Ventilation–perfusion inequality and carbon dioxide sensitivity in hypoxaemic chronic obstructive pulmonary disease (COPD) and effects of 6 months of long‐term oxygen treatment (LTOT)

The aim of our study was to find out how blood gas disturbances in stable, eucapnic, severe chronic obstructive pulmonary disease (COPD) patients with an arterial oxygen tension (PaO₂) value of 7·7 (6·1–8·4) kPa are affected by ventilation–perfusion (V_A/Q) relationships and carbon dioxide (CO₂) sensitivity and how these parameters are influenced by 6 months of long‐term oxygen treatment (LTOT). V_A/Q ratios were measured using the multiple inert gas elimination technique (MIGET). Mouth occlusion pressure 0·1 s after onset of inspiration (Pi0·1) and minute ventilation (V_E) were measured to assess respiratory drive response (ΔPi0·1/ΔPCO₂) and hypercapnic ventilatory response (HCVR) to CO₂ rebreathing. At the start of LTOT, a normal median respiratory drive response level of 1·2 (0·2–2·3) cm H₂O/kPa and a low median HCVR as compared with healthy individuals (P<0·001) were found. However, 7·9 (0–29·8)% of the V_E, was directed towards hypoperfused lung areas. The dispersion of ventilation (log SDV; 0·47–1·76), and the dispersion of perfusion (log SDQ; 0·66–1·07) were wider than normal. The PaO₂ level correlated inversely with mean V_A/Q ratio for ventilation (V mean) and shunt. The PaCO₂ level correlated inversely with HCVR and vital capacity. After 6 months of LTOT, no significant changes in daytime blood gas levels, CO₂‐sensitivity or V_A/Q ratios were found. V_E tended to be reduced by 1·0 l min^–1. Conclusions: An elevated V mean and probably shunting are important contributing factors for the reduced PaO₂ and hypercapnic ventilatory response is a major determinant of PaCO₂ in eucapnic stable hypoxaemic COPD. Six months of LTOT does not affect blood gases, CO₂ sensitivity or ventilation–perfusion relationships.     

A comparison of head motion and prefrontal haemodynamics during upright and recumbent cycling exercise

The aim of this observational study was to compare head motion and prefrontal haemodynamics during exercise using three commercial cycling ergometers. Participants (n = 12) completed an incremental exercise test to exhaustion during upright, recumbent and semi‐recumbent cycling. Head motion (using accelerometry), physiological data (oxygen uptake, end‐tidal carbon dioxide [P_ETCO₂] and heart rate) and changes in prefrontal haemodynamics (oxygenation, deoxygenation and blood volume using near infrared spectroscopy [NIRS]) were recorded. Despite no difference in oxygen uptake and heart rate, head motion was higher and P_ETCO₂ was lower during upright cycling at maximal exercise (P<0·05). Analyses of covariance (covariates: head motion P>0·05; P_ETCO₂, P<0·01) revealed that prefrontal oxygenation was higher during semi‐recumbent than recumbent cycling and deoxygenation and blood volume were higher during upright than recumbent and semi‐recumbent cycling (respectively; P<0·05). This work highlights the robustness of the utility of NIRS to head motion and describes the potential postural effects upon the prefrontal haemodynamic response during upright and recumbent cycling exercise.     

Regional V˙A/Q˙ ratios in man using 133Xe and single photon emission computed tomography (SPECT) corrected for attenuation

We describe a technique to obtain non-invasively regional pulmonary ventilation–perfusion ratios (V˙_A/Q˙) using single photon emission computed tomography (SPECT) and continuous infusion of ¹³³Xe. Single photon transmission tomography was used for attenuation correction, for delineation of the lungs and for V˙_A/Q˙ calculations. Data are presented for six normal subjects and compared to those for two patients with moderate chronic obstructive pulmonary disease (COPD). The mean V˙_A/Q˙ for the whole lung of the normal subjects ranged from 0·49 to 0·65, group mean 0·56 ± 0·07 (1 SD), and there was no significant difference between the right and left lung. The consistently too low V˙_A/Q˙ values are related to the inability to measure regional blood volume and the low resolution of the scintillation camera, giving an under-estimation of tracer input. For the normal subjects, the dispersion of V˙_A/Q˙, as defined by the standard deviation of the individual distribution functions, ranged from 0·12 to 0·19. One of the patients was characterized by a low mean V˙_A/Q˙ of 0·35, and the other patient had a wide dispersion (SD) of V˙_A/Q˙ of 0·37. In the normal subjects, a consistent V˙_A/Q˙ gradient was found only in the ventrodorsal direction. ¹³³Xe and SPECT can be used to obtain meaningful biological information regarding ventilation/perfusion relationships of potential clinical value.     

