Respiratory muscle performance with stretch‐shortening cycle manoeuvres: maximal inspiratory pressure–flow curves

Aim: To test the hypothesis that the maximal inspiratory muscle (IM) performance, as assessed by the maximal IM pressure–flow relationship, is enhanced with the stretch‐shortening cycle (SSC). Methods: Maximal inspiratory flow–pressure curves were measured in 12 healthy volunteers (35 ± 6 years) during maximal single efforts through a range of graded resistors (4‐, 6‐, and 8‐mm diameter orifices), against an occluded airway, and with a minimal load (wide‐open resistor). Maximal inspiratory efforts were initiated at a volume near residual lung volume (RV). The subjects exhaled to RV using slow (S) or fast (F) manoeuvres. With the S manoeuvre, they exhaled slowly to RV and held the breath at RV for about 4 s prior to maximal inspiration. With the F manoeuvre, they exhaled rapidly to RV and immediately inhaled maximally without a post‐expiratory hold; a strategy designed to enhance inspiratory pressure via the SSC. Results: The maximal inspiratory pressure–flow relationship was linear with the S and F manoeuvres (r² = 0.88 for S and r² = 0.88 for F manoeuvre, P < 0.0005 in all subjects). With the F manoeuvre, the pressure–flow relationship shifted to the right in a parallel fashion and the calculated maximal power increased by approximately 10% (P < 0.05) over that calculated with the S manoeuvre. Conclusion: The maximal inspiratory pressure–flow capacity can be enhanced with SSC manoeuvres in a manner analogous to increases in the force–velocity relationship with SSC reported for skeletal muscles.     

Maximal activation of the human diaphragm but not inspiratory intercostal muscles during static inspiratory efforts

It is widely held that transdiaphragmatic pressure is a reliable index of the extent of central activation of the diaphragm but the maximal voluntary transdiaphragmatic pressure is lower during inspiratory than expulsive efforts. To determine whether the diaphragm is fully activated during the two manoeuvres supramaximal stimuli were delivered to both phrenic nerves during maximal efforts. No discernible twitch was evoked during 30-55% of attempted maximal efforts with either voluntary manoeuvre. Thus the difference in maximal transdiaphragmatic pressure between the manoeuvres must reflect changes in chest-wall geometry or mechanics rather than in the phrenic motor outflow. Inspiratory intercostal muscle activity was consistently submaximal during maximal inspiratory efforts.     

Inspiratory muscle adaptations following pressure or flow training in humans

Skeletal muscle adapts differently to training with high forces or with high velocities. The effects of these disparate training protocols on the inspiratory muscles were investigated in ten healthy volunteers. Five subjects trained using high force (pressure) loads (pressure trainers) and five trained using high velocity (flow) loads (flow trainers). Pressure training entailed performing 30 maximal static inspiratory efforts against a closed airway. Flow training entailed performing 30 sets of three maximal dynamic inspiratory efforts against a minimal resistance. Training was supervised and carried out 5 days a week for 6 weeks. Inspiratory flow rates and oesophageal pressure-time curves were measured before and after training. Peak inspiratory pressures during maximal static and dynamic efforts and peak flows during the maximal dynamic efforts were calculated. The time-to-peak pressure and rate of rise in peak pressure during maximal static and dynamic manoeuvres were also calculated before and following training. Maximal static pressure increased in the pressure training group and maximal dynamic pressure increased in the flow training group. Both groups increased the rate of pressure production (dP/dt) during their respective maximal efforts. The post-training decrease in time-to-peak pressure was proportionately greater in the flow trainers than in the pressure trainers. The differences in time-to-peak pressure between the two groups were consistent with the different effects of force and velocity training on the time-to-peak tension of skeletal muscle.     

Cerebral haemodynamics during the Mueller manoeuvre in humans.

