A Novel Model of Selective Lung Ventilation to Investigate the Long-Term Effects of Ventilation-Induced Lung Injury

In this study, we aim to quantify the differences in lung metrics measured in free‐breathing and mechanically ventilated rodents using respiratory‐gated micro‐computed tomography. Healthy male Sprague‐Dawley rats were anesthetized with ketamine/xylazine and scanned with a retrospective respiratory gating protocol on a GE Locus Ultra micro‐CT scanner. Each animal was scanned while free‐breathing, then intubated and mechanically ventilated (MV) and rescanned with a standard ventilation protocol (56 bpm, 8 mL/kg and PEEP of 5 cm H2O) and again with a ventilation protocol that approximates the free‐breathing parameters (88 bpm, 2.14 mL/kg and PEEP of 2.5 cm H2O). Images were reconstructed representing inspiration and end expiration with 0.15 mm voxel spacing. Image‐based measurements of the lung lengths, airway diameters, lung volume, and air content were compared and used to calculate the functional residual capacity (FRC) and tidal volume. Images acquired during MV appeared darker in the airspaces and the airways appeared larger. Image‐based measurements showed an increase in lung volume and air content during standard MV, for both respiratory phases, compared with matched MV and free‐breathing. Comparisons of the functional metrics showed an increase in FRC for mechanically ventilated rats, but only the standard MV exhibited a significantly higher tidal volume than free‐breathing or matched MV. Although standard mechanical ventilation protocols may be useful in promoting consistent respiratory patterns, the amount of air in the lungs is higher than in free‐breathing animals. Matching the respiratory patterns with the free‐breathing case allowed similar lung morphology and physiology measurements while reducing the variability in the measurements.

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“…; Schreiber et al. ) to overdistension or collapse of airways (Bailey et al. ; Vazquez de Anda et al.…”

Section: Introductionmentioning

confidence: 99%

A respiratory‐gated micro‐CT comparison of respiratory patterns in free‐breathing and mechanically ventilated rats

Ford

McCaig

Jeklin

et al. 2017

Physiological Reports

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“…One method to build right-OLV is deeply intubating the tracheal tube into the right main bronchus (13). In the present study, the right main bronchus of rabbit (~0.5 cm long) was found to be markedly shorter than the left main bronchus.…”

Section: Discussionmentioning

confidence: 44%

“…Several different methods are used to build in vivo right-OLV model in rabbits, including deeply intubating the endotracheal tube into the right main bronchus (13), clamping the left main bronchus with a clip (14) and other methods, such as inserting an artificial double-lumen endotracheal tube (DLT) into the trachea, and inserting a bronchial blocker through the ventilation tube into the left primary bronchus (6,15). However, these methods each have disadvantages.…”

Section: Introductionmentioning

confidence: 99%

A novel method for right one-lung ventilation modeling in rabbits

Bian

et al. 2016

Experimental and Therapeutic Medicine

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There is no standard method by which to establish a right one-lung ventilation (OLV) model in rabbits. In the present study, a novel method is proposed to compare with two other methods. After 0.5 h of baseline two-lung ventilation (TLV), 40 rabbits were randomly divided into sham group (TLV for 3 h as a contrast) and three right-OLV groups (right OLV for 3 h with different methods): Deep intubation group, clamp group and blocker group (deeply intubate the self-made bronchial blocker into the left main bronchus, the novel method). These three methods were compared using a number of variables: Circulation by heart rate (HR), mean arterial pressure (MAP); oxygenation by arterial blood gas analysis; airway pressure; lung injury by histopathology; and time, blood loss, success rate of modeling. Following OLV, compared with the sham group, arterial partial pressure of oxygen and arterial hemoglobin oxygen saturation decreased, peak pressure increased and lung injury scores were higher in three OLV groups at 3 h of OLV. All these indexes showed no differences between the three OLV groups. During right-OLV modeling, less time was spent in the blocker group (6±2 min), compared with the other two OLV groups (13±4 min in deep intubation group, P<0.05; 33±9 min in clamp group, P<0.001); more blood loss was observed in clamp group (11.7±2.8 ml), compared with the other two OLV groups (2.3±0.5 ml in deep intubation group, P<0.001; 2.1±0.6 ml in blocker group, P<0.001). The first-time and final success rate of modeling showed no differences among the three OLV groups. Deep intubation of the self-made bronchial blocker into the left main bronchus is an easy, effective and reliable method to establish a right-OLV model in rabbits.

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“…Human lung development is a complex process, which is characterized by five stages of development based on histological appearance, including embryonic, pseudoglandular, canalicular, saccular and alveolar stages (9). Premature infants delivered at 26-36 weeks of gestation are born in the saccular phase of lung development and are particularly susceptible to BPD.…”

Section: Discussionmentioning

confidence: 99%

Theophylline improves lipopolysaccharide-induced alveolarization arrest through inflammatory regulation

Chen

et al. 2014

Molecular Medicine Reports

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Bronchopulmonary dysplasia (BPD) is characterized by alveolar simplification with decreased numbers of alveoli and increased airspace. BPD, frequently suffered by very low birth weight infants, has been closely associated with intrauterine infection. However, the underlying mechanisms of BPD remain unclear. In the present study, it was identified that administration of intra-amniotic lipopolysaccharide (LPS) to pregnant rats on embryonal day 16.5 (E16.5) induced significant alveolarization arrest similar to that of BPD in neonatal pups, and theophylline injected subcutaneously into the newborns improved the pathological changes. To further investigate the underlying mechanism of the morphogenesis amelioration of theophylline, cytokine antibody arrays were performed with the lung lysates of neonatal rats. The results indicated that LPS upregulated a series of pro-inflammatory cytokines and theophylline significantly attenuated the expression levels of pro-inflammatory cytokines tumor necrosis factor‑α, macrophage inflammatory protein (MIP)-1α and MIP-2, and markedly elevated the production of tumor growth factor (TGF)-β family members TGF-β1, TGF-β2 and TGF-β3, which are anti‑inflammatory cytokines. Accordingly, it was hypothesized that theophylline may protect against BPD and improve chorioamnionitis‑induced alveolar arrest by regulating the balance between pro‑and anti-inflammatory cytokine expression.

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A Novel Model of Selective Lung Ventilation to Investigate the Long-Term Effects of Ventilation-Induced Lung Injury

Cited by 8 publications

References 16 publications

A respiratory‐gated micro‐CT comparison of respiratory patterns in free‐breathing and mechanically ventilated rats

A respiratory‐gated micro‐CT comparison of respiratory patterns in free‐breathing and mechanically ventilated rats

A novel method for right one-lung ventilation modeling in rabbits

Theophylline improves lipopolysaccharide-induced alveolarization arrest through inflammatory regulation

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