Bronchoconstriction elicited by isocapnic hyperpnea in guinea pigs

We demonstrated spontaneous self-limited bronchoconstriction after eucapnic dry gas hyperpnea in 22 anesthetized, mechanically ventilated guinea pigs pretreated with propranolol (1 mg/kg iv). Eucapnic hyperpnea "challenges" of room temperature dry or humidified gas (5% CO2-95% O2) were performed by mechanically ventilating animals (150 breaths/min, 3-6 ml tidal volume) for 5 min. During a "recovery" period after hyperpnea, animals were returned to standard ventilation conditions (6 ml/kg, 60 breaths/min, 50% O2 in air, fully saturated at room temperature). After dry gas hyperpnea (5 ml, 150 breaths/min), respiratory system resistance (Rrs) increased in the recovery period by 7.7-fold and dynamic compliance (Cdyn) decreased by 79.7%; changes were maximal at approximately 3 min posthyperpnea and spontaneously returned to base line in 10-40 min. This response was markedly attenuated by humidification of inspired air. Four consecutive identical dry air challenges resulted in similar posthyperpnea responses in four animals. Increasing the minute ventilation during hyperpnea (by varying tidal volume from 3 to 6 ml) caused increased bronchoconstriction in a dose-dependent fashion in six animals. Neither vagotomy nor atropine altered the airway response to dry gas hyperpnea. We conclude that dry gas hyperpnea in anesthetized guinea pigs results in a bronchoconstrictor response that shares five similar features with hyperpnea-induced bronchoconstriction in human asthma: 1) time course of onset and spontaneous resolution, 2) diminution with humidification of inspired gas, 3) reproducibility on consecutive identical challenges, 4) stimulus-response relationship with minute ventilation during hyperpnea, and 5) independence of parasympathetic neurotransmission.     

Time course of bronchoconstriction induced by dry gas hyperpnea in guinea pigs

We examined the effects of hyperpnea duration and abrupt changes in inspired gas heat and water content on the magnitude and time course of hyperpnea-induced bronchoconstriction (HIB) in anesthetized mechanically ventilated male Hartley guinea pigs. In 12 animals subjected to 5, 10, and 15 min (random order) of dry gas isocapnic hyperpnea [tidal volume (VT) 4-6 ml, 150 breaths/min) followed by quiet breathing of humidified air (VT 2-3 ml, 60 breaths/min), severe bronchoconstriction developed only after the cessation of hyperpnea; the magnitude of respiratory system resistance (Rrs) increased with the duration of dry gas hyperpnea [peak Rrs 1.0 +/- 0.2, 1.8 +/- 0.3, and 2.3 +/- 0.3 (SE) cmH2O.ml-1.s, respectively]. Seven other guinea pigs received, in random order, 10 min of warm humidified gas hyperpnea, 10 min of room temperature dry gas hyperpnea, and 5 min of dry gas hyperpnea immediately followed by 5 min of warm humidified gas hyperpnea. After each hyperpnea period, the animal was returned to quiet breathing of humidified gas. Rrs rose appreciably after the 10 min of dry and 5 min of dry-5 min of humidified hyperpnea challenges (peak Rrs 1.3 +/- 0.2 and 0.7 +/- 0.2 cmH2O.ml-1.s, respectively) but not after 10 min of humidified hyperpnea (0.2 +/- 0.04 cmH2O.ml-1.s). An additional five animals received 10 min of room temperature dry gas hyperpnea followed by quiet breathing of warm humidified air and 10 min of room temperature dry gas hyperpnea followed by 30 min of warm humidified gas hyperpnea in random order.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tachykinins mediate bronchoconstriction elicited by isocapnic hyperpnea in guinea pigs