Voluntary negative intra-thoracic pressure (Mueller manoeuvre) is known to reduce arterial blood pressure (ABP). To investigate changes in cerebral blood flow velocity (CBFV) during 15 s Mueller manoeuvres at -30 mmHg intra-thoracic pressure, 27 young (aged 21-31 years, group A) and 11 older (52-64 years, group B) healthy adults were studied using transcranial Doppler and non-invasive ABP measurement (Finapres). After closely following the initial ABP drop, CBFV showed an overshoot during temporary recovery of ABP. Then ABP and CBFV decreased significantly to below baseline. While ABP declined further until the end of the manoeuvre, CBFV increased in group A 4.7 s (2.4-8.5) (median and range) and in group B 5.7 s (4. 1-7.2) after the onset of the CBFV decrease. Critical closing pressure (CCP), calculated for each cardiac cycle from the dynamic pressure-flow relationship (DPFR), indicated a reduction of intra-cranial pressure during the first half of the strain. DPFR-related estimation of cerebrovascular resistance provided a more physiological response than the conventional cerebrovascular resistance quotient ABP/CBFV, and decreased about 1.5 s before the observed CBFV increase. A modification of the previously described dynamic auto-regulation index ROR correlated significantly with CO2 reactivity values (r=0.61, P=0.001). In conclusion, changes in CBFV during Mueller manoeuvres are likely to reflect dynamic cerebral auto-regulation and may provide an estimate of dynamic cerebral auto-regulation capacity. In older adults, the maximal dynamic auto-regulatory response seems to be unchanged, but the onset of reaction is slightly delayed.     

Effects of muscle group recruitment on sniff transdiaphragmatic pressure and its components

Measuring maximal sniff pressures is an easy way of assessing inspiratory muscle strength. During a static manoeuvre, the pattern of inspiratory muscle recruitment during a sniff can vary from one individual to another. We therefore assessed how voluntarily changing muscle recruitment would affect sniff oesophageal, gastric and transdiaphragmatic pressures (Pes,sn, Pga,sn and Pdi,sn, respectively). Ten normal subjects (age 27–38 years) performed natural sniff manoeuvres ("nat"), and preferentially diaphragmatic ("dia") or extradiaphragmatic ("extradia") sniff manoeuvres, after having learnt to dissociate between the inspiratory muscle groups. Abdominal displacements were monitored using a belt-mounted strain gauge. Natural patterns of muscle recruitment varied among subjects. On average, Pes,sn,nat was [median (range)] 81 (21–105) cmH₂O. All of the subjects were able to modify inspiratory muscle recruitment voluntarily. Pes,sn was not significantly affected by the type of manoeuvre performed, as opposed to Pdi,sn, which, as expected, increased with both the diaphragmatic and extradiaphragmatic manoeuvres [Pdi,sn,dia 132 (99–157) cmH₂O, Pdi,sn,extradia 96 (50–146) cmH₂O, P<0.05]. Whatever the manoeuvre, there was no correlation between Pes and Pdi, but Pga and Pdi were correlated during both the diaphragmatic (r=0.82, P<0.05) and the extradiaphragmatic manoeuvre (r=0.70, P< 0.05). Pes,sn may have limitations as an index of diaphragm function, but by showing its independence from inspiratory muscle recruitment, this study contributes to its validation as a robust index of global inspiratory muscle strength that is particularly well suited for follow-up studies. This should extend to Pes,sn substitutes measured at the airway opening. Electronic Publication     

