Establishment and Evaluation of Rabbit Model of Ventilator-Induced Lung Injury_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

AN Li , ZHOU Meiling , QIN Xuebing , LIU Qinghui , LIU Changting , YU Senyang

Department of Respiratory Medicine,General Hospital of PLA. Beijing, 100853, ChinaCorresponding Author: YUSen-yang, E-mail: senyangyu@ sina. com;

Corresponding author：

Keywords：

Ventilator-induced lung injury; Mechanical ventilation; Animal model; Rabbit

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Objective To establish a rabbit model of ventilator-induced lung injury. Methods Fourty healthy New Zealand rabbits were randomly divided into 3 groups: ie. a routine 8 mL/kg tidal volume group( VT8 group) , 25 mL/kg large tidal volume group( VT25 group) , and 40 mL/kg large tidal volume group( VT40 group) . VT25 and VT40 group were further divided into 2 hours and 4 hours ventilation subgroups. Arterial blood gas, lung mechanical force and hemodynamic parameters were monitored. Lung
tissue was sampled for evaluate lung wet/dry ratio and lung injury by HE stain. Bronchoalveolar lavage fluid ( BALF) was collected for measurement of protein concentration, total and differential cell counts. Results Compared with VT8 group, lung injury score in both VT40 and VT25 groups were elevated significantly, of
which 4 hour VT40 subgroup was the highest. Lung pathology examination of VT40 group revealed apparent alveolar deformation, interstitial and alveolar space exudation, inflammatory cells infiltration, pulmonary consolidation and alveolar hemorrhage. Lung pathology examination of VT25 group showed pulmonary interval
thickening, inflammatory cells infiltration, while alveolar intravasation was mild. Blood gas analysis showed that PaO2 /FiO2 was deteriorated with time in VT25 and VT40 groups, and PaO2 /FiO2 at the 3 hours in VT40 group( lt; 300 mm Hg) had met the acute lung injury standard, while which in VVT25 group was above 300 mmHg. Lung wet/dry ratio, BALF protein concentration, total nucleated cell and neutrophilic leukocyte were elevated in both VT25 and VT40 groups, of which 4 hours VT40 group was the highest. Conclusion Using 4 hours ventilation at a tidal volume of 40 mL/kg can successfully establish the rabbit model of ventilator-induced lung injury.

Citation： AN Li,ZHOU Meiling,QIN Xuebing,LIU Qinghui,LIU Changting,YU Senyang. Establishment and Evaluation of Rabbit Model of Ventilator-Induced Lung Injury. Chinese Journal of Respiratory and Critical Care Medicine, 2010, 9(2): 163-167. doi: Copy

1.	Torsten C, Schreiber MD, Walter A, et al. Lung injury caused by mechanical ventilation. Contem Crit Care, 2005, 3: 1 -12 .
2.	Sinclair SE, Altemeier WA, Matute-Bello G, et al. Augmented lung injury due to interaction between hyperoxia and mechanical ventilation. Crit Care Med, 2004 , 32 : 2496-2501.
3.	Sinclair SE, Kregenow DA, Lamm WJ, et al. Hypercapnic acidosis is protective in an in vivo model of ventilator-induced lung injury. Am J Respir Crit Care Med, 2002 , 166: 403-408.
4.	Wilson MR, Choudhury S, Goddard ME, et al. High tidal volume upregulates intrapulmonary cytokines in an in vivo mouse model of ventilator-induced lung injury. J Appl Physiol, 2003 , 95 : 1385 -1393.
5.	Verbrugge SJ, Uhlig S, Neggers SJ, et al. Different ventilation strategies affect lung function but do not increase tumor necrosis factor-alpha and prostacyclin production in lavaged rat lungs in vivo. Anesthesiology, 1999, 91 : 1834-1843.
6.	Chiumello D, Pristine G, Slutsky AS. Mechanical ventilation affects local and systemic cytokines in an animal model of acute respiratory distress syndrome. Am J Respir Crit Care Med, 1999, 160: 109-116 .
7.	DiRocco JD, Pavone LA, Carney DE, et al. Dynamic alveolar mechanics in four models of lung injury. Intensive Care Med, 2006 ,32: 140-148 .
8.	Altemeier WA, Matute-Bello G, Frevert CW, et al. Mechanical ventilation with moderate tidal volumes synergistically increases lung cytokine response to systemic endotoxin. Am J Physiol Lung Cell Mol Physiol, 2004, 287 : L533-L542.
9.	Walder B, Fontao E, Totsch M, et al. Time and tidal volumedependent ventilator-induced lung injury in healthy rats. Eur J Anaesthesiol, 2005, 22: 785 -794.
10.	Egan EA, Nelson RM, Olver RE. Lung inflation and alveolar permeability to non-electrolytes in the adult sheep in vivo. J Physiol, 1976 , 260: 409-424.
11.	Parker JC, Townsley MI, Rippe B, et al. Increased microvascular permeability in dog lungs due to high peak airway pressures. JAppl Physiol, 1984 , 57: 1809-1816.
12.	Dreyfuss D, Ricard JD, Saumon G. On the physiologic and clinical relevance of lung-borne cytokines during ventilator-induced lung injury. Am J Respir Crit Care Med, 2003 , 167: 1467-1471.