We tested the hypothesis that tachykinins mediate hyperpnea-induced bronchoconstriction (HIB) in 28 guinea pigs. Stimulus-response curves to increasing minute ventilation with dry gas were generated in animals depleted of tachykinins by capsaicin pretreatment and in animals pretreated with phosphoramidon, a neutral metalloendopeptidase inhibitor. Sixteen anesthetized guinea pigs received capsaicin (50 mg/kg sc) after aminophylline (10 mg/kg ip) and terbutaline (0.1 mg/kg sc). An additional 12 animals received saline (1 ml sc) instead of capsaicin. One week later, all animals were anesthetized, given propranolol (1 mg/kg iv), and mechanically ventilated (6 ml/kg, 60 breaths/min, 50% O2 in air fully water saturated). Phosphoramidon (0.5 mg iv) was administered to five of the noncapsaicin-treated guinea pigs. Eucapnic dry gas (95% O2-5% CO2) hyperpnea "challenges" were performed by increasing the tidal volume (2-6 ml) and frequency (150 breaths/min) for 5 min. Capsaicin-pretreated animals showed marked attenuation in HIB, with a rightward shift of the stimulus-response curve compared with controls; the estimated tidal volume required to elicit a twofold increase in respiratory system resistance (ES200) was 5.0 ml for capsaicin-pretreated animals vs. 3.7 ml for controls (P less than 0.03). Phosphoramidon-treated animals were more reactive to dry gas hyperpnea compared with control (ES200 = 2.6 ml; P less than 0.0001). Methacholine dose-response curves (10(-11) to 10(-7) mol iv) obtained at the conclusion of the experiments were similar among capsaicin, phosphoramidon, and control groups. These findings implicate tachykinin release as an important mechanism of HIB in guinea pigs.     

Role of nitric oxide during hyperventilation-induced bronchoconstriction in the guinea pig.

Airway function is largely preserved during exercise or isocapnic hyperventilation in humans and guinea pigs despite likely changes in airway milieu during hyperpnea. It is only on cessation of a hyperpneic challenge that airway function deteriorates significantly. We tested the hypothesis that nitric oxide, a known bronchodilator that is produced in the lungs and bronchi, might be responsible for the relative bronchodilation observed during hyperventilation (HV) in guinea pigs. Three groups of anesthetized guinea pigs were given saline and three groups given 50 mg/kg N(G)-monomethyl-L-arginine (L-NMMA), a potent nitric oxide synthase inhibitor. Three isocapnic ventilation groups included normal ventilation [40 breaths/min, 6 ml/kg tidal volume (VT)], increased respiratory rate only (150 breaths/min, 6 ml/kg VT), and increased respiratory rate and increased volume (100 breaths/min, 8 ml/kg VT). L-NMMA reduced expired nitric oxide in all groups. Expired nitric oxide was slightly but significantly increased by HV in the saline groups. However, inhibition of nitric oxide production had no significant effect on rate of rise of respiratory system resistance (Rrs) during HV or on the larger rise in Rrs seen 6 min after HV. We conclude that nitric oxide synthase inhibition has no effect on changes in Rrs, either during or after HV in guinea pigs.     

Role of tachykinins in hyperpnea-induced bronchovascular hyperpermeability in guinea pigs

Isocapnic dry gas hyperpnea causes bronchoconstriction in guinea pigs that is mediated by release of tachykinins from airway sensory nerves. Exogenous neuropeptides can induce microvascular leak. Therefore we tested whether dry gas hyperpnea also elicits bronchovascular hyperpermeability by measuring Evans blue-labeled albumin extravasation along the airways of mechanically ventilated guinea pigs. We found that 1) room temperature dry gas hyperpnea increased Evans blue extravasation in extrapulmonary and intrapulmonary airways as a specific consequence of local airway heat/water losses, 2) capsaicin pretreatment ablated the bronchoconstrictor response to dry gas hyperpnea and reduced bronchovascular leak only in intrapulmonary airways, 3) phosphoramidon given to capsaicin-pretreated animals partially restored dry gas hyperpnea-induced bronchoconstriction and increased the vascular hyperpermeability response to hyperpnea in intrapulmonary airways, and 4) propranolol administration had no important effects on any of these airway responses. We conclude that dry gas hyperpnea causes bronchovascular hyperpermeability in guinea pigs. Tachykinins have a dominant role in this response in the intrapulmonary airways, although another mechanism may also contribute to the microvascular leak in the extrapulmonary airways.     

