Euoxic Hypercapnia Research Articles

Cerebrovascular Responsiveness to Hypercapnia Is Stable over Six Months in Older Adults.

The primary purpose of this Brain in Motion (BIM) sub-study was to determine the 6-month stability of resting blood flow velocity and cerebrovascular responsiveness to a euoxic hypercapnic challenge in a group of physically inactive community dwelling men and men aged ≥55 yrs (range 55–92 yrs). At baseline and 6 months later 88 women (65±6 yr) and 78 men (67±7 yr) completed a hypercapnic challenge (step changes from resting end-tidal PCO2 ((PETCO2) to +1, +5 and +8 mmHg above rest) while cerebral blood flow velocity was assessed using transcranial Doppler ultrasound. Peak velocity of the middle cerebral artery (MCAv) was increased (p<0.05) at the second visit during rest (51±2 vs. 52±4); however, these differences were abolished (p>0.05) when MCAv was normalized to PETCO2. During hypercapnia, MCAv tended to be increased at follow-up, but this finding was absent when MCAv/PETCO2 was compared across time. Cerebrovascular reactivity (i.e., ΔMCAv/ΔPETCO2) was similar (p>0.05) between testing occasions regardless of the approach taken (i.e., considering only the lower step [from +1 to +5 mmHg]; the upper step [+5 to +8 mmHg]; or the complete test taken together). In conclusion, this study has shown that cerebral blood flow and cerebrovascular responsiveness to acute euoxic hypercapnia are stable in older, healthy adults over a 6-month period. Modest changes in MCAv over time must be viewed in the context of underlying differences in PETCO2, an important finding with implications for future studies considering cerebral blood flow velocity.

Nonstationary multivariate modeling of cerebral autoregulation during resting state and hypercapnia (1184.10)

We examined the time‐varying characteristics of cerebral autoregulation and hemodynamics during resting state and hypercapnia by using recursively estimated multivariate (two‐input) models which quantify the dynamic effects of mean arterial blood pressure (ABP) and end‐tidal CO2 tension (PETCO2) on middle cerebral artery blood flow velocity (CBFV). Experimental measurements of spontaneous variations of these signals were obtained from thirteen healthy subjects under normal, free‐breathing conditions. Beat‐to‐beat values of ABP and CBFV, as well as breath‐to‐breath values of PETCO2 were also obtained in 8 female subjects during baseline and sustained euoxic hypercapnia. The multiple‐input, single‐output linear models used to describe the relationship between ABP, PETCO2 and CBFV were based on the Laguerre expansion technique. In order to account for the different dynamics associated with each input, the model parameters were updated using a recursive least squares scheme with constant and adaptive multiple forgetting factors. The results reveal the presence of nonstationarities that are more pronounced in the very low frequency range. By comparing one‐input (MABP) and two‐input (MABP and PETCO2) models, our results point out that the incorporation of PETCO2 as an additional input yields less time‐varying estimates of dynamic pressure autoregulation obtained from single‐input (MABP‐CBFV) models, suggesting the important role of PETCO2 and the possible shortcomings of assessing dynamic autoregulation using such models.

Chapter 17 - The Peripheral Actions of the Central Neuropeptide Somatostatin on Control of Breathing: Effect on Metabolic Rate and Chemoreflex Responses in Humans

Peripherally infused somatostatin in humans reduces the acute ventilatory response to hypoxia but it is not known if it reduces basal minute ventilation, and there are conflicting results as to whether or not it reduces the acute hypercapnic ventilatory response. One explanatory mechanism for all these possible effects is that somatostatin reduces metabolic rate. We therefore tested the hypothesis that somatostatin can reduce whole-body metabolic rate (measured by gas exchange at the mouth) in a manner that (a) reduces basal minute ventilation, (b) reduces ventilatory response to acute hypoxia, and (c) reduces ventilatory response to acute hypercapnia. Seven healthy volunteers underwent two protocols, one with saline control and one with somatostatin infusion (0.5mg/h) consisting of a 15-min period of resting breathing (end-tidal [Formula: see text] held at 100Torr with background isocapnia) followed by 5min of isocapnic hypoxia (end-tidal [Formula: see text] 50Torr), and after 1min euoxic recovery, 5min of euoxic hypercapnia (end-tidal [Formula: see text] 45Torr), followed by recovery. Somatostatin modestly but significantly (p<0.05) reduced CO2 output, but not O2 uptake. However, somatostatin did not change basal minute ventilation. Acute hypoxic ventilatory response was greatly reduced by 82% and acute hypercapnic ventilatory response by 26% (p<0.05). We conclude that while somatostatin does influence metabolism, this effect is too subtle to explain the large reduction in chemoreflex activity, which is more likely due to direct effects of the drug on the carotid body.