Effect of lung inhomogeneity on partial flow-volume manoeuvres

We evaluated the effects of inhomogeneous lung emptying on the relationship of partial to maximal complete expiratory flow by obtaining pre- and post-metaproterenol maximal (MEFV) and partial flow-volume curves in normal subjects and asthmatics. Partial curves were initiated between 65-70% of vital capacity after inspiration from functional residual capacity (PEFV curve) or after deflation from total lung capacity (PEFVDI curve). Since PEFVDI curves were initiated at lower lung volumes than MEFV manoeuvres (but with a similar volume history), non-homogeneous emptying should cause higher flow on PEFVDI than on MEFV manoeuvres. Expiratory flow (Vmax) was highest on MEFV manoeuvres in normals and PEFV curves in asthmatics. Pre- and post-metaproterenol Vmax was very similar on MEFV and PEFVDI manoeuvres in both groups, although Vmax(MEFV) slightly but significantly exceeded Vmax(PEFVDI) in normals and the reverse was true in asthmatics. Lung elastic recoil did not differ significantly on MEFV and PEFVDI manoeuvres in either group. We conclude that asthmatics demonstrate inhomogeneous emptying. However, because flow-volume curves are relatively insensitive to sequences of lung emptying, inhomogeneous emptying during forced expiration only has minor effects on the relationship of partial to maximal expiratory flow.     

Pressure-flow characteristics in the right and left ventricular perfusion territories of the right coronary artery in swine

Regional pressure-flow relationships within the right coronary artery (RCA) circulation of swine were determined. Enflurane-anaesthetized swine (n=7) were studied during step-wise reductions of RCA perfusion pressure using an extracorporeal circuit. Regional blood flow was measured using microspheres and contractile function of the right ventricle was measured using sonomicrometry. The RCA perfusion territory was divided into its anatomic components: right ventricular free wall (RV), interventricular septum (with further division in transmural thirds; SEP-LV, SEP-MID and SEP-RV) and right atrium (RA). Pressure-flow relations were constructed for each region and autoregulatory capacity assessed through calculation of an autoregulatory index (AI, closed-loop gain). The pressure-flow relationship for the entire RCA exhibited autoregulation down to a pressure of 40 mmHg. The SEP-LV exhibited a similar relationship with loss of autoregulation at approximately 40 mmHg. The pressure-flow relationship of the RV, however, showed autoregulation to a pressure of 30 mmHg with a decrease of blood flow only at a pressure of 20 mmHg. Little autoregulation was observed in the RA. Autoregulatory gain assessed by AI was similar in RV, SEP-LV and SEP-RV as pressure was reduced from 90 to 55 mmHg (RV=0.54±0.41; SEP-LV=0.58±0.36; SEP-RV=0.83±0.36). With further reductions of pressure, AI was highest in the RV, followed by the SEP-RV and then SEP-LV. AI of the SEP-LV and SEP-RV was negative when pressure was reduced from 30 to 20 mmHg. AI of the RA was negative at the high and low pressure ranges and demonstrated little autoregulatory gain otherwise. Regional contractile function of the RV was maintained to a pressure of 30 mmHg and appeared to be closely related to regional blood flow. Thus, the RCA perfusion bed is characterized by a markedly heterogeneous autoregulatory capacity based on its anatomical makeup.     

Changes in maximal performance of inspiratory and skeletal muscles during and after the 7.1-MPa Hydra 10 record human dive

 During the 7.1-MPa hydrogen-helium-oxygen record human dive, we tested the hypothesis that the increased ambient pressure would alter the maximal muscle performance, specifically that breathing dense gas would lead to fatigue of the respiratory muscle. A group of hand muscles (adductor pollicis, AP) and the inspiratory muscles (IM) were studied in three professional divers. Maximal voluntary contractions (MVC) of AP and maximal inspiratory pressure (P _imax) generated by IM were measured prior to the dive, during compression and decompression, and then 1 and 2 months after the dive. The decrease in MVC (−22%) was significant at 3.1 MPa, i.e. at the beginning of the introduction of hydrogen into the breathing mixture, whereas P _imax fell progressively during the dive and decompression (maximal ΔP _imax = −55%), a significant reduction still being measured 1 month after the dive. The altered IM function was attributed to the consequences of long-term ventilatory loading, a condition associated with breathing a dense gas. The transient decrease in MVC of the skeletal muscle would indicate a possible effect of the hyperbaric environment, possibly the high partial pressure of hydrogen, on neuromuscular drive. Accepted: 16 September 1999     