Effect of exercise, hyperpnea, and bronchoconstriction on plasma atrial natriuretic peptide

To examine whether endogenous secretion of atrial natriuretic peptide (ANP) modifies the bronchomotor response to moderately strenuous exercise and, conversely, whether hyperpnea of exercise or bronchoconstriction alone modulates the release of ANP, we compared the rise in specific airway resistance and the rise in circulating immunoreactive ANP (IR-ANP) induced by a 5-min submaximal exercise and by eucapnic hyperpnea with cold dry air and exercise-matched minute ventilation in six healthy individuals and in five subjects with clinically stable asthma. As expected, the increase in specific airway resistance from base line provoked by exercise was greater in the asthmatic subjects (from 11.8 +/- 7.1 to 34.0 +/- 18.6 l.cmH2O.l-1.s-1) than in the healthy subjects (from 3.7 +/- 1.2 to 4.5 +/- 1.9 l.cmH2O.l-1.s-1). In both groups, exercise was associated with a similar and significant rise in plasma IR-ANP levels, ranging from 222 to 550% from base-line value in the healthy group and from 176 to 1,120% from base-line value in the asthmatic group. Peak plasma IR-ANP levels occurred from 3 to 15 min after completion of exercise with a return to base-line values within 60 min. Although eucapnic hyperpnea was associated with a similar increase in specific airway resistance as was exercise, it provoked an increase in circulating IR-ANP in only one subject.(ABSTRACT TRUNCATED AT 250 WORDS)     

Radiographic visualization of airway wall movement during oscillatory flow in dogs

It has been suggested that radial movement of the central airway walls during oscillatory flow might contribute to the increased frequency dependence of compliance seen in chronic obstructive pulmonary disease (COPD) (J. Appl. Physiol. 26: 670-677, 1969). Radial airway wall motion has also been invoked to explain the frequency-dependent decreases in the efficiency of gas exchange during low-volume high-frequency ventilation (HFV) in histamine-bronchoconstricted dogs and in patients with respiratory insufficiency. To test the possibility that airway wall motion increases with bronchoconstriction, we measured central airway diameters using cinebronchoradiography in anesthetized tracheostomized dogs during oscillatory HFV [50 and 100 ml tidal volume (VT) at frequencies (f) of 2, 6, and 12 Hz], under control conditions, during electrical stimulation of the vagi, and after exposure to histamine aerosol. Cineradiobronchograms from two dogs were evaluated quantitatively for tracheal diameter and for lengths and diameters of a number of major airways. Under control conditions, the diameter of the airways fluctuated 7-9% of the mean with VT of 50 ml and 9-18% with VT of 100 ml in the range of frequencies studied. Bronchoconstriction produced by aerosolized histamine increased radial airway wall movement to 10-47% with VT of 50 ml, and during vagal stimulation diameters changed 7-20% at VT of 50 ml. After histamine, the central airways displayed large diameter changes during HFV, whereas more peripheral airways were markedly constricted and did not change in diameter.(ABSTRACT TRUNCATED AT 250 WORDS)     

Frequency and amplitude effects during high-frequency vibration ventilation in dogs

High-frequency external body vibration, combined with constant gas flow at the tracheal carina, was previously shown to be an effective method of ventilation in normal dogs. The effects of frequency (f) and amplitude of the vibration were investigated in the present study. Eleven anesthetized and paralyzed dogs were placed on a vibrating table (4-32 Hz). O2 was delivered near the tracheal carina at 0.51.kg-1.min-1, while mean airway pressure was kept at 2.4 +/- 0.9 cmH2O. Table vertical displacement (D) and acceleration (a), esophageal (Pes), and tracheal (Ptr) peak-to-peak pressures, and tidal volume (VT) were measured as estimates of the input amplitude applied to the animal. Steady-state arterial PCO2 (PaCO2) and arterial PO2 (PaO2) values were used to monitor overall gas exchange. Typically, eucapnia was achieved with f greater than 16 Hz, D = 1 mm, a = 1 G, Pes = Ptr = 4 +/- 2 cmH2O, and VT less than 2 ml. Inverse exponential relationships were found between PaCO2 and f, a, Pes, and Ptr (exponents: -0.69, -0.38, -0.48, and -0.54, respectively); PaCO2 decreased linearly with increased displacement or VT at a fixed frequency (17 +/- 1 Hz). PaO2 was independent of both f and D (393 +/- 78 Torr, mean +/- SD). These data demonstrate the very small VT, Ptr, and Pes associated with vibration ventilation. It is clear, however, that mechanisms other then those described for conventional ventilation and high-frequency ventilation must be evoked to explain our data. One such possible mechanism is forcing of flow oscillation between lung regions (i.e., forced pendelluft).     