Nonstationary multivariate modeling of cerebral autoregulation during hypercapnia

We examined the time-varying characteristics of cerebral autoregulation and hemodynamics during a step hypercapnic stimulus by using recursively estimated multivariate (two-input) models which quantify the dynamic effects of mean arterial blood pressure (ABP) and end-tidal CO2 tension (PETCO2) on middle cerebral artery blood flow velocity (CBFV). Beat-to-beat values of ABP and CBFV, as well as breath-to-breath values of PETCO2 during baseline and sustained euoxic hypercapnia were obtained in 8 female subjects. The multiple-input, single-output models used were based on the Laguerre expansion technique, and their parameters were updated using recursive least squares with multiple forgetting factors. The results reveal the presence of nonstationarities that confirm previously reported effects of hypercapnia on autoregulation, i.e. a decrease in the MABP phase lead, and suggest that the incorporation of PETCO2 as an additional model input yields less time-varying estimates of dynamic pressure autoregulation obtained from single-input (ABP–CBFV) models.

Differential regulation of sympathetic burst frequency and amplitude following acute hypoxia in humans

Current evidence suggests that the persistent sympathetic nerve activity (SNA), commonly observed after exposure to hypoxia (HX), is mediated by chemoreceptor sensitization and or baroreflex resetting. Evidence in humans and animals suggests that these reflexes may independently regulate the frequency (gating) and amplitude (neuronal recruitment) of SNA bursts. In humans (n = 7), we examined the regulation of SNA following acute isocapnic HX (5 min; end-tidal P(O2) = 45 Torr) and euoxic hypercapnia (HC; 5 min; end-tidal P(CO2) = +10 from baseline). HX increased SNA burst frequency (21 ± 7 to 28 ± 8 bursts/min, P < 0.05) and amplitude (99 ± 10 to 125 ± 19 au, P < 0.05) as did HC (14 ± 6 to 22 ± 10 bursts/min, P < 0.05 and 100 ± 12 to 133 ± 29 au, P < 0.05, respectively). Burst frequency (26 ± 7 bursts/min, P < 0.05), but not amplitude (97 ± 12 au), remained elevated 10 min post-HX. The change in burst amplitude (but not frequency) was significantly related to the measured change in ventilation (r(2) = 0.527, P < 0.001). Both frequency and amplitude decreased during recovery following HC. These data indicate the differential regulation of pattern and magnitude of sympathetic outflow in humans with sympathetic persistence following HX being specific to burst frequency and not amplitude.

Differential regulation of sympathetic burst frequency and amplitude following acute hypoxia

Current evidence suggests that the persistent sympathetic nerve activity (SNA), commonly observed following exposure to hypoxia (HX), is mediated by chemoreceptor sensitization and baroreflex resetting. Evidence in animals suggests that these reflexes may independently regulate the frequency (gating) and amplitude (neuronal recruitment) of SNA bursts. In humans (n=7) we examined the regulation of SNA following acute isocapnic HX (5 min; end‐tidal PO2 = 45 Torr) and euoxic hypercapnia (HC; 5 min; end‐tidal PCO2 = +10 from baseline). HX increased SNA burst frequency (21±7 to 28±8 Burst/min, P&lt;0.05) and amplitude (99±10 to 125±19 au, P&lt;0.05) as did HC (14±6 to 22±10 bursts/min, P&lt;0.05 and 100±12 to 133±29 au, P&lt;0.05 respectively). Burst frequency (26±7 bursts/min, P&lt;0.05), but not amplitude (97±12 au), remained elevated 10 min post HX. Both frequency and amplitude decreased during recovery following HC. These data clearly indicate two separate mechanisms, related to HX, regulating the pattern and magnitude of sympathetic outflow in humans. This study was supported by NSERC.

