Airway blood flow response to eucapnic dry air hyperventilation in sheep

Eucapnic hyperventilation, breathing dry air, produces a two- to fivefold increase in airway blood flow in the dog. To determine whether airway blood flow responds similarly in the sheep we studied 16 anesthetized sheep. Seven sheep (1-7) were subjected to two 30-min periods of eucapnic hyperventilation breathing 1) warm humid air [100% relative humidity (rh)] followed by 2) warm dry air [0% rh] at 40 breaths/min. To determine whether there was a dose-response effect on blood flow of increasing levels of hyperventilation of dry air, another nine sheep (8-16) were subjected to four 30-min periods of eucapnic hyperventilation breathing warm humid O2 followed by warm dry O2 at 20 or 40 breaths/min in random sequence. Five minutes before the end of each period of hyperventilation, hemodynamics, blood gases, and tracheal mucosal temperature were measured, and tracheal and bronchial blood flows were determined by injection of 15- or 50-micron-diam radiolabeled microspheres. After the last measurements had been made, all sheep were killed, and the lungs and trachea were removed for determination of blood flow to trachea, bronchi, and parenchyma. In sheep 1-7, warm dry air hyperventilation at 40 breaths/min produced an increase in blood flow to trachea (7.6 +/- 3.5 to 17.0 +/- 6.2 ml/min, P less than 0.05) and bronchi (9.0 +/- 5.4 to 18.2 +/- 8.2 ml/min, P less than 0.05) but not to the parenchyma. When blood flow was compared with the two ventilatory rates (sheep 8-16), tracheal blood flow increased (9.1 +/- 3.3 to 18.2 +/- 6.1 ml/min, P less than 0.05) at a rate of 40 breaths/min but not at 20 breaths/min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of cold and warm dry air hyperventilation on canine airway blood flow

Tracheobronchial blood flow increases with cold air hyperventilation in the dog. The present study was designed to determine whether the cooling or the drying of the airway mucosa was the principal stimulus for this response. Six anesthetized dogs (group 1) were subjected to four periods of eucapnic hyperventilation for 30 min with warm humid air [100% relative humidity (rh)], cold dry air (-12 degrees C, 0% rh), warm humid air, and warm dry air (43 degrees C, 0% rh). Five minutes before the end of each period of hyperventilation, tracheal and central airway blood flow was determined using four differently labeled 15-micron diam radioactive microspheres. We studied another three dogs (group 2) in which 15- and 50-micron microspheres were injected simultaneously to determine whether there were any arteriovenous communications in the bronchovasculature greater than 15 micron diam. After the last measurements had been made, all dogs were killed, and the lungs, including the trachea, were excised and blood flow to the trachea, left lung bronchi, and parenchyma was calculated. Warm dry air hyperventilation produced a consistently greater increase in tracheobronchial blood flow (P less than 0.01) than cold dry air hyperventilation, despite the fact that there was a smaller fall (6 degrees C) in tracheal tissue temperature during warm dry air hyperventilation than during cold dry air hyperventilation (11 degrees C), suggesting that drying may be a more important stimulus than cold for increasing airway blood flow. In group 2, the 15-micron microspheres accurately reflected the distribution of airway blood flow but did not always give reliable measurements of parenchymal blood flow.     

Tracheobronchial and upper airway blood flow in dogs during thermally induced panting