Time-dependent recruitment effects in ventilated healthy and lung-injured rats: "Recruitment-memory"

We investigated the sustained effects of recruitment manoeuvres in terms of "recruitment memory" in healthy and lung injured rats. 46 ventilated rats were allocated to either the control (sham) or the lavage group. Two consecutive low-flow manoeuvres were performed before sham/lavage and hourly during a 2-h-observation period. The slopes of the inspiratory limbs of the two resulting pressure-volume loops were translated into compliance-volume curves. The difference between the two compliance curves was smaller after lavage (root-mean-square deviation: 0.065ml/cmH(2)O control group, 0.038ml/cmH(2)O lavage group; p<0.05) and stayed small during the whole experiment. In the control group, the deviation was small after sham manoeuvre but increased throughout the experiment. Compliance gain after recruitment was higher in the control group (0.1ml/cmH(2)O) compared to the lavage group (0.02ml/cmH(2)O, p<0.05). We conclude that lung lavage led to alveolar collapse not susceptible to recruitment manoeuvres. On the contrary in healthy lungs recruitment manoeuvres led to persistent lung recruitment which we interpret as recruitment memory.     

The effect of decreased intrathoracic pressure on ventricular function

SUMMARY  Large decreases in inspiratory intrathoracic pressure (ITP) occur during obstructive apnoeas. The cardiac effects of apnoea-associated decreased ITP come from the interaction of increased preload (venous return) on the right ventricle (RV) and increased afterload on the left ventricle (LV), and are modulated by the autonomic effects of shifts in blood volume and hypoxaemia. During obstructed breathing, venous return increases by as much as three-fold during inspiration even though mean flow may change little. This leads to a substantial inspiratory increase in RV end-diastolic and stroke volume. Because of ventricular interdependence, there is a decrease in LV diastolic compliance and corresponding decrease LV preload.
Sustained decreases in ITP (Müller manoeuvre) inhibit LV ejection, and hence increase LV afterload. However, breathing against an obstructed airway (repetitive short Müller manoeuvre) is not necessarily modelled by the sustained manoeuvre. Animal studies indicate that with airway obstruction, for the first beat or two of inspiration the primary effect on the LV is a reduction in stroke volume related to a decrease in preload, and afterload, if anything, decreases. In fact, afterload only increases during early expiration when stroke volume increases. When obstructive and central apnoeas are paired for duration and blood-gas alterations, there are increases in pulmonary blood volume with central apnoeas and in RV volume with obstructive apnoeas, consistent with the postulation that the primary effect of obstructive apnoeas is on venous return.
In conclusion, the putative role of decreased ITP in increasing LV afterload under conditions appropriate to OSA is not well supported by experimental studies. However, effects with very large swings in ITP as might be seen under the most extreme forms of OSA, and differences in timing of the swings between diastole and systole have yet to be investigated.     

Trend of maximal inspiratory pressure in mechanically ventilated patients: predictors

INTRODUCTION: It is known that mechanical ventilation and many of its features may affect the evolution of inspiratory muscle strength during ventilation. However, this evolution has not been described, nor have its predictors been studied. In addition, a probable parallel between inspiratory and limb muscle strength evolution has not been investigated. OBJECTIVE: To describe the variation over time of maximal inspiratory pressure during mechanical ventilation and its predictors. We also studied the possible relationship between the evolution of maximal inspiratory pressure and limb muscle strength. METHODS: A prospective observational study was performed in consecutive patients submitted to mechanical ventilation for > 72 hours. The maximal inspiratory pressure trend was evaluated by the linear regression of the daily maximal inspiratory pressure and a logistic regression analysis was used to look for independent maximal inspiratory pressure trend predictors. Limb muscle strength was evaluated using the Medical Research Council score. RESULTS: One hundred and sixteen patients were studied, forty-four of whom (37.9%) presented a decrease in maximal inspiratory pressure over time. The members of the group in which maximal inspiratory pressure decreased underwent deeper sedation, spent less time in pressure support ventilation and were extubated less frequently. The only independent predictor of the maximal inspiratory pressure trend was the level of sedation (OR=1.55, 95% CI 1.003 - 2.408; p = 0.049). There was no relationship between the maximal inspiratory pressure trend and limb muscle strength. CONCLUSIONS: Around forty percent of the mechanically ventilated patients had a decreased maximal inspiratory pressure during mechanical ventilation, which was independently associated with deeper levels of sedation. There was no relationship between the evolution of maximal inspiratory pressure and the muscular strength of the limb.     

