone. A third, 'matched ventilation', exercise test was performed during metabolic acidosis but with end-tidal PCO2 controlled to a normal level (mean workload, 56 W; range, 17-103 W). Breathlessness was assessed using a visual analogue scale (VAS). 3. Progressive hypercapnic ventilatory stimulation was given before (mean maximum end-tidal PCO2 (PET,CO2), 61 mmHg) and during metabolic acidosis (mean maximum PET,CO2, 57 mmHg) to achieve the same peak level of ventilation (mean maximum, 59 l min-1). Breathlessness was assessed with the VAS. 4. As ventilation increased during a test, there were no statistically significant differences in the increasing breathlessness scores with metabolic acidosis compared to control, for either exercise (mean VAS, 22 mm vs. 24 mm) or progressive hypercapnia (mean peak VAS, 31 mm vs. 32 mm). 5. These results do not support the idea that metabolic acidosis is associated with a change in the relationship between the intensity of breathlessness and ventilation; this is similar to results found with other reflex ventilatory stimuli. 6. These findings are consistent with the hypothesis that the degree of reflex ventilatory activation is an important determinant of the intensity of the sensation of breathlessness in healthy humans, irrespective of the exact nature of ventilatory stimulus.

Separate resistive loading of the respiratory phases during mild hypercapnia in man.

Eleven human subjects were studied during steady state, controlled mild hypercapnia with resistive loading of either inspiration (RI) or expiration (RE). Minute ventilation and frequency were significantly reduced by RI (P = less than 0.01) and even more so by RE (P = less than 0.001). Tidal volume was unchanged. Both RI and RE reduced mean flow in the loaded phase - an effect relatively greater with RE. Neither RI nor RE altered mean flow in the unloaded phase. Although mean inspiratory flow was unchanged with RE, mouth occlusion pressure (P0.1) was increased (P = less than 0.01). Functional residual capacity (seven subjects) was increased with RE, but not with RI (P = less than 0.05). Five additional subjects were similarly studied with and without RE in whom transdiaphragmatic pressure (PDi) and peak diaphragmatic EMG (EMGDi) were examined. Changes in ventilation, breathing pattern and P0.1 were similar to those described above. Neither PDi nor EMGDi were significantly altered by RE, but with RE, diaphragmatic EMG activity began 50-190 ms before inspiratory flow. In conclusion, ventilation is reduced more by RE than by RI due to greater respiratory phase time. Moderately heavy RE does not augment inspiratory drive as reflected by mean flow, PDi or EMGDi. With RE and increased FRC, P0.1 does not accurately reflect inspiratory drive because of dissociation between EMG and flow.

Acid—Base Balance Nomogram—A Boston—Copenhagen Detente

Quantitation of actual and expected complete compensation for chronic hypercapnia in man is facilitated by addition of data of Brackett et al. in the form of an arc to the Siggaard-Andersen alignment nomogram. Percentage of compensation is defined as 100 times the ratio of observed to predicted (fully compensated) base excess at the patient's PCO2. Extracellular fluid base excess, defined as BE3, is estimated from a 3-g hemoglobin line added to the nomogram.

Proposed standard determination of ventilatory responses to hypoxia and hypercapnia in man

Proposed standard determination of ventilatory responses to hypoxia and hypercapnia in man

Proposed Standard Determination of Ventilatory Responses to Hypoxia and Hypercapnia in Man

The Harrison House workshop on methods of measuring ventilatory responses to hypoxia and hypercapnia served to point up both the difficulties and advantages of the various methods in use. The following proposal draws on those discussions in defining a protocol for a pseudo-steady state 20-minute five point test. Subsequent discussion with Cunningham, Lloyd and Cherniack helped to resolve some of the nomenclature differences, and to formulate methods of data reduction which do not require extrapolation or assumptions regarding asymptotes of either PO2 or ventilation.