Excessive exercise ventilation in moderate left heart dysfunction. Influence of postural changes in central haemodynamics and blood gases

To evaluate the relative importance of pulmonary congestion and peripheral hypoxia as causes for the excessive exercise ventilation in left heart dysfunction, seven patients with excessive ventilation and distinct left heart dysfunction during moderate exercise (LHD), and seven control patients with essentially normal exertional functions (CTR), had ventilation, central haemodynamics, arterial and mixed venous blood gases examined at rest and exercise, 32 W (25–40) in the LHD group and 44 W (33–49) in the CTR group, in lying and sitting positions. Change from lying to sitting exercise, led to fall in pulmonary artery wedge pressure (PAWP) from 31·0 ± 5·5 to 8·8 ± 5·0 mmHg in the LHD group, compared with from 13·7 ± 1·0 to 2·1 ± 2·4 mmHg in the controls, while ventilation/O₂ intake ratio (V˙/V˙O₂) and physiological dead space/tidal volume ratio (V_D/V_T) showed a tendency to rise, from 36·3 ± 8·8 to 39·2 ± 7·4, and from 0·35 ± 0·11 to 0·39 ± 0·09, respectively, in the LHD group, and from 27·5 ± 3·1 to 28·7 ± 5·3, and from 0·19 ± 0·09 to 0·21 ± 0·12 in the controls. Mixed venous O₂ tension (PvO ₂) showed a marked decline from 3·60 ± 0·33 to 3·26 ± 0·36 kPa in the LHD group, as compared with from 3·94 ± 0·28 to 3·71 ± 0·29 kPa in the controls, while the calculated physiologic shunt (Q˙_s/Q˙_t) suggested improved alveolo‐arterial gas exchange. The data fit in with recent studies ascribing the excessive exercise ventilation to a combination of signals from hypoxia‐induced changes, particularly in the exercising muscles, and augmented ergoreflex and central and peripheral chemoreceptor activity, partly to changes in the integrated control of ventilation and circulation, not to mechanisms related to pulmonary congestion.     

Relationship between peak cardiac pumping capability and indices of cardio-respiratory fitness in healthy individuals

Cardiac power output (CPO) is a unique and direct measure of overall cardiac function (i.e. cardiac pumping capability) that integrates both flow‐ and pressure‐generating capacities of the heart. The present study assessed the relationship between peak exercise CPO and selected indices of cardio‐respiratory fitness. Thirty‐seven healthy adults (23 men and 14 women) performed an incremental exercise test to volitional fatigue using the Bruce protocol with gas exchange and ventilatory measurements. Following a 40‐min recovery, the subjects performed a constant maximum workload exercise test at or above 95% of maximal oxygen consumption. Cardiac output was measured using the exponential CO₂ rebreathing method. The CPO, expressed in W, was calculated as the product of the mean arterial blood pressure and cardiac output. At peak exercise, CPO was well correlated with cardiac output (r = 0·92, P<0·01), stroke volume (r = 0·90, P<0·01) and peak oxygen consumption (r = 0·77, P<0·01). The coefficient of correlation was moderate between CPO and anaerobic threshold (r = 0·47, P<0·01), oxygen pulse (r = 0·57, P<0·01), minute ventilation (r = 0·53, P<0·01) and carbon dioxide production (r = 0·56, P<0·01). Small but significant relationship was found between peak CPO and peak heart rate (r = 0·23, P<0·05). These findings suggest that only peak cardiac output and stroke volume truly reflect CPO. Other indices of cardio‐respiratory fitness such as oxygen consumption, anaerobic threshold, oxygen pulse, minute ventilation, carbon dioxide production and heart rate should not be used as surrogates for overall cardiac function and pumping capability of the heart.     