Tracheobronchial blood flow increases two- to fivefold in response to isocapnic hyperventilation with warm dry or cold dry air in anesthetized, tracheostomized dogs. To determine whether this response is governed by central nervous system thermoregulatory control or is a local response to the drying and/or cooling of the airway mucosa, we studied eight anesthetized spontaneously breathing dogs in a thermally controlled chamber designed so that inspired air temperature, humidity, and body temperature could be separately regulated. Four dogs breathed through the nose and mouth (group 1), and four breathed through a short tracheostomy tube (group 2). Dogs were studied under the following conditions: 1) a normothermic control period and 2) two periods of hyperthermia in which the dogs panted with either warm 100% humidified air or warm dry (approximately 10% humidified) air. Radiolabeled microspheres (15 +/- 3 micron diam) were injected into the left ventricle as a marker of nasal, lingual, and tracheobronchial blood flow. After the final measurements, the dogs were killed and tissues of interest excised. Results showed that lingual and nasal blood flow (ml.min-1.g-1) increased during panting (P less than 0.01) in both groups and were not affected by the inspired air conditions. In group 1, tracheal mucosal blood flow barely doubled (P less than 0.01) and bronchial blood flow did not change during humid and dry air panting. In group 2, there was a sevenfold increase in tracheal mucosal and about a threefold increase in bronchial blood flow (P less than 0.01), which was only observed during dry air panting.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechanism for increase in tracheobronchial blood flow induced by hyperventilation of dry air in dogs

To test whether the consistent increase in tracheal and bronchial blood flow observed in dogs during hyperventilation of dry air might be the result of release of mediators such as vasodilatory prostaglandins or neuropeptides, we studied two groups of anesthetized mechanically ventilated dogs. Group 1 (n = 6) was hyperventilated for four 30-min periods with 1) warm humid air (38-40 degrees C, 100% relative humidity), 2) warm dry air (38-40 degrees C, 0% relative humidity), 3) warm humid air, and 4) warm dry air. After period 2, a loading dose of indomethacin (4 mg/kg iv) was given over 15 min followed by a constant infusion (4 mg.kg-1.h-1). Group 2 (n = 10) was hyperventilated for four 15- to 20-min periods by use of the protocol described above. After period 3 (group 2a) or period 2 (group 2b), topical 4% lidocaine hydrochloride solution was instilled into the trachea and main stem bronchi. Five minutes before the end of each period of hyperventilation, cardiac output and vascular pressures were measured. To determine airway blood flow, differently labeled radioactive microspheres were injected into the left atrium. After the last measurements, dogs were killed and the lungs excised. Blood flow to the trachea, main stem bronchi, and parenchyma (group 1 only) was calculated. Results showed that hyperventilation of dry air produced a significant increase in blood flow to the trachea and bronchi (period 2). In group 1, this increase was attenuated (P less than 0.02) after administration of indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of autonomic blockade on tracheobronchial blood flow

Tracheobronchial blood flow increases two to five times in response to cold and warm dry air hyperventilation in anesthetized tracheostomized dogs. In this series of experiments we have attempted to attenuate this increase by blockade of the autonomic nervous system. Four groups of anesthetized, tracheostomized, open-chest dogs were studied. Group 1 (n = 5) were hyperventilated for 30 min with 1) warm humid [approximately 26 degrees C, 100% relative humidity, (rh)] air followed by bilateral vagotomy, 2) warm humid air, 3) cold (-22 degrees C, 0% rh) dry air, and 4) warm humid air. Groups 2, 3, and 4 (n = 3/group) were hyperventilated for 30 min with 1) warm humid (approximately 41 degrees C, 100% rh) air, 2) warm dry (approximately 41 degrees C) air, 3) warm humid air, and 4) warm dry air. Group 2 were controls. Group 3 were given phentolamine, 0.6 mg/kg intravenously, as an alpha-blockade, and group 4 were given propranolol, 1 mg/kg, as a beta-blockade after warm dry air hyperventilation (period 2). Five minutes before the end of each 30-min period of hyperventilation, measurements of vascular pressures, cardiac output, arterial blood gases, and inspired, body, and tracheal temperatures were measured, and differently labeled radioactive microspheres were injected into the left atrium to make separate measurements of airway blood flow. After the last measurements had been made animals were killed and their lungs were excised. Blood flow to the airways and lung parenchyma was calculated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypertonic aerosol inhalation does not alter central airway blood flow in dogs

