Neural control of airway pressures in rabbits

In twenty anaesthetized and spontaneously breathing rabbits airway pressures were measured above and below the larynx during tidal respiration through the larynx. Peak inspiratory and expiratory pressures at both sites were recorded in control conditions and then compared to values obtained in the course of progressive denervation of the airways. The two methods of denervation consisted of (1) bilateral section of superior and recurrent laryngeal nerves and of the midcervical vagotomy (horizontal method); (2) right-sided sections of the three nerves followed by left-sided sections (vertical method). Motor denervation of the larynx due to RLNs neurotomy (horizontal method) produced significant increases in intratracheal pressures in both phases of the respiratory cycle. Less prominent increments in pressures were achieved on RLNs neurotomy in the vertical method. SLNs section and vagotomy had little additional effect on airway pressures. Our results indicate that unilateral laryngeal palsy poses far smaller obstruction to breathing than simultaneous bilateral denervation, and that afferent denervation of the larynx has no effect on airway pressures.     

Hemodynamic effects of pressures applied to the upper airway during sleep.

The increase in systemic blood pressure after an obstructive apnea is due, in part, to sympathetically mediated vasoconstriction. We questioned whether upper airway (UA) receptors could contribute reflexly to this vasoconstriction. Four unanesthetized dogs were studied during wakefulness and non-rapid-eye-movement (NREM) sleep. The dogs breathed via a fenestrated tracheostomy tube sealed around the tracheal stoma. The snout was sealed with an airtight mask, thereby isolating the UA when the fenestration was closed and exposing the UA to negative inspiratory intrathoracic pressure when it was open. The blood pressure response to three UA perturbations was studied: 1) square-wave negative pressures sufficient to cause UA collapse with the fenestration closed during a mechanical hyperventilation-induced central apnea; 2) tracheal occlusion with the fenestration open vs. closed; and 3) high-frequency pressure oscillations (HFPO) with the fenestration closed. During NREM sleep, 1) blood pressure response to tracheal occlusion was similar with the fenestration open or closed; 2) collapsing the UA with negative pressures failed to alter blood pressure during a central apnea; and 3) application of HFPO to the UA during eupnea and resistive-loaded breaths increased heart rate and blood pressure. However, these changes were likely to be secondary to the effects of HFPO-induced reflex changes on prolonging expiratory time. These findings suggest that activation of UA pressure-sensitive receptors does not contribute directly to the pressor response associated with sleep-disordered breathing events.     

Pressure-volume properties of the upper airway of rabbits

In 10 anesthetized rabbits the upper airway cephalad of the vocal cords was isolated from the distal airway and sealed. Static deflation pressure-volume data were recorded from the isolated upper airway. The relationship between pressure and volume in the upper airway was a straight line; the correlation coefficient (r) ranged from 0.97 to 1.00. The following quantities were derived from the data: the pressure-volume ratio (upper airway elastance, cmH2O/ml), the pressure in the airway at airway closure (closing pressure, cmH2O), and the airway volume at zero airway pressure (reserve volume, ml). Mean upper airway elastance was 8.13 +/- 1.45 [95% confidence intervals (CI)] cmH2O/ml, closing pressure was -6.93 +/- 1.53 (95% CI) cmH2O, and reserve volume was 0.74 +/- 0.15 (95% CI) ml. There was no significant correlation between elastance and closing pressure (r = 0.47, P greater than 0.1), but closing pressure and reserve volume were significantly correlated (r = 0.77, P less than 0.01). Pressure-volume data recorded from newly dead animals exhibited the same linear relationship between pressure and volume observed in living animals. It is concluded that the pressure-volume properties of the isolated upper airway of the rabbit can be expressed as a single value for airway elastance, that estimation of pressure-volume properties over part of the volume range is representative of the whole volume range, and that pressure-volume properties are determined by passive elastic properties of the airway tissues. It appears that the resistance of the upper airway to collapse by negative intraluminal pressure is more dependent on the initial size of the airway than on its elastance.     

