Respiration physiology

Respiratory mechanics, chest wall configuration, and lung morphometry were determined in rats before and at 30 (PTX.30) and 60 (PTX.60) min after pneumothorax induction (intrathoracic injection of 8 ml of room air; 50% collapse). Pneumothorax increased respiratory system and lung elastances and viscoelastic/inhomogeneous pressures in both groups, but respiratory system and lung resistive pressures increased only in PTX.60 group. Antero-posterior diameters at the third intercostal space and xiphoid levels, circumference at xiphoid level, and thoracic cephalo-caudal diameter increased significantly after pneumothorax induction independently of temporal evolution. In both groups lung collapse, hyperinflation, and interstitial and alveolar edema were present. Additionally, in PTX.60 group the central airways calibre diminished in relation to PTX.30. In conclusion pneumothorax yields changes in respiratory system and lung elastic and viscoelastic parameters, which are related to alveolar collapse and edema, respectively. Temporal evolution of pneumothorax also leads to changes in lung resistive pressure, probably because of airway narrowing.

Increased circadian variability of airway caliber is a key feature of asthmatic patients, but it has not been addressed in animal models of asthma. Furthermore, animal studies on circadian rhythmicity of airway resistance are very scanty. We used a plethysmographic method for unrestrained guinea pigs to monitor a lung resistance index (iRL) during 24 h. We found circadian variability of iRL values, which were fitted by a sinusoidal curve. Acrophase and bathyphase, characterizing the timing of narrowest and widest airway caliber, respectively, were found at 02:03, and 15:34 h. iRL values at these time-points were statistically different (P<10−5). Moreover, average resistance during the dark period was significantly higher (P<0.0001) than during the light period. Immediately after an acute ozone exposure (3 ppm for 1 h) an increase in iRL was demonstrated (P<0.01), which lasted for 2 h, and tended to remain high for the next hour. After guinea pigs recovered from this obstruction, the circadian rhythm and variability of airway caliber were unaffected. Our results show that a circadian rhythm of iRL takes place in guinea pigs, greatly resembling what occurs in humans, and that ozone exposure causes a transient airway obstruction, but fails to reproduce the increased variability of airway caliber observed in asthmatic patients.

Elephants have had to adapt to gravitational stresses imposed on their very large respiratory structures. We describe some unusual features of the elephant&#39;s respiratory system and speculate on their functional significance. A distensible network of collagen fibers fills the pleural space, loosely connects lung to chest wall but appears not to constrain lung-chest wall movements. Myriad spaces within the network and its rich supply of capillaries suggest effective local sources and sinks for pleural fluid that may replace the gravity-dependent flows of smaller mammals. The lung is partitioned into approximately equal to 1 cm3 parenchymal units by a system of thick, elastic septa that ramify throughout the lung from origins on the lung&#39;s elastic external capsule. Parenchymal units suspended upon the elastic septal system protect dependent alveoli from compression, thereby reducing the usual gravitational gradient of lung expansion. Intra-pulmonary airways are devoid of cartil...

The quality of morphometric data obtained by stereological methods depends on the sampling scheme adopted. In the light of recent advances in sampling theory for stereology a sampling strategy has been developed which differs significantly from that used in previous studies. It operates with a cascade of four sampling levels and adopts the principle of A-weighted sampling, a method that should eliminate bias and possibly yield smaller variances. This method is described and discussed in detail. When compared with the old simpler sampling approach it is found that the new method (1) is at least as efficient and (2) that the estimates of morphometric parameters obtained by this method are similar to the data generated by the old method.

The concept of &#39;vascular waterfall&#39; has been used for collapsible vessels in different hemodynamic states which have little similarity to each other from a dynamic standpoint. Examples include (a) flow through large systemic veins entering the thorax, (b) flow through microvessels, such as pulmonary, cardiac, hepatic, cerebral, and (c) flow through the jugular vein of the giraffe. The dynamics of freely falling liquids (waterfall) as compared with flow through collapsible blood vessels (in vivo and in vitro) and in collapsible tubes are dissimilar in too many respects to justify analogy. The flow through collapsible tubes and blood vessels can be explained satisfactorily on the basis of elementary principles of fluid mechanics (Bernoulli-Poiseuille). Hence, the term waterfall as a metaphor is misleading and unjustified. We suggest that the use of the term be discontinued for describing vascular dynamics.

