Effects of cold dry air nasal stimulation on airway mucosal blood flow in humans

Several studies have demonstrated that nasal challenges can induce reflex responses in the respiratory system. Some authors have described bronchoconstriction and modification of the pattern of breathing following nasal challenges by irritants and cold air. We propose to determine the effect of nasal stimulation with cold dry air on airway mucosal blood flow (Qaw) in the proximal tracheal bronchial tree of healthy humans. Nine healthy subjects participated in the study. Baseline measurement Qaw, nasal airway resistance (NAR) and airway caliber by specific airways conductance (SGaw) were followed by nasal challenge with cold dry air. Qaw, NAR and Sgaw were determined after the challenge. In those subjects in which a significant decline in Qaw was recorded the protocol was repeated after pretreatment with nasal anesthesia using topical lidocaine. Cold dry air challenge produced a significant decrease in mean Qaw for the nine subjects and this response was abolished by pretreatment with nasal anesthesia using topical lidocaine. There was no significant change in Sgaw and NAR after the challenge and topical lidocaine anesthesia. Our data indicates that nasal stimulation with cold dry air leads to a reduction in Qaw and that this effect may be mediated by a nasal reflex.     

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)     

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 air humidity on spinability and transport capacity of canine airway secretions

The effect of varying the inspired air humidity on a rheological property (spinability) and transport capacity of airway mucus has been analyzed in 10 mongrel dogs. Tracheal mucus was collected in anesthetized dogs inspiring through an endotracheal tube the air of a climate chamber maintained at constant temperature (T degrees:20 degrees C). In one test, the dogs inspired air at an absolute humidity (AH) of 9 g water/m3 air directly through the endotracheal tube. In the other test, the dogs inspired through an artificial nose connected to the endotracheal tube giving a AH of 30 g water/m3 air. Tracheal mucus was collected at the external distal end of the endotracheal tube. The spinability (Sp) or thread-forming properties of mucus was measured. The relative mucociliary transport rate (TR) of mucus was analyzed on a frog palate epithelium preparation. The transport rate was significantly (p less than 0.01) lower (range: 0.59-0.80) when the AH of the inspired air was low in comparison to that obtained with high AH (range: 0.70-1.13). The variations in mucus Sp due to changing AH were positively and significantly correlated (r = 0.80, p less than 0.01) with the corresponding variations in TR. These results suggest that lowering the AH of air induces a decrease in the transport capacity which appears to be dependent on the change of spinability that occurs in the mucus.     

Effect of cold air inhalation and isometric exercise on coronary blood flow and myocardial function in humans

The effects of cold air inhalation and isometric exercise on coronary blood flow are currently unknown, despite the fact that both cold air and acute exertion trigger angina in clinical populations. In this study, we used transthoracic Doppler echocardiography to measure coronary blood flow velocity (CBV; left anterior descending coronary artery) and myocardial function during cold air inhalation and handgrip exercise. Ten young healthy subjects underwent the following protocols: 5 min of inhaling cold air (cold air protocol), 5 min of inhaling thermoneutral air (sham protocol), 2 min of isometric handgrip at 30% of maximal voluntary contraction (grip protocol), and 5 min of isometric handgrip at 30% maximal voluntary contraction while breathing cold air (cold + grip protocol). Heart rate, blood pressure, inspired air temperature, CBV, myocardial function (tissue Doppler imaging), O(2) saturation, and pulmonary function were measured. The rate-pressure product (RPP) was used as an index of myocardial O(2) demand, whereas CBV was used as an index of myocardial O(2) supply. Compared with the sham protocol, the cold air protocol caused a significantly higher RPP, but there was a significant reduction in CBV. The cold + grip protocol caused a significantly greater increase in RPP compared with the grip protocol (P = 0.045), but the increase in CBV was significantly less (P = 0.039). However, myocardial function was not impaired during the cold + grip protocol relative to the grip protocol alone. Collectively, these data indicate that there is a supply-demand mismatch in the coronary vascular bed when cold ambient air is breathed during acute exertion but myocardial function is preserved, suggesting an adequate redistribution of blood flow.     

Effect of exercise-induced hyperventilation on airway resistance and cycling endurance

The purpose of the present study was to investigate the effect of exercise induced hyperventilation and hypocapnia on airway resistance (R _aw), and to try to answer the question whether a reduction of R _aw is a mechanism contributing to the increase of endurance time associated with a reduction of exercise induced hyperventilation as for example has been observed after respiratory training. Eight healthy volunteers of both sexes participated in the study. Cycling endurance tests (CET) at 223 (SD 47) W, i.e. at 74 (SD 5)% of the subject's peak exercise intensity, breathing endurance tests and body plethysmograph measurements of pre- and postexercise R _aw were carried out before and after a 4-week period of respiratory training. In one of the two CET before the respiratory training CO₂ was added to the inspired air to keep its end-tidal concentration at 5.4% to avoid hyperventilatory hypocapnia (CO₂-test); the other test was the control. The pre-exercise values of specific expiratory R _aw were 8.1 (SD 2.8), 6.8 (SD 2.6) and 8.0 (SD 2.1) cm H₂O · s and the postexercise values were 8.5 (SD 2.6), 7.4 (SD 1.9) and 8.0 (SD 2.7) cm H₂O · s for control CET, CO₂-CET and CET after respiratory training, respectively, all differences between these tests being nonsignificant. The respiratory training significantly increased the respiratory endurance time during breathing of 70% of maximal voluntary ventilation from 5.8 (SD 2.9) min to 26.7 (SD 12.5) min. Mean values of the cycling endurance time (t _cend) were 22.7 (SD 6.5) min in the control, 19.4 (SD 5.4) min in the CO₂-test and 18.4 (SD 6.0) min after respiratory training. Mean values of ventilation ( _E) during the last 3␣min of CET were 123 (SD 35.8) l · min⁻¹ in the control, 133.5 (SD 35.1) l · min⁻¹ in the CO₂-test and 130.9 (SD 29.1) l · min⁻¹ after respiratory training. In fact, six subjects ventilated more and cycled for a shorter time, whereas two subjects ventilated less and cycled for a longer time after the respiratory training than in the control CET. In general, the subjects cycled longer the lower the _E, if all three CET are compared. It is concluded that R _aw measured immediately after exercise is independent of exercise-induced hyperventilation and hypocapnia and is probably not involved in limiting t _cend, and that t _cend at a given exercise intensity is shorter when _E is higher, no matter whether the higher _E occurs before or after respiratory training or after CO₂ inhalation. Accepted: 11 September 1996     

Changes in airway resistance induced by nasal inhalation of cold dry, dry, or moist air in normal individuals

Fontanari, Pierre, Henri Burnet, Marie CarolineZattara-Hartmann, and Yves Jammes. Changes in airway resistanceinduced by nasal inhalation of cold dry, dry, or moist air in normalindividuals. J. Appl. Physiol. 81(4):1739-1743, 1996.Nasopulmonary bronchomotor reflexes elicited bymechanical or irritant stimulation of the nose have been described inanimals and asthmatic patients. However, few studies were devoted tothe consequences of nasal breathing of cold and dry air or of only dryor only moist air on the bronchomotor control in normal individuals.The present study reported changes in interruption resistance (Rint)measured during eupneic breathing of moderately cold (4 or10°C) and dry [0.3% relative humidity (RH)] airor of room air at 23°C that is either dry (0.3% RH) or moist (97%RH). Nasal inhalation of cold (4°C) dry air or of only dryair significantly increased baseline Rint value (17 and 21%,respectively) throughout the 15-min test periods. The response to cold was significantly accentuated when the air temperature was lowered to 10°C (42%). After nasal anesthesia orinhalation of a cholinergic antagonist, cold air did not induce achange in Rint. Nasal inhalation of moist room air had no effect. No Rint changes were measured during oral breathing of the three testagents. It is concluded that the activation of cold receptors orosmoreceptors in the nasal mucosa induces protective bronchoconstrictor responses in normal individuals.

     

Electrical activity of the brain during isocapnic hyperventilation with cold air

The influence of hyperventilation on the electrical activity of the brain has conventionally been the subject of study of physiologists. The role of the brain in the adaptation to the inhalation of cold air remains to be understood in more detail. The aim of the study was to determine certain features of the cerebral response to isocapnic hyperventilation with cold air and to reveal the correlation of its electric activity in different modes of ventilation, with the pattern of quiet breathing and the forced expiration parameters. Twenty-one apparently healthy volunteers were subjected to comprehensive functional examination. Qualitative differences in the ?-rhythm relative power were revealed under the conditions of isocapnic hyperventilation with cold air. The specific features of the correlation of the electrical activity of the brain provoked by cold with the breathing pattern and the bronchomotor tone were revealed.     

Effects of hyperventilation on pulmonary blood flow and recirculation time of humans

We used direct invasive techniques to measure the effects of hyperventilation on the pulmonary blood flow (Q) and on recirculation time of helium and of carbon dioxide in humans. The subjects hyperventilated with a tidal volume of 1.5 liters (BTPS) and a frequency of 20 or 30 breaths/min. There was no significant change in Q from control at either level of hyperventilation. Helium first appeared in the pulmonary artery within 12 s from the onset of hyperventilation and increased by approximately 0.7% of its equilibrium arterial value per second at both levels of hyperventilation. In contrast, the PVCO2 remained at base-line level until 43 s from the onset of hyperventilation. We conclude that hyperventilation at 30 or 45 l/min with constant tidal volume does not significantly affect the value of Q and that the amount of recirculation of the two gases does not result in underestimation of Q when this variable is measured by indirect respiratory rebreathing techniques.     

Effects of airway pressure on bronchial blood flow

We studied the effects of increased airway pressure caused by increasing levels of positive end-expiratory pressure (PEEP) on bronchial arterial pressure-flow relationships. In eight alpha-chloralose-anesthetized mechanically ventilated sheep (23-27 kg), the common bronchial artery, the bronchial branch of the bronchoesophageal artery, was cannulated and perfused with a pump. The control bronchial blood flow (avg 12 +/- 1 ml/min or 0.48 ml X min-1 X kg-1) was set to maintain mean bronchial arterial pressure equal to systemic blood pressure. Pressure-flow curves of the bronchial circulation were measured by making step changes in bronchial blood flow, and changes in these curves were analyzed with measurements of the pressure at zero flow and the slope of the linearized curve. The zero-flow pressure represents the effective downstream pressure, and the slope represents the resistance through the bronchial vasculature. At a constant bronchial arterial pressure of 100 mmHg, an 8 mmHg increase in mean airway pressure caused a 40% reduction in bronchial blood flow. Under constant flow conditions, increases in mean airway pressure with the application of PEEP caused substantial increases in bronchial arterial pressure, averaging 4.6 mmHg for every millimeters of mercury increase in mean airway pressure. However, bronchial arterial pressure at zero flow increased approximately one-for-one with increases in mean airway pressure. Thus the acute sensitivity of the bronchial artery to changes in mean airway pressure results primarily from changes in bronchovascular resistance and not downstream pressure.     

Nasal flow-resistive responses to challenge with cold dry air.

Recent studies have suggested that the inhalation of cold air through the nose is associated with the subsequent release of mediators of immediate hypersensitivity. To determine if mucosal surface heat and water loss influence the nasal functional response to cold air, we measured nasal resistance by posterior rhinomanometry before and 1, 5, and 10 min after a 4-min period of isocapnic hyperventilation (30 l/min) through the nose in nine healthy subjects (5 males, 4 females; aged 25-39 yr) while they inhaled air at 0 degrees C. During the challenge period, the subjects breathed either in and out of the nose or in through the nose and out through the mouth. No changes in nasal resistance developed when subjects breathed exclusively through the nose; however, when subjects breathed in through the nose and out through the mouth, nasal resistance was increased 200% at 1 min (P less than 0.01) after the challenge and returned to baseline values by 10 min after cessation of the challenge. These data indicate that nasal functional responses to cold dry air are dependent on the pattern of the ventilatory challenge. If the heat given up from the nasal mucosa to the incoming air is not recovered during expiration (as is the case with inspiration through the nose and expiration through the mouth), nasal obstruction will occur. Hyperpnea of cold air, per se, does not influence nasal resistance.     