Effects of estrogen and progesterone on cerebrovascular responses to euoxic hypercapnia in women

ABSTRACTObjectives To determine the cerebral blood flow response to step changes in end-tidal Pco2 in premenopausal women (n = 10; mean age±standard deviation 27.0±6.4 years) during the follicular (FP), mid-cycle (MC) and luteal (LP) phases of the menstrual cycle.Methods Transcranial Doppler ultrasound was used to measure beat-by-beat averaged peak blood flow velocity () in the middle cerebral artery in response to 20 min of euoxic hypercapnia (end-tidal Po2 = 88 Torr; end-tidal Pco2 = 7.0 Torr above resting values). The responses to euoxic hypercapnia were fitted to a simple mathematical model that included gain terms for the on (Gon) and off (Goff) responses, time constants for the on (τon) and off (τoff) responses, baseline terms and a time delay (Td).Results Serum progesterone levels were significantly greater for LP compared to FP and MC (40.6±13.2 vs. 32.6±1.4 nmol/l (p < 0.001) and 8.8±3.8 nmol/l (p < 0.001), respectively). Serum estrogen concentrations were significantly lower in FP compared to MC and LP (150.9±51.2 vs. 506.5±220.5 pmol/l (p = 0.002) and 589.1±222.8 pmol/l (p < 0.001), respectively). Arterial Pco2 was significantly greater in MC compared to LP (35.0±2.1 and 32.6±1.4 Torr, respectively; p = 0.02). There was a significant increase in Goff during LP compared with FP and MC (3.38±0.68 vs. 2.79±0.82 cm s−1 Torr−1 (p = 0.021) and 2.74±0.90 (p = 0.018) cm s−1 Torr21, respectively). Progesterone and the estrogen/progesterone ratio contributed to the observed differences in Goff.Conclusion There is an increase in Goff during LP that is explained, at least in part, by increases in serum progesterone and estrogen and a decrease in arterial Pco2.

Cerebral and myocardial blood flow responses to hypercapnia and hypoxia in humans

In humans, cerebrovascular responses to alterations in arterial Pco(2) and Po(2) are well documented. However, few studies have investigated human coronary vascular responses to alterations in blood gases. This study investigated the extent to which the cerebral and coronary vasculatures differ in their responses to euoxic hypercapnia and isocapnic hypoxia in healthy volunteers. Participants (n = 15) were tested at rest on two occasions. On the first visit, middle cerebral artery blood velocity (V(P)) was assessed using transcranial Doppler ultrasound. On the second visit, coronary sinus blood flow (CSBF) was measured using cardiac MRI. For comparison with V(P), CSBF was normalized to the rate pressure product [an index of myocardial oxygen consumption; normalized (n)CSBF]. Both testing sessions began with 5 min of euoxic [end-tidal Po(2) (Pet(O(2))) = 88 Torr] isocapnia [end-tidal Pco(2) (Pet(CO(2))) = +1 Torr above resting values]. Pet(O(2)) was next held at 88 Torr, and Pet(CO(2)) was increased to 40 and 45 Torr in 5-min increments. Participants were then returned to euoxic isocapnia for 5 min, after which Pet(O(2)) was decreased from 88 to 60, 52 and 45 Torr in 5-min decrements. Changes in V(P) and nCSBF were normalized to isocapnic euoxic conditions and indexed against Pet(CO(2)) and arterial oxyhemoglobin saturation. The V(P) gain for euoxic hypercapnia (%/Torr) was significantly higher than nCSBF (P = 0.030). Conversely, the V(P) gain for isocapnic hypoxia (%/%desaturation) was not different from nCSBF (P = 0.518). These findings demonstrate, compared with coronary circulation, that the cerebral circulation is more sensitive to hypercapnia but similarly sensitive to hypoxia.

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.

Effects of ovarian hormones and aging on respiratory sinus arrhythmia and breathing patterns in women

