Pulmonary mechanics during the ventilatory response to hypoxemia in the newborn monkey

1983 ◽  
Vol 55 (3) ◽  
pp. 1008-1014 ◽  
Author(s):  
W. A. LaFramboise ◽  
R. D. Guthrie ◽  
T. A. Standaert ◽  
D. E. Woodrum

Dynamic lung compliance (CL), inspiratory pulmonary resistance (RL), and functional residual capacity (FRC) were measured in 10 unanesthetized 48 h-old newborn monkeys and seven 21-day-old infant monkeys during acute exposures to an equivalent level of hypoxemia. End-expiratory airway occlusions were performed and the pressure developed by 200 ms (P0.2) was utilized as an index of central respiratory drive. P0.2 demonstrated a sustained increase throughout the period of hypoxemia on day 2 despite the fact that minute ventilation (VI) initially increased but then fell back to base-line levels. Dynamic lung compliance fell and FRC increased by 5 min of hypoxemia in the newborns. The 21-day-old monkeys exhibited a sustained increase in both VI and P0.2 throughout the hypoxic period with no change in CL and FRC. RL did not change at either postnatal age during hypoxemia. These data indicate that the neonatal monkey is subject to changes in pulmonary mechanics (decreased CL and increased FRC) during hypoxemia and that these changes are eliminated with maturation.

1982 ◽  
Vol 53 (5) ◽  
pp. 1071-1079 ◽  
Author(s):  
W. J. Lamm ◽  
J. R. Hildebrandt ◽  
J. Hildebrandt ◽  
Y. L. Lai

Functional residual capacity (FRC), tidal volume (VT), and frequency (f) were compared in 23 rats while either awake and unrestrained or anesthetized. FRC was determined from gas compression with closed airway inside a cone-shaped body plethysmograph. In the awake state (mean +/- SD), FRC was 1.02 +/- 0.22 ml/100 g, VT was 0.38 +/- 0.06 ml/100 g, and f was 142 +/- 22 breaths/min. During anesthesia, FRC decreased (P less than 0.01) to 52.9% of awake values, VT increased (P less than 0.01) to 147.4%, and f decreased (P less than 0.01) to 71.8%, leaving minute ventilation almost unchanged. An additional seven rats were used to examine postural effects on FRC during anesthesia, and in another seven animals pleural pressure changes were monitored. Dynamic lung compliance (0.80 ml . kg-1 X cmH2O-1) was not altered by anesthesia, but the pressure-volume curve was shifted 6 cmH2O higher. Thoracic compression, followed by a time-dependent effect of volume history, may account for the major change in FRC. The remainder of the decrease in FRC may be due to lower breathing frequency, loss of inspiratory muscle activity, and/or less airway resistance after anesthesia. Peak diaphragmatic electromyogram per unit VT was shown to increase almost linearly with FRC, indicating that diaphragmatic efficiency was decreased as lung volume was elevated. Functional residual capacity (FRC), tidal volume (VT), and frequency (f) were compared in 23 rats while either awake and unrestrained or anesthetized. FRC was determined from gas compression with closed airway inside a cone-shaped body plethysmograph. In the awake state (mean +/- SD), FRC was 1.02 +/- 0.22 ml/100 g, VT was 0.38 +/- 0.06 ml/100 g, and f was 142 +/- 22 breaths/min. During anesthesia, FRC decreased (P less than 0.01) to 52.9% of awake values, VT increased (P less than 0.01) to 147.4%, and f decreased (P less than 0.01) to 71.8%, leaving minute ventilation almost unchanged. An additional seven rats were used to examine postural effects on FRC during anesthesia, and in another seven animals pleural pressure changes were monitored. Dynamic lung compliance (0.80 ml . kg-1 X cmH2O-1) was not altered by anesthesia, but the pressure-volume curve was shifted 6 cmH2O higher. Thoracic compression, followed by a time-dependent effect of volume history, may account for the major change in FRC. The remainder of the decrease in FRC may be due to lower breathing frequency, loss of inspiratory muscle activity, and/or less airway resistance after anesthesia. Peak diaphragmatic electromyogram per unit VT was shown to increase almost linearly with FRC, indicating that diaphragmatic efficiency was decreased as lung volume was elevated. Functional residual capacity (FRC), tidal volume (VT), and frequency (f) were compared in 23 rats while either awake and unrestrained or anesthetized. FRC was determined from gas compression with closed airway inside a cone-shaped body plethysmograph. In the awake state (mean +/- SD), FRC was 1.02 +/- 0.22 ml/100 g, VT was 0.38 +/- 0.06 ml/100 g, and f was 142 +/- 22 breaths/min. During anesthesia, FRC decreased (P less than 0.01) to 52.9% of awake values, VT increased (P less than 0.01) to 147.4%, and f decreased (P less than 0.01) to 71.8%, leaving minute ventilation almost unchanged. An additional seven rats were used to examine postural effects on FRC during anesthesia, and in another seven animals pleural pressure changes were monitored. Dynamic lung compliance (0.80 ml . kg-1 X cmH2O-1) was not altered by anesthesia, but the pressure-volume curve was shifted 6 cmH2O higher. Thoracic compression, followed by a time-dependent effect of volume history, may account for the major change in FRC. The remainder of the decrease in FRC may be due to lower breathing frequency, loss of inspiratory muscle activity, and/or less airway resistance after anesthesia. Peak diaphragmatic electromyogram per unit VT was shown to increase almost linearly with FRC, indicating that diaphragmatic efficiency was decreased as lung volume was elevated. Functional residual capacity (FRC), tidal volume (VT), and frequency (f) were compared in 23 rats while either awake and unrestrained or anesthetized. FRC was determined from gas compression with closed airway inside a cone-shaped body plethysmograph. In the awake state (mean +/- SD), FRC was 1.02 +/- 0.22 ml/100 g, VT was 0.38 +/- 0.06 ml/100 g, and f was 142 +/- 22 breaths/min. During anesthesia, FRC decreased (P less than 0.01) to 52.9% of awake values, VT increased (P less than 0.01) to 147.4%, and f decreased (P less than 0.01) to 71.8%, leaving minute ventilation almost unchanged. An additional seven rats were used to examine postural effects on FRC during anesthesia, and in another seven animals pleural pressure changes were monitored. Dynamic lung compliance (0.80 ml . kg-1 X cmH2O-1) was not altered by anesthesia, but the pressure-volume curve was shifted 6 cmH2O higher. Thoracic compression, followed by a time-dependent effect of volume history, may account for the major change in FRC. The remainder of the decrease in FRC may be due to lower breathing frequency, loss of inspiratory muscle activity, and/or less airway resistance after anesthesia. Peak diaphragmatic electromyogram per unit VT was shown to increase almost linearly with FRC, indicating that diaphragmatic efficiency was decreased as lung volume was elevated.