Comparative study of antioxidant enzymes in tissues surrounding implant in rabbits

There is a possible role of reactive oxygen species (SROS) in the complication of implants although there is presently little information. The aim of this study was to investigate the alterations in lipid peroxidation (LP) and antioxidant enzyme activities in tissues surrounding implants in rabbits. Thirty New Zealand albino male rabbits were used. They were randomly divided into five groups. The first group (I) was used as control. Groups II, III, IV and V were implanted with stainless steel, ceramic, titanium and polyethylene, respectively. One month after the administration of implant, the tissues surrounding the implant were carefully removed for antioxidant enzyme analysis. Glucose-6-phosphate dehydrogenase (G6PD), glutathione reductase (GR), superoxide dismutases (SOD), glutathione peroxidase (GPx), catalase (CAT) in tissues surrounding the implants in the groups II, III and IV were significantly (p<0.05-p<0.001) lower than in the control group although glutathione S-transferase (GST) activities and LP values were increased. CAT activity and LP level did not decrease in group V. In conclusion, these data demonstrate that there is an increase in lipid peroxidation in the tissues surrounding ceramic and titanium implants of animals whereas there is a decrease in antioxidant enzymes. Oxidative stress plays a very important role in the complications of ceramic and titanium implants. The polyethylene implant seems to be the best of the four implant materials tested.     

Influence of muscle activity on the elastance of the upper airway of rabbits

This study sought to assess the effect of variations in upper airway muscle activity on upper airway pressure-volume properties. Upper airway elastance, closing pressure, and reserve volume were measured in the isolated upper airways of anesthetized rabbits under control conditions and after administration of gallamine (2 mg/kg iv) or after 10 min of spontaneous respiration of 7% CO2 in O2. Administration of gallamine to seven animals was associated with a fall in reserve volume from 0.94 +/- 0.24 to 0.69 +/- 0.17 (95% confidence interval) ml (P less than 0.01) and of closing pressure from -7.53 +/- 0.23 to -5.75 +/- 1.05 cmH2O (P less than 0.01), but airway elastance did not change significantly. Hypercapnia in seven animals was associated with a rise in elastance from 7.06 +/- 0.91 to 7.67 +/- 0.86 cmH2O/ml (P less than 0.001) and in reserve volume from 0.68 +/- 0.06 to 0.86 +/- 0.13 ml (P less than 0.05). Closing pressure also changed from -5.88 +/- 0.94 to -7.92 +/- 1.85 cmH2O. This change was correlated with the change in reserve volume but not with the change in elastance. In three animals exposed to hypercapnia, return to room air breathing was associated with return of elastance, reserve volume, and closing pressure to control levels. It is concluded that muscle activity in the upper airway affects both the size and elastance of the airway, but the dominant mechanism by which upper airway muscles increase the resistance of the upper airway to collapse is by increasing airway volume.     

Developmental changes in upper airway dynamics.

Normal children have a less collapsible upper airway in response to subatmospheric pressure administration (P(NEG)) during sleep than normal adults do, and this upper airway response appears to be modulated by the central ventilatory drive. Children have a greater ventilatory drive than adults. We, therefore, hypothesized that children have increased neuromotor activation of their pharyngeal airway during sleep compared with adults. As infants have few obstructive apneas during sleep, we hypothesized that infants would have an upper airway that was resistant to collapse. We, therefore, compared the upper airway pressure-flow (V) relationship during sleep between normal infants, prepubertal children, and adults. We evaluated the upper airway response to 1). intermittent, acute P(NEG) (infants, children, and adults), and 2). hypercapnia (children and adults). We found that adults had a more collapsible upper airway during sleep than either infants or children. The children exhibited a vigorous response to both P(NEG) and hypercapnia during sleep (P < 0.01), whereas adults had no significant change. Infants had an airway that was resistant to collapse and showed a very rapid response to P(NEG). We conclude that the upper airway is resistant to collapse during sleep in infants and children. Normal children have preservation of upper airway responses to P(NEG) and hypercapnia during sleep, whereas responses are diminished in adults. Infants appear to have a different pattern of upper airway activation than older children. We speculate that the pharyngeal airway responses present in normal children are a compensatory response for a relatively narrow upper airway.     

Influence of gender on upper airway mechanics: upper airway resistance and Pcrit.

It has been proposed that the difference in sleep apnea prevalence is related to gender differences in upper airway anatomy and physiology. To explain the prevalence difference, we hypothesized that men would have an increased upper airway resistance and increased critical closing pressure (Pcrit) compared with women. In protocol 1, resistance at two points, fixed flow of 0.2 l/s (RL) and peak flow (Rpk), was measured in 33 men and 27 women without significant sleep-disordered breathing. We found no difference in either RL (-6.9 +/- 5.9 vs. -8.6 +/- 8.2 cmH2O) or Rpk (-9.3 +/- 6.8 vs. -10.0 +/- 11.9 cmH2O) between the men and women. A multiple linear regression to correct for the effects of age and body mass index confirmed that gender had no effect on resistance. In protocol 2, Pcrit was measured in eight men and eight women without sleep-disordered breathing. We found no difference in Pcrit (-10.4 +/- 3.1 vs. -8.8 +/- 2.7 cmH2O) between men and women. We conclude that there are no significant differences in collapsibility between men and women. We present an unifying hypothesis to explain the divergent findings of gender differences in upper airway physiology.     

Simulation of upper airway occlusion without and with mandibular advancement in obstructive sleep apnea using fluid-structure interaction

Obstructive Sleep Apnea (OSA) is a common sleep disorder characterized by repetitive collapse of the upper airway (UA). One treatment option is a mandibular advancement splint (MAS) which protrudes the lower jaw, stabilizing the airway. However not all patients respond to MAS therapy and individual effects are not well understood. Simulations of airway behavior may represent a non-invasive means to understand OSA and individual treatment responses. Our aims were (1) to analyze UA occlusion and flow dynamics in OSA using the fluid structure interaction (FSI) method, and (2) to observe changes with MAS. Magnetic resonance imaging (MRI) scans were obtained at baseline and with MAS in a known treatment responder. Computational models of the patients' UA geometry were reconstructed for both conditions. The FSI model demonstrated full collapse of the UA (maximum 5.83 mm) pre-treatment (without MAS). The UA collapse was located at the oropharynx with low oropharyngeal pressure (−51.18 Pa to −39.08 Pa) induced by velopharyngeal jet flow (maximum 10.0 m/s). By comparison, simulation results from the UA with MAS, showed smaller deformation (maximum 2.03 mm), matching the known clinical response. Our FSI modeling method was validated by physical experiment on a 1:1 flexible UA model fabricated using 3D steriolithography. This is the first study of airflow dynamics in a deformable UA structure and inspiratory flow. These results expand on previous UA models using computational fluid dynamics (CFD), and lay a platform for application of computational models to study biomechanical properties of the UA in the pathogenesis and treatment of OSA.     

Erythropoietin acutely decreases airway resistance in the rat

While some experimental data suggest that erythropoietin (EPO) influences respiratory mechanics, reports on scientific trials are lacking. In the present work, respiratory mechanics were measured using the end-inflation occlusion method in control and EPO treated anaesthetised and positive-pressure ventilated rats. Causing an abrupt inspiratory flow arrest, the end-inflation occlusion method makes it possible to measure the ohmic airway resistance and the respiratory system elastance. It was found that EPO induces a significant decrement in the ohmic airway resistance, not noted in control animals, 20 and 30min after intraperitoneal EPO injection. The elastic characteristics of the respiratory system did not vary. Hypotheses about the mechanism (s) explaining these results were addressed. In particular, additional experiments have indicated that the decrement in airway resistance could be related to an increase in nitric oxide production induced by EPO. Spontaneous increments in plasmatic erythropoietin levels, such as those that take place in association with hypoxia and/or blood loss, appear to be related to the decrement in airway resistance, allowing pulmonary ventilation to increase without altering respiratory mechanics leading to deleterious increments in energy dissipation during breathing.     

Stiffness of peripheral airway folding membrane in rabbits.

We have observed that small, membranous bronchioles from rabbits, in which the smooth muscle is not activated, experience a critical elastic buckling involving the whole airway wall during deflation of the lung. This implies that, at some point during the deflation, the airway wall goes from being in a state of tension to a state of compression. At the transition, there is neither net tension nor net compression in the wall, and the transmural pressure difference must, therefore, be zero. Thus at this point, the pressure difference across the muscle that results from the passive stress in the muscle is just balanced by the pressure difference across the folded mucosal membrane. We estimated the muscle stress, and hence the pressure across the muscle, from published data on rabbit trachealis (Opazo-Saez A and Paré PD, J Appl Physiol 77: 1638-1643, 1994) and equated this to the pressure across the folded membrane. By using a theoretical prediction of this pressure (Lambert RK, Codd SL, Alley MR, and Pack RJ, J Appl Physiol 77: 1206-1216, 1994), together with the results of our morphometric measurements on these airways, we estimated that the flexural rigidity of the folding membrane in peripheral rabbit airways is of the order of 10(-12) Pa x m3. This value implies that, in these airways, membrane folding provides significant resistance to airway smooth muscle shortening.     

Differences in airway structure in immature and mature rabbits.

Our laboratory has previously demonstrated that maximal bronchoconstriction produces a greater degree of airway narrowing in immature than in mature rabbit lungs (33). To determine whether these maturational differences could be related to airway structure, we compared the fraction of the airway wall occupied by airway smooth muscle (ASM) and cartilage, the proportion of wall area internal to ASM, and the number of alveolar attachments to the airways, from mature and immature (6-mo- and 4-wk-old, respectively) rabbit lungs that were formalin fixed at total lung capacity. The results demonstrate that the airway walls of immature rabbits had a greater percentage of smooth muscle, a lower percentage of cartilage, and fewer alveolar attachments compared with mature rabbit airways; however, we did not find maturational differences in the airway wall thickness relative to airway size. We conclude that structural differences in the airway wall may contribute to the greater airway narrowing observed in immature rabbits during bronchoconstriction.     

Zinc supplementation decreases the development of atherosclerosis in rabbits

Developing atherosclerotic plaques in cholesterol-fed rabbits are enriched in iron but depleted in zinc. In order to examine further the role of zinc, New Zealand White rabbits were fed a high-cholesterol 1% (w/w) diet with zinc (1 g/kg) supplementation for 8 weeks. After the 8-week period, the average atherosclerotic lesion cross-sectional areas in the aortas of the animals fed with the zinc supplement were significantly decreased (1.0 mm2) compared with lesion areas of the animals fed only on the high-cholesterol diet (3.1 mm2). Using nuclear microscopy, a technique for mapping and measuring trace elements in tissue sections, lesion zinc levels (24 ppm) were observed to be unchanged in the zinc-fed rabbits compared to controls. However, average lesion Fe levels in the zinc-fed group were measured at 32 ppm, whereas in the control group the average Fe levels were significantly higher at 43 ppm (P = 0.03). Our data support the concept that zinc may have an antiatherogenic effect by decreasing iron levels in the lesion, possibly leading to inhibition of iron-catalyzed free radical reactions.     

Low-volume ventilation causes peripheral airway injury and increased airway resistance in normal rabbits.

Lung mechanics and morphometry of 10 normal open-chest rabbits (group A), mechanically ventilated (MV) with physiological tidal volumes (8-12 ml/kg), at zero end-expiratory pressure (ZEEP), for 3-4 h, were compared with those of five rabbits (group B) after 3-4 h of MV with a positive end-expiratory pressure (PEEP) of 2.3 cmH(2)O. Relative to initial MV on PEEP, MV on ZEEP caused a progressive increase in quasi-static elastance (+36%) and airway (Rint; +71%) and viscoelastic resistance (+29%), with no change in the viscoelastic time constant. After restoration of PEEP, quasi-static elastance and viscoelastic resistance returned to control levels, whereas Rint remained elevated (+22%). On PEEP, MV had no effect on lung mechanics. Gas exchange on PEEP was equally preserved in groups A and B, and the lung wet-to-dry ratios were normal. Both groups had normal alveolar morphology, whereas only group A had injured respiratory and membranous bronchioles. In conclusion, prolonged MV on ZEEP induces histological evidence of peripheral airway injury with a concurrent increase in Rint, which persists after restoration of normal end-expiratory volumes. This is probably due to cyclic opening and closing of peripheral airways on ZEEP.     

Microcirculatory changes in the tissues surrounding a gunshot wound

An examination was carried out of microcirculation disorders as the main link of the pathogenetic process in the tissues surrounding a gunshot wound. Microcirculatory disorders were assessed in rabbits (924) with the help of radionuclide method (tissue radiometry and scannography) and the method of vital contact microscopy in gunshot wounds of posterior extremity soft tissues. After the injury the formation of four zones of tissue damage was revealed, with different character of microcirculatory changes in wound process dynamics. The obtained data may serve as the basis for working out zonal disorder classification and local treatment of gunshot wounds.