Tracheobronchial blood flow in dogs increases with cold or dry air hyperventilation, possibly as a result of airway drying leading to increased osmolarity of airway surface fluid. This study was designed to examine whether administration of aerosols of various tonicity to alter airway surface fluid osmolarity would induce similar blood flow changes. Tracheobronchial blood flow was measured by the radioactive microsphere technique in six anesthetized dogs ventilated with warm humid air (100% relative humidity) for 15 min (period 1), air containing ultrasonically nebulized saline aerosol (1,711 mosmol/kg) for 3 min (period 2) and 12 min (period 3), and the same aerosol at a higher nebulizer output for a further 3 min (period 4). Between periods 3 and 4, the dogs were ventilated with warm humid air for 30 min to reestablish base-line conditions. In another five dogs, measurements were made after 30 min of ventilation with 1) warm humid air, 2) isotonic saline aerosol, 3) warm humid air, 4) distilled water aerosol (3 dogs), and hypertonic saline aerosol (2 dogs). After the last measurement was made, each dog was killed, the trachea and major bronchi were excised, and blood flow was calculated. No change in blood flow was found during any period of aerosol inhalation. The osmolar load imposed on the airways was estimated and was similar to that occurring during cold or dry air hyperventilation. These data suggest that increasing osmolarity of airway surface fluid does not explain the blood flow changes seen during hyperventilation of cold or dry air.     

Tracheal vascular and smooth muscle responses to air temperature and humidity in dogs

Twenty-five dogs were anesthetized, paralyzed, and artificially ventilated. Their cranial tracheal arteries were perfused bilaterally with blood at constant flow, and the perfusion pressures (Patr) were measured. Tracheal smooth muscle function was assessed by recording changes in external diameter (delta Dtr). The perfused segment of the trachea was exposed to air at a constant unidirectional airflow of 25 l/min. Group 1 (n = 6) was exposed to cold dry air, ambient room air, and hot dry and hot humid air, each for 10 min with exposures starting from zero flow. The tracheal vascular responses to all four conditions were small vasodilations (delta Patr from -2 to -6%) followed by recovery or small vasoconstrictions. In group 2 (n = 19), exposures to cold dry and hot humid air were preceded and followed by body-temperature fully humidified air. Cold dry air caused a sustained vasodilation (delta Patr -9.0 +/- 1.1%), and hot humid air usually caused a biphasic response: a vasoconstriction (delta Patr 4.4 +/- 1.0%) followed by a vasodilation (delta Patr -5.7 +/- 1.9%). The warm humid air after cold dry air or hot humid air caused a further vasodilation, which lasted a short time after cold dry air (delta Patr -3.7 +/- 0.4%) but greater than 10 min after hot humid air (delta Patr -13.8 +/- 1.4%). In both groups, all exposures that cooled the trachea (cold dry air, ambient room air, and hot dry air) caused smooth muscle contraction, and hot humid air that warmed the trachea caused relaxation.     

Temperature alters bronchial blood flow response to pulmonary arterial obstruction

Lobar bronchial blood flow has been reported to increase and decrease acutely after pulmonary arterial obstruction (PAO). Because bronchial blood flow (Qbr) to the trachea and bronchi is influenced by inspired air temperature, we investigated whether temperature differences could explain these disparate results. In 10 open-chested dogs the left lower lobe (LLL) was isolated and perfused in situ with autologous blood at a controlled temperature with an independent vascular circuit. The abdomen and the chest of the dog were enclosed in a Plexiglas box in which air was fully humidified and temperature could be regulated. Qbr, determined by the reference flow technique using 16 micron microspheres, was measured before and 30 min after onset of PAO with the air in the box being either at 27 or 39 degrees C and with warmed LLL blood (37 degrees C) in the latter condition. Anastomotic bronchial blood flow [Qbr(s-p), determined as overflow from the closed LLL vascular circuit and measured in ml X min-1 X 100 g dry lung wt-1 X 100 Torr mean systemic pressure-1] was measured continuously at both temperatures. Both before and after PAO, Qbr and Qbr(s-p) were closely correlated: Qbr (ml/min) = 1.12 + 0.978Qbr(s-p); R = 0.912. This was true regardless of the presence or the absence of pulmonary flow, showing that the distribution of bronchial blood flow between the anastomotic and the nonanastomotic portion does not change acutely during PAO. When the air in the box was 27 degrees C, Qbr(s-p) was 19.5 +/- 5.2 (SE) and increased to 38.6 +/- 8.1 with PAO (P less than 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)     

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).     