Evaluation of a modified acetylene rebreathing method for the determination of cardiac output

Summary. In order to evaluate a computerized modified acetylene rebreathing method for the determination of cardiac output, 15 healthy subjects were studied at different levels of their maximal oxygen uptake (V?o_2max). Submaximal exercise was performed on a cycle ergometer and maximal exercise on a treadmill. Oxygen uptake, heart rate, and cardiac output (acetylene method) were determined in all test situations. In seven subjects simultaneous determinations of cardiac output were made by a modified acetylene rebreathing method (Q?_A) and a dye dilution method (Q?_D) Furthermore, a new resting rebreathing technique was used. The methodological error for (Q?_A)(means of double samples) was 0·37 litre min^-1 (2·8%) in the same individual at 150 W. The corresponding values between individuals were 0·71 (rest), 0·41 (50 W), 0·69 (150 W), and 0·40 litre min^-1 (V?o_2max). Thus the methodological error of the modified acetylene method was very low. There was a significant difference (P<0·01), however, between the acetylene method and the dye dilution method, which showed a lower value for Q?_A at all levels. This was probably due to the long response time of the mass spectrometer combined with anatomical and physiological arteriovenous shunt effects in the lungs during exercise. When these factors were considered the correcting formula was:Q?_Ac=Q?_A+0·005·Q²_A There was no significant difference between the corrected cardiac output values (Q?_Ac) and the corresponding Q?_D values. In conclusion, this modified acetylene rebreathing method is a very useful non-invasive method for measuring cardiac output at rest as well as during heavy exercise.     

Validation of the acetylene rebreathing method for measurement of cardiac output at rest and during high-intensity exercise

The use of the acetylene rebreathing method to estimate cardiac output (CO) during high-intensity exercise, which may be influenced by recirculation of acetylene, has not been validated. This study was designed to validate the acetylene rebreathing method to measure CO during high-intensity exercise using the direct Fick method. CO was measured at rest and during exercise at 25%, 50%, 75% and 90% of the nine subjects maximum oxygen uptake (VO _2max) by the direct Fick and acetylene rebreathing method. CO measured by the acetylene rebreathing method correlated with work rate (r=0·90, P<0·01) and with oxygen uptake (r=0·94, P<0·01). The correlation coefficient of CO between both methods was r=0·91 (P<0·01). There was no significant difference in CO measured by each method at rest as well as at each work rate. The difference in CO between each method was greater at lower CO than at higher CO. At 90% of VO _2max, the CO measured by acetylene rebreathing was nearly identical to that measured by the Fick method. It can be concluded that acetylene rebreathing for measurement of CO is valid not only at rest but also during exercise, especially during high-intensity exercise.     

Non‐invasive measurement of cardiac output by Finometer in patients with cirrhosis

The Finometer measures haemodynamic parameters including cardiac output (CO) using non‐invasive volume‐clamp techniques. The aim of this study was to determine the accuracy of the Finometer in hyperdynamic cirrhotic patients using an invasive indicator dilution technique as control. CO was measured in twenty‐three patients referred for invasive measurements of the hepatic venous pressure gradient on suspicion of cirrhosis. Invasive measurements of CO were performed using indicator dilution technique (CO_I) and simultaneous measurements of CO were recorded with the Finometer (CO_F). In six patients, measurements of CO were performed with invasive technique and the Finometer both before and after β‐blockade using 80 mg of propranolol and the changes in CO (ΔCO_I and ΔCO_F respectively) were calculated to evaluate the Finometers ability to detect relative changes in CO. Mean CO_I was 6·1 ± 1·6 [3·9;9·7] l min^?1 (mean ± SD [range]) compared to mean CO_F of 7·2 ± 2·3 [3·1;11·9] l min^?1. There was a mean difference between CO_F and CO_I of 1·0 ± 1·8 [?2·1;4·0] l min^?1 and 95% confidence interval of [0·2;1·8], P<0·001. In patients with measurements before and after β‐blockade, mean ΔCO_I was 1·6 ± 1·4 [?0·1;3·3] l min^?1 compared to mean ΔCO_F of 1·9 ± 1·3 [0·4;3·8] l min^?1. Mean difference between ΔCO_F and ΔCO_I was 0·3 ± 0·3 [?0·2;0·7] l min^?1 with a 95% confidence interval of [?0·1;0·6], P = 0·11. Compared with invasive measurements, the Finometer can be used to measure changes in CO, whereas absolute measurements are associated with higher variation in patients with cirrhosis. The Finometer seems useful for repeated determinations such as in studies of effect of pharmacotherapy.     

