Mouth pressure twitches induced by cervical magnetic stimulation to assess inspiratory muscle fatigue

This study aimed at determining whether twitch mouth pressure (TwPmo) induced by cervical magnetic stimulation (CMS) was sensitive to inspiratory muscle fatigue produced by whole body exercise (WBE) in normal subjects. Twenty subjects performed one or two of the following protocols: (i). cycling at 85% V(O(2),max) until exhaustion; (ii). inspiratory resistive load (IRL) breathing at 62% of maximal inspiratory pressure until task failure. In eight subjects, oesophageal (TwPoes), gastric (TwPga) and transdiaphragmatic (TwPdi) pressures were recorded. The TwPmo was significantly reduced (P<0.05) 20 min after both WBE and IRL, from 17.5+/-4.4 to 15.9+/-3.9 cmH(2)O and from 19.4+/-4.9 to 17.7+/-4.5 cmH(2)O, respectively. Subsequently to IRL, the TwPdi decrease was associated with a reduction in TwPoes/TwPga ratio; not after WBE. Independently of the mode of ventilatory loading, inspiratory muscle fatigue was detected. Thus, inspiratory muscle fatigue after WBE can be assessed in normal subjects with a noninvasive technique.     

Post-exercise diaphragm shielding: a novel approach to exercise-induced diaphragmatic fatigue

Based on the "post-exercise diaphragm shielding" hypothesis this study tested whether both diaphragmatic force-generation (DFG) and diaphragmatic fatigue (DF) remain unchanged during consecutive exercise-trials. Twelve subjects ( [Formula: see text] 58.4+/-6.6mlkg(-1)min(-1)) performed three consecutive exercise-trials (T(alpha)/T(beta)/T(gamma); workload(max) 85% [Formula: see text] ) each followed by recovery (6min). Twitch transdiaphragmatic pressure during supramaximal magnetic phrenic nerve stimulation (TwPdi, every 30s), ratings of perceived exertion (RPE, every 90s) and ergospirometric data (continuously) were assessed throughout the entire protocol (46.5min). DFG and DF did not differ among all trials (TwPdi-baseline: 2.2+/-0.7kPa; TwPdi-peak: T(alpha)/T(beta)/T(gamma) 3.1+/-0.7kPa vs 3.0+/-0.8kPa vs 3.2+/-0.8kPa; TwPdi-bottom: T(alpha)/T(beta)/T(gamma) 1.9+/-0.6kPa vs 2.0+/-0.7kPa vs 1.8+/-0.5kPa, both p>0.4, RM-ANOVA). Furthermore, TwPdi revealed close relationships with RPE (r=0.91, p<0.0001) and oxygen uptake (r=0.94, p<0.0001) during exercise. In conclusion, both DFG (baseline-to-peak) and DF (baseline-to-bottom) achieve similar magnitudes during and after consecutive exercise-trials and are closely linked to RPE and oxygen uptake. This suggests that DF neither reflects impaired diaphragmatic function nor impairs exercise performance; rather it is likely to reflect post-exercise diaphragm shielding.     