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)     

Response of the bronchial circulation to acute hypoxemia and hypercarbia in the dog

We have examined the effect of acute hypoxemia and hypercarbia on bronchial blood flow (Qbr) in 10 anesthetized, ventilated, open-chest dogs using a modification of the radioactive microsphere technique. After surgery, dogs were divided into two groups of five. Group 1 was ventilated for 30 min with each of the following gas mixtures: 1) room air; 2) 15% O2-85% N2; 3) 10% O2-90% N2, and group 2 with 1) room air; 2) 5% CO2-30% O2-65% N2; 3) 10% CO2-30% O2-60% N2. Measurements of pulmonary arterial, left atrial and aortic pressures, cardiac output, and blood gases were made before injection of 46Sc-, 153Gd-, and 103Ru-labeled microspheres into the left atrium as a marker of Qbr. After the final measurements, dogs were killed and the lungs removed and the parenchyma stripped off the large and small airways of the left lung. Knowing the radioactivity in the trachea, bronchi, parenchyma, and in the blood from the reference-flow sample and also the aortic and left atrial pressures, total and regional Qbr, and bronchovascular resistance (BVR) were calculated. Results showed that acute hypoxemia (10% O2) caused a significant (P less than 0.05) decrease in Qbr and increase in BVR and acute hypercarbia (10% CO2) caused a significant (P less than 0.05) increase in Qbr and decrease in BVR.     

Tracheobronchial perfusion during exercise in ponies

Tracheobronchial circulation during exercise has previously not been examined. Therefore blood flow to the trachea and bronchi (up to 7th generation of branching) was studied in seven healthy adult ponies at rest and during the 3rd and 10th min of exercise performed at a treadmill speed setting of 25 km/h. The ambient air temperature varied from 19 to 20 degrees C and humidity from 35 to 45%. To determine blood flow radionuclide-labeled 15-microns-diameter microspheres were injected into the left ventricle via a catheter advanced from the left carotid artery (exposed using local anesthesia), and a reference sample was obtained from the aorta. Adequate mixing of microspheres with blood was demonstrated by similar perfusion values for left and right kidneys. Exercise increased heart rate (194 +/- 9 and 200 +/- 7 beats/min) and mean aortic pressure (169 +/- 8 and 156 +/- 4 mmHg) of ponies at 3rd and 10th min. Tracheal blood flow (6.7 +/- 0.5 ml.min-1 x 100 g-1) of resting ponies was only one-third of the bronchial blood flow (21.6 +/- 4.9 ml.min-1 x 100 g-1) Significant changes in tracheal perfusion did not occur at 3rd or 10th min of exercise. Although bronchial perfusion also did not change at the 3rd min of exercise, it rose dramatically to 202.8 +/- 30.3 ml.min-1 x 100 g-1 during the 10th min. Concomitantly, renal blood flow decreased at 10th min of exertion. The large increase in bronchial blood flow at 10th min of exertion may have been necessitated by the need to help dissipate body heat.     

Effect of inspired air temperature on genioglossus activity during nose breathing in awake humans

Experimental data suggest the presence of sensory receptors specific to the nasopharynx that may reflexly influence respiratory activity. To investigate the effects of inspired air temperature on upper airway dilator muscle activity during nose breathing, we compared phasic genioglossus electromyograms (EMGgg) in eight normal awake adults breathing cold dry or warm humidified air through the nose. EMGgg was measured with peroral bipolar electrodes during successive trials of cold air (less than or equal to 15 degrees C) and warm air (greater than or equal to 34 degrees C) nasal breathing and quantified for each condition as percent activity at baseline (room temperature). In four of the subjects, the protocol was repeated after topical nasal anesthesia. For all eight subjects, mean EMGgg was greater during cold air breathing than during baseline (P less than 0.005) or warm air breathing (P less than 0.01); mean EMGgg during warm air breathing was not significantly changed from baseline. Nasal anesthesia significantly decreased the mean EMGgg response to cold air breathing. Nasal airway inspiratory resistance, measured by posterior rhinomanometry in six subjects under similar conditions, was no different for cold or warm air nose breathing [cold 1.4 +/- 0.7 vs. warm 1.4 +/- 1.1 (SD) cmH2O.l-1.s at 0.4 l/s flow]. These data suggest the presence of superficially located nasal cold receptors that may reflexly influence upper airway dilating muscle activity independently of pressure changes in awake normal humans.     

Effect of tracheal bias flow on gas exchange during high-frequency chest percussion

High-frequency chest percussion (HFP) with constant fresh gas flow (VBF) at the tracheal carina is a variant of high-frequency ventilation (HFV) previously shown to be effective with extremely low tracheal oscillatory volumes (approximately 0.1 ml/kg). We studied the effects of VBF on gas exchange during HFP. In eight anesthetized and paralyzed dogs we measured arterial and alveolar partial pressures of CO2 (PaCO2) and O2 (PaO2) during total body vibration at a frequency of 30 Hz, amplitude of 0.17 +/- 0.019 cm, and tidal volume of 1.56 +/- 0.58 ml. VBF was incrementally varied from 0.1 to 1.2 l.kg-1.min-1. At low flows (0.1-0.4 l.kg-1.min-1), gas exchange was strongly dependent on flow rate but became essentially flow independent with higher VBF (i.e., hyperbolic pattern). At VBF greater than 0.4 l.kg-1.min-1, hyperventilatory blood gas levels were consistently sustained (i.e., PaCO2 less than 20 Torr, PaO2 greater than 90 Torr). The resistance to CO2 transport of the airways was 1.785 +/- 0.657 l-1.kg.min and was independent of VBF. The alveolar-arterial difference of O2 was also independent of the flow. In four of five additional dogs studied as a control group, where constant flow of O2 was used without oscillations, the pattern of PaCO2 vs. VBF was also hyperbolic but at substantially higher levels of PaCO2. It is concluded that, in the range of VBF used, intraairway gas exchange was limited by the 30-Hz vibration. The fresh gas flow was important only to maintain near atmospheric conditions at the tracheal carina.     

Influence of airway resistance on hypoxia-induced periodic breathing.

We studied the effects of changing upper airway pressure on the variability of the dynamic response of ventilation to a hypoxic disturbance in 11 spontaneously breathing dogs. Supralaryngeal pressure, instantaneous inspiratory flow, end-expiratory lung volume, and the inspiratory and expiratory O2 and CO2 concentrations were continuously recorded at baseline and after a 1.5-min hypoxic stimulus (abrupt normoxic recovery). Arterial blood gases were obtained at baseline, at the end of the hypoxic period, and after 1 min of recovery. Airway resistances were modified during the recovery by changing the composition of the inspired gas (all with an inspiratory O2 fraction of 20.9%) among four different trials: two trials were realized with air (density 1.12 g/l), and the other two were with He or SF6 (respective density 0.42 and 4.20) in random order. There was no difference between baseline minute ventilation, arterial blood gases, and supralaryngeal resistance values preceding the trials. The hypoxemic and hypocapnic levels and the hypoxia-induced hyperventilation reached during the hypoxic tests were identical for the different hypoxic stimuli. The supralaryngeal resistance measured at peak flow was dramatically influenced by the composition of the inspired gas: 8.8 +/- 1.8 and 6.9 +/- 1.7 (SE) cmH2O.l-1.s with air, 7.2 +/- 2.2 with He, 21.9 +/- 5.5 with SF6 (P less than 0.05). Ventilatory fluctuations were consistently seen during the posthypoxic period. They were characterized by a strength index value (M) (Waggener et al. J. Appl. Physiol. 56: 576-581, 1984).(ABSTRACT TRUNCATED AT 250 WORDS)     

Cold and hyperosmolar fluids in canine trachea: vascular and smooth muscle tone and albumin flux

We have studied the effects of liquids of various osmolalities and temperatures on the tracheal vasculature, smooth muscle tone, and transepithelial albumin flux. In 10 anesthetized dogs a 10- to 13-cm length of cervical trachea was cannulated to allow instillation of fluids into its lumen. The cranial tracheal arteries were perfused at constant flow, with monitoring of the perfusion pressures (Ptr) and the external tracheal diameter (Dtr). Control fluid was Krebs-Henseleit solution (KH) with NaCl added to result in a 325-mosM solution (isotonic). Hypertonic solutions were KH with NaCl (warm hypertonic) or glucose (hypertonic glucose) added to result in a 800-mosM solution. All solutions were at 38 degrees C, with isotonic and the hypertonic NaCl solutions also given at 18 degrees C (cold isotonic and cold hypertonic). Fluorescent labeled albumin was given intravenously, and the change in fluorescence in the fluid was measured during each 15-min period. Changing from warm isotonic to cold isotonic decreased Dtr and Ptr. Changing from warm isotonic to warm hypertonic or hypertonic glucose decreased Ptr with no change in Dtr. The cold hypertonic responses were not different from cold isotonic responses. Warm hypertonic solution increased albumin flux into the tracheal lumen over a 15-min period to three times that of the control period, persisting for 15 min after replacement with warm isotonic solution. Cooling induces a vasodilation and smooth muscle contraction of the trachea, whereas hypertonic solutions result in vasodilation and, if osmolality is increased with NaCl, an increase in albumin flux into the tracheal lumen.     

Effect of a dopamine antagonist on ventilation during sustained hypoxia in mice

To test the hypothesis that dopamine accumulated in the carotid body limits hyperventilation during acclimatization to sustained hypoxia, we administered the dopamine antagonist droperidol to mice undergoing acclimatization to an inspired O2 fraction (FIo2) of 0.1. Twelve mice were exposed to hypoxia for 10 days and ventilation in 10% O2 and in 7% CO2 in air were measured daily by a plethysmographic method. Under both conditions ventilation increased during acclimatization to hypoxia: ventilation in 10% O2 increased from 39.4 +/- 3.8 (mean +/- SE) ml/min before exposure to sustained hypoxia to 72.2 +/- 4.2 ml/min after 3 days of continuous hypoxia, and ventilation in 7% CO2 in air at the same time increased from 113.2 +/- 5.4 ml/min to 140.0 +/- 5.6 ml/min. Twelve mice were exposed to FIo2 of 0.1 for 10 days and received droperidol (300 micrograms/kg intraperitoneally) before exposure to sustained hypoxia and on the 2nd, 4th, and 8th days of continuous hypoxia. Before exposure to sustained hypoxia, droperidol increased ventilation in 10% O2 from 40.1 +/- 2.5 ml/min to 72.5 +/- 5.2 ml/min, but after 2, 4, and 8 days of continuous hypoxia droperidol caused an acute fall in ventilation (ventilation in 10% O2 after droperidol on day 2: 49.1 +/- 3.1 ml/min, on day 4: 44.4 +/- 3.7 ml/min, and on day 8: 27.8 +/- 3.4 ml/min). Two days after the animals were returned to room air, ventilation in 10% O2 again increased in response to droperidol. We conclude that dopamine in the carotid body does not limit ventilatory responses to hypoxia during acclimatization to sustained hypoxia.     

Dry air-induced constriction in lung periphery: a canine model of exercise-induced asthma

We studied the effects of the flow of dry air on collateral tone in the lung periphery. A bronchoscope was wedged in sublobar segments of anesthetized dogs, and measurements of collateral resistance (Rcs) were recorded before and after flow was increased from 200 to 2,000 ml/min for a 5-min period. Five minutes after exposure was completed, Rcs increased by an average of 117 +/- 25.2% (SE) over control. Maximum Rcs occurred 5 min after the challenge was concluded and required 48 +/- 10.5 min to return to base line. When flow rate was held constant and exposure period varied, Rcs increased with increased stimulus duration. With exposure times held constant, the response of the collateral system was positively associated with changes in stimulus strength (flow rate). No refractory period was observed with repetitive challenges. Finally, when dry air (delivered at 22 degrees C) and conditioned air (i.e., delivered at 28 degrees C; relative humidity = 80%) challenges were alternated in the same wedged segment, dry air produced a mean increase in Rcs of 93.2%, whereas challenge with warm moist air increased Rcs only 33.5%. Regardless of which challenge was presented first, dry air consistently produced a greater constrictor response. This response is similar to that observed in cold air- and exercise-induced asthma and indicates that the lung periphery in dogs, like larger airways in asthmatic subjects, has the potential to increase tone when exposed to dry air. Peripheral airways in dogs thus constitute a model that can be used for the investigation of exercise-induced asthma.     