Middle cerebral artery blood flow velocity in response to lower body positive pressure

Lower body positive pressure (LBPP) has been used in the treatment of haemorrhagic shock and in offsetting g‐force induced fluid shifts. However, the middle cerebral artery blood flow velocity (MCAv) response to supine LBPP is unknown. Fifteen healthy volunteers (mean ± SD: age, 26 ± 5 year; body mass, 79 ± 10 kg; height, 174 ± 9 cm) completed 5 minutes of 20 and 40 mm Hg LBPP, in a randomized order, separated by 5 minutes rest (baseline). Beat‐to‐beat MCAv and blood pressure, partial pressure of end‐tidal carbon dioxide (P_ETCO₂) and heart rate were recorded and presented as the change from the preceding baseline. All measures were similar between baseline periods (all P>0·30). Mean arterial pressure (MAP) increased by 7 ± 6 (8 ± 7%) and 13 ± 7 mm Hg (19 ± 11%) from baseline during 20 and 40 mm Hg (P<0·01), respectively. The greater MAP increase at 40 mm Hg (P<0·01 versus 20 mm Hg) was mediated via a greater increase in total peripheral resistance (P<0·01), with heart rate, cardiac output (Model flow) and P_ETCO₂ remaining unchanged (all P>0·05) throughout. MCAv increased from baseline by 3 ± 4 cm s^?1 (5 ± 5%) during 20 mm Hg (P = 0·003), whilst no change (P = 0·18) was observed during 40 mm Hg. Our results indicate a divergent response, in that 20 mm Hg LBPP‐induced modest increases in both MCAv and MAP, yet no change in MCAv was observed at the higher LBPP of 40 mm Hg despite a further increase in MAP.     

Inert gas rebreathing: the effect of haemoglobin based pulmonary shunt flow correction on the accuracy of cardiac output measurements in clinical practice

Background: Cardiac output (CO) is an important cardiac parameter, however its determination is difficult in clinical routine. Non‐invasive inert gas rebreathing (IGR) measurements yielded promising results in recent studies. It directly measures pulmonary blood flow (PBF) which equals CO in absence of significant pulmonary shunt flow (Q_S). A reliable shunt correction requiring the haemoglobin concentration (c_Hb) as only value to be entered manually has been implemented. Therefore, the aim of the study was to evaluate the effect of various approaches to Q_S correction on the accuracy of IGR. Methods: Cardiac output determined by cardiac magnetic resonance imaging (CMR) served as reference values. The data was analysed in four groups: PBF without correcting for Q_S (group A), shunt correction using the patients’ individual c_Hb values (group B), a fixed standard c_Hb of 14·0 g dl^?1 (group C) and a gender‐adapted standard c_Hb for male (15·0 g dl^?1) and female (13·5 g dl^?1) probands each (group D). Results: 147 patients were analysed. Mean CO_CMR was 5·2 ± 1·4 l min^?1, mean CO_IGR was 4·8 ± 1·3 l min^?1 in group A, 5·1 ± 1·3 in group B, 5·1 ± 1·3 l min^?1 in group C and 5·1 ± 1·4 l min^?1 in group D. The accuracy in group A (mean bias 0·5 ± 1·1 l min^?1) was significantly lower as compared to groups B, C and D (0·1 ± 1·1 l min^?1; P<0·01). Conclusion: IGR allows a reliable non‐invasive determination of CO. Since PBF significantly increased the measurement bias, shunt correction should always be applied. A fixed c_Hb of 14·0 g dl^?1 can be used for both genders if the exact c_Hb value is not known. Nevertheless, the individual value should be used if any possible.     