Effect of specific inspiratory muscle warm-up on intense intermittent run to exhaustion

The effects of inspiratory muscle (IM) warm-up on the maximum dynamic IM function and the maximum repetitions of 20-m shuttle run (Ex) in the Yo-Yo intermittent recovery test were examined. Ten men were recruited to perform identical IM function test and exercise test in three different trials randomly. The control trial was without IM warm-up while the placebo and experimental trials were with IM warm-up by performing two sets of 30 breaths with inspiratory pressure-threshold load equivalent to 15% (IMW_P) and 40% (IMW) maximum inspiratory mouth pressure, respectively. In IMW, maximum dynamic IM functions including the maximal inspiratory pressure at zero flow (P ₀) and maximal rate of P ₀ development (MRPD) were increased compared with control values (P<0.05). The Ex was also augmented [mean (SD)] [19.5% (12.6)] while the slope of the linear relationship of the increase in rating of perceived breathlessness for every 4th exercise interval (RPB/4i) was reduced (P<0.05). In IMW_P, although increase in Ex and reduction in RPB/4i were occurred concomitantly in some subjects, the differences in Ex, RPB/4i and dynamic IM functions between control and IMW_P trials were not statistically significant. For the changes (Δ) in parameters in IMW and IMW_P (n=20), negative correlations were found between Δ RPB/4i and Δ Ex (r=−0.92), ΔP ₀ and Δ RPB/4i (r=−0.48), and Δ MRPD and Δ RPB/4i (r=−0.54). Such findings suggested that the specific IM warm-up in IMW may entail reduction in breathlessness sensation, partly attributable to the enhancement of dynamic IM functions, in subsequent exhaustive intermittent run and, in turn, improve the exercise tolerance.     

Power absorption and production during slow,large-amplitude stretch-shorten cycle motions

The purpose of this study was to determine the important predictors of power absorption and power production during slow, large-amplitude stretch-shorten cycle (SSC) motions. The relationship between power absorption (mean eccentric power output) and production (mean concentric power output) across different inertial loads was also investigated. Fifty-four subjects with a sporting background performed concentric (CBP) and rebound bench-presses (RBP) at 40% and 80% of their one-repetition maximum (1RM). The relationship between kinematic and kinetic variables and mean eccentric power and RBP mean power output was determined using correlation and multiple regression analysis. Maximal strength was found to be the best single predictor of power absorption, explaining between 44.2% and 69.1% of the variability that was associated with mean eccentric power output for 40% and 80% 1RM loads. Stretch velocity in combination with maximal strength was found to be the best two-predictor model of power absorption (R ²=83.7–97.3%). The best single predictor of SSC power production was found to be concentric mean power output (R ²=49.2–88.0%). The utilisation of the power absorbed during the power production phase differed across loads. It was suggested that as maximal strength is more trainable than speed, training to improve power absorption might emphasise maximal strength development. It was also suggested that SSC power output might benefit from training methods that focus on concentric force development. Further research is needed to evaluate these hypotheses and whether the findings of this study are similar for fast SSC motion. Electronic Publication     