Influence of hyperpnea on airway surface fluid volume and osmolarity in normal humans.

To determine the effect of hyperpnea on the characteristics of periciliary liquid, we collected airway surface fluid (ASF) and measured its osmolarity in 11 normal people while they breathed dry, frigid air (-17 +/- 1.2 degrees C) at minute ventilations (VE) of 10, 40, and 80 l/min through a heat exchanger. The ASF was collected at the fifth tracheal ring by absorption onto filter paper pledgets inserted via fiber-optic bronchoscopy. Hyperpnea had no influence on the amount of ASF recovered (ASF volume at a VE of 10 l/min = 12.0 +/- 2.0 microl; at 80 l/min = 8.8 +/- 1.5 microl; P = 0.28) or its osmolarity (at a VE of 10, 40, and 80 l/min = 326 +/- 15, 323 +/- 11, and 337 +/- 12 mosM, respectively; P = 0.65). These findings demonstrate that the tracheal mucosa of normal subjects does not dessicate during hyperpnea and that hypertonicity of the periciliary fluid does not develop even at high levels of ventilation.     

Longitudinal distribution of canine respiratory heat and water exchanges

We assessed the longitudinal distribution of intra-airway heat and water exchanges and their effects on airway wall temperature by directly measuring respiratory fluctuations in airstream temperature and humidity, as well as airway wall temperature, at multiple sites along the airways of endotracheally intubated dogs. By comparing these axial thermal and water profiles, we have demonstrated that increasing minute ventilation of cold or warm dry air leads to 1) further penetration of unconditioned air into the lung, 2) a shift of the principal site of total respiratory heat loss from the trachea to the bronchi, and 3) alteration of the relative contributions of conductive and evaporative heat losses to local total (conductive plus evaporative) heat loss. These changes were not accurately reflected in global measurements of respiratory heat and water exchange made at the free end of the endotracheal tube. Raising the temperature of inspired dry air from frigid to near body temperature principally altered the mechanism of airway cooling but did not influence airway mucosal temperature substantially. When local heat loss was increased from both trachea and bronchi (by increasing minute ventilation), only the tracheal mucosal temperature fell appreciably (up to 4.0 degrees C), even though the rise in heat loss from the bronchi about doubled that in the trachea. Thus it appears that the bronchi are better able to resist changes in airway wall temperature than is the trachea. These data indicate that the sites, magnitudes, and mechanisms of respiratory heat loss vary appreciably with breathing pattern and inspired gas temperature and that these changes cannot be predicted from measurements made at the mouth. In addition, they demonstrate that local heat (and presumably, water) sources that replenish mucosal heat and water lost to the airstream are important in determining the degree of local airway cooling (and presumably, drying).     

High-frequency oscillations via the pleural surface: an alternative mode of ventilation?

We applied high-frequency oscillatory ventilation (HFOV) of low amplitude to the pleural surface of the isolated rat lung (IPL) perfused at 10 ml X min-1 with Krebs bicarbonate containing 4.5% albumin (hematocrit 34%). Lung volume was held constant by a continuous positive airways pressure (CPAP) of 5 cmH2O. Varying CPAP from 2 to 15 cmH2O did not affect O2 uptake. Tidal volume (VT) was estimated with an impedance pneumograph, and it bore a direct linear relationship to the amplitude of both the loudspeaker input signal and the pressure change in the chamber up to 30 Hz; VT was inversely proportional to the frequency (f). However, at a constant loudspeaker input of 10 V, minute expired ventilation (VE) remained constant (mean 104 ml X min-1) as f increased from 5 to 30 Hz. Hemoglobin saturation increased by more than 80% during HFOV of 5-40 Hz and amplitude of 10 V, the maximum O2 uptake being 14.6 ml O2 per 100 ml perfusate. Whereas dead space was approximately 335 microliters, a VT of less than 40 microliters could effect normal O2 uptake, suggesting that bulk flow is playing only a minor role in gas exchange. HFOV for 60 min (CPAP 5 cmH2O) did not affect the amount of alveolar surfactant compared with conventional ventilation at the same mean airway pressure. We conclude that normal O2 uptake can be maintained by applying HFOV to the pleural surface of the IPL held at constant volume.     