1982 ◽  
Vol 52 (4) ◽  
pp. 832-837 ◽  
Author(s):  
A. Vinegar ◽  
E. E. Sinnett ◽  
P. C. Kosch

The ferret, Mustela putorius furo, is a small relatively inexpensive carnivore with minimal housing requirements. Measurements were made from anesthetized tracheotomized supine males. Values obtained during tidal breathing for six animals (576 +/- 12 g) were as follows: tidal volume, 6.06 +/- 0.30 ml; respiratory frequency, 26.7 +/- 3.9 breaths min-1; dynamic lung compliance, 2.48 +/- 0.21 ml cmH2O-1; pulmonary resistance, 22.56 +/- 1.61 cmH2O . l–1 . s. Pressure-volume curves from nine ferrets revealed almost infinitely compliant chest walls so that lung and total respiratory system curves were essentially the same. Total lung capacity (TLC, 89 +/- 5 ml) and functional residual capacity (17.8 +/- 2.0 ml) were determined by gas freeing the lungs in vivo. The TLC of these ferrets is about the same as in 2.5-kg rabbits. Maximum expiratory flow-volume curves showed peak flows of 10.1 vital capacities (VC) . s-1 at 75% VC and flows of 8.4 and 5.4 VC . s-1 at 50 and 25% VC.


1978 ◽  
Vol 44 (3) ◽  
pp. 479-482 ◽  
Author(s):  
A. Wanner ◽  
M. E. Reinhart

Most currently used animal models of allergic airway diseases differ from human asthma in that induced bronchospasm in the former is not accompanied by pulmonary hyperinflation. In the present investigation, we chose unsedated, restrained sheep to determine the effect of cholinergic bronchial provocation on respiratory mechanics, functional residual capacity (FRC), and arterial blood gases. Seven animals had been actively sensitized by intramuscular injections of Ascaris suum extract, and four untreated animals served as controls. After inhalation of nebulized 1% methacholine solution, mean pulmonary resistance increased significantly in the sensitized sheep from a base line of 2.4 +/- 0.7 (SD) cmH2O/(l/s) to a peak value after 5 min of 7.9 +/- 4.0 cmH2O/(l/s). This was accompanied by a significant increase of mean FRC from 0.99 +/- 0.14 liters to 1.31 +/- 0.24 liters. The observed changes were transient, and after 60 min, pulmonary resistance and FRC had returned to base-line values. No significant changes occurred in static lung compliance, PaO2, PaCO2, and pH. In the control animals, methacholine provocation did not produce changes in pulmonary function. These results indicate that, in sensitized conscious sheep, induced bronchospasm is associated with pulmonary hyperinflation.