Structure-function relationship of soleus muscle fibres from the rhesus monkey

Functional and structural properties of rhesus monkey skinned fibres were studied in order to examine the relationship between calcium/strontium (Ca/Sr) activation characteristics and protein composition. The fibres were classified according to their Ca/Sr affinity into slow (61%) and fast groups (39%). According to the myosin isoform composition, two additional hybrid types were defined. Thus, four profiles were characterized: two corresponding to slow (S) and fast (F) isoforms and two corresponding to a mixed proportion of slow and fast isoforms. They were called hybrid slow (HS) or hybrid fast (HF) based on the predominant myosin isoform. Tension/pCa parameters and maximal shortening velocities were determined. S fibres showed a higher pCa threshold and affinity as well as shallower slopes of their tension/pCa curve than did F fibres. HS and HF fibres exhibited tension/pCa curves which were positioned close to those of S and F fibres, respectively. No significant difference was observed between S and HS fibres or between F and HF fibres. Maximal shortening velocity values were higher for fibres expressing predominantly fast myosin isoforms. We suggest than when both S and F isoforms of myofibrillar proteins are expressed in a muscle fibre, the functional properties are mainly governed by the predominant isoform.     

Disturbances in pulmonary mechanics during serotonin perfusion.

The effect of i.v. perfused serotonin (75 microgram.kg-1.min-1) on bronchomotor tone was assessed in dogs by mechanical studies, with the result in an increase in total lung resistance. The increased residual volume (RV), closing capacity (CC) and slope of phase III (nitrogen single-breath washout) as well as the reduction of the helium response at low lung volumes suggest a peripheral action of the drug. Because of the large increase in total lung resistance and the decreased dead space (VD), bronchoconstriction of large airways must also be present. Vagal tone inhibition is incomplete whether by volume history or bilateral vagotomy and could be limited mainly to a segment which is situated between the equal pressure point and the most peripheral airways: maximal flows during partial expiratory flow-volume manoeuvres (PEFV) are lower than during maximal expiratory flow-volume manoeuvres (MEFV) and the volume of isoflow is higher in PEFV than in MEFV manoeuvers, suggesting that full inspiration reduces the bronchoconstriction induced by serotonin. On the other hand, the bilateral vagotomy did not reverse CC, RV, slope of phase III or VD back to control values. Isoproterenol i.v. injection improved all physiological measurements almost to the level of control values: beta-adrenergic stimulating drugs seem to inhibit completely serotonin induced bronchospasm, at all levels of the bronchial tree.     

Increased carbon monoxide in exhaled air of patients with seasonal allergic rhinitis

BACKGROUND: Carbon monoxide (CO) can be detected in exhaled air and is increased in asthmatic patients. However, it is uncertain whether exhaled CO is increased in patients with allergic rhinitis. OBJECTIVE AND METHODS: To study whether exhaled CO is increased in patients with allergic rhinitis, exhaled CO concentrations were measured on a CO monitor by vital capacity manoeuvre in 86 patients with seasonal allergic rhinitis during and out of the cedar pollen season. RESULTS: During the season, exhaled CO concentrations were 3. 6 +/- 0.3 p.p.m. and decreased to 1.2 +/- 0.1 p.p.m. out of the season. The values of exhaled CO out of the season were similar to those in age-matched non-smoking healthy control subjects (1.2 +/- 0. 1 p.p.m.). Exhaled CO concentrations were significantly higher in patients with symptoms than in those without symptoms (P < 0.01). Exhaled CO concentrations in patients did not differ significantly among oral and nasal exhalation, and oral exhalation with an expiratory resistance (P > 0.20). CONCLUSION: These findings suggest that allergic rhinitis increases the concentration of CO in exhaled air and increases in exhaled CO may be derived from lower airways.     