We investigated the effect of ovarian hormones and aging on breathing pattern [pulmonary minute ventilation (V(E))], tidal volume (V(T)), breathing frequency (F(b)), and respiratory sinus arrhythmia (RSA) in women. Recordings of V(E) and electrocardiogram (ECG) were obtained from 23 healthy women (10 premenopausal, 13 postmenopausal) under resting, isocapnic hypoxia (IH), and euoxic hypercapnia (EH) conditions. Premenopausal women were tested on three different days, each day corresponding to a specific phase of the menstrual cycle (follicular, mid-cycle, and luteal); postmenopausal women (PMW) were tested on 1 day only. On each test day, subjects were challenged with IH and EH. The order of the two tests was randomized and separated by at least 1 hour. Due to the low F (b) of several PMW, the band limits for RSA analysis had to be adjusted. The spectral coherence between respiratory flow and ECG RR-interval was used to determine the spectral band. Within the spectral band, there was a consistent phase relationship between the two variables where high values of spectral coherence indicate a well-defined phase relationship between respiratory flow and RR-interval variability. The main findings in this study for RSA are fourfold. First, RSA did not change with different levels of ovarian hormones (progesterone, serum 17beta-estradiol) during the menstrual cycle. Second, RSA was not influenced by hormone replacement therapy. Third, RSA did not change with age. Fourth, RSA did not change with IH and EH-induced changes in breathing patterns. Finally, high individual variability of average RR-interval change per breath was found.

Variability of Middle Cerebral Artery Blood Flow with Hypercapnia in Women

We examined the effect of euoxic hypercapnia on middle cerebral artery (MCA) blood flow velocity waveform parameters in pre- and postmenopausal women by exposing 24 healthy women (12 pre-, 12 postmenopausal) to hypercapnia for 20 min. MCA blood flow velocity was measured continuously by transcranial Doppler ultrasound. The data were run through an algorithm that detected the feature points of the waveforms and then analyzed for statistically significant group differences. The changes in mean blood flow velocity with euoxic hypercapnia were not significant between the two groups. However, certain feature points, particularly the velocity of the reflected shoulder (V REFLEC), increased (89.4 ± 14.6 to 110.0 ± 20.5 cm/s and 102.3 ± 14.1 to 125.1 ± 14.9 cm/s from euoxic eucapnia to euoxic hypercapnia in pre- and postmenopausal women, respectively), as did the augmentation index (79.9 ± 10.4 to 85.9 ± 12.6% and 114.7 ± 12.8 to 119.0 ± 12.6%) and pulsatility index (0.86 ± 0.18 to 0.74 ± 0.15 and 0.71 ± 0.11 to 0.66 ± 0.11). Furthermore, while systolic peak velocity (V SYS) was the highest point of the waveform in premenopausal women, V REFLEC was the highest point for the postmenopausal cohort. The implications of this finding become obvious when calculating pulsatility index (PI), the values of which varied significantly for the postmenopausal women, depending on whether V SYS or the absolute maximum was used. These findings suggest that hypercapnia increases blood flow velocity waveform reflections, and that PI calculations, particularly for older age groups, may need to be considered more carefully, since these reflections often exceed the systolic peak velocity. (E-mail: poulin@ucalgary.ca)

Effects of the nitric oxide synthase inhibitor L‐NMMA on cerebrovascular and cardiovascular responses to hypoxia and hypercapnia in humans

Cerebral blood flow is highly sensitive to alterations in the partial pressures of O(2) and CO(2) (P(O(2)) and P(CO(2)), respectively) in the arterial blood. In humans, the extent to which nitric oxide (NO) is involved in this regulation is unclear. We hypothesized that the NO synthase (NOS) inhibitor N(G)-monomethyl-l-arginine (l-NMMA), attenuates the sensitivity of middle cerebral artery blood velocity (V(p)) to isocapnic hypoxia (end-tidal P(O(2)) = 50 Torr) and euoxic hypercapnia (end-tidal P(CO(2)) = +9 Torr above resting values) in 10 volunteers (age, 28.7 +/- 1.3 years; height, 179.2 +/- 2.4 cm; weight, 78.0 +/- 3.7 kg; mean +/- s.e.m.). The techniques of transcranial Doppler ultrasound and dynamic end-tidal forcing were used to measure(V(p)), and control end-tidal P(O(2)) and end-tidal P(CO(2)), respectively. At baseline (isocapnic euoxia), following intravenous administration of l-NMMA, mean arterial blood pressure (MAP) increased (76.3 +/- 7.3 to 86.2 +/- 9.4 mmHg) and heart rate (HR) decreased (59.5 +/- 9.0 to 55.2 +/- 9.5 beats min(-1)) but (V(p)) was unchanged. Hypoxia-induced increases in MAP, HR and were similar with and without l-NMMA (5.0 +/- 0.7 versus 7.1 +/- 1.0 mmHg, 11.5 +/- 1.4 versus 12.4 +/- 1.5 beats min(-1), 6.5 +/- 0.8 versus 6.6 +/- 0.8 cm s(-1) for DeltaMAP, DeltaHR and Delta , respectively). Hypercapnia-induced increases in MAP, HR and (V(p)) were similar with and without l-NMMA (7.4 +/- 3.1 versus 8.1 +/- 2.2 mmHg, 10.4 +/- 4.6 versus 10.0 +/- 4.2 beats min(-1), 16.5 +/- 1.5 versus 17.6 +/- 1.5 cm s(-1) for DeltaMAP, DeltaHR and Delta(V(p)) , respectively) but the sensitivity of the(V(p)) response at the removal of hypercapnia was attenuated with l-NMMA. In young healthy humans, pharmacological blockade of nitric oxide synthesis does not affect the increases in cerebral blood flow with hypoxia and hypercapnia, suggesting that nitric oxide is not required for the cerbrovascular responses to hypoxia and hypercapnia.

