Rats surviving injurious mechanical ventilation show reversible pulmonary, vascular and inflammatory changes.
OBJECTIVE
To describe the time course of the changes in pulmonary and vascular function, and systemic inflammation induced by injurious mechanical ventilation.


METHODS
Experimental study in an animal model of ventilator-induced lung injury.


METHODS
Animal research laboratory.


METHODS
Anesthetized male adult Sprague-Dawley rats were ventilated with VT 9 ml/kg and PEEP 5 cmH2O, or VT 35 ml/kg and zero PEEP for 1 h, and were killed. Other rats received ventilation for 1 h with high VT, to observe survival (n=36), or to be monitored and killed at different points in time (24, 72 and 168 h; n=7 in each group). Blood samples for measuring biochemical parameters were obtained. Post-mortem, a bronchoalveolar lavage (BAL) was performed, the aorta and pulmonary microvessels were isolated to examine ex-vivo vascular responses and pulmonary slices were examined (light microscopy).


RESULTS
Mortality in rats ventilated with high VT was 19 of 36 (54%). Mechanical ventilation was associated with hypotