Usefulness of phrenic nerve stimulation to measure upper airway collapsibility in normal awake subjects

Upper airway (UA) collapsibility can be characterized during sleep by looking at the changes in inspiratory flow limitation (IFL) with changing nasal pressure. IFL can be induced during wakefulness using phrenic nerve stimulation (PNS) applied during exclusive nasal breathing. The aim of the study was to evaluate the possibility of measuring UA critical pressure (Pcrit) in normal awaked subjects using electrical PNS (EPNS) or bilateral anterior magnetic phrenic stimulation (BAMPS). Instantaneous flow, esophageal (Peso) and mask pressures (Pmask), and genioglossal (GG) end-expiratory EMG activity were recorded in 13 normal subjects (4F, 9M) with randomly changing Pmask (0 to -20 cmH2O). For each trial, we examined the relationship between maximal inspiratory flow (Vtmax) of IFL twitches and the corresponding Pmask. Pcrit could be determined in 12 subjects (mean -33.5 +/- 16.3 cmH2O). No difference in Pcrit values was found between the EPNS and BAMPS methods but the strength of the Vtmax/Pmask relationship was higher with BAMPS. GG end-expiratory EMG activity increased with decreasing Pmask but no significant relationship was found between the slope of the GG end-expiratory EMG activity/Pmask relationship and Pcrit. We conclude that: (1) Pcrit can be measured during wakefulness in normal using PNS: (2) Pcrit measurements may be easier and more reliable with BAMPS than EPNS: and (3) Pcrit does not seem to be influenced by the pressure-related changes in GG end-expiratory EMG.     

Constant mean airway pressure with different patterns of positive pressure breathing during the adult respiratory distress syndrome

Twenty-one ARDS patients were divided into two groups of severity according to FIO2 and PEEP required to maintain an adequate gas exchange. The 10 most severe patients (group A) underwent continuous positive pressure ventilation (CPPV) (I/E 3:1) with the mean airway pressure maintained at 21 +/- 6.2 cmH2O. The PEEP values were 12.6 +/- 4.3 cmH2O during CPPV and 6.5 +/- 3.7 cmH2O during IRV (p less than 0.01). Eleven less severe ARDS patients (group B) underwent CPPV and positive pressure spontaneous breathing (CPAP) at constant mean airway pressure of 14.3 +/- 3.8 cmH2O. The PEEP was 7 +/- 2.5 cmH2O during CPPV and 14.9 +/- 4.3 cmH2O during CPAP (p less than 0.001). In five patients of each group, the SF6 shunt was measured as representative of true shunt. The results showed that gas exchange, including true shunt, and haemodynamics did not change between CPPV and IRV and between CPPV and CPAP tests. Taken with previous work on mean airway pressure, our results further support the concept that the main determinant of oxygenation and haemodynamics is the mean airway pressure, irrespective of the PEEP level and of the mode of ventilation.     

Non-linear dependence of interstitial fluid pressure on joint cavity pressure and implications for interstitial resistance in rabbit knee

AIMS: Synovium retains lubricating fluid in the joint cavity. Synovial outflow resistance estimated as dPj/dQs (Pj, joint fluid pressure and Qs trans-synovial flow) is greater, however, than expected from interstitial glycosaminoglycan concentration. This study investigates whether subsynovial fluid pressure increases with intra-articular pressure, as this would reduce the estimated resistance estimate. METHODS: Interstitial fluid pressure (Pif) was measured as a function of distance from the joint cavity in knees of anaesthetized rabbits, using servo-null pressure-measuring micropipettes and using an external 'window'. Joint fluid pressure Pj was either endogenous (-2.4 +/- 0.4 cmH2O, mean +/- SEM) or held at approximately 4, 8 or 15.0 cmH2O by a continuous intra-articular saline infusion that matched the trans-synovial interstitial drainage rate. RESULTS: At endogenous Pj the peri-articular Pif was subatmospheric (-1.9 +/- 0.3 cmH2O, n = 19). At raised Pj the Pif values became positive. Gradient dPif /dx was approximately 20 times steeper across synovium than subsynovium. Pif close to the synovium-subsynovium border (Pif*) increased as a non-linear function of Pj to 1.4 +/- 0.2 cmH2O (n = 23) at Pj = 4.3 +/- 0.1 cmH2O : 2.3 +/- 0.2 cmH2O (n = 17) at Pj = 7.6 +/- 0.2 cmH2O: and 3.0 +/- 0.4 cmH2O (n = 26) at Pj = 15 +/- 0.2 cmH2O (P = 0.03, anova). CONCLUSIONS: Synovial resistivity is approximately 20x subsynovial resistivity. The increase in Pif*with Pj means that true synovial resistance d(Pj-Pif*)/dQs is overestimated 1.5x by dPj/dQs. This narrows but does not eliminate the gap between analysed glycosaminoglycan concentration, 4 mg ml(-1), and the net interstitial biopolymer concentration of 11.5 mg ml(-1) needed to generate the resistance.     

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.     

Respiratory response to inspiratory resistive load changes in patients with obstructive sleep apnea syndrome

Patients with OSA have many episodes of increased airway resistance because of repeated collapses of upper airways during night. The aim of this work was to evaluate respiratory response during chemical stimulation without and with added inspiratory resistive load (10 cmH2O/L/sec). The studies were performed during quiet breathing with air and during hypercapnic and hypoxic rebreathing tests without and with inspiratory resistive loading in 23 obese (BMI = 34.4 +/- 4.3 kg/m2) patients with OSA and in 10 healthy subjects with similar weight (BMI = 32.4 +/- 4.3 kg/m2). The measurements of respiratory responses (ventilation, mouth occlusion pressure) were performed with the use of computerized equipment. During quiet breathing in response to added load an increase of P0.1 in controls and in OSA patients was observed. During hypercapnic stimulation the ventilatory response with additional load decreased in patients as well as in controls. The slope of mouth occlusion pressure response increased significantly in controls (from 4.40 to 6.83 cmH2O/kPa, p < 0.001) and slightly weaker in OSA patients (from 4.21 to 5.43 cmH2O/kPa, p < 0.05). Although the difference between the slopes was not significant, we found that the absolute increase of P0.1 measured at point 8 kPa of PEtCO2 during loaded breathing was significantly smaller in OSA patients in comparison to controls. (2.1 vs. 10.3 cm H2O; p < 0.001). During hypoxic stimulation occlusion pressure responses were similar in both examined groups. In conclusion we postulate that OSA patients have impaired respiratory compensation of additional inspiratory load, what was demonstrated during hypercapnic rebreathing test.     

Neutrophil influx into guinea-pig airway lumen during cholinergic and non-cholinergic bronchoconstriction.

Sensory nerve activation will produce adherence of neutrophils to tracheobronchial microvessels. The aim of the present study was to investigate whether this adherence would lead to an influx of neutrophils into the airway lumen. To do this, we studied the effects of 20 minutes of vagal stimulation (1 Hz, 5 ms, 5 V) in anaesthetized and tracheostomized guinea-pigs on both lung resistance, and the cell picture in bronchoalveolar lavage. Any changes were compared to those of intravenous methacholine infusion, producing similar changes in lung resistance. Since high pressure ventilation could produce lung damage, we also studied the effects of ventilation through an extracorporeal resistor, producing a similar change in transpulmonary pressure (45 +/- 2 cmH2O) as vagal stimulation (42 +/- 4 cmH2O). The total number of cells recovered in the lavage was not increased by vagal stimulation, methacholine infusion or the extracorporeal resistor. However, both vagal stimulation and methacholine infusion significantly increased the relative number of neutrophils in the lavage compared to sham stimulated animals (21 +/- 11%, 13 +/- 4% and 4 +/- 1% respectively), but the extracorporeal resistor had no effect (4 +/- 2%). Our data suggests that prolonged bronchoconstriction per se may induce an influx of neutrophils into the airway lumen of the guinea-pig.     

Pulmonary vascular pressure profile in adult ferrets: measurements in vivo and in isolated lungs

We have determined the vascular pressure profile in lungs of adult ferrets utilizing an anaesthetized open chested preparation and have compared the pressure profile in vivo with that in isolated, perfused lungs. Ten adult ferrets, mean body weight 980 +/- 108 g, were studied. For in vivo measurements, five ferrets were anaesthetized, mechanically ventilated and the left chest wall resected. Pressures were measured in the pulmonary artery, left atrium and by micropuncture, in 20-50 microns diameter subpleural arterioles and venules. During micropuncture, ventilation was stopped for 1-2 min and the lungs kept distended at an airway pressure of 6 cmH2O. Left atrial pressure was raised to approximately 8 cmH2O with saline infusion so that lungs were in Zone 3. Cardiac output was measured by thermodilution. Lungs of five other ferrets were isolated and perfused with a steady flow roller pump. In these lungs blood flow was adjusted so that pulmonary artery pressure was similar to that in anaesthetized ferrets, with airway and left atrial pressures at 6 and 8 cmH2O respectively (Zone 3). Blood haematocrit (35 +/- 7%) was similar in the two groups. In lungs of anaesthetized ferrets total arteriovenous pressure drop was 12.1 +/- 1.9 cmH2O, with cardiac output being 210 +/- 80 ml kg body weight-1 min-1. Fractional resistance in arteries was 37%, 37% in microvessels and 26% in veins. In isolated ferret lungs, though blood flow was only 48 +/- 10 ml kg body wt-1 min-1 for the same total arteriovenous pressure drop as in vivo, the longitudinal distribution of vascular resistance was similar to that in live ferrets.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of airflow resistance variations on resistive load detection in normal subjects

The sensitivity to airflow resistance variations produced by externally added resistive loads, with modification of background load, was studied in 15 normal subjects, using "Sensory Decision Theory" (SDT), a psychophysical method that gives an index of accuracy, P(A), unaffected by response bias. In six subjects, asked to detect three increasingly added loads (delta R) at different levels of basal resistance (1.6 and 3.6 cmH2O X 1(-1) X s), inspiratory resistive load detection (RLD) improved with background loading, and a highly significant relationship was found between P(A) and peak mouth pressure (Pm). The relationship between P(A) and the change in Pm, i.e. delta Pm, was less significant. These results suggest that, although tension developed by the respiratory muscles reflected by mouth pressure may be an important stimulus to respiratory RLD, other factors must also be considered. In seven subjects, in whom airway resistance was increased at least 50% by inhalation of carbachol, inconsistent variations in P(A) were found. In seven subjects, in whom airflow resistance was decreased by inhalation of heliox, and in six of seven subjects after salbutamol inhalation, RLD was significantly impaired. The results of this study lead us to the conclusion that Weber's law is not verified for weak internal or external background loading.     

Influence of head extension, flexion, and rotation on collapsibility of the passive upper airway