Evoked corticospinal output to the human scalene muscles is altered by lung volume

Increases in lung volume inhibit the inspiratory output from the medulla, but the effect of lung inflation on the voluntary control of breathing in humans is not known. We tested corticospinal excitability using transcranial magnetic stimulation (TMS) to evoke a response in the scalene muscles. TMS was delivered at rest at three different lung volumes between functional residual capacity (FRC) and total lung capacity (TLC) during incremental inspiratory and incremental expiratory manoeuvres. Motor evoked potentials (MEPs) in scalenes were ～50% larger at a high lung volume (FRC+～90% inspiratory capacity [IC]) compared to lower lung volumes (FRC and FRC+～40% IC) in both inspiratory and expiratory manoeuvres (p<0.001). The change in MEP size was not due to differences in pre-stimulus EMG amplitude (p=0.29). The results suggest a differential effect of lung inflation on the automatic and voluntary control of breathing in humans.     

Relation between exhaled carbon monoxide levels and clinical severity of asthma

Carbon monoxide (CO) can be detected in exhaled air and is increased in asthmatic patients not treated with corticosteroids. However, it is uncertain whether exhaled CO is related to severity of asthma. To study whether exhaled CO is related to severity of asthma in clinical courses, exhaled CO concentrations were measured on a CO monitor by vital capacity manoeuvre in 20 mild asthmatics treated with inhaled beta2-agonists alone, 20 moderate asthmatics treated with inhaled corticosteroids, and 15 stable asthmatics treated with high dose inhaled corticosteroids and oral corticosteroids once a month over 1 years. Exhaled CO concentrations were also measured in 16 unstable severe asthmatics who visited the hospital every 7 or 14 days for treatment with high dose inhaled corticosteroids and oral corticosteroids. The mean values of exhaled CO in severe asthma over 1 year were 6.7 +/- 9.5 p.p.m. (n = 31, mean +/- SD) and significantly higher than those of non-smoking control subjects (1.2 +/- 0.9 p.p.m., n = 20, P < 0.01). Exhaled CO concentrations in unstable severe asthmatics were significantly higher than those in stable severe asthmatics. However, exhaled CO concentrations in mild and moderate asthmatics did not differ significantly from those in non-smoking control subjects (P > 0.20). There was a significant relationship between the exhaled CO concentrations and forced expiratory volume in one second in all asthmatic patients. These findings suggest that exhaled CO concentrations may relate to the severity of asthma and measurements of exhaled CO concentrations may be a useful means of monitoring airway inflammation in asthma.     

Role of the mechanical impairment on the ventilatory response to CO2 in chronic airway obstruction

The purpose of this study was to assess the relationship between the breathing pattern response to CO2 and the severity of mechanical impairment in twenty patients with COLD. The CO2 response was compared to that of a control group of twelve normal subjects. All patients had airway obstruction (FEV1 = 40 +/- 14% of predicted; means +/- SD) and hyperinflation (FRC = 154 +/- 23% of predicted). Tidal volume (VT), inspiratory and total cycle duration (TI, TT), occlusion pressure (P0.1) and endtidal PCO2 were measured at rest and during hyperoxic CO2 rebreathing. On the same day, in all patients, arterial blood gas analysis, spirometric and plethysmographic measurements were made. The slope (S) of the P0.1 response (SP 0.1) to increasing endtidal PCO2 was negatively correlated with airway resistance (r = -0.59; p less than 0.01). Although the flow response, S(VT/TI), was positively and closely correlated with SP 0.1 (r = 0.88; p less than 0.001), it also appeared to be independently influenced by obstruction (p less than 0.01). The tidal volume response, SVT, was principally correlated with inspiratory capacity (r = 0.90; p less than 0.001) and also, independently, with Vmax50 (p less than 0.01). SVT was diminished in seventeen patients, ten of whom only had a decreased S(VT/TI). The shortening in TI during hypercapnia was most marked in patients with the greatest S(P0.1), who did not have arterial hypercapnia at rest. These results suggest: that the poor VT response to CO2 in COLD patients is principally caused by a limitation in inspiratory volume expansion.(ABSTRACT TRUNCATED AT 250 WORDS)