In these studies, we determined the contribution of central mechanisms and the role of GABA(A)-receptor signal transduction pathways in mediating hypercapnia-induced slowing of breathing frequency. Experiments were performed in decerebrate, vagotomized, paralyzed and mechanically ventilated piglets of 3-5 days and 2-3 weeks of age (n=19). Repeated exposure to progressive hyperoxic hypercapnia induced a reproducible increase in phrenic nerve activity, accompanied by a CO2 concentration-dependent increase in expiratory duration. No differences were observed in piglets with intact or cut carotid sinus nerves. Intravenous administration of bicuculline (2 mg/kg: n=7), a gamma-aminobutyric acid (GABA(A)) receptor antagonist, significantly reduced the CO2-induced prolongation of TE. These data demonstrate for the first time that in early postnatal life, hypercapnia induced increase in phrenic activity is associated with centrally mediated prolongation of expiratory duration. Furthermore. the results suggest that brainstem GABAergic mechanisms play an important role in CO2-induced prolongation of expiratory time during early development.

We investigated structural characteristics for high O2 flux in hummingbird flight muscle, i.e. the most O2 demanding skeletal muscle per unit tissue mass among vertebrates. Pectoralis and supracoracoideus muscles of 3-4 g hummingbirds (Selaphorus rufus) were perfusion fixed in situ, processed for electron microscopy and analyzed by morphometry. Small fiber size (group mean +/- SE, 201 +/- 14 microns 2 at 2.1 microns sarcomere length), large capillary length per fiber volume (8947 +/- 869 mm-2) and high mitochondrial volume density per volume of muscle fiber (34.5 +/- 0.9%) were characteristic features of the muscles. Considering capillary supply and mitochondrial volume on an individual fiber basis showed that the size of the capillary-to-fiber interface (i.e. capillary surface per fiber surface) was also high in the muscles. Comparison with mammalian hindlimb pointed to a major role of the size of the capillary-to-fiber interface in providing a great potential for O2 flux rate from...

The recruitment and derecruitment of lung units is one explanation of the hysteresis observed in an excised lung during inflation and deflation. A simplified model has been proposed in which the recruitment-derecruitment process is a function of end-expiratory pressure (Frazer, D.G., K.C. Weber and G.N. Franz, Respir. Physiol. 61: 277-288, 1985). The object of this study was to test this model with three experimental procedures. During the first set of experiments, progressively larger pressure-volume (PL-VL) loops were recorded with end-expiratory pressure held at either -5 cmH2O, where all lung units are assumed to be closed, or +5 cmH2O, where all recruited lung units are assumed to be open. In the first case hysteresis is maximal, in the second, minimal. The difference in hysteresis is presumed to arise from the recruitment-derecruitment process. In the second set of experiments, excised lungs are slowly inflated and then deflated at a constant rate while constant-amplitude sinu...

The effects of sustained constriction of the rib cage (RCC), constriction of the abdomen (AC) and of breathing against a positive pressure of 10 cms of water (PPB) were studied in four normal subjects with moderate constant hypercapnia. Intercostal electrical activity (Eic) was measured by implanted wire electrodes and diaphragmatic electrical activity (Edia) by oesophageal electrodes. There was no fixed relation between Edia and VT. VT was unaltered during AC and RCC: Edia was unaltered during AC but increased during RCC. The response to PPB without constriction varied: three subjects increased end-expiratory VL with increase in Edia and inspiratory Eic. One subject initially, and one subject after training, maintained end-expiratory VL constant with no change in Edia and an increase in expiratory Eic. When PPB was applied during AC and RCC there was an increase in Edia proportional to end-expiratory lung volume. The overall response to distortion was determined by voluntary choice...

Blood flow into the pulmonary capillaries and the volume of blood within the capillary bed are both pulsatile with the cardiac cycle. We have developed a quantitative model of diffusional gas exchange in the lung to investigate the effects of coupling between these two time-varying parameters on lung O2 and CO2 exchange. For normal man breathing room air at rest, the computed results agree well with previous predictions for the constant flow and volume case, and for the case of pulsatile flow alone. When coupled time-varying pulmonary capillary blood flow and volume are included, using the best data available in the literature to define these parameters, diffusional O2 exchange is improved over the cases of pulsatile flow or volume alone, and closely approximates that obtained for the hypothetical constant flow and volume case. CO2 exchanges, and O2 exchange during hypoxia, are not affected by pulsatile flow and/or volume. These results suggest that O2 exchange is efficient in the p...