STUDY OBJECTIVES: To determine the effect of head posture on upper airway collapsibility and site of collapse of the passive human upper airway. DESIGN: Pharyngeal critical closing pressure (Pcrit) and site of airway collapse were assessed during head flexion, extension and rotation in individuals undergoing propofol anesthesia. SETTING: Operating theatre of major teaching hospital. PARTICIPANTS: Fifteen healthy volunteers (8 male), including 7 who were undergoing surgery unrelated to the head or neck. MEASUREMENTS AND RESULTS: Applied upper airway pressure was progressively decreased to induce variable degrees of inspiratory flow limitation and to define Pcrit. Upper airway and oesophageal pressure transducers identified the site of collapse. Genioglossus muscle activity (EMGgg) was assessed using intramuscular fine wire electrodes inserted percutaneously. Data from 3 subjects were excluded from analysis due to persistent EMGgg. In the neutral posture Pcrit was -0.4 +/- 4.4 cm H2O and collapsed most frequently in the velopharyngeal region. Relative to neutral, Pcrit increased to 3.7 +/- 2.9 cm H2O (P < 0.01) and decreased to -9.4 +/- 3.8 cm H2O (P < 0.01) when the head was flexed and extended, respectively but was unchanged by rotation (-2.6 +/- 3.3 cm H2O; n = 10; P = 0.44). The site of collapse varied, in no consistent pattern, with change in head posture in 5 subjects. CONCLUSIONS: Head posture has a marked effect on the collapsibility and site of collapse of the passive upper airway (measured by EMGgg) indicating that controlling head posture during sleep or recovery from anesthesia may alter the propensity for airway obstruction. Further, manipulating head posture during propofol sedation may assist with identification of pharyngeal regions vulnerable to collapse during sleep and may be useful for guiding surgical intervention.     

The contribution of the pulmonary microvascular pressure in the maintenance of an open lung during mechanical ventilation

Changes in pulmonary hemodynamics modify the mechanical properties of the lungs. The effects of alterations in pulmonary capillary pressure (Pc) were investigated on the airway and lung tissue mechanics during positive-pressure ventilation and following lung recruitment maneuvers. Isolated, mechanically normoventilated (PEEP 2.5 cmH(2)O) rat lungs were perfused with Pc set to 0 (unperfused), 5, 10 or 15 mmHg, in random sequence. The pulmonary input impedance (ZL) was measured at end-expiration before and after a 10-min long ventilation. After inflation of the lung to 30 cmH(2)O during P-V curve recordings, another set of ZL was measured to evaluate the degree of recruitment. The PEEP was then decreased to 0.5 cmH(2)O and the sequence was repeated. Airway resistance and parenchymal damping and elastance (H) were estimated from ZL by model fitting. From the P-V curves, elastance (E) and hysteresis indices were determined. Mechanical ventilation at both PEEP levels resulted primarily in elevations in the tissue parameters, with the greatest increases at the 0 Pc level (H changes of 27.8+/-4.2 and 61.3+/-3.7% at 2.5 and 0.5 cmH(2)O PEEP, respectively). The maintenance of physiological Pc (10 mmHg) led to a significantly lower elevation in H (11.6+/-1.5% versus 31.4+/-3.6%). The changes in the oscillatory mechanics were also reflected in E and the hysteresis of the P-V curves. These findings indicate that pulmonary hypoperfusion during mechanical ventilation forecasts a parenchymal mechanical deterioration. Physiological pressure in the pulmonary capillaries is therefore an important mechanical factor promoting maintenance of the stability of the alveolar architecture during positive-pressure mechanical ventilation.     

A practical protocol for titrating "optimal" PEEP in acute lung injury: recruitment maneuver and PEEP decrement

This study was conducted to evaluate the effectiveness and safety of a practical protocol for titrating positive end-expiratory pressure (PEEP) involving recruitment maneuver (RM) and decremental PEEP. Seventeen consecutive patients with acute lung injury who underwent PEEP titration were included in the analysis. After baseline ventilation, RM (continuous positive airway pressure, 35 cm H2O for 45 sec) was performed and PEEP was increased to 20 cmH2O or the highest PEEP guaranteeing the minimal tidal volume of 5 mL/kg. Then PEEP was decreased every 20 min in 2 cmH2O decrements. The "optimal" PEEP was defined as the lowest PEEP attainable without causing a significant drop (>10%) in PaO2. The "optimal PEEP" was 14.5 +/- 3.8 cmH2O. PaO2 /FI O2 ratio was 154.8 +/- 63.3 mmHg at baseline and improved to 290.0 +/- 96.4 mmHg at highest PEEP and 302.7 +/- 94.2 mmHg at "optimal PEEP", both significantly higher than baseline (p<0.05). Static compliance was significantly higher at "optimal" PEEP (27.2 +/- 10.4 mL/ cmH2O) compared to highest PEEP (22.3 +/- 7.7 mL/cmH2O) (p<0.05). Three patients experienced transient hypotension and one patient experienced atrial premature contractions. No patient had gross barotrauma. PEEP titration protocol involving RM and PEEP decrement was effective in improving oxygenation and was generally well-tolerated.     