Assessment of Ventilatory Response to Hypoxia Methods and Interpretation

Study of the ventilatory response to hypoxia in man is contributing important information concerning the physiology of ventilatory control and providing new insights concerning the pathogenesis of respiratory failure. Assessment of ventilatory responses to hypoxia in man may be carried out using a variety of procedures. Most commonly, such responses are measured under conditions in which arterial carbon dioxide tension remains unchanged so that the response of ventilation to hypoxia may be examined independent of inhibiting effects which hyperventilation-induced hypoeapnia would have on such a response. Several techniques are used, but methods employed generally fit into one of four categories. Steady-state techniques involve measurement of ventilation during stepwise decrement of inspired O2 tension where each step is of several minutes' duration. 1 Cormack RS Cunningham DJC Gee JBL The effect of carbon dioxide on the respiratory response to want of oxygen in man.. Quart J Exp Physiol. 1957; 42: 303 Crossref PubMed Scopus (57) Google Scholar Second is the technique of progressive hypoxia. Because the ventilatory response to hypoxia has a relatively short time constant of approximately 18 seconds, the ventilatory response can be described as a continuous function while the oxygen tension of the gas being breathed is gradually lowered. 2 Weil JV Byrne-Quinn E Sodal IE et al. Hypoxic ventilatory drive in normal man.. J Clin Invest. 1970; 49: 1061 Crossref PubMed Scopus (296) Google Scholar This technique yields data comparable to steady-state method. 3 Kronenberg R Hamilton FN Gabel R et al. Comparison of three methods for quantitating respiratory response to hypoxia in man.. Respiration Physiol. 1972; 16: 109 Crossref PubMed Scopus (72) Google Scholar There is concern that these first two methods entail relatively persistent hypoxia which may in time result in depression of ventilation. Hence, a number of investigators have used a third technique—rapid tests involving hypoxic periods lasting no more than a few breaths. The increase in tidal volume of subsequent breaths is used to gauge the response. 4 Dejours P Labrousse Y Raynaud J et al. Etude du stimulus gaz carbonique de la ventilation chez l'homme.. J Physiol. 1958; 50: 239 Google Scholar These latter tests in general suffer from the disadvantage that the stimulus is so rapidly changing and so transient that its precise magnitude cannot be accurately assessed. In addition, the response is also fleeting and it is not certain that the response has become fully developed. Although some investigators have shown reasonably good agreement between transient and steady-state results, 5 Edelman NH Epstein PE Lahiri S et al. Ventilatory responses to transient hypoxia and hypercapnia in man.. Respir Physiol. 1973; 17: 302 Crossref PubMed Scopus (115) Google Scholar transient tests are generally considered less quantitatively rigorous. A fourth method for measuring hypoxic responses depends upon the fact that hypoxia augments the ventilatory response to hypercapnia. The ventilatory response to carbon dioxide is measured at high and low oxygen tensions 6 Nielsen M Smith H Studies on the regulation of respiration in acute hypoxia.. Acta Physiol Scand. 1951; 24: 293 Crossref Scopus (168) Google Scholar , 7 Lloyd BB Jukes MGM Cunningham DJC The relation between alveolar oxygen pressure and the respiratory response to carbon dioxide in man.. Quart J Exp Physiol. 1958; 43: 214 Crossref PubMed Scopus (134) Google Scholar and the change in slope of the hypercapnic response is used as a measure of the hypoxic drive.

Ventilatory responses to transient hypoxia and hypercapnia in man

The contribution of the peripheral (arterial) chemoreceptors to the ventilatory response to acute hypoxia and hypercapnia in intact unanesthetized man has been evaluated by methods which assume that ventilatory responses to transient stimuli reflect their effects upon the arterial chemoreceptors while responses to steady-state stimuli reflect their effects upon both arterial chemoreceptors and the central nervous system. Transient eucapneic hypoxia was produced by inhalation of several breaths of N 2 while breathing room air; transient hypercapneic hypoxia was produced by inhalation of several breaths of N 2 with CO 2 added while breathing CO 2 enriched air. Transient euoxic hypercapnia was produced by inhalation of single breaths of from 6 to 20% CO 2 in 21 % O 2 while the subject breathed air; transient hypoxic hypercapnia was produced by inhalation of single breaths of CO 2 enriched hypoxic gas while the subjects breathed a similarly hypoxic gas mixture. The ventilatory responses to transient hypoxia were qualitatively similar to the responses to steady-state hypoxia although they were quantitatively significantly greater by an average of 18%. The responses to transient euoxic hypercapnia averaged approximately one-third the responses to steady-state euoxic hypercapnia. Responses to transient hypercapnia were much less enhanced by hypoxia than were responses to steady-state hypercapnia. The findings suggest that: (1) A slight. centrally mediated, depressant effect of hypoxia may be present in unanesthetized man; (2) The peripheral chemoreceptors are responsible for approximately one-third of the overall (steady-state) ventilatory response to hypercapnia; (3) The phenomenon of stimulus interaction (enhancement of ventilatory response to hypercapnia by hypoxia) occurs at both the peripheral chemoreceptors and within the central nervous system but the central effect is the predominant one.

Transient ventilatory response to graded hypercapnia in man.

Transient ventilatory response to graded hypercapnia in man.

Respiratory-renal adjustments in chronic hypercapnia in man: Extracellular bicarbonate concentration and the regulation of ventilation

In patients with stable mechanical ventilatory limitation and chronic hypercapnia, chloride depletion by administration of diuretics leads to elevations in extracellular bicarbonate levels which are inordinate for the carbon dioxide tension (PaCO 2). Chloride replacement returns this bicarbonate-PaCo 2 relationship o a predicted level. Ammonium chloride induces an inordinate reduction in extracellular bicarbonate concentrations for the levels of PaCO 2 in arterial blood. The ventilatory responsiveness to inhalation of 5 per cent carbon dioxide following these interventions is related exponentially to the extracellular bicarbonate concentration and not to the level of extracellular hydrogen ion activity measured prior to carbon dioxide inhalation. However, the increase in ventilation per unit increment in extracellular hydrogen ion activity induced by carbon dioxide inhalation ( ΔV E ΔH+ ) is constant. This suggests that the extracellular bicarbonate concentration acts to modulate the ventilatory response to stimulation with carbon dioxide whereas the changes in hydrogen ion activity during carbon dioxide inhalation act as the determinants of the ventilatory response to inhaled carbon dioxide.

The influence of graded degrees of chronic hypercapnia on the acute carbon dioxide titration curve.

Studies were carried out to determine the influence of the chronic level of arterial carbon dioxide tension upon the buffering response to acute changes in arterial carbon dioxide tension. After chronic adaptation to six levels of arterial CO(2) tension, ranging between 35 and 110 mm Hg, unanesthetized dogs underwent acute whole body CO(2) titrations. In each instance a linear relationship was observed between the plasma hydrogen ion concentration and the arterial carbon dioxide tension. Because of this linear relationship, it has been convenient to compare the acute buffering responses among dogs in terms of the slope, dH(+)/dPaco(2). With increasing chronic hypercapnia there was a decrease in this slope, i.e. an improvement in buffer capacity, which is expressed by the equation dH(+)/dPaco(2)=-0.005 (Paco(2))(chronic) + 0.95. In effect, the ability to defend pH during acute titration virtually doubled as chronic Paco(2) increased from 35 to 110 mm Hg. The change in slope, dH(+)/dPaco(2), was the consequence of the following two factors: the rise in plasma bicarbonate concentration which occurs with chronic hypercapnia of increasing severity, and the greater change in bicarbonate concentration which occurred during the acute CO(2) titration in the animals with more severe chronic hypercapnia. These findings demonstrate the importance of the acid-base status before acute titration in determining the character of the carbon dioxide titration curve. They also suggest that a quantitative definition of the interplay between acute and chronic hypercapnia in man should assist in the rational analysis of acid-base disorders in chronic pulmonary insufficiency.

Acid-base changes of arterial plasma during exogenous and endogenous hypercapnia in man

Acute hypercapnic conditions have been produced in man by exogenously given and endogenously accumulated CO 2 in order to compare the nature of the CO 2 titration curves of blood in vivo between these conditions. Effects of general anesthesia on these curves have also been investigated. In the anesthetized subjects there was no significant difference between the slopes of the titration curves for these two modes of hypercapnia. Neither were the slopes of the curves for the unanesthetized subjects determined during exogenous hypercapnia greatly different from those of the anesthetized subjects. A clinical implication of these findings is that a CO 2 titration curve of blood defined in any of the above conditions can be applied to other circumstances without serious error. Non-respiratory acidosis did not occur during the hypercapnic period while apparent non-respiratory acidosis developed during the reversal of hypercapnia. Discrepancy in the length of time spent for the establishment and reversal of hypercapnia is thought responsible for the development of this apparent non-respiratory acidosis.

Acid-base response to chronic hypercapnia in man.

To define "steady-state" chronic hypercapnia in man, we studied 20 patients with stable carbon dioxide tensions from 34 to 103 mm of mercury and with no apparent complicating disorders. The whole-body titration curve in chronic uncomplicated hypercapnia is characterized by a linear increase in estimated hydrogen ion activity as carbon dioxide tension increases. Over a range of carbon dioxide tensions from 34 to 103 mm of mercury the arterial-blood hydrogen ion activity increased by 0.24 nM per liter per millimeter of mercury increase in carbon dioxide tension. Thus, the whole-body defense of arterial-blood pH appears equally effective over the range of carbon dioxide tensions observed in this study. The physiologic response to chronic hypercapnia in man is defined by a zone that is approximately 11 nM per liter (0.10 pH unit) wide for hydrogen ion and 10 mEq wide for bicarbonate. These significance bands may be used to separate mixed acid-base disorders in patients with chronic hypercapnia.