We have investigated structure and function of the external gill filaments, which occur transiently in the embryonic little skate, Raja erinacea. Approximately 25-30 days after spawning (body mass 0.03-0.05 g) external gill filaments appear as an outgrowth from the caudal side of the gill arches. These filaments are thread-like, each containing one afferent and one efferent blood vessel, and by day 70-75 (body mass 0.4-0.5 g) they reach their maximum size at a length of about 1 cm and a blood vessel diameter of 70-80 microns. Subsequent resorption of the filaments is characterized by a decrease in both length and diameter of the blood vessel. By day 90-95 (body mass 0.9-1.0 g) the external gill filaments are completely resorbed and replaced by internal gills. Blood velocity, measured in these external filaments, increased with development from 0.1 mm.sec-1 to about 0.7 min.sec-1, and decreased again during resorption. Blood flow, calculated therefrom with blood vessel diameter, show...

The lungs of 7 children (age: 26 days to 5 years 4 months) who died from non-respiratory causes were morphometrically investigated by means of light and electron microscopy. For analysis, the set of data was supplemented with results obtained previously on 8 normal adult lungs using similar quantitative techniques (Gehr et al., 1978). The results allowed us to distinguish two phases of postnatal lung development and growth, the first phase lasting from birth to about 18 months and the second phase from then to adulthood. The first phase was characterized by an overproportionate volume increase in the O2-transporting media, air and blood, at the expense of the parenchymal tissue compartment. In the second phase, the volumetric composition of the lung did not change further because there was proportionate growth of all lung compartments. The growth curves for the airspace and capillary surface areas were not biphasic: they increased in direct proportion to lung volume from birth to ad...

Using a mathematical model, the effects of water and blood flow inequality on gas exchange in the fish gill were investigated. The results show that O2 exchange is more sensitive to flow inequalities than CO2 exchange. Oxygen exchange is most sensitive to blood flow inequality, whereas carbon dioxide exchange is equally sensitive to inequalities in water and blood flow. Furthermore, it is shown that the effects of flow inequalities cannot be abolished by matching the two flows exactly. The results suggest that the greatest potential for regulation of gas exchange lies on the blood side of the exchanger, and that adjustments in flow distributions to maintain homeostasis in oxygen exchange in the face of changing environmental conditions and/or changing organismic demands, most likely will be accompanied by a change in the acid-base status of the animal.

To detect and quantify diffusion limitation in alveolar-capillary O2 transfer, measurements of pulmonary gas exchange were performed in 6 awake, chronically tracheostomized dogs (mean body weight 28.3 kg) breathing low O2 (arterial PO2 35-39 Torr), with or without CO2 added to inspired gas. From rest to exercise, with O2 uptake averaging 23 ml/(min X kg), the ideal-alveolar-to-arterial PO2 difference (PAiO2-PaO2) increased from 2.1 +/- 0.2 Torr (mean +/- SE) to 2.9 +/- 0.2 in hypoxia, and from 1.9 +/- 0.7 Torr to 3.0 +/- 0.5 in hypercapnic hypoxia. The apparent pulmonary O2 diffusing capacity (DLO2), calculated from O2 uptake, mixed-venous PO2, arterial PO2, and ideal-alveolar PO2, was found to be increased by hypercapnia and exercise. During exercise DLO2 averaged 74 ml/(min X Torr) in hypoxia and 76 ml/(min X Torr) in hypercapnic hypoxia. Because of the influence of inhomogeneity effects, these values should be considered as minimum values for the true pulmonary O2 diffusing capac...

The effects of recurrent hypoxia on cardiorespiratory reflexes were characterized in anesthetized piglets at 2-10 d (n=15), 2-3 weeks (n=11) and 8-10 weeks (n=8). Responses of phrenic and hypoglossal electroneurograms (ENG(phr) and ENG (hyp)) to hypoxia (8% 0(2), bal N(2), 5 min), hypercapnia (7% CO(2) bal O(2), 5 min) and intravenous capsaicin were tested before and after recurrent exposure to 11 episodes of hypoxia (8% O(2) bal N(2), 5 min). In piglets 2-10 d, ENG(phr) response to hypoxia declined in proportion to the number of hypoxic exposures; however, ENG (hyp) response to hypoxia was unchanged. In piglets at 2-10 d, intracisternal injection of bicuculline (GABA(A) receptor antagonist) reversed effects of recurrent hypoxia on ENG(phr) hypoxic response, eliminated apnea during hypoxia, as well as the delay in appearance of ENG(phr) after hypoxia. The ENG(phr) response to 7% CO(2) inhalation also decreased after recurrent hypoxia; however, the ENG(phr) response to C-fiber stimulation by capsaicin was unaltered. Piglets at 2-3 and 8-10 weeks were resistant to the depressive effects of recurrent hypoxia on respiratory reflex responses. We conclude that the response of the anesthetized newborn piglet to recurrent hypoxia is dominated by increasing inhibition of phrenic neuroelectrical output during successive hypoxic exposures. Central GABAergic inhibition may contribute significantly to the cumulative effects of repeated hypoxia in the newborn piglet experimental model.