1. Torsten C, Schreiber MD, Walter A, et al. Lung injury caused by mechanical ventilation. Contem Crit Care, 2005, 3: 1 -12 .
2. Sinclair SE, Altemeier WA, Matute-Bello G, et al. Augmented lung injury due to interaction between hyperoxia and mechanical ventilation. Crit Care Med, 2004 , 32 : 2496-2501.
3. Sinclair SE, Kregenow DA, Lamm WJ, et al. Hypercapnic acidosis is protective in an in vivo model of ventilator-induced lung injury. Am J Respir Crit Care Med, 2002 , 166: 403-408.
4. Wilson MR, Choudhury S, Goddard ME, et al. High tidal volume upregulates intrapulmonary cytokines in an in vivo mouse model of ventilator-induced lung injury. J Appl Physiol, 2003 , 95 : 1385 -1393.
5. Verbrugge SJ, Uhlig S, Neggers SJ, et al. Different ventilation strategies affect lung function but do not increase tumor necrosis factor-alpha and prostacyclin production in lavaged rat lungs in vivo. Anesthesiology, 1999, 91 : 1834-1843.
6. Chiumello D, Pristine G, Slutsky AS. Mechanical ventilation affects local and systemic cytokines in an animal model of acute respiratory distress syndrome. Am J Respir Crit Care Med, 1999, 160: 109-116 .
7. DiRocco JD, Pavone LA, Carney DE, et al. Dynamic alveolar mechanics in four models of lung injury. Intensive Care Med, 2006 ,32: 140-148 .
8. Altemeier WA, Matute-Bello G, Frevert CW, et al. Mechanical ventilation with moderate tidal volumes synergistically increases lung cytokine response to systemic endotoxin. Am J Physiol Lung Cell Mol Physiol, 2004, 287 : L533-L542.
9. Walder B, Fontao E, Totsch M, et al. Time and tidal volumedependent ventilator-induced lung injury in healthy rats. Eur J Anaesthesiol, 2005, 22: 785 -794.
10. Egan EA, Nelson RM, Olver RE. Lung inflation and alveolar permeability to non-electrolytes in the adult sheep in vivo. J Physiol, 1976 , 260: 409-424.
11. Parker JC, Townsley MI, Rippe B, et al. Increased microvascular permeability in dog lungs due to high peak airway pressures. JAppl Physiol, 1984 , 57: 1809-1816.
12. Dreyfuss D, Ricard JD, Saumon G. On the physiologic and clinical relevance of lung-borne cytokines during ventilator-induced lung injury. Am J Respir Crit Care Med, 2003 , 167: 1467-1471.

Chinese Journal of Respiratory and Critical Care Medicine

Establishment and Evaluation of Rabbit Model of Ventilator-Induced Lung Injury

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