Contractile properties of the human diaphragm during chronic hyperinflation

BACKGROUND. In patients with chronic obstructive pulmonary disease (COPD) and hyperinflation of the lungs, dysfunction of the diaphragm may contribute to respiratory decompensation. We evaluated the contractile function of the diaphragm in well-nourished patients with stable COPD, using supramaximal, bilateral phrenic-nerve stimulation, which provides information about the strength and inspiratory action of the diaphragm. METHODS. In eight patients with COPD and five control subjects of similar age, the transdiaphragmatic pressure generated by the twitch response to phrenic-nerve stimulation was recorded at various base-line lung volumes, from functional residual capacity to total lung capacity, and during relaxation and graded voluntary efforts at functional residual capacity (twitch occlusion). RESULTS. At functional residual capacity, the twitch transdiaphragmatic pressure ranged from 10.9 to 26.6 cm of water (1.07 to 2.60 kPa) in the patients and from 19.8 to 37.1 cm of water (1.94 to 3.64 kPa) in the controls, indicating considerable overlap between the two groups. The ratio of esophageal pressure to twitch transdiaphragmatic pressure, an index of the inspiratory action of the diaphragm, was -0.50 +/- 0.05 in the patients, as compared with -0.43 +/- 0.02 in the controls (indicating more efficient inspiratory action in the patients than in the controls). At comparable volumes, the twitch transdiaphragmatic pressure and esophageal-to-transdiaphragmatic pressure ratio were higher in the patients than in normal subjects, indicating that the strength and inspiratory action of the diaphragm in the patients were actually better than in the controls. Twitch occlusion (a measure of the maximal activation of the diaphragm) indicated near-maximal activation in the patients with COPD, and the maximal transdiaphragmatic pressure was 106.9 +/- 13.8 cm of water (10.48 +/- 1.35 kPa). CONCLUSIONS. The functioning of the diaphragms of the patients with stable COPD is as good as in normal subjects at the same lung volume. Compensatory phenomena appear to counterbalance the deleterious effects of hyperinflation on the contractility and inspiratory action of the diaphragm in patients with COPD. Our findings cast doubt on the existence of chronic fatigue of the diaphragm in such patients and therefore on the need for therapeutic interventions aimed at improving diaphragm function.     

Glottis constriction response in healthy subjects

The purpose of this study was to evaluate the glottis constriction response induced by a sudden and involuntary increase in gastric and oesophageal pressures by Tll-Ll intervertebral magnetic stimulation of the abdominal muscle roots in nine healthy subjects. Twitch flow, twitch gastric, and oesophageal pressures were measured after abdominal muscle root stimulation, which allowed pharyngo-laryngeal muscle activation to be characterized. Pharyngeal endoscopies were performed on five subjects to assess vocal cord movements. All stimulations induced positive gastric and oesophageal pressures and expiratory flow, which increased with stimulation intensity (flow: R=0.32; p<0.0001; oesophageal pressure: R=0.26; p=0.001; gastric pressure: R=0.37; p<0.0001). Twitch gastric pressure and twitch oesophageal pressure were negatively correlated with twitch flow (respectively, R=-0.183, p<0.05; R=-0.35, p<0.0001). Upper airway resistance was higher at peak oesophageal pressure than at peak flow (p<0.001). Peak twitch gastric and twitch oesophageal pressure latencies were similar (133+/-4ms and 122+/-4ms) but longer than peak twitch flow and EMG latencies (62+/-2ms and 73+/-4ms, p<0.0001). Glottis constriction following magnetic abdominal muscle root stimulation was seen in all subjects during endoscopy, with a latency estimated at between 80 and 100ms. This method could be a new, simple tool for assessing the upper airway constriction protective reflex.     

New physiological insights into exercise-induced diaphragmatic fatigue

Data on the dynamic process and time-point of manifestation of exercise-induced diaphragmatic fatigue (DF) are lacking. Therefore, this study was aimed assessing dynamic changes of diaphragmatic strength during exercise and determining the time-point of DF manifestation. Fourteen trained subjects (maximal oxygen uptake (VO2(max)) 59.3+/-5.5 ml/min/kg) performed standardized exercise protocols (maximal workload: 85% VO2(max)) followed by recovery (6 min). Ergospirometric data and twitch transdiaphragmatic pressure (TwPdi) were consecutively assessed. DF was induced (TwPdi-rest: 2.34+/-0.26 versus TwPdi-end-recovery 2.01+/-0.21 kPa, p<0.01). TwPdi progressively increased during exercise (TwPdi-rest: 2.34+/-0.26 versus TwPdi-maximal-workload: 3.28+/-0.38 kPa, p<0.001). DF was detectable immediately after exercise-termination (TwPdi-maximal-workload: 3.28+/-0.38 versus TwPdi-early-recovery 2.55+/-0.34 kPa, p<0.001). TwPdi during exercise was highly correlated to workload, VO2(max) and dyspnea (r=0.96/r=0.92/r=0.97; all p<0.0001). In conclusion, diaphragmatic strength progressively increases with increasing workload, and DF manifests after - rather than during - exercise. In addition, TwPdi is highly correlated to key-measures of ergospirometry, approving the physiological thesis that muscle strength is progressively enhanced and escapes fatiguing failure during high-intensity exercise performance.     