Evaluation of impaired dynamic cerebral autoregulation by the Mueller manoeuvre

Arterial blood pressure (ABP) shows polyphasic changes during the Mueller manoeuvre (voluntary negative intrathoracic pressure). The aim of the present study was to investigate (1) whether these changes could be applied to detect impaired dynamic cerebral autoregulation (dCA) in carotid stenosis and (2) whether the degree of indicated impairment correlates with transfer function phase as another current measure for dCA (deep breathing method) and CO₂‐reactivity. We examined 13 patients with severe unilateral carotid artery stenosis and 16 age‐matched controls during 15‐s Mueller manoeuvres (MM) at ?30 mmHg using bilateral transcranial Doppler sonography and non‐invasive ABP recordings (Finapres, 2300, Ohmeda, Englewood, CO, USA). After an initial biphasic oscillation, cerebral blood flow velocity (CBFV) and ABP decreased to below baseline. CBFV reincreased in controls and on contralateral sides in patients 6·0 s (3·8–9·5 s, median and range) after the onset of the decrease, despite a further fall in ABP. CBFV over the affected side revealed a significantly delayed reincrease (8·0 (5·6–10·3) s; P<0·01) combined with a relatively flat and inertial amplitude behaviour. An applied autoregulation index derived from the MM (mROR), phase shift and CO₂‐reactivity were severely reduced on the affected side in patients (P<0·01). Reduction of the mROR correlated significantly with reduction of phase shift (r=0·69; P=0·002) and CO₂‐reactivity (r=0·78; P=0·002). In conclusion, the different cerebral haemodynamic pattern during the MM in patients is likely to reflect impaired dCA. The degree of indicated impairment correlates with that of transfer function phase and CO₂‐reactivity. Therefore, the MM represents a convenient method for grading of compromised cerebral haemodynamics in patients with carotid artery stenosis.     

Passive leg raising during cardiopulmonary resuscitation in out-of-hospital cardiac arrest—Does it improve circulation and outcome?

Background

Passive leg raising (PLR), to augment the artificial circulation, was deleted from cardiopulmonary resuscitation (CPR) guidelines in 1992. Increases in end-tidal carbon dioxide (P_ETCO₂) during CPR have been associated with increased pulmonary blood flow reflecting cardiac output. Measurements of P_ETCO₂ after PLR might therefore increase our understanding of its potential value in CPR. We also observed the alteration in P_ETCO₂ in relation to the return of spontaneous circulation (ROSC) and no ROSC.

Methods and results

The P_ETCO₂ was measured, subsequent to intubation, in 126 patients suffering an out-of-hospital cardiac arrest (OHCA), during 15 min or until ROSC. Forty-four patients were selected by the study protocol to PLR 35 cm; 21 patients received manual chest compressions and 23 mechanical compressions. The PLR was initiated during uninterrupted CPR, 5 min from the start of P_ETCO₂ measurements. During PLR, an increase in P_ETCO₂ was found in all 44 patients within 15 s (p = 0.003), 45 s (p = 0.002) and 75 s (p = 0.0001). Survival to hospital discharge was 7% among patients with PLR and 1% among those without PLR (p = 0.12). Among patients experiencing ROSC (60 of 126), we found a marked increase in P_ETCO₂ 1 min before the detection of a palpable pulse.

Conclusion

Since PLR during CPR appears to increase P_ETCO₂ after OHCA, larger studies are needed to evaluate its potential effects on survival. Further, the measurement of P_ETCO₂ could help to minimise the hands-off periods and pulse checks.     

Non-invasive determination of effective stroke volume. Evaluation of a CO2-rebreathing method in normal subjects and patients

Summary. A CO₂-rebreathing method for the determination of stroke volume (SV) was evaluated at rest by comparison with the direct Fick technique in 50 randomly selected patients with valvular heart disease. Patients with intracardiac shunts were excluded. Objective criteria for acceptance of a measurement were set to ensure reliable results. Forty-six of the 50 patients fulfilled these criteria. The rebreathing manoeuvre is, in itself, an effort for the patient, leading to a change in steady state which excludes simultaneous comparison with the direct Fick method. Day-to-day variation of the SV measured with the CO₂-method was therefore assessed first, and found to be low. Because of this low day-to-day variation, a comparison of stroke volumes measured one day with the CO₂-method and next day with the direct Fick technique was found to be acceptable. In the determination of SV in the supine position, there was no significant difference between the two methods (SV_CO2= 5·2 + 0·90 ×SV_Fick, r= 0·90, SD_res= 9·4 ml, n= 46), while cardiac output was significantly higher when measured with the CO₂ technique than with the direct Fick method (22%, P < 0·001). Ten of 12 patients with signs of obstructive lung disease managed to produce registrations which fulfilled the criteria of acceptance. The method is well suited for clinical use.     