Physiological dead space during high-frequency ventilation in dogs

Tidal volumes used in high-frequency ventilation (HFV) may be smaller than anatomic dead space, but since gas exchange does take place, physiological dead space (VD) must be smaller than tidal volume (VT). We quantified changes in VD in three dogs at constant alveolar ventilation using the Bohr equation as VT was varied from 3 to 15 ml/kg and frequency (f) from 0.2 to 8 Hz, ranges that include normal as well as HFV. We found that VD was relatively constant at tidal volumes associated with normal ventilation (7-15 ml/kg) but fell sharply as VT was reduced further to tidal volumes associated with HFV (less than 7 ml/kg). The frequency required to maintain constant alveolar ventilation increased slowly as tidal volume was decreased from 15 to 7 ml/kg but rose sharply with attendant rapid increases in minute ventilation as tidal volumes were decreased to less than 7 ml/kg. At tidal volumes less than 7 ml/kg, the data deviated substantially from the conventional alveolar ventilation equation [f(VT - VD) = constant] but fit well a model derived previously for HFV. This model predicts that gas exchange with volumes smaller than dead space should vary approximately as the product of f and VT2.     

Effects of increased ventilation on lung lymph flow in unanesthetized sheep

To determine the effect of an increase in spontaneous minute ventilation on lung fluid balance, we added external dead space to the breathing circuit of six tracheostomized, unanesthetized, spontaneously breathing sheep in which lung lymph fistulas had been created surgically. The addition of 120-180 ml of dead space caused minute ventilation to increase by 50-100% (secondary to increases in both tidal volume and frequency), without changing pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac output, or arterial blood gas tensions. The increase in spontaneous ventilation was associated with an average increase of 27% in lung lymph flow (P less than 0.05) and an average reduction of 11% in the lymph-to-plasma concentration ratio (L/P) for total protein (P less than 0.05). Lymph flow and L/P for total protein approached stable values after 2-3 h of hyperpnea, and the increase in lymph flow persisted for at least 18 h of dead-space breathing. Removal of dead space was associated with a rapid return (within 45 min) of lymph flow to base-line levels. These results suggest that hyperpnea increases the pulmonary transvascular filtration rate. Since no changes in vascular pressures or cardiac output were observed, this increase in transvascular filtration is most likely due to a fall in interstitial fluid pressure.     

Effects of bronchoconstriction and external resistive loading on the sensation of dyspnea.

To determine whether the intensity of dyspnea at a given level of respiratory motor output differs between bronchoconstriction and the presence of an external resistance, we compared the sensation of difficulty in breathing during isocapnic voluntary hyperventilation in six normal subjects. An external resistance of 1.9 cmH2O.1-1.s was applied during both inspiration and expiration. To induce bronchoconstriction, histamine aerosol (5 mg/ml) was inhaled until airway resistance (Raw) increased to a level approximately equal to the subject's control Raw plus the added external resistance. To clarify the role of vagal afferents on the genesis of dyspnea during both forms of obstruction to airflow, the effect of airway anesthesia by lidocaine aerosol inhalation was also examined after histamine and during external resistive loading. The sensation of difficulty in breathing was rated at 30-s intervals on a visual analog scale during isocapnic voluntary hyperpnea, in which the subjects were asked to copy an oscilloscope volume trace obtained previously during progressive hypercapnia. Histamine inhalation significantly increased the intensity of the dyspneic sensation over the equivalent external resistive load at the same levels of ventilation and occlusion pressure during voluntary hyperpnea. Inhaled lidocaine decreased the sensation of dyspnea during bronchoconstriction with no change in Raw, but it did not significantly change the sensation during external resistive loading. These results suggest that afferent vagal activity plays a role in the genesis of dyspnea during bronchoconstriction.     

