Repeated endo-tracheal tube disconnection generates pulmonary edema in a model of volume overload: an experimental study.

BACKGROUND: An abrupt lung deflation in rodents results in lung injury through vascular mechanisms. Ventilator disconnections during endo-tracheal suctioning in humans often cause cardio-respiratory instability. Whether repeated disconnections or lung deflations cause lung injury or oedema is not known and was tested here in a porcine large animal model. METHODS: Yorkshire pigs (~ 12 weeks) were studied in three series. First, we compared PEEP abruptly deflated from 26 cmH2O or from PEEP 5 cmH2O to zero. Second, pigs were randomly crossed over to receive rapid versus gradual PEEP removal from 20 cmH2O. Third, pigs with relative volume overload, were ventilated with PEEP 15 cmH2O and randomized to repeated ETT disconnections (15 s every 15 min) or no disconnection for 3 h. Hemodynamics, pulmonary variables were monitored, and lung histology and bronchoalveolar lavage studied. RESULTS: As compared to PEEP 5 cmH2O, abrupt deflation from PEEP 26 cmH2O increased PVR, lowered oxygenation, and increased lung wet-to-dry ratio. From PEEP 20 cmH2O, gradual versus abrupt deflation mitigated the changes in oxygenation and vascular resistance. From PEEP 15, repeated disconnections in presence of fluid loading led to reduced compliance, lower oxygenation, higher pulmonary artery pressure, higher lung wet-to-dry ratio, higher lung injury score and increased oedema on morphometry, compared to no disconnects. CONCLUSION: Single abrupt deflation from high PEEP, and repeated short deflations from moderate PEEP cause pulmonary oedema, impaired oxygenation, and increased PVR, in this large animal model, thus replicating our previous finding from rodents. Rapid deflation may thus be a clinically relevant cause of impaired lung function, which may be attenuated by gradual pressure release.

Hyperpolarized 129Xe magnetic resonance spectroscopy in a rat model of bronchopulmonary dysplasia.

Premature infants often require mechanical ventilation and oxygen therapy, which can result in bronchopulmonary dysplasia (BPD), characterized by developmental arrest and impaired lung function. Conventional clinical methods for assessing the prenatal lung are not adequate for the detection and assessment of long-term health risks in infants with BPD, highlighting the need for a noninvasive tool for the characterization of lung microstructure and function. Theoretical diffusion models, like the model of xenon exchange (MOXE), interrogate alveolar gas exchange by predicting the uptake of inert hyperpolarized (HP) 129Xe gas measured with HP 129Xe magnetic resonance spectroscopy (MRS). To investigate HP 129Xe MRS as a tool for noninvasive characterization of pulmonary microstructural and functional changes in vivo, HP 129Xe gas exchange data were acquired in an oxygen exposure rat model of BPD that recapitulates the fewer and larger distal airways and pulmonary vascular stunting characteristics of BPD. Gas exchange parameters from MOXE, including airspace mean chord length (Lm), apparent hematocrit in the pulmonary capillaries (HCT), and pulmonary capillary transit time (tx), were compared with airspace mean axis length and area density (MAL and ρA) and percentage area of tissue and air (PTA and PAA) from histology. Lm was significantly larger in the exposed rats (P = 0.003) and correlated with MAL, ρA, PTA, and PAA (0.59<|ρ|<0.66 and P < 0.05). Observed increase in HCT (P = 0.012) and changes in tx are also discussed. These findings support the use of HP 129Xe MRS for detecting fewer, enlarged distal airways in this rat model of BPD, and potentially in humans.

Effect of inhaled oxygen concentration on 129 Xe chemical shift of red blood cells in rat lungs.

PURPOSE: To investigate the dependence of dissolved 129 Xe chemical shift on the fraction of inhaled oxygen, Fi O2 , in the lungs of healthy rats. METHODS: The chemical shifts of 129 Xe dissolved in red blood cells, δRBC , and blood plasma and/or tissue, δPlasma , were measured using MRS in 12 Sprague Dawley rats mechanically ventilated at Fi O2 values of 0.14, 0.19, and 0.22. Regional effects on the chemical shifts were controlled using a chemical shift saturation recovery sequence with a fixed delay time. MRS was also performed at an Fi CO2 value of 0.085 to investigate the potential effect of the vascular response on δRBC and δPlasma . RESULTS: δRBC increased with decreasing Fi O2 (P = .0002), and δPlasma showed no dependence on Fi O2 (P = .23). δRBC at Fi CO2 = 0 (210.7 ppm ± 0.1) and at Fi CO2 = 0.085 (210.6 ppm ± 0.2) were not significantly different (P = .67). δPlasma at Fi CO2 = 0 (196.9 ppm ± 0.3) and at Fi CO2 = 0.085 (197.0 ppm ± 0.1) were also not significantly different (P = .81). CONCLUSION: Rat lung δRBC showed an inverse relationship to Fi O2 , opposite to the relationship previously demonstrated for in vitro human blood. Rat lung δRBC did not depend on Fi CO2 .