Respiratory diseases are a frequent reason for using health care. In 1995-1996, diseases of the respiratory tract (ICD 460-519) contributed seven of the top 15 reasons for visits to physician offices among children under 15 years of age in the United States. Environmental tobacco smoke (ETS) is a wide-spread environmental pollutant that has been long linked with respiratory problems. This paper will review the available literature on the role ETS plays in respiratory diseases, including asthma. This review focuses not only on the respiratory problems caused by ETS, but also examines the influence of age at exposure on the consequences of ETS and the importance of the differing sources of ETS exposure. As ETS is a completely preventable form of environmental pollution, the success or failure of various types of interventions will also be reviewed.

To quantify any mechanical inhibitory effect of nasal intermittent positive pressure ventilation (IPPV) on inspiratory activity of the diaphragm we ventilated five conscious relaxed subjects on two occasions at respiratory rates similar to quiet breathing (QB) and at three levels of applied pressure (Pappl)--6, 9 and 12 cmH2O, each during hypocapnia (P(CO2) allowed to decrease) and eucapnia (CO2 added to inspired gas). Diaphragm activity was assessed from transdiaphragmatic pressure (esophageal and gastric balloons) and diaphragm EMG (surface electrodes) both integrated with time (integral(Pdi x dt) and integral(EMGdi x dt), respectively). Neural inspiratory time (Tin) was measured as onset to peak of the integral(EMGdi x dt) signal. Relative to QB, integral(Pdi x dt) was 50-69% less during eucapnic IPPV 6-12 cmH2O (P &lt; 0.005) and 67-85% less during hypocapnic IPPV (P &lt; 0.005). Tin decreased (P &lt; 0.05) with IPPV and, on ceasing IPPV, there was apnoea (prolonged expiratory t...

To assess the suitability of the miniature swine for studies of the control of breathing we evaluated the response of these animals to commonly used respiratory stimuli. Hanford miniature pigs were anesthetized with alpha chloralose and allowed to breathe spontaneously. Rapid lung inflations induced a prolonged expiratory pause proportional to load. Mechanical stimulation of the upper airways induced coughing. Central venous injections of C-fiber stimulants produced bradycardia, hypotension with apnea and/or rapid shallow breathing. CO2 rebreathing increased ventilation primarily through an increase in tidal volume; inspiratory time was not changed. Bilateral vagotomy caused a slower, deeper pattern of breathing, and significantly attenuated the ventilatory response to CO2; all other reflexes were abolished by vagotomy. Cooling the vagus nerves caused reversible blockade of the cough, inflation and C-fiber mediated reflexes in that order. We conclude that the pig can serve as a usef...

A computer program is described, relating blood flow with venous PO2 for any given set of the following parameters: oxygen uptake, respiratory quotient, the 2,3-DPG/Hb molar concentration ratio (G), arterial PO2, PCO2, and pH. Two compartments (total body and one leg) and two conditions (rest and maximal exercise) are considered. Calculations are performed at five altitudes (0, 3850, 5400, 6300 and 8848 m), for which the above variables are known. The results indicate that an increased G value has a negative effect on the oxygen delivery to tissues at very high altitudes (greater than 5400 m), irrespectively of the work load, since larger blood flows (delta Q on the summit of Mt. Everest is +4 to +71/min, and +1 to +2.5 l/min, for whole body and one leg, respectively) are required for a given oxygen uptake. For submaximal work at altitudes ranging from sea level up to 5400 m, as well as for moderate work at 5400 m, high G values improve the oxygen delivery to tissues.

The aim of this ex-vivo study on excised tracheas of healthy horses was to characterise the microscopic heterogeneity of mucus quality by a visual grading system based on transparency and to determine whether differences in mucus quality, assessed by a visual grading system, influence tracheal mucus velocity (TMV). Small pieces of each trachea were mounted into a humidified chamber under a microscope. Mucus quality was visually subdivided into four grades (MG) and ciliary beat frequency and TMV were determined. Mucus on excised horse tracheal epithelium does not form a homogenous layer. We observed flakes and streams of a great heterogeneity, which by the characteristic of transparency can be qualified and quantified. Visual characterisation of mucus was able to explain a considerable part of TMV variation. Therefore, it can be considered as a suitable non-invasive method for the evaluation of mucus quality and transport effectiveness.