Regional mapping of gas transport during high-frequency and conventional ventilation

The effects of changing tidal volume (VT) and frequency (f) on the distribution of ventilation during high-frequency ventilation (HFV) were assessed from the washout of nitrogen-13 by positron emission tomography. Six dogs, anesthetized and paralyzed, were studied in the supine position during conventional ventilation (CV) and during HFV at f of 3, 6, and 9 Hz. In CV and HFV at 6 Hz, VT was selected to achieve eucapnic arterial partial pressure of CO2 (37 +/- 3 Torr). At 3 and 9 Hz, VT was proportionally changed so that the product of VT and f remained constant and equal to that at 6 Hz. Mean residence time (MRT) of nitrogen-13 during washout was calculated for apical, midheart, and basal transverse sections of the lung and further analyzed for gravity-dependent, cephalocaudal and radial gradients. An index of local alveolar ventilation per unit of lung volume, or specific ventilation (spV), was calculated as the reciprocal of MRT. During CV vertical gradients of regional spV were seen in all sections with ventral (nondependent) regions less ventilated than dorsal (dependent) regions. Regional nonuniformity in gas transport was greatest for HFV at 3 and 6 Hz and lowest at 9 Hz and during CV. During HFV, a central region at the base of the lungs was preferentially ventilated, resulting in a regional time-averaged tracer concentration equivalent to that of the main bronchi. Because the main bronchi were certainly receiving fresh gas, the presence of this preferentially ventilated area, whose ventilation increased with VT, strongly supports the hypothesis that direct convection of fresh gas is an important mechanism of gas transport during eucapnic HFV. Aside from the local effect of increasing overall lung ventilation, this central area probably served as an intermediate shuttle station for the transport of gas between mouth and deeper alveoli when VT was less than the anatomic dead space.     

Constant-flow ventilation in pigs

Constant-flow ventilation (CFV) is a ventilatory technique in which physiological blood gases can be maintained in dogs by a constant flow of fresh gas introduced via two catheters placed in the main-stem bronchi (J. Appl. Physiol. 53: 483-489, 1982). High-velocity gas exiting from the catheters can create uneven pressure differences in adjacent lung segments, and these pressure differences could lead to gas flow through collateral channels. To examine this hypothesis, we studied CFV in pigs, animals known to have a high resistance to collateral ventilation. In three pigs we examined steady-state gas exchange, and in six others we studied unsteady gas exchange at three flow rates (20, 35, and 50 l/min) and three catheter positions (0.5, 1.5, and 2.5 cm distal to the tracheal carina). During steady-state runs we were unable to attain normocapnia; the arterial CO2 partial pressure (PaCO2) was approximately 300 Torr at all flow rates and all catheter positions, compared with 20-50 Torr at similar flows and positions in dogs studied previously. The initial unsteady gas-exchange experiments indicated no consistent effect of catheter position or flow rate on the rate of rise of PaCO2. In three other pigs, the rates of rise of PaCO2 were compared with the rates observed with apneic oxygenation (AO). At the maximum flow and deepest position, the rate of rise of PaCO2 was lower during CFV than during AO. These data suggest that flow through collateral channels might be important in producing adequate gas transport during CFV; however, other factors such as airway morphometry and the effects of cardiogenic oscillations may explain the differences between the results in pigs and dogs.     

Role of VCO2 in control of breathing of awake exercising dogs

Steady-state ventilatory responses to CO2 inhalation, intravenous CO2 loading (loading), and intravenous CO2 unloading (unloading) were measured in chronic awake dogs while they exercised on an air-conditioned treadmill at 3 mph and 0% grade. End-tidal PO2 was maintained at control levels by manipulation of inspired gas. Responses obtained in three dogs demonstrated that the response to CO2 loading [average increase in CO2 output (Vco2) of 216 ml/min or 35%] was a hypercapnic hyperpnea in every instance. Also, the response to CO2 unloading [average decrease in Vco2 of 90 ml/min or 15% decrease] was a hypocapnic hypopnea in every case. Also, the analysis of the data by directional statistics indicates that there was no difference in the slopes of the responses (change in expiratory ventilation divided by change in arterial Pco2) for loading, unloading, and inhalation. These results indicate that the increased CO2 flow to the lung that occurs in exercise does not provide a direct signal to the respiratory controller that accounts for the exercise hyperpnea. Therefore, other mechanisms must be important in the regulation of ventilation during exercise.     

Integrated response of the upper and lower respiratory tract of asthmatic subjects to frigid air.