Effect of blood flow and muscle contraction on noradrenaline spillover in the canine gracilis muscle

Many authors have reported that, during exercise, noradrenaline spillover increases and fractional extraction decreases. It has been suggested that the increase in blood flow to active muscles may contribute to these effects. Muscle contraction also causes changes in many factors that may affect noradrenaline spillover and fractional extraction. In this experiment, we studied the effect of muscle contraction and blood flow on noradrenaline and adrenaline spillover and fractional extraction in the in situ canine gracilis muscle. The low intensity stimulation protocol enabled us to have muscle contractions without any effect on the local concentration of noradrenaline, as measured by microdialysis, and noradrenaline spillover. Fractional extraction of both noradrenaline and adrenaline was unaffected by increasing blood flow three and four times its resting value. In addition, noradrenaline spillover was increased by the higher blood flow, from 188 to 452 pg x min(-1) at rest and from 246 to 880 pg x min(-1) during stimulation. Stimulation of muscle contraction caused a significant increase in fractional extraction of noradrenaline and a nonsignificant increase in adrenaline extraction. In addition, an adrenaline spillover was observed in certain conditions. In light of our results, it seems that blood flow may not be the main factor decreasing fractional extraction of noradrenaline during exercise. However, blood flow could contribute to the increase in noradrenaline spillover observed in the active muscles during exercise.     

Acute post-irradiation canine intestinal blood flow

Radiation-induced early transient incapacitation (ETI) is accompanied by severe systemic hypotension, during which arterial blood pressure often decreases to less than 50 per cent of normal. One haemodynamic compensatory mechanism is increased peripheral resistance due to vasoconstriction. This vasoconstriction in the small intestine of dogs is disproportionately increased during haemorrhagic or endotoxic shock, and intestinal ischaemia is frequent. In an attempt to elucidate mechanisms underlying radiation-induced ETI and the gastrointestinal radiation syndrome, canine intestinal submucosal blood flow was measured by the hydrogen polarographic technique, both before and after exposure to gamma radiation. Systemic blood pressures, blood gases and haematocrits were determined simultaneously. Data obtained from 12 sham-irradiated dogs and 12 irradiated dogs indicated that 90 Gy, whole-body, gamma radiation produced a 31 per cent decrease in systemic mean blood pressure beginning within 20 min post-irradiation and lasting for at least 90 min. However, the intestinal submucosal blood flow did not decrease as anticipated, but it exhibited an actual post-irradiation increase. This increase in post-irradiation intestinal submucosal blood flow began within 5 min after irradiation and lasted for at least 90 min. Post-irradiation haematocrits were 10.5 per cent higher than those obtained before irradiation and those obtained from sham-irradiated subjects. Histopathological examination of ileal mucosa revealed significant pathologic lesions in some irradiated animals within two hours after exposure.     

Regional and temporal variation in canine peripheral lung responses to dry air

Variation in dry airflow-induced broncho-constriction (AIB) in the canine lung periphery was examined using a wedged bronchoscope technique. Collateral system resistance (Rcs) was measured before and after dry-air challenge. Base-line Rcs was similar throughout the lung periphery, between dogs, and over time. Increasing base-line Rcs was correlated with increasing maximum Rcs 5 min postchallenge (Rcs5), increasing change in Rcs (dRcs5), and decreasing percent change in Rcs above base line (%Rcs5). In contrast to repeated challenge in which base-line Rcs was similar, the magnitude of AIB associated with consecutive challenges with unequal base lines depended on the parameter used to evaluate the response (i.e., Rcs5, dRcs5, or %Rcs5). Peripheral lung resistance then increased to a stimulus specific maximum regardless of base-line Rcs, although data expressed as %Rcs5 or dRcs5 may obscure this observation. Although a change in peripheral lung resistance does not necessarily imply airway narrowing, it is consistent with the idea that changes in Rcs are independent of the collateral system's resting tone.