Differential sensitivities of cerebral and brachial blood flow to hypercapnia in humans

Although it is known that the vasculatures of the brain and the forearm are sensitive to changes in arterial Pco(2), previous investigations have not made direct comparisons of the sensitivities of cerebral blood flow (CBF) (middle cerebral artery blood velocity associated with maximum frequency of Doppler shift; Vp) and brachial blood flow (BBF) to hypercapnia. We compared the sensitivities of Vp and BBF to hypercapnia in humans. On the basis of the critical importance of the brain for the survival of the organism, we hypothesized that Vp would be more sensitive than BBF to hypercapnia. Nine healthy males (30.1 +/- 5.2 yr, mean +/- SD) participated. Euoxic hypercapnia (end-tidal Po(2) = 88 Torr, end-tidal Pco(2) = 9 Torr above resting) was achieved by using the technique of dynamic end-tidal forcing. Vp was measured by transcranial Doppler ultrasound as an index of CBF, whereas BBF was measured in the brachial artery by echo Doppler. Vp and BBF were measured during two 60-min trials of hypercapnia, each trial separated by 60 min. Since no differences in the responses were found between trials, data from both trials were averaged to make comparisons between Vp and BBF. During hypercapnia, Vp and BBF increased by 34 +/- 8 and 14 +/- 8%, respectively. Vp remained elevated throughout the hypercapnic period, but BBF returned to baseline levels by 60 min. The Vp CO(2) sensitivity was greater than BBF (4 +/- 1 vs. 2 +/- 1%/Torr; P < 0.05). Our findings confirm that Vp has a greater sensitivity than BBF in response to hypercapnia and show an adaptive response of BBF that is not evident in Vp.

Differential responses to CO2 and sympathetic stimulation in the cerebral and femoral circulations in humans

The relative importance of CO2 and sympathetic stimulation in the regulation of cerebral and peripheral vasculatures has not been previously studied in humans. We investigated the effect of sympathetic activation, produced by isometric handgrip (HG) exercise, on cerebral and femoral vasculatures during periods of isocapnia and hypercapnia. In 14 healthy males (28.1 +/- 3.7 (mean +/- S.D.) years), we measured flow velocity (VP; transcranial Doppler ultrasound) in the middle cerebral artery during euoxic isocapnia (ISO, +1 mmHg above rest) and two levels of euoxic hypercapnia (HC5, end-tidal P(CO(2)), P(ET,CO2), = +5 mmHg above ISO; HC10, P(ET,CO2) = +10 above ISO). Each P(ET,CO2) level was maintained for 10 min using the dynamic end-tidal forcing technique, during which increases in sympathetic activity were elicited by a 2-min HG at 30% of maximal voluntary contraction. Femoral blood flow (FBF; Doppler ultrasound), muscle sympathetic nerve activity (MSNA; microneurography) and mean arterial pressure (MAP; Portapres) were also measured. Hypercapnia increased VP and FBF by 5.0 and 0.6% mmHg-1, respectively, and MSNA by 20-220%. Isometric HG increased MSNA by 50% and MAP by 20%, with no differences between ISO, HC5 and HC10. During the ISO HG there was an increase in cerebral vascular resistance (CVR; 20 +/- 11%), while VP remained unchanged. During HC5 and HC10 HG, VP increased (13% and 14%, respectively), but CVR was unchanged. In contrast, HG-induced sympathetic stimulation increased femoral vascular resistance (FVR) during ISO, HC5 and HC10 (17-41%), while there was a general decrease in FBF below ISO. The HG-induced increases in MSNA were associated with increases in FVR in all conditions (r = 0.76-0.87), whereas increases in MSNA were associated with increases in CVR only during ISO (r = 0.91). In summary, in the absence of hypercapnia, HG exercise caused cerebral vasoconstriction, myogenically and/or neurally, which was reflected by increases in CVR and a maintained VP. In contrast, HG increased FVR during conditions of ISO, HC5 and HC10. Therefore, the cerebral circulation is more responsive to alterations in PCO2, and less responsive to sympathetic stimulation than the femoral circulation.

