Alveolar Overdistension as a Cause of Lung Injury: Differences among Three Animal Species

García-Delgado, Manuel; Navarrete-Sánchez, I.; Chamorro-Marín, Virginia; Díaz-Monrové, Juan Carlos; Esquivias, Javier; Mondéjar, E. Fernández

doi:10.1100/2012/985923

Cited by 9 publications

(9 citation statements)

References 17 publications

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“…As depicted in Figure 1, rabbits were allowed to free-breathe from a chamber filled with O 2 , or O 2 containing HDI vapor for 60 minutes. Given the observed respiration rate (12–20 breaths per/minute) during the exposure period and the average rabbit tidal volume (10 mL/kg) (Garcia-Delgado et al, 2012), the total HDI vapor exposure dose was estimated to be ~30–50 µg. Immediately following exposure, the airways were lavaged through the endotracheal tube.…”

Section: Resultsmentioning

confidence: 99%

Reaction products of hexamethylene diisocyanate vapors with “self” molecules in the airways of rabbits exposed via tracheostomy

et al. 2017

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Hexamethylenediisocyanate (HDI) is a widely used aliphatic diisocyanate and a well-recognized cause of occupational asthma.“Self” molecules (peptides/proteins) in the lower airways, susceptible to chemical reactivity with HDI, have been hypothesized to play a role in asthma pathogenesis and/or chemical metabolism, but remain poorly characterized.This study employed unique approaches to identify and characterize “self” targets of HDI reactivity in the lower airways. Anesthetized rabbits free breathed through a tracheostomy tube connected to chambers containing either, O2, or O2 plus ~200 ppb HDI vapors. Following 60 minutes of exposure, the airways were lavaged and the fluid was analyzed by LC-MS and LC-MS/MS.The low-molecular weight (<3 kDa) fraction of HDI exposed, but not control rabbit bronchoalveolar lavage (BAL) fluid identified 783.26 and 476.18 m/z [M+H]+ ions with high energy collision-induced dissociation (HCD) fragmentation patterns consistent with bis glutathione (GSH)-HDI and mono(GSH)-HDI. Proteomic analyses of the high molecular weight (>3 kDa) fraction of exposed rabbit BAL fluid identified HDI modification of specific lysines in uteroglobin (aka clara cell protein) and albumin.In summary, this study utilized a unique approach to chemical vapor exposure in rabbits, to identify HDI reaction products with “self” molecules in the lower airways.

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Section: Resultsmentioning

confidence: 99%

Reaction products of hexamethylene diisocyanate vapors with “self” molecules in the airways of rabbits exposed via tracheostomy

et al. 2017

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“…Higher RRs should also be examined. Furthermore, the TV in rabbits in CMV is considered to be 8-10 mL/kg, 42,43 therefore, the TV of the CMV group was set to 8 mL/kg in this study. The preliminary study indicated that efficiency of CO 2 elimination could be better with the MBV rather than the CMV method.…”

Section: Discussionmentioning

confidence: 99%

Marathoners’ Breathing Pattern Protects Against Lung Injury by Mechanical Ventilation: An Ex Vivo Study Using Rabbit Lungs

et al. 2020

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Background Breathing during a marathon is often empirically conducted in a so-called "2:2 breathing rhythm," which is based on a four-phase cycle, consisting of the 1st and 2nd inspiratory and the 1st and 2nd expiratory phases. We developed a prototype ventilator that can perform intermittent positive pressure ventilation, mimicking the breathing cycle of the 2:2 breathing rhythm. This mode of ventilation was named the marathoners' breathing rhythm ventilation (MBV). We hypothesized that MBV may have a lung protective effect. Methods We examined the effects of the MBV on the pulmonary pre-edema model in isolated perfused rabbit lungs. The pulmonary pre-edema state was induced using bloodless perfusate with low colloid osmotic pressure. The 14 isolated rabbit lung preparations were randomly divided into the conventional mechanical ventilation (CMV) group and MBV group, (both had an inspiratory/expiratory ratio of 1/1). In the CMV group, seven rabbit lungs were ventilated using the Harvard Ventilator 683 with a tidal volume (TV) of 8 mL/kg, a respiratory rate (RR) of 30 cycles/min, and a positive end-expiratory pressure (PEEP) of 2 cmH 2 O for 60 min. In the MBV group, seven rabbit lungs were ventilated using the prototype ventilator with a TV of 6 mL/kg, an RR of 30 cycles/min, and a PEEP of 4 cmH 2 O (first step) and 2 cmH 2 O (second step) for 60 min. The time allocation of the MBV for one cycle was 0.3 s for each of the 1st and 2nd inspiratory and expiratory phases with 0.2 s of intermittent resting between each phase. Results Peak airway pressure and lung wet-to-dry ratio after 60 min of ventilation were lower in the MBV group than in the CMV group. Conclusion MBV was considered to have a lungprotective effect compared to CMV.