Chemical control of tracheal vascular resistance in dogs

With anesthetized dogs we have measured upper tracheal vascular resistance on both sides of the trachea simultaneously by perfusing the cranial tracheal arteries and measuring inflow pressures at constant flows. The ratio of pressure to flow gave vascular resistance (Rtv). Lung airflow, blood pressure (BP), heart rate, and pressure in a cervical tracheal balloon (Ptr) were also measured. In paralyzed dogs, systemic hypoxia due to artificial ventilation with 10% O2-90% N2 increased Rtv by +8.1 +/- 1.0% (SE), Ptr by +76 +/- 22.8%, and BP by +18.9 +/- 24%. After bilateral cervical vagosympathectomy the increases in Rtv and BP were present (+8.8 +/- 0.9 and +22.3 +/- 0.3%, respectively). After carotid body denervation Rtv, Ptr, and BP increased (+6.4 +/- 1.3, +58.6 +/- 31.6, and +14.6 +/- 3.3%, respectively). After vagotomy Rtv and BP increased (+14.1 +/- 1.7 and +22.4 +/- 10.1%, respectively). Tracheal perfusion with hypoxic blood caused a small vasodilation (-2.2 +/- 1.1%). Systemic hypercapnia due to artificial ventilation with 8% CO2-92% air increased Rtv by +16.7 +/- 3.8%, Ptr by +67 +/- 2.0%, and BP by +12.9 +/- 9.9%. Tracheal perfusion with hypercapnic blood caused a small vasodilation (-2.5 +/- 1.2%). Stimulation of the carotid body chemoreceptors with KCN caused a small increase in Rtv (+1.2 +/- 0.5%) and increases in Ptr (+49.8 +/- 13.6%) and BP (+11.1 +/- 2.1%). Systemic hypoxia and hypercapnia caused tracheal vasoconstriction mainly by an action on the central nervous system.     

Thermal mapping of the airways in humans

To characterize the intrathoracic thermal events that occur during breathing in humans, we developed a flexible probe (OD 1.4 mm) containing multiple thermistors evenly spaced over 30.2 cm, that could be inserted into the tracheobronchial tree with a fiberoptic bronchoscope. With this device we simultaneously recorded the airstream temperature at six points from the trachea to beyond the subsegmental bronchi in six normal subjects while they breathed ambient and frigid air at multiple levels of ventilation (VE). During quiet breathing of room air the average temperature ranged from 32.0 +/- 0.05 degrees C in the upper trachea to 35.5 +/- 0.3 degrees C in the subsegmental bronchi. As ventilation was increased, the temperature along the airways progressively decreased, and at a VE of 100+ 1/min the temperature at the above two sites fell to 29.2 +/- 0.5 and 33.9 +/- 0.8 degrees C, respectively. Interval points were intermediate between these extremes. With cold air, the changes were considerably more profound. During quiet breathing, local temperatures approximated those recorded in the maximum VE room-air trial, and at maximum VE, the temperatures in the proximal and distal airways were 20.5 +/- 0.6 and 31.6 +/- 1.2 degrees C, respectively. During expiration, the temperature along the airways progressively decreased as the air flowed from the periphery of the lung to the mouth: the more the cooling during inspiration, the lower the temperature during expiration. These data demonstrate that in the course of conditioning inspired air the intrathoracic and intrapulmonic airways undergo profound thermal changes that extend well into the periphery of the lung.