Tracheal traction effects on upper airway patency in rabbits: the role of tissue pressure

STUDY OBJECTIVES: To investigate the mechanisms via which lung volume related caudal tracheal traction decreases upper airway collapsibility. DESIGN: Acute physiological study. PARTICIPANTS: 20 male, supine, anesthetised, tracheostomised, spontaneously breathing, NZ white rabbits fitted with a sealed face mask. SETTING: N/A. MEASUREMENTS AND RESULTS: Upper airway extraluminal tissue pressure (ETP) was measured in the lateral (ETPlat) and anterior (ETPant) pharyngeal walls (pressure transducer tipped catheters). Graded traction was applied to the isolated upper airway (n = 17, 0-140 g). Subsequently, inflation and deflation was performed (with and without traction, 48 g, n = 13) with measurement of intraluminal pressure. Upper airway transmural pressure (PTM) was calculated (at closure and reopening) for both ETP sites (PTMlat and PTMant, respectively). A traction force of 144 g decreased ETPlat from 2.6 +/- 0.7 cm H2O (mean +/- SEM) to 2.1 +/- 0.7 cm H2O and ETPant from 1.1 +/- 0.4 cm H2O to 0.8 +/- 0.4 cm H2O (both P < 0.001). Increasing traction decreased closing and reopening pressures by 1.4 +/- 0.2 cm H2O for 48 g of traction (n = 13, P < 0.0001). In addition, 48 g of traction decreased ETPlat (at closure and reopening) by 0.2 +/- 0.05 cm H2O (P < 0.0001), and decreased ETPant by 0.5 +/- 0.1 cm H2O at closing pressure and 0.8 +/- 0.1 cm H2O at reopening (both p < 0.0001). Thus, for 48 g of traction, PTMlat (at closure and reopening) fell by 1.1 +/- 0.2 cm H2O and PTMant (reopening only) fell by 0.9 +/- 0.3 cm H2O (all P < 0.0001). CONCLUSIONS: Since tracheal traction decreased PTMlat and PTMant by a greater amount than ETPlat and ETPant, we conclude that the decrease in upper airway collapsibility mediated by lung volume related caudal tracheal traction is partially explained by reductions in ETP.     

Mucopolysaccharide osmotic pressure in the measurement of interstitial pressure.

Subatmospheric pressures were recorded from cotton wicks inserted into Wharton's jelly of human umbilical cords (mean=-7.6+/-5.0 (SD) cmH2O; n=10). Hyaluronate concentrations (mean=0.69+/-0.30 g/100 g) and wick pressures correlated negatively (r=-0.825; P less than 0.01) but calculated hyaluronate osmotic pressures (mean=4.0+/-2.7 cmH2O) were insufficient to explain the full wick pressure. In model systems composed of asbestos fibers (mean radius=0.5 micron) and 0.9% saline, subatmospheric pressures were recorded which varied with the volume of saline added. When hyaluronate (1 g/100 g) was substituted for saline, lower wick pressures were recorded at each volume. The pressure lowering effect of hyaluronate was not seen in a matrix of glass fibers (mean radius=1.0 micron). It is suggested that the effect of hyaluronate in asbestos fibers is due to its immobilization by the matrix and the consequent development of osmotic pressure recorded via the wick. In the coarser glass-fiber matrix, hyaluronate was not immobilized and therefore had no osmotic effect. These experiments support the hypothesis that subatmospheric interstitial pressures result from osmotic pressure of immobilized mucopolysaccharide macromolecules.     

气道内高压力促进3种气道重塑相关因子的表达

目的探讨机械通气情况下气道内不同压力水平对气道重塑相关因子表达的影响。方法手术室经全麻行机械通气的42例慢性阻塞性肺疾病(COPD)作为COPD组和33例无基础肺疾病患者作为对照组。机械通气根据吸气峰压(PIP)水平又分为高、中、低压力组(分别为24、22和20 cm H_2O),呼气末正压均为5 cm H_2O。机械通气前及3 h后收集支气管肺泡灌洗液(BALF)。酶联免疫吸附法和Western blot法检测BALF中气道重塑相关因子成纤维生长因子2(FGF-2)、转化生长因子-β1(TGF-β1)和基质金属蛋白酶-9(MMP-9)蛋白表达水平。结果 1)机械通气前COPD组BALF中的FGF-2、TGF-β1和MMP-9蛋白水平明显高于对照组(P0.01)。2)机械通气后对照组在高压力刺激下FGF-2、TGF-β1和MMP-9表达水平升高(P0.05);而COPD组压力刺激下上述3种蛋白表达升高更明显(P0.05),且高压力组中及低压力组(P0.05)。3)相关性分析显示,COPD组BALF中FGF-2、TGF-β1、MMP-9表达水平与气道压力成正相关(P0.01)。结论机械通气时气道内的持续高压力可能通过作用于气道上皮细胞内压力敏感通道进而提高气道重塑因子FGF-2、TGF-β1、MMP-9的表达水平,COPD患者尤为显著。     

Lymph capillary pressure of rat intestinal villi during fluid absorption.

A newly developed intestinal preparation is described for determining lymph capillary pressure (PL) in the villi in vivo and in vitro. Determination of PL provided an estimate of tissue fluid pressure in the villi. PL was related to the fluid absorption rate and increased by lymphatic obstruction. During fluid absorption from isotonic mucosal fluid, PL was 1.4 +/- 0.5 or 1.1 +/- 0.4 cmH2O determined in vivo or in vitro, respectively. Both pressures were essentially in the same range as that (0.7 +/- 0.3--1.3 +/- 0.5 cmH2O) in which the mucosal fluid was isotonic Na2SO4 solution or Na-free solutions from which little fluid absorption occurred. This range of pressures may be taken as the normal tissue fluid pressure in the villi. At a high rate of fluid absorption from hypotonic mucosal fluid, PL increased to 5.2 +/- 1.4 cmH2O and tissue fluid pressure was also similarly increased. It is concluded that the fluid absorptive process by the epithelium could not develop an appreciable hydrostatic pressure in the villus tissue space or in the lymphatics.     

Comparison of mouth and oesophageal pressure fluctuations during panting against an occlusion

In four normal volunteers, differences between oesophageal pressure fluctuations (delta Pes) in the upper and lower parts of the oesophagus and mouth pressure fluctuations (delta Pm), simultaneously measured during panting against an occlusion, were evaluated. Averaged quasi static pressure-volume curves were obtained by measuring pressure in the upper and lower thirds of the oesophagus. The differences between delta Pes and delta Pm during panting, due to elastic recoil changes, were predicted from an exponential relationship fitted to the pressure-volume curves. The calculated errors were compared with those observed experimentally. In the lower part of the oesophagus, delta Pes was similar to delta Pm at lung volumes in the range of 50 to 70% of Vmax. Vmax was deduced from the asymptote of the exponential curve. Mean delta Pes/delta Pm was 0.98 +/- 0.08 (SD). In the upper oesophagus, delta Pes was lower than delta Pm. Mean delta Pes/delta Pm was 0.87 in the range of 50 up to 90% of Vmax with an SD +/- 0.15. At lung volumes above 90% of Vmax for the upper oesophagus and above 70% of Vmax for the lower oesophagus, the ratio of delta Pes to delta Pm exceeded 1 and progressively increased. The measured values were often higher than those predicted from the fitted curves, presumably due to a narrowed glottic aperture. We concluded that in normals both the positioning of the oesophageal balloon in the lower oesophagus and a lung volume near functional residual capacity (FRC) are prerequisites for the use of delta Pm as a control for delta Pes, or vice versa, during panting against an occlusion.     

Nasal admixture during mouth breathing in awake normal subjects

We tested the flow-impeding properties of the nasopharynx in 27 healthy subjects with normal nasal resistance (mean +/- SD: 2.45 +/- 1.92 cmH20.l-1 X s). While the subjects inspired and expired deliberately through a rubber mouth-piece, a tight-fitting nose-mask was supplied with 100% O2 from a filled 30-1 rubber bag. Recording instantaneous FEO2 at the mouth was a sensitive indicator of whether nasal flow was present during the preceding inspiration. On a theoretical basis, we are describing a method of calculating the mean percentage of nasal admixture during inspiration. Fluctuations in FEO2 in relation to time revealed varying nasal flow in some individuals. The mean nasal admixture differed considerably between all subjects (mean +/- SD: 20.9 +/- 16.5%; range: 1-70%), showing no correlation to nasal resistance. Five of 27 subjects with a history of habitual mouth breathing had a significantly lower nasal admixture (2.5 +/- 1.7% vs 25.1 +/- 15.4%; p less than 0.005), with no statistical difference in nasal resistance. Present data indicate that upper airway patency is variable in normals during voluntary mouth breathing. We suggest that habitual mouth breathing with absence of nasal obstruction may be associated with velopharyngeal narrowing.     

Interstitial pressure gradients around joints; location of chief resistance to fluid drainage from the rabbit knee

The hypothesis has been advanced that synovium offers the main resistance to fluid escape from joints, even though it is under 20 microm thick. To test this, fluid was infused into the knee joint cavity of anaesthetised rabbits to set up a pressure gradient, then the profile of periarticular interstitial fluid pressure (P(if)) was measured by advancing a micropipette, connected to a servo-null pressure recorder, in steps through a periarticular tissue 'window' until the joint cavity was entered. With intra-articular pressure (P(j)) raised to 15 cmH(2)O (the pressure of an acute joint effusion) the pressure gradient dP(if) /dx (where x is distance) across the synovial lining was 0.47 +/- 0.04 cmH(2)O microm(-1) (n = 10 joints). This was 23.5-fold greater than the gradient in the subsynovium (0.02 +/- 0.01 cmH(2)O microm(-1); P < 0.0001, Student's t test), indicating that the hydraulic resistivity of the subsynovium is 4 % of that of the synovium. The pressure profile was not altered by circulatory arrest. To test the hypothesis further, the effect of a stab perforation of the synovial lining on fluid drainage rate ((.Q(s)) was studied. Perforation raised both.Q(s) and the conductance term d.Q(s)/dP(j) more than 10-fold (n = 6 joints; P < 0.0001, ANOVA). The results thus support the view that, despite its thinness, the synovial lining offers the main hydraulic resistance to fluid drainage from a synovial joint.     