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“…However, emphysema is rarely noted in younger rabbits. Although rabbits are reported to be highly sensitive to overdistension of alveoli during ventilation, 17 we excluded barotrauma as the cause of the lesions observed. Only the RSI:NZW rabbits with iatrogenic carotid aneurysm were anesthetized using positive pressure ventilation and only during the initial creation of aneurysm (occurring from 3.9 to 6.4 years prior to necropsy); all subsequent anesthetic events for imaging and gamma knife treatment used injectable agents only, with no intubation or ventilation.…”

Section: Discussionmentioning

confidence: 99%

Spontaneous Lung Lesions in Aging Laboratory Rabbits (Oryctolagus cuniculus)

et al. 2016

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Spontaneous age-related lesions of laboratory rabbits are not well documented in the contemporary scientific literature. A retrospective study of diagnostic necropsies of 36 rabbits >2 years of age found a number of common lung lesions. Fibromuscular intimal hyperplasia affected medium and to a lesser extent large pulmonary arteries and was present to a variable extent in all 36 rabbits >2 years of age. The lesions were characterized by fragmentation and/or reduplication of the internal elastic lamina (IEL), proliferation of smoothelinþ/alpha-smooth muscle actin (a-SMA)þ/vimentinÀ smooth muscle cells and fewer smoothelinÀ/a-SMAþ/vimentinþ myofibroblasts, and intimal deposition of collagen without thrombosis, embolism, or evidence of pulmonary hypertension. Pulmonary emphysema, present in 30/36 rabbits, was characterized by the loss of alveolar septa; most affected rabbits did not have clinical signs of respiratory disease. In 8/13 rabbits of the inbred EIII/JC audiogenic strain, we identified a unique syndrome of granulomatous pneumonia containing hyaline brown to gray, globular to ring-like acellular material that was Alcian blue and periodic acid-Schiff positive. The material was immunoreactive for surfactant protein-A and had the ultrastructural appearance of multilamellar vesicles, suggesting a genetic defect in surfactant metabolism. Additionally, we found small benign primary lung tumors (fibropapillomas, 5 rabbits) not previously described. Other findings included heterotopic bone (5 rabbits), subacute to chronic suppurative bronchopneumonia, pyogranulomatous pneumonia with plant material, and pulmonary artifacts from barbiturate euthanasia solution.Although spontaneous background lesions of aging laboratory mice and rats are well documented and described, 7,9,19,23,31 there is less information on spontaneous lesions of aging laboratory rabbits. 14,15,21 In part this is because of the types of acute or relatively short-term studies for which rabbits are commonly used. In some cases where age-related lesions are described, such as spontaneous pulmonary emphysema, 42 other more recent references are contradictory, based apparently on the lack of additional confirmatory reporting. 4,8 Other spontaneous age-related lesions, such as unique intimal proliferations in the pulmonary arteries, are poorly documented in the English language literature, 20 and can resemble iatrogenic lesions caused by experimental manipulation. 27 While most rabbits used in research are outbred New Zealand White (NZW) or Dutch-belted stock, inbred rabbits strains do exist, including the audiogenic (EIII/JC) strain. The inbred III/J parent rabbit strain was originally developed at the Jackson Laboratory in 1932 by Dr Paul B. Sawin using NZW rabbits from Dr William Ernest Castle. The audiogenic (EIII/J) substrain was selected for a predisposition to sound-induced seizures by Dr Richard R. Fox in 1961. 13 The strain came to Penn State Hershey in 1988 from the National Cancer Institute. 37 Rabbits have been used as an induced experimental...

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Alveolar Overdistension as a Cause of Lung Injury: Differences among Three Animal Species

Cited by 9 publications

References 17 publications

Reaction products of hexamethylene diisocyanate vapors with “self” molecules in the airways of rabbits exposed via tracheostomy

Reaction products of hexamethylene diisocyanate vapors with “self” molecules in the airways of rabbits exposed via tracheostomy

Marathoners’ Breathing Pattern Protects Against Lung Injury by Mechanical Ventilation: An Ex Vivo Study Using Rabbit Lungs

Spontaneous Lung Lesions in Aging Laboratory Rabbits (Oryctolagus cuniculus)

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