1981 ◽  
Vol 51 (5) ◽  
pp. 1169-1174 ◽  
Author(s):  
W. A. LaFramboise ◽  
T. A. Standaert ◽  
D. E. Woodrum ◽  
R. D. Guthrie

End-expiratory airway occlusions were performed in eight unanesthetized premature newborn monkeys during acute hypoxemia to investigate mechanisms involved in the newborn's biphasic ventilatory response to hypoxia. Two-day-old monkeys demonstrated an immediate increase in minute ventilation (VI) and a decrease in PaCO2 followed within 5 min by a return of VI and PaCO2 to base-line levels. The decline in VI was associated with a decrease in tidal volume (VT) and inspiratory flow (VT/TI) and an increase in respiratory frequency. Occlusion pressures (PO.2) remained elevated throughout the hypoxic stimulus, and end-expiratory lung volume increased during the late response. “Effective” impedance (P0.1/V0.1, P0.2/V0.2, etc.) and “effective” elastance (Pmax/VT) were also elevated. At 21 days of age, the monkeys demonstrated a sustained ventilatory response as VI, VT, VT/TI, and P0.2 remained elevated throughout the period of hypoxemia. End-expiratory lung volume increases as on day 2, but effective impedance and effective elastance did not change. These data suggest that the biphasic response to hypoxia in the newborn may result from a change in respiratory timing and an alteration in respiratory mechanics and is not due to a decrease in central respiratory drive.


1984 ◽  
Vol 57 (4) ◽  
pp. 1150-1157 ◽  
Author(s):  
R. H. Holle ◽  
R. B. Schoene ◽  
E. J. Pavlin

Mouth occlusion pressure 0.1 s after onset of inspiration (P0.1) reflects central respiratory drive (CRD), but its dependence on respiratory muscle strength is unknown. To clarify this relationship, we produced progressive levels of respiratory muscle weakness by infusion of d-tubocurarine in eight supine spontaneously breathing normal subjects. Hypercapnic ventilatory response (HCVR) was measured before curarization and at mild (mean inspiratory effort 62 +/- 3% of control), moderate (42 +/- 3%), and severe (23 +/- 1%) weakness. At the severe level of weakness 1) supine functional residual capacity was not significantly changed from base line, 2) the percent of base-line slope of delta P0.1/delta PCO2 (122 +/- 27%) was significantly greater (P less than 0.01) than that for change in expired minute ventilation (delta VE)/delta PCO2 (39 +/- 10%), 3) the percent of base-line delta P0.1/delta VE (381 +/- 46%) during HCVR was significantly increased (P less than 0.01), 4) the P0.1 response was significantly increased from base line at two out of three specific levels of PCO2 while the VE was unchanged or significantly decreased, and 5) peak inspiratory resistance did not significantly change. Thus P0.1, unlike VE, did not decrease with even severe respiratory muscle weakness. Indeed, P0.1 increased at two out of three levels of PCO2 under circumstances when higher CRD is expected. One potential explanation for the results is that P0.1 may at least qualitatively reflect CRD up to the level of severe respiratory muscle weakness attained in this study.


1986 ◽  
Vol 61 (1) ◽  
pp. 103-112 ◽  
Author(s):  
L. J. Jin ◽  
C. Lalonde ◽  
R. H. Demling

We studied whether changes in lung function after burns (1- to 12-h period) were due to changes in lung water or airways resistance and the relationship of the changes to prostanoid and O2 radical activity (measured as lipid peroxidation). Twenty-five anesthetized mechanically ventilated adult sheep were given a 40% of body surface scald burn and resuscitated to restore and maintain base-line filling pressures. Dynamic lung compliance (Cdyn) decreased by 40% from 38 +/- 5 to 24 +/- 4 ml/cmH2O at 12 h. Venous thromboxane B2 transiently increased from 210 +/- 40 to 1,100 +/- 210 pg/ml, and the value in lung lymph increased from 180 +/- 80 to 520 +/- 80 pg/ml. Prostacyclin levels in lung lymph and plasma remained at base line. Protein-poor lung lymph flow increased two- to threefold, but postmortem lung analysis revealed no increase in lung water from the control of 3.5 +/- 0.3 g H2O/g dry wt. No increase in protein permeability was seen. However, the lipid peroxidation of lung tissue measured as malondialdehyde was significantly increased from the control value of 56 +/- 4 nmol/g lung to a value of 69 +/- 6. Ibuprofen pretreatment (12.5 mg/kg) markedly attenuated the decrease in Cdyn, with the value at 12 h being 90% of base line. Ibuprofen also decreased the amount of lung lipid peroxidation but did not decrease the lung lymph response. We conclude that the decrease in Cdyn seen early postburn is not due to increased lung water, but, rather, is due to a mediator-induced bronchoconstriction, attenuated by ibuprofen; the mediator being either thromboxane or a byproduct of O2 radicals as evidenced by increased lipid peroxide production in lung tissue.


2001 ◽  
Vol 91 (5) ◽  
pp. 2301-2313 ◽  
Author(s):  
Salim Lalani ◽  
John E. Remmers ◽  
Francis H. Green ◽  
Ashfaq Bukhari ◽  
Gordon T. Ford ◽  
...  

Recently, Wong et al. (Wong KA, Bano A, Rigaux A, Wang B, Bharadwaj B, Schurch S, Green F, Remmers JE, and Hasan SU, J Appl Physiol 85: 849–859, 1998) demonstrated that fetal lambs that have undergone vagal denervation prenatally do not establish adequate alveolar ventilation shortly after birth. In their study, however, vagal denervation was performed prenatally and the deleterious effects of vagal denervation on breathing patterns and gas exchange could have resulted from the prenatal actions of the neurotomy. To quantify the relative roles of pre- vs. postnatal vagal denervation on control of breathing, we studied 14 newborn lambs; 6 were sham operated, and 8 were vagally denervated below the origin of the recurrent laryngeal nerve. Postoperatively, all denervated animals became hypoxemic and seven of eight succumbed to respiratory failure. In vagally denervated lambs, expiratory time increased, whereas respiratory rate, minute ventilation, and lung compliance decreased compared with the sham-operated animals. In the early postoperative period, the frequency of augmented breaths was lower but gradually increased over time in the denervated vs. sham-operated group. The dynamic functional residual capacity was significantly higher than the passive functional residual capacity among the sham-operated group compared with the denervated group. No significant differences were observed in the prevalence of various sleep states and in the amount of total phospholipids or large- and small-aggregate surfactants between the two groups. We provide new evidence indicating that intrauterine actions of denervation are not required to explain the effects of vagal denervation on postnatal survival. Our data suggest that vagal input is critical in the maintenance of normal breathing patterns, end-expiratory lung volume, and gas exchange during the early neonatal period.


1985 ◽  
Vol 58 (2) ◽  
pp. 528-533 ◽  
Author(s):  
J. P. Mortola ◽  
D. Magnante ◽  
M. Saetta

The passive mechanical time constant (tau pass) of the respiratory system is relatively similar among newborn mammalian species, approximately 0.15–0.2 s. However, breathing rate (f) is higher in smaller species than larger species in order to accommodate the relatively larger metabolic demands. Since tidal volume per kilogram is an interspecies constant, in the fastest breathing species the short expiratory time should determine a substantial dynamic elevation of the functional residual capacity (FRC). We examined the possibility of a difference in expiratory time constant between dynamic and passive conditions by analyzing the expiratory flow pattern of nine newborn unanesthetized species during resting breathing. In most newborns the late portion of the expiratory flow-volume curve was linear, suggesting muscle relaxation. The slope of the curve, which represents the dynamic expiratory time constant of the respiratory system (tau exp), varied considerably among animals (from 0.1 to 0.7 s), being directly related to the inspiratory time and inversely proportional to f. In relatively slow-breathing newborns, such as infants and piglets, tau exp is longer than tau pass most likely due to an increase in the expiratory laryngeal resistance and FRC is substantially elevated. On the contrary, in the fastest breathing newborns (such as rats and mice) tau exp is similar or even less than tau pass, because at these high rates dynamic lung compliance is lower than its passive value and the dynamic elevation of FRC is small. In dynamic conditions, therefore, the product of tau exp and f is maintained within narrow limits.


1979 ◽  
Vol 47 (2) ◽  
pp. 418-424 ◽  
Author(s):  
J. W. Ramsdell ◽  
P. F. Georghiou

We studied the effect of prolonged airways obstruction induced by extended cholinergic stimulation in five anesthetized, mechanically ventilated dogs. A continuous intravenous metacholine infusion was utilized to maintain pulmonary resistance (RL) at 200--1500% preinfusion levels for 13--23 h. At maximum RL (18.86 +/- 7.74 vs. 2.09 +/- 0.18 (mean +/- SD) cmH2O/ (L/S) PREINfusion; P less than 0.01), dynamic lung compliance (Cdyn) fell from 67.5 +/- 14.6 to 32.7 +/- 11.6 ml/cmH2O (P less than 0.005) and arterial partial pressure of oxygen (PaO2) fell modestly from 95.8 +/- 6.1 Torr preinfusion to 83.2 +/- 12.7 Torr (P less than 0.05). Tachyphylaxis to methacholine developed, requiring increases in infusion rates to maintain elevated RL. Abnormalities in lung function resolved promptly upon termination of the infusion. Two similarly instrumented control animals ventilated for 19 and 25 h without metacholine infusion had no change in RL, Cdyn, or PaO2. Histological examination of the lungs revealed no differences between infused and control animals. In spite of marked increases in RL, prolonged cholinergic stimulation produced only mild changes in gas exchange and no sustained changes in lung function or structure.


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