The role of free radical in the pathogenesis of impotence in streptozotocin-induced diabetic rats

Diabetes is the most common cause of erectile dysfunction (ED). Oxidative stress has been suggested to be a contributory factor in vascular complications of diabetes in various organs. In the present study, we investigated whether oxidative stress is associated with erectile function in non-insulin dependent diabetes mellitus (NIDDM) rats. Fifty-four Sprague-Dawley rats were the subjects of this study. In each rat, NIDDM was induced by an intraperitoneal injection of 90 mg/Kg of streptozotocin on the second day after birth. Based on the diabetic period, they were classified into either short-term or long-term diabetics (avg. 22 weeks, n=18 and avg. 38 weeks, n=20), respectively, and their age-matched controls (n=16). To evaluate the erectile function in each rat, the intracavernous pressure, and latency to maximal pressure, following cavernous nerve stimulation (frequency: 1 Hz, intensity: 3 - 6 V, pulse width: 1 msec, pulse duration: 1 min.) was analyzed. To evaluate both oxidative stress from reactive oxygen species, and antioxidant function as a defense against them, total malondialdehyde and glutathione levels were measured in the corpus cavernosum of the penis, using a spectrophotometric assay. The intracavernous pressure following cavernous nerve stimulation was significantly lower in the long-term (49.8 +/- 9.4 cmH2O) than the short-term diabetics (75.9 +/- 14.8 cm H2O), and markedly decreased in the diabetic rats, compared with their age-matched controls (long-term controls; 60.7 +/- 17.2 cmH2O, short-term controls; 95.2 +/- 20.4 cmH2O). The malondialdehyde content in the corpus cavernosum was markedly increased in the diabetics (2.13 +/- 0.27 nM/mg protein) compared to the controls (1.48 +/- 0.22 nM/mg protein). Furthermore, the glutathione level was significantly decreased in the diabetics, compared to age-matched controls (short-term control; 218.3 +/- 25.6 microM/mg protein, long-term control; 150.2 +/- 9.8 microM/mg protein). In the diabetic groups, it was more significantly decreased in the long-term diabetics (134.8 +/- 11.3 microM/mg protein) than in short-term diabetics (182.1 +/- 18.8 microM/mg protein). NIDDM causes erectile dysfunction, which slowly progresses. Oxidative stress to cavernous tissue may be a contributory factor in erectile dysfunction in diabetics.     

The effect of sleep on reflex genioglossus muscle activation by stimuli of negative airway pressure in humans.

The present study was designed to determine the effect of sleep on reflex pharyngeal dilator muscle activation by stimuli of negative airway pressure in human subjects. Intra-oral bipolar surface electrodes were used to record genioglossus electromyogram (EMG) responses to 500 ms duration pressure stimuli of 0 and -25 cmH2O applied, via a face-mask, in four normal subjects. Stimuli were applied during early inspiration in wakefulness and in periods of non-rapid-eye-movement (non-REM) sleep, defined by electroencephalographic (EEG) criteria. The rectified and integrated EMG responses to repeated interventions were bin averaged for the 0 and -25 cmH2O stimuli applied in wakefulness and sleep. Response latency was defined as the time when the EMG activity significantly increased above prestimulus levels. Response magnitude was quantified as the in ratio of the EMG activity for an 80 ms post-stimulus period to an 80 ms prestimulus period; data from after the subject's voluntary reaction time for tongue protrusion (range, 150-230 ms) were not analysed. Application of the -25 cmH2O stimuli caused genioglossus muscle activation in wakefulness and sleep, but in all subjects response magnitude was reduced in sleep (mean decrease, 61%; range, 52-82%; P = 0.011, Student's paired t test). In addition, response latency was increased in sleep in each subject (mean latency awake, 38 ms; range, 30-50 ms; mean latency asleep, 75 ms; range, 40-110 ms; P = 0.072, Student's paired t test). Application of the -25 cmH2O stimuli caused arousal from sleep on 90% occasions, but in all cases the reflex genioglossus muscle responses (maximum latency, 110 ms) always proceeded any sign of EEG arousal (mean time to arousal, 643 ms; range, 424-760 ms). These results show that non-REM sleep attenuates reflex genioglossus muscle activation by stimuli of negative airway pressure. Attenuation of this reflex by sleep may impair the ability of the upper airway to defend itself from suction collapse by negative pressures generated during inspiration; this may have implications for the pathogenesis of obstructive sleep apnoea.