Comparison between ventilatory and mouth occlusion pressure responses to hypoxia and hypercapnia in healthy sleeping man

Summary. Ventilatory and mouth occlusion pressure (P_0·1) responses to progressive isocapnic-hypoxia and hyperoxic-hypercapnia were compared in eleven healthy sleeping men during the same night. Hypoxic and hypercapnic responses were determined during wakefulness, non-rapid and rapid-eye-movement sleep. The following parameters were measured: minute ventilation (V?E), tidal volume (V_T), ‘duty cycle’ (T_l/T_T), mean inspiratory flow rate (V_T/T_l) and P_0·1, an index of the neuromuscular inspiratory drive. To allow a direct comparison between the two types of chemostimuli, responses were characterized by the value of the different parameters at ‘equivalent’ levels of hypoxia and hypercapnia, i.e., at levels which produced the same P_0·1 during wakefulness: an oxyhaemoglobin saturation (Sao₂) of 94% during the isocapnic-hypoxic tests (P_ETco₂=42·5±1·2 mmHg) was found to be equivalent to a P_etco₂ of 47·4±3·7 mmHg during hypoxic-hypercapnic tests. For both tests, the arousal levels of the stimulus and of P_0·1 were similar in all sleep stages. Sleep did not significantly modify P_0·1 or breathing pattern responses to hypoxia (Sao₂=94%). In contrast, at the ‘equivalent’ level of hypercapnic stimulation, P_0·1 (P<0·05) and V?_E (P<0·01) responses were significantly impaired, particularly in REM sleep, with a decrease in V_T (P<0·01) and V_T/T_l (P<0·05) responses. The results suggest that CO₂ intracranial receptor mechanisms are more affected by sleep than the O₂ peripheral receptor activity.     

Respiratory drive during carbachol challenge in allergic sheep

Diaphragmatic activity is the standard assessment of respiratory neural output but is difficult to measure and cannot be used for long‐term clinical monitoring. The tidal breathing minute ventilation ( ) and mean inspiratory flow (V_T/t_I) reflect respiratory drive and can be monitored non‐invasively using respiratory inductive plethysmography (RIP). Recent findings indicate that peak inspiratory acceleration (PIA) correlates to diaphragmatic activity during CO₂ rebreathing in piglets. The aim of the present study was to assess whether tidal breathing peak inspiratory acceleration reflects respiratory drive during carbachol challenge. Aerosolized carbachol was administered to 15 allergic sheep until pulmonary resistance increased by at least 400%. After threshold dose, slight increases in
and V_T/t_I were seen (8 and 5%, respectively; P=NS), while PIA increased by 30% (P<0·05). The change in PIA was closely correlated to changes in
and V_T/t_I (r=0·73, P<0·01 and r=0·88, P<0·001, respectively). In conclusion, peak inspiratory acceleration reflected respiratory drive during bronchoprovocation. Further, this new measure of drive has the potential to accurately estimate drive in chronic obstructive lung disease where intrinsic positive end expiratory pressure prevents accurate selection of beginning inspiration necessary for computation of, e.g. V_T/t_I.     

