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Biomedical subjects

Peter D Sly

Publications and source records attributed to Peter D Sly.

59 records · Page 4Linked to original sources
PubMed2002

Deficiency of SP-B reveals protective role of SP-C during oxygen lung injury.

Although the surface properties of surfactant protein (SP)-B and SP-C are similar, the contributions that either protein may make to lung function have not been identified in vivo. Mutations in SP-B cause lethal respiratory failure at birth; however, SP-B null mice are deficient in both SP-B and SP-C. To identify potential contributions of SP-C to lung function in vivo, the following transgenic mice were generated and exposed to 95% O(2) for 3 days: (SP-B(+/+),SP-C(+/+)), (SP-B(+/+), SP-C(-/-)), (SP-B(+/-),SP-C(+/+)), (SP-B(+/-),SP-C(+/-)), and (SP-B(+/-),SP-C(-/-)). Hyperoxia altered pressure-volume curves in mice that were heterozygous for SP-B, and these values were further decreased in (SP-B(+/-),SP-C(-/-)) mice. Likewise, alveolar interleukin (IL)-6 and IL-1 beta were maximally increased by O(2) exposure of (SP-B(+/-),SP-C(-/-)) mice compared with the other genotypes. Lung hysteresivity was lower in the (SP-B(+/-),SP-C(-/-)) mice. Surfactant isolated from (SP-B(+/+),SP-C(-/-)) and (SP-B(+/-),SP-C(-/-)) mice failed to stabilize the surface tension of microbubbles, showing that SP-C plays a role in stabilization or recruitment of phospholipid films at low bubble radius. Genetically decreased levels of SP-B combined with superimposed O(2)-induced injury reveals the distinct contribution of SP-C to pulmonary function in vivo.

Animals↗
PubMed2002

Postnatal alveolar development of the rabbit.

Previous studies of alveolarization have used rats or lambs; however, neither closely reflects human alveolar development. We characterized alveolar development in rabbits (n = 3-7 /group) at 28 days gestation (dg) to 9 mo to determine whether they followed the human pattern more closely. The right lung was made up of 30% alveolar and 50% duct space at 28 dg to 3 days and of 50 and 30%, respectively, at 14 days to 9 mo. Tissue fraction and alveolar wall thickness decreased by 40% 28 dg to birth. At birth, approximately 4.5% of the number of alveoli seen at 9 mo were present, with alveolar number increasing progressively well into adulthood. The rate of alveolar formation was high around birth, decreasing progressively with age. Alveolar volume increased more than twofold (28 dg to birth) and continued to increase postnatally to 16 wk. Surface fraction decreased by 17% (28 dg to 3 days), after which it remained uniform. Our findings suggest that the timing of onset of alveolarization in humans and rabbits is similar and that rabbits may be used to model postnatal influences on alveolar development.

Age Factors↗
PubMed2002

Modification of acute and late-phase allergic responses to ovalbumin with lipopolysaccharide.

BACKGROUND: We have previously shown that lipopolysaccharide (LPS) exposure in sensitised animals 18 h after ovalbumin (OVA) challenge inhibits OVA-induced airway hyper-responsiveness (AHR). In the present study, we investigated the effect of LPS on OVA-induced acute and late-phase allergic responses in sensitised rats when challenged with OVA. METHODS: Rats were sensitised with OVA and 11 days later challenged with 1% OVA in the presence or absence of LPS (0.5-50 microg/ml) given in the same nebulizer. Acute responses to OVA were measured each minute for 30 min after challenge. In a separate group of animals, late-phase responses to OVA were determined at 24 h. At the end of each study, Evans blue dye was injected and animals sacrificed 30 min later. Bronchoalveolar lavage was obtained to monitor inflammatory cell migration and microvascular leakage. RESULTS: OVA challenge in sensitised animals produced an acute response with changes in lung mechanics peaking 10.0 +/- 0.9 min after OVA and returning to baseline within 30 min. This was followed 24 h later by increased responses to methacholine chloride (MCh), inflammatory cell influx and increased Evans blue leakage into the lungs. Presence of 5 or 50 microg/ml LPS in the nebulizer during OVA challenge altered the kinetics of the acute-phase response, with an immediate decrease in lung function (time to peak decreased from 10.3 +/- 1.2 to 1.8 +/- 0.2 and 2.2 +/- 0.3 min, respectively: p < 0.001, n = 6) and a dose-dependent attenuation of late-phase AHR, cellular influx (n = 5, p < 0.001) and Evans blue leakage (n = 5, p < 0.001) at 24 h. CONCLUSIONS: In summary, co-administration of OVA with LPS modifies both the acute and late-phase responses to the allergen, inducing an earlier acute change in lung function and a dose-dependent inhibition of late-phase responses to the allergen.

Acute-Phase Reaction↗
PubMed2002

Dependence of intrapulmonary pressure amplitudes on respiratory mechanics during high-frequency oscillatory ventilation in preterm lambs.

In the healthy animal lung, high-frequency oscillatory ventilation (HFOV) achieves effective ventilation at tidal volumes (V(T)) less than or equal to dead space while generating very small pressure fluctuations in the alveolar spaces (deltaP(A)). We hypothesized that the respiratory mechanical parameters influence the magnitude of the intrapulmonary pressure fluctuations during HFOV. A computer model of the neonatal respiratory system was used to examine the independent effects of altering the compliance, nonlinear and linear resistance, and inertance of the respiratory system on V(T), and cyclic intrapulmonary pressures under homogeneous and heterogeneous conditions. The impact of low compliance on the transmission of pressure from the airway opening to the trachea (deltaP(tr)/deltaP(ao)) and alveolar compartment (deltaP(A)/deltaP(ao)) during HFOV was determined in a preterm lamb lung model. In the computer model, an increase in flow-dependent resistance to simulate changing the internal diameter of the tracheal tube from 4.0 mm to 2.5 mm halved the transmission of the pressure waveform to both the carina and the alveolar compartment. Increased peripheral resistance was associated with an increased deltaP(tr)/deltaP(ao) but a reduction in deltaP(A)/deltaP(ao). The deltaP(A)/deltaP(ao) also decreased with increasing alveolar compartment compliance, a finding that was verified in the preterm lamb lung. There was an exponential decrease in the magnitude of deltaP(A1) compared with deltaP(A2) as the ratio of the time constants of the two parallel compartments (tau(1)/tau(2)) increased in the heterogeneous computer lung model. The transmission of driving pressure amplitude to both the proximal airways and lung tissue during HFOV is dependent on lung mechanics and may be greater in the poorly compliant lung than that observed previously in experiments on healthy animals.

Animals↗