Acute and chronic responses of the upper airway to inspiratory loading in healthy awake humans: an MRI study

We assessed upper airway responses to acute and chronic inspiratory loading. In Experiment I, 11 healthy subjects underwent T(2)-weighted magnetic resonance imaging (MRI) of upper airway dilator muscles (genioglossus and geniohyoid) before and up to 10 min after a single bout of pressure threshold inspiratory muscle training (IMT) at 60% maximal inspiratory mouth pressure (MIP). T(2) values for genioglossus and geniohyoid were increased versus control (p<0.001), suggesting that these airway dilator muscles are activated in response to acute IMT. In Experiment II, nine subjects underwent 2D-Flash sequence MRI of the upper airway during quiet breathing and while performing single inspirations against resistive loads (10%, 30% and 50% MIP); this procedure was repeated after 6 weeks of IMT. Lateral narrowing of the upper airway occurred at all loads, whilst anteroposterior narrowing occurred at the level of the laryngopharynx at loads > or =30% MIP. Changes in upper airway morphology and narrowing after IMT were undetectable using MRI.     

Characteristics of diaphragmatic fatigue during exhaustive exercise until task failure

The diaphragm was postulated to fatigue relatively early during exhaustive whole body exercise without further loss in contractility as exercise proceeds towards task failure. Diaphragmatic contractility was investigated prior/during/after exhaustive whole body exercise until task failure by using lung volume corrected twitch transdiaphragmatic pressure (TwPdi(c)) during magnetic phrenic nerve stimulation (every 45s). Eleven cyclists exercised to exhaustion (workloads ≥85% maximal oxygen uptake; 20.7±9.8min). Individual post hoc calculation of TwPdi(c) was conducted (diaphragmatic contractility versus lung volume). Diaphragmatic fatigue (i.e. TwPdi reduction baseline/recovery ≥10%) occurred in 9/11 subjects (82% "fatiguers"; baseline/recovery TwPdi(c) -16±13%, p<0.01). Fatiguers TwPdi(c) was: baseline: 2.99±0.40kPa, exercise-onset: 2.98±0.41kPa, initial third: 2.80±0.67kPa, second third: 2.54±0.55kPa, final third-task failure: 2.51±0.44kPa, recovery: 2.50±0.52kPa. Diaphragmatic contractility and lung volume (rest) were strongly related (r(2)=0.98, mean TwPdi(c) gradient 0.78kPa/l). To conclude, diaphragmatic contractility (lung volume corrected) decreases relatively early (initial two thirds) during exhaustive exercise and remains preserved towards task failure. This confirms previous assumptions postulating that respiratory performance is sustained without further fatigue of the primary inspiratory muscle.     

Nocturnal non-invasive positive pressure ventilation: physiological effects on spontaneous breathing

The dynamic process of how non-invasive positive pressure ventilation (NPPV) improves spontaneous ventilation is unclear. Therefore, daytime trends of blood gases and breathing pattern were assessed by measurements 0, 0.5, 1, 3, 7, 11 and 15 h after cessation of nocturnal controlled NPPV in patients with chronic hypercapnic respiratory failure. Twelve patients (six COPD/six restrictive) who were established on NPPV and 12 controls (six COPD/six restrictive) completed. PaCO2 decreased during controlled NPPV (P < 0.02). PaCO2 additionally decreased step by step during the first 3 h of spontaneous breathing after switching from NPPV to spontaneous breathing (P < 0.05), but remained unchanged in controls. The PaCO2 decrease was due to a stepwise increase in tidal volume (P < 0.05) at an unchanged breathing frequency. Accordingly, minute ventilation also stepwise increased (P < 0.03). There were no significant changes in controls. Improvements of PaCO2 and tidal volume occurred even after 5.7 +/- 3.1 days following first NPPV trials, but became more evident after 2 months. Maximal inspiratory mouth pressures increased in chronic obstructive pulmonary disease (COPD) patients (P < 0.05), and respiratory drive increased in restrictive patients (P < 0.05) following 2 months of NPPV. Lung function parameters and inspiratory impedance remained unchanged. Improvements in health-related quality of life were evident and were correlated to the decline of elevated bicarbonate levels (r = 0.72, P < 0.01). In conclusion, there is a stepwise adaptation process lasting 3h when switching from nocturnal controlled NPPV to daytime spontaneous breathing in which tidal volume increases and PaCO2 drops after an initial PaCO2 decrease while on NPPV.     

Collagen of slow twitch and fast twitch muscle fibres in different types of rat skeletal muscle

Summary The appearance of collagen around individual fast twitch (FT) and slow twitch (ST) muscle fibres was investigated in skeletal muscles with different contractile properties using endurance trained and untrained rats as experimental animals. The collagenous connective tissue was analyzed by measuring hydroxyproline biochemically and by staining collagenous material histochemically in M. soleus (MS), M. rectus femoris (MRF), and M. gastrocnemius (MG). The concentration of hydroxyproline in the ST fibres dissected from MS (2.72±0.35 g·mg^–1 d.w.) was significantly higher than that of the FT fibres dissected from MRF (1.52±0.33 g·mg^–1 d.w.). Similarly, the concentration of hydroxyproline was higher in ST (2.54±0.51 g·mg^–1 d.w.) than in FT fibres (1.60±0.43 g·mg^–1 d.w.), when the fibres were dissected from the same muscle, MG. Histochemical staining of collagenous material agreed with the biochemical evidence that MS and the slow twitch area of MG are more collagenous than MRF and the fast twitch area of MG both at the level of perimysium and endomysium. The variables were not affected by endurance training. When discussing the role of collagen in the function of skeletal muscle it is suggested that the different functional demands of different skeletal muscles are also reflected in the structure of intramuscular connective tissue, even at the level of endomysial collagen. It is supposed that the known differences in the elastic properties of fast tetanic muscle compared to slow tonic muscle as, e.g., the higher compliance of fast muscle could at least partly be explained in terms of the amount, type, and structure of intramuscular collagen.This study was supported by grants from the Finnish Research Council for Physical Education and Sport (Ministry of Education) and the Academy of Finnland     

Oxidative stress in soleus and extensor digitorum longus (EDL) muscles of spontaneously hypertensive rats

Systemic diseases affect skeletal muscle, and inflammation and oxidative stress are some of the involved mechanisms. There is scarce information about the effects of essential hypertension on skeletal muscle. The soleus and extensor digitorum longus (EDL) muscles of spontaneously hypertensive rats (SHR) were studied compared to control Wistar Kyoto (WKY) rats. The levels of nitrite and nitrate in micromol/mg-protein; endothelial (eNOS), neuronal (nNOS), and inducible (iNOS) nitric oxide synthases, nitrotyrosine and tumour necrosis factor alpha (TNF-alpha) in ng/mg-protein were determined. Compared with controls, the SHR showed increased levels of nitrotyrosine (soleus 24.4 +/- 5.0 vs. 3.3 +/- 0.3, p<0.001; EDL 20.2 +/- 4.3 vs. 4.5 +/- 0.4, p<0.0037), iNOS (soleus 26.6 +/- 3.7 vs. 8.3 +/- 0.9; EDL 21.3 +/- 3.7 vs. 11.0 +/- 0.8, both p<0.0001) and TNF-alpha (soleus 2.2 +/- 0.5 vs. 0.6 +/- 0.1, p<0.05; EDL 1.9 +/- 0.2 vs. 0.6 +/- 0.1, p<0.02). A decrease of eNOS was found in soleus muscle (20.6 +/- 1.4 vs. 30.3 +/- 1.2, p<0.00001); of nNOS (soleus 16.8 +/- 1.4 vs. 20.7 +/- 1.8, p< 0.05; EDL 13.6 +/- 1.3 vs. 21.9 +/- 1.8, p<.005) and nitrite in EDL (5.8 +/- 0.3 vs. 7.1 +/- 0.5, p<0.026).There was a positive correlation between TNF-alpha vs. nitrotyrosine in soleus (r=0.798; p<0.031) and a tendency in EDL (r=0.739; p=0.059); iNOS vs. nitrotyrosine (soleus: r=0.908; p<0.0001; EDL: r=0.707; p<0.01), a tendency between TNF-alpha and iNOS (EDL: r=0.736; p<0.059); and a negative correlation between eNOS vs. nitrotyrosine in soleus muscle (r=-0.816; p<0.0012). In conclusion, in skeletal muscles of SHR an inflammatory process was found evidenced by the increase in TNF-alpha, nitrotyrosine and iNOS. The decreased levels of constitutive synthases, together with the higher level of iNOS, are indicative of endothelial dysfunction.     

Reproducibility of the self-controlled six-minute walking test in heart failure patients

INTRODUCTION: The six-minute walk test (6WT) has been proposed to be a submaximal test, but could actually demand a high level of exercise intensity from the patient, expressed by a respiratory quotient >1.0, following the guideline recommendations. Standardizing the 6WT using the Borg scale was proposed to make sure that all patients undergo a submaximal walking test. PURPOSE: To test the reproducibility of the six-minute treadmill cardiopulmonary walk test (6CWT) using the Borg scale and to make sure that all patients undergo a submaximal test. METHODS: Twenty-three male heart failure patients (50+/-9 years) were included; these patients had both ischemic (5) and non-ischemic (18) heart failure with a left ventricle ejection fraction of 23+/-7%, were diagnosed as functional class NYHA II-III and were undergoing optimized drug therapy. Patients were guided to walk at a pace between "relatively easy and slightly tiring" (11 and 13 on Borg scale). The 6CWT using the Borg scale was performed two times on a treadmill with zero inclination and patient control of speed with an interval of 24 hours. During the sixth minute, we analyzed ventilation (VE, L/min), respiratory quotient, Oxygen consumption (VO2, ml/kg/min), VE/VCO2 slope, heart rate (HR, bpm), systolic blood pressure (SBP, mmHg), diastolic (DBP, mmHg) blood pressure and distance. RESULTS: The intraclass correlation coefficients at the sixth minute were: HR (r i=0.96, p<0.0001), VE (r i=0.84, p<0.0001), SBP (r i=0.72, p=0.001), distance (r i=0.88, p<0.0001), VO2 (r i=0.92, p<0.0001), SlopeVE/VCO2 (r i=0.86, p<0.0001) and RQ<1 (r i=0.6, p=0.004). CONCLUSION: Using the 6CWT with the Borg scale was reproducible, and it seems to be an appropriate method to evaluate the functional capacity of heart failure patients while making sure that they undergo a submaximal walking test.     

Effects of intra-abdominal pressure on respiratory system mechanics in mechanically ventilated rats

We investigated the effects of intra-abdominal pressure on respiratory system compliance at different PEEP levels. 20 ventilated rats underwent four pressure levels (7, 9, 11, 13 mm Hg) of helium pneumoperitoneum and were allocated to one of the four PEEP groups (0, 3, 6 and 9 cm H(2)O). From the expiratory pressure-volume curve the mathematical inflection point (MIP) was calculated. Volume-dependent compliance was analyzed using the SLICE-method. MIP-pressure correlated to the intra-abdominal pressure (r(2)=0.94, p<0.001). Peak inspiratory pressure increased with intra-abdominal pressure, and was lower after recruitment-maneuvers (p<0.001). The compliance gain following recruitment-maneuvers depended on PEEP, intra-abdominal pressure and intratidal volume (all p<0.001). Mean arterial pressure was independent of PEEP (p=0.068) and intra-abdominal pressure (p=0.293). Volume-dependent compliance courses varied according to PEEP and intra-abdominal pressure. The level of intra-abdominal pressure alters respiratory system mechanics in healthy lungs. Intratidal compliance can be used to guide the PEEP adjustment in intra-abdominal hypertension. If counterbalanced by PEEP, elevated intra-abdominal pressure has no negative effects on oxygenation or hemodynamics.     

Nutritional Status is Related to Fat-Free Mass, Exercise Capacity and Inspiratory Strength in Severe Chronic Obstructive Pulmonary Disease Patients

INTRODUCTION:

Being overweight or obese is associated with a higher rate of survival in patients with advanced chronic obstructive pulmonary disease (COPD). This paradoxical relationship indicates that the influence of nutritional status on functional parameters should be further investigated.

OBJECTIVE:

To investigate the impact of nutritional status on body composition, exercise capacity and respiratory muscle strength in severe chronic obstructive pulmonary disease patients.

METHODS:

Thirty-two patients (nine women) were divided into three groups according to their body mass indices (BMI): overweight/obese (25 ≤ BMI ≤ 34.9 kg/m², n=8), normal weight (18.5 ≤ BMI ≤ 24.9 kg/m², n=17) and underweight (BMI <18.5 kg/m², n=7). Spirometry, bioelectrical impedance, a six-minute walking distance test and maximal inspiratory and expiratory pressures were assessed.

RESULTS:

Airway obstruction was similar among the groups (p=0.30); however, overweight/obese patients had a higher fat-free mass (FFM) index [FFMI=FFM/body weight² (mean±SEM: 17±0.3 vs. 15±0.3 vs. 14±0.5 m/kg², p<0.01)], exercise capacity (90±8 vs. 79±6 vs. 57±8 m, p=0.02) and maximal inspiratory pressure (63±7 vs. 57±5 vs. 35±8 % predicted, p=0.03) in comparison to normal weight and underweight patients, respectively. In addition, on backward multiple regression analysis, FFMI was the unique independent predictor of exercise capacity (partial r=0.52, p<0.01).

CONCLUSIONS:

Severe chronic obstructive pulmonary disease (COPD) patients who were overweight or obese had a greater FFM, exercise capacity and inspiratory muscle strength than patients with the same degree of airflow obstruction who were of normal weight or underweight, and higher FFM was independently associated with higher exercise capacity. These characteristics of overweight or obese patients might counteract the drawbacks of excess weight and lead to an improved prognosis in COPD.     

Breath-by-breath determinations of airway occlusion pressure in the developing lamb

The ventilatory effects of breath-by-breath measurements of airway occlusion pressure, i.e., airway pressure determined 100 ms after initiation of inspiration (P _{0. 1}) were evaluated in seven lambs studied sequentially between 7 and 28 days after birth. P _0.1 was determined by computer-aided, on-line regression analysis of the inspiratory pressure versus time (dP/dt) by means of a pneumatic occlusion valve that allowed occlusion times to vary in proportion to respiratory rate. No significant changes were found in minute ventilation, tidal volume, respiratory rate or end-tidal CO₂ concentration when the valve was operating as a one-way valve (opening pressure 0.02 kPa or 0.2 cm H₂0) compared to when in occlusion mode [opening pressure 0.18–0.2 kPa or 1.8–2.0 cmH₂0, mean occlusion time 44 (25) ms]. The calculated P _0.1 values correlated well with those obtained from manual occlusions (r = 0.87, P < 0.0001). This new technique, which detects and discards irregular or non-linear (r < 0.95) inspiratory pressure profiles, enables breath-by-breath determinations of inspiratory drive in rapidly breathing lambs with minimal impact on respiratory pattern and ventilation.These results were presented in part at the annual meetings of the American Pediatric Society and the Society for Pediatric Research 1992     

Effect of lung volume reduction surgery for emphysema on diaphragm function

Preoperative prediction of a successful outcome following lung volume reduction surgery (LVRS) for emphysema is imperfect. One mechanism could be improvement in respiratory muscle function yet controversy exists regarding the magnitude and mechanism of such an improvement. Therefore, we measured diaphragm strength in 18 patients before and after LVRS. Mean (S.D.) FRC fell from 6.53 to 5.40 l (p = 0.0001). Mean sniff transdiaphragmatic pressure increased from 76 to 87 cm H2O (14%, p < 0.03) and mean twitch transdiaphragmatic pressure (Tw Pdi) increased by 2.5 cm H2O at 3 months (12%, p = 0.03). There was a highly significant increase in twitch esophageal pressure (Tw Pes) (60%, p < 0.0001), which was maintained at 12 months (46% increase, p = 0.0004). No change was observed in quadriceps twitch tension in nine subjects in whom it was measured. After LVRS the ratio Tw Pes:Tw Pdi increased from 0.24 to 0.37 at 3 months (p = 0.0003) and 0.36 at 12 months (p = 008). Low values of Sn Pdi, Sn Pes, Tw Pes and a high RV/TLC ratio were the preoperative variables most predictive of improvement in shuttle walking distance. We conclude that LVRS improves diaphragm function primarily by alteration of lung volume. Patients with poor diaphragm function and high RV/TLC ratio preoperatively are most likely to benefit from the procedure.     

Assessment of murine lung tumour development: a comparison of two techniques

Two techniques (surface photographic analysis [SPA] and microscopic tumour analysis [MTA]) are described for assessing the stage of tumour development induced by intraperitoneal 4-(methyl nitrosamino)- 1-(3 pyridyl)-1-butanone in syngeneic A/J mice. Parameters used to assess the number and size of tumours were surface tumour count (STC), surface tumour area (STA). and relative tumour surface area (RTSA)--all using SPA; and mean tumour count (MTC), mean tumour area, and relative tumour area (RTA)--all using MTA. In a study examining the possible effects of Millipore chamber implantation on lung tumours, the stage of tumour development was assessed in 239 mice using both SPA and MTA. Statistically significant correlations (Spearman-Rank) were apparent between the derived parameters: STC vs. MTC (r = 0.6, P <0.0001); STA vs. mean tumour area (r = 0.5, P <0.0001); RTSA vs. RTA (r = 0.4, P <0.0001). Therefore, it is concluded that SPA--the simpler technique--is an appropriate method for assessing the stage of tumour development in this model.     

Attenuated inspiratory muscle metaboreflex in endurance-trained individuals

The inspiratory metaboreflex is activated during loaded breathing to task failure and induces sympathetic activation and peripheral vasoconstriction that may limit exercise performance. Inspiratory muscle training appears to attenuate the inspiratory metaboreflex in healthy subjects. Since whole body aerobic exercise training improves breathing endurance and inspiratory muscle strength, we hypothesized that endurance-trained individuals would demonstrate a blunted inspiratory muscle metaboreflex in comparison to sedentary individuals. We studied 9 runners (23±0.7 years; maximal oxygen uptake [VO2 max] = 53 ± 4 ml kg(-1) min(-1)) and 9 sedentary healthy volunteers (24±0.7 years; VO2 max = 37 ±2 ml kg(-1) min(-1)). The inspiratory muscle metaboreflex was induced by breathing against an inspiratory load of 60% of maximal inspiratory pressure (MIP), with prolonged duty cycle. Arterial pressure, popliteal blood flow, and heart rate were measured throughout the protocol. Loaded breathing to task failure increased mean arterial pressure in both sedentary and endurance-trained individuals (96±3 to 100±4 mmHg and 101±3 to 110±5 mmHg). Popliteal blood flow decreased in sedentary but not in trained individuals (0.179±0.01 to 0.141±0.01 cm/s, and 0.211±0.02 to 0.214±0.02 cm/s). Similarly, popliteal vascular resistance increased in sedentary but not in trained individuals (559±35 to 757±56 mmHg s/cm, and 528±69 to 558±64 mmHg s/cm). These data demonstrate that endurance-trained individuals have an attenuated inspiratory muscle metaboreflex.     

Effect of changes in intrathoracic pressure on cardiac function at rest and during moderate exercise in health and heart failure

This study investigated the effect of changes in inspiratory intrathoracic pressure on stroke volume at rest and during moderate exercise in patients with heart failure and reduced ejection fraction (HFREF) as well as healthy individuals. Stroke volume was obtained by echocardiography during 2 min of spontaneous breathing (S), two progressive levels of inspiratory unloading (UL1 and UL2) using a ventilator, and two progressive levels of inspiratory loading using resistors in 11 patients with HFREF (61 ± 9 years old; ejection fraction 32 ± 4%; NYHA class I-II) and 11 age-matched healthy individuals at rest and during exercise at 60% of maximal aerobic capacity on a semi-recumbent cycle ergometer. At rest, inspiratory unloading progressively decreased stroke volume index (SVI; S, 35.2 ± 5.4 ml m(-2); UL1, 33.3 ± 5.1 ml m(-2); and UL2, 32.2 ± 4.4 ml m(-2)) in healthy individuals, while it increased SVI (S, 31.4 ± 4.6 ml m(-2); UL1, 32.0 ± 5.9 ml m(-2); and UL2, 34.0 ± 7.2 ml m(-2)) in patients with HFREF (P = 0.04). During moderate exercise, inspiratory unloading decreased SVI in a similar manner (S, 43.9 ± 7.1 ml m(-2); UL1, 40.7 ± 4.7 ml m(-2); and UL2, 39.9 ± 3.7 ml m(-1)) in healthy individuals, while it increased SVI (S, 40.8 ± 6.5 ml m(-2); UL1, 42.8 ± 6.9 ml m(-2); and UL2, 44.1 ± 4. ml m(-2)) in patients with HFREF (P = 0.02). Inspiratory loading did not significantly change SVI at rest or during moderate exercise in both groups. It is concluded that inspiratory unloading improved SVI at rest and during moderate exercise in patients with HFREF, possibly due to a reduction in left ventricular afterload.     

Scalene muscle activity during progressive inspiratory loading under pressure support ventilation in normal humans

We hypothesized that (1) in healthy humans subjected to intermittent positive pressure non-invasive ventilation, changes in the ventilator trigger sensitivity would be associated with increased scalene activity, (2) if properly processed – through inspiratory phase-locked averaging – surface electromyograms (EMG) of the scalenes would reliably detect and quantify this, (3) there would be a correlation between dyspnea and scalene EMG. Surface and intramuscular EMG activity of scalene muscles were measured in 10 subjects. They breathed quietly through a face mask for 10 min and then were connected to a mechanical ventilator. Recordings were performed during three 15-min epochs where the subjects breathed against an increasingly negative pressure trigger (−5%, −10% and −15% of maximal inspiratory pressure). With increasing values of the inspiratory trigger, inspiratory efforts, dyspnea and the scalene activity increased significantly. The scalene EMG activity level was correlated with the esophageal pressure time product and with dyspnea intensity. Inspiration-adjusted surface EMG averaging could be useful to detect small increases of the scalene muscles activity during mechanical ventilation.     

The influence on the breathing pattern in man of moderate levels of continuous positive and negative airway pressure and of positive end-expiratory pressure during air and CO2 inhalation

The purpose of this study was to determine in man the effect on the breathing pattern of continuous positive (CPAP), continuous negative (CNAP) and positive end-expiratory (PEEP) airway pressure during air breathing and CO₂ inhalation. Six subjects were exposed to CPAP, CNAP and PEEP 0.5 kPa, while five subjects were exposed to CPAP and CNAP 0.8 kPa. End-expiratory lung volume increased during CPAP 0.8 kPa and decreased during CNAP 0.8 kPa. CPAP induced more extensive changes in the ventilatory pattern, and the changes in each parameter were larger than observed during CNAP and PEEP at the same pressure level. In contrast to previous reports we found the effect of CO₂ inhalation combined with the effect of pressure breathing to be not stronger than additive. Even moderate CPAP induced alveolar hyperventilation with marked reduction in arterial PCO₂ (PaCO₂) when breathing air. With increasing fraction of CO₂ in the inspiratory gas, the difference in PaCO₂ between CPAP and no CPAP disappeared. PEEP also affected the breathing pattern in that it induced an increase in mean inspiratory flow and mean expiratory flow and a reduction in inspiratory duration. Occurrence of ventilatory pauses depended on whether mouthpiece or facemask was used. CPAP and CNAP did not influence the occurrence of pauses, while PEEP prolonged post-expiratory pauses. We conclude that CPAP, CNAP and PEEP induce active ventilatory responses in man and that strong mechanisms are involved during CPAP since PaCO₂ is markedly reduced.