To evaluate the influence of cold air hyperpnea on integrated upper and lower airway behavior, 22 asthmatic volunteers hyperventilated through their mouths (OHV) and noses (NHV) while pulmonary and nasal function were determined individually and in combination. In the isolated studies, OHV at a minute ventilation of 65 +/- 3 l/min lowered the 1-s forced expiratory volume (FEV(1)) 24 +/- 2% (P < 0. 001) and NHV (40 l/min) induced a 31 +/- 9% (P < 0.001) increase in nasal resistance (NR). In the combined studies, oral hyperpnea reduced the FEV(1) (DeltaFEV(1) 26 +/- 2%, P < 0.001) and evoked a significant rise in NR (DeltaNR 26 +/- 9%, P = 0.01). In contrast, NHV only affected the upper airway. NR rose 33 +/- 9% (P = 0.01), but airway caliber did not change (DeltaFEV(1) 2%, P = 0.27). The results of this investigation demonstrate that increasing the transfer of heat and water in the lower respiratory tract alters bronchial and nasal function in a linked fashion. Forcing the nose to augment its heat-exchanging activity, however, reduces nasal caliber but has no effect on the intrathoracic airways.     

Phonospirometry for noninvasive measurement of ventilation: methodology and preliminary results.

We measured tracheal flow from tracheal sounds to estimate tidal volume, minute ventilation (VI), respiratory frequency, mean inspiratory flow (VT/TI), and duty cycle (TI/Ttot). In 11 normal subjects, 3 patients with unstable airway obstruction, and 3 stable asthmatic patients, we measured tracheal sounds and flow twice: first to derive flow-sound relationships and second to obtain flow-volume relationships from the sound signal. The flow-volume relationship was compared with pneumotach-derived volume. When subjects were seated, facing forward and with neck rotation, flexion, and standing, flow-volume relationship was within 15% of pneumotach-derived volume. Error increased with neck extension and while supine. We then measured ventilation without mouthpiece or nose clip from tracheal sounds during quiet breathing for up to 30 min. Normal results +/- SD revealed tidal volume = 0.37 +/- 0.065 liter, respiratory frequency = 19.3 +/- 3.5 breaths/min, VI = 6.9 +/- 1.2 l/min, VT/TI = 0.31 +/- 0.06 l/s, and TI/Ttot = 0.37 +/- 0.04. Unstable airway obstruction had large VI due to increased VT/TI. With the exception of TI/Ttot, variations in ventilatory parameters were closer to log normal than normal distributions and tended to be greater in patients. We conclude that phonospirometry measures ventilation reasonably accurately without mouthpiece, nose clip, or rigid postural constraints.     

Combination of constant-flow and continuous positive-pressure ventilation in canine pulmonary edema

Constant-flow ventilation (CFV) maintains alveolar ventilation without tidal excursion in dogs with normal lungs, but this ventilatory mode requires high CFV and bronchoscopic guidance for effective subcarinal placement of two inflow catheters. We designed a circuit that combines CFV with continuous positive-pressure ventilation (CPPV; CFV-CPPV), which negates the need for bronchoscopic positioning of CFV cannula, and tested this system in seven dogs having oleic acid-induced pulmonary edema. Addition of positive end-expiratory pressure (PEEP, 10 cmH2O) reduced venous admixture from 44 +/- 17 to 10.4 +/- 5.4% and kept arterial CO2 tension (PaCO2) normal. With the innovative CFV-CPPV circuit at the same PEEP and respiratory rate (RR), we were able to reduce tidal volume (VT) from 437 +/- 28 to 184 +/- 18 ml (P less than 0.001) and elastic end-inspiratory pressures (PEI) from 25.6 +/- 4.6 to 17.7 +/- 2.8 cmH2O (P less than 0.001) without adverse effects on cardiac output or pulmonary exchange of O2 or CO2; indeed, PaCO2 remained at 35 +/- 4 Torr even though CFV was delivered above the carina and at lower (1.6 l.kg-1.min-1) flows than usually required to maintain eucapnia during CFV alone. At the same PEEP and RR, reduction of VT in the CPPV mode without CFV resulted in CO2 retention (PaCO2 59 +/- 8 Torr). We conclude that CFV-CPPV allows CFV to effectively mix alveolar and dead spaces by a small bulk flow bypassing the zone of increased resistance to gas mixing, thereby allowing reduction of the CFV rate, VT, and PEI for adequate gas exchange.