Anatomical vertebral artery hypoplasia and insufficiency impairs dynamic blood flow regulation

Recent studies have suggested that vertebral artery (VA) hypoplasia is a predisposing factor for posterior cerebral stroke. We examined whether anatomical vertebrobasilar ischemia, i.e., unilateral VA hypoplasia and insufficiency, impairs dynamic blood flow regulation. Twenty‐eight female subjects were divided into three groups by defined criteria: (i) unilateral VA hypoplasia (n = 8), (ii) VA insufficiency (n = 6), and (iii) control (n = 14). Hypoplastic VA criterion was VA blood flow of 40 ml min^?1, whereas VA insufficiency criterion was net (left + right) VA blood flow of 100 ml min^?1 or less. We evaluated left, right, and net VA blood flows by ultrasonography during hypercapnia, normocapnia, and hypocapnia to evaluate VA CO₂ reactivity. The unilateral VA hypoplasia group showed lower CO₂ reactivity at hypoplastic VA than at non‐hypoplastic VA (2·65 ± 0·58 versus 3·00 ± 0·48% per mmHg, P = 0·027) and net VA CO₂ reactivity was preserved (Unilateral VA hypoplasia, 2·95 ± 0·48 versus Control, 2·93 ± 0·42% per mmHg, P = 0·992). However, the VA insufficiency group showed a lower net VA CO₂ reactivity compared to the control (2·29 ± 0·55 versus 2·93 ± 0·42% per mmHg, P = 0·032) and the unilateral VA hypoplasia (P = 0·046). VA hypoplasia reduced CO₂ reactivity, although non‐hypoplastic VA may compensate this regulatory limitation. In subjects with VA insufficiency, lowered CO₂ reactivity at the both VA could not preserve normal net VA CO₂ reactivity. These findings provide a possible physiological mechanism for the increased risk of posterior cerebral stroke in subjects with VA hypoplasia and insufficiency.     

Kinetics of 13CO2 elimination after ingestion of 13C bicarbonate: the effects of exercise and acid base balance

Abstract. In order to investigate the effects of muscular work and preceding exercise on the retention of exogenous labelled bicarbonate, we studied the effects of oral administration of [¹³C]bicarbonate (0·1 mg kg^-1) in five subjects at rest before exercise and during and after 1 h of treadmill walking at 73% VO_2max on three separate occasions. Elimination of CO₂ from labelled bicarbonate was 62·6±8·1% at rest, 103·6±11·3% during exercise (P<0·01) and 43·0±4·7% during recovery from exercise (P= 0·01). During exercise mean residence time (MRT) was shorter than at rest (35±7 min vs. 54±9min, P < 0·02) and CO₂ pool size was larger (998±160 ml CO₂kg^-1, vs. 194±28ml CO₂kg^-1, P < 0·001). Compared to values obtained at rest, during recovery from exercise, MRT and CO₂ pool size were reduced (34±5min, P < 0·05; 116±19 ml CO₂kg^-1, P < 0·02, respectively). In an additional five subjects acidosis and alkalosis were induced prior to administration of oral [¹³C]bicarbonate at rest. Elimination of bicarbonate was lower during acidosis (46·1±5·6%, P < 0·01) but was unaltered (50·9±5·6%, NS) during alkalosis, compared to the values obtained at resting pH. During acidosis MRT and CO₂ pool size decreased (37±3min, P<0·01 and 123±10ml CO₂kg^-1, P < 0·01, respectively) whereas in alkalosis MRT was unchanged (65±8 min NS) but CO₂ pool size was increased (230±23ml CO₂kg^-1, P < 0·05). The kinetics of elimination of ¹³CO₂ from administered bicarbonate after exercise are different to those at rest and resemble acidosis. The appropriate correction factor for sequestered ¹³C should be used in metabolic studies of the post-exercise state when using ¹³C tracers.     

Pulmonary clearance of inhaled [99Tcm]DTPA: effects of ventilation pattern

Summary. While a rise in lung volume is known to increase the pulmonary clearance of technetium-99m-labelled dietylene triamine pentaacetate ([⁹⁹Tc^m]DTPA), little interest has been focused on the effects of changes in ventilation frequency, tidal volume and airway pressure. We studied adult, anaesthetized and intubated rabbits during three ventilation patterns (VP) using pressure controlled ventilation (Servo Ventilator 900C). VP was either deep slow (f=20 min^-1, tidal volume (V_T) = 30 ± 4 ml kg^-1 and positive end-expiratory pressure (PEEP) = 0·2 kPa [VP 20/ 0·2, n= 8]) or rapid shallow (f=80 min^-1, V_T= 11 ±2 ml kg^-1 and PEEP = 0·2 or 0·4 kPa [VP 80/0·2, n= 6 and VP 80/0·4, n= 6]). The mean airway pressure was similar at VP 20/0·2 and VP 80/0·4. During administration of [⁹⁹Tc^m]DTPA aerosol all animals were ventilated under the same conditions (f=40 min^-1 and PEEP = 0·2 kPa). The pulmonary clearance rate expressed as the half-life time (T^1/2) of [⁹⁹Tc^m]DTPA was at VP 80/0·2 = 113 ± 31 min, at VP 80/0·4 = 70 ± 24 min (P < 0·01 compared to VP 80/0·2) and at VP 20/0·2 = 36± 18 min (P <0·001 compared to VP 80/0·2 and P <0·01 compared to VP 80/0·4). We conclude that the pulmonary clearance of [⁹⁹Tc^m]DTPA increases