Human pulmonary vascular response to 4 h of hypercapnia and hypocapnia measured using Doppler echocardiography.

Hypercapnia has been shown in animal experiments to induce pulmonary hypertension. This study measured the sensitivity and time course of the human pulmonary vascular response to sustained (4 h) hypercapnia and hypocapnia. Twelve volunteers undertook three protocols: 1) 4-h euoxic (end-tidal Po(2) = 100 Torr) hypercapnia (end-tidal Pco(2) was 10 Torr above normal), followed by 2 h of recovery with euoxic eucapnia; 2) 4-h euoxic hypocapnia (end-tidal Pco(2) was 10 Torr below normal) followed by 2 h of recovery; and 3) 6-h air breathing (control). Pulmonary vascular resistance was assessed at 0.5- to 1-h intervals by using Doppler echocardiography via the maximum tricuspid pressure gradient during systole. Results show progressive changes in pressure gradient over 1-2 h after the onset or offset of the stimuli, and sensitivities of 0.6 to 1 Torr change in pressure gradient per Torr change in end-tidal Pco(2). The human pulmonary circulatory response to changes in Pco(2) has a slower time course and greater sensitivity than is commonly assumed. Vascular tone in the normal pulmonary circulation is substantial.

Human ventilatory response to 8 h of euoxic hypercapnia

Ventilation (VE) rises throughout 40 min of constant elevated end-tidal PCO2 without reaching steady state (S. Khamnei and P. A. Robbins. Respir. Physiol. 81: 117-134, 1990). The present study investigates 8 h of euoxic hypercapnia to determine whether VE reaches steady state within this time. Two protocols were employed: 1) 8-h euoxic hypercapnia (end-tidal PCO2 = 6.5 Torr above prestudy value, end-tidal PO2 = 100 Torr) followed by 8-h poikilocapnic euoxia; and 2) control, where the inspired gas was air. VE was measured over a 5-min period before the experiment and then hourly over a 16-h period. In the hypercapnia protocol, VE had not reached a steady state by the first hour (P < 0.001, analysis of variance), but there were no further significant differences in VE over hours 2-8 (analysis of variance). VE fell promptly on return to eucapnic conditions. We conclude that, whereas there is a component of the VE response to hypercapnia that is slow, there is no progressive rise in VE throughout the 8-h period.

Circulatory effects of ventilator rate and PEEP in unparalysed preterm infants : Sandie Bohin, Alan C. Fenton, David H. Evans, Kent L. Woods and David J. Field, Neonatal Unit, Leicester Royal Infirmary, Leicester LE1 5 WW, UK

We examined the time-varying characteristics of cerebral autoregulation and hemodynamics during a step hypercapnic stimulus by using recursively estimated multivariate (two-input) models which quantify the dynamic effects of mean arterial blood pressure (ABP) and end-tidal CO2 tension (PETCO2) on middle cerebral artery blood flow velocity (CBFV). Beat-to-beat values of ABP and CBFV, as well as breath-to-breath values of PETCO2 during baseline and sustained euoxic hypercapnia were obtained in 8 female subjects. The multiple-input, single-output models used were based on the Laguerre expansion technique, and their parameters were updated using recursive least squares with multiple forgetting factors. The results reveal the presence of nonstationarities that confirm previously reported effects of hypercapnia on autoregulation, i.e. a decrease in the MABP phase lead, and suggest that the incorporation of PETCO2 as an additional model input yields less time-varying estimates of dynamic pressure autoregulation obtained from single-input (ABP–CBFV) models.

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.