• 1 during rapid shallow ventilation when PEEP is increased from 0·2 to 0·4 kPa;
• 2 during deep slow ventilation relative to rapid shallow ventilation even when the mean airway pressure is similar.

     

A Sudden Increase in Partial Pressure End-Tidal Carbon Dioxide (PETCO2) at the Moment of Return of Spontaneous Circulation

Background: Previous studies established that a level of partial pressure end-tidal carbon dioxide (P_ETCO₂) of 10 mm Hg divided patients undergoing advanced life support (ALS) into those likely to be resuscitated (values > 10 mm Hg) and those likely to die during ALS (values < 10 mm Hg). Objective: The study tested the significance of a sudden increase in the P_ETCO₂ in signaling the return of spontaneous circulation (ROSC) during ALS. Material and Methods: P_ETCO₂ values were continuously recorded during ALS in out-of-hospital patients with cardiac arrest. Constant ventilation was maintained by an automatic device. There were 108 patients, representing two extreme outcomes of ALS, who were subdivided into two groups. The first group included 59 patients with a single ROSC followed by a stable spontaneous circulation. The second group included 49 patients with no signs of ROSC. Results: ROSC was associated with a sudden increase in P_ETCO₂ that remained significantly higher than before ROSC. P_ETCO₂ did not rise during the entire ALS in the second group of patients without ROSC and was lower than in the first group of patients. Conclusions: In constantly ventilated patients, P_ETCO₂ is significantly higher (about 10 mm Hg) after ROSC than before ROSC. A sudden increase in P_ETCO₂ exceeding 10 mm Hg may indicate ROSC. Consequently, the rule of 10 mm Hg may be extended to include a sudden increase in continuously recorded P_ETCO₂ by more than 10 mm Hg as an indicator of the possibility of ROSC.     

Dynamics of the heart rate variability and oxygen saturation response to acute normobaric hypoxia within the first 10 min of exposure

Although the heart rate variability (HRV) response to hypoxia has been studied, little is known about the dynamics of HRV after hypoxia exposure. The purpose of this study was to assess the HRV and oxygen saturation (SpO₂) responses to normobaric hypoxia (FiO₂ = 9·6%) comparing 1 min segments to baseline (normoxia). Electrocardiogram and SpO₂ were recorded during a 10‐min hypoxia exposure in 29 healthy male subjects aged 26·0 ± 4·9 years. Baseline HRV values were obtained from a 5‐min recording period prior to hypoxia. The hypoxia period was split into 10 non‐overlapping 1‐min segments and time domain HRV indexes (RMSSD and SDNN) were calculated for each segment. Differences (Δ) from baseline values were calculated and transformed using natural logarithm (Ln). This study revealed that the decrease in ΔSpO₂ became significant (P<0·001) in the first minute of hypoxia, the decrease in ΔLn RMSSD became significant (P = 0·002) in the second minute, and the decrease in ΔLn SDNN became significant (P = 0·001) in the third minute. Between the second and fifth minute of hypoxia, ΔSpO₂ correlated with ΔLn RMSSD (r = 0·57, P<0·001) and ΔLn SDNN (r = 0·44, P<0·001). Five min after the onset of hypoxia, ΔSpO₂ was significantly (P = 0·002) decreased but changes in ΔLn RMSSD (P = 0·344) and ΔLn SDNN (P = 0·558) were not significant. In conclusion, the decrease in HRV was proportional to desaturation but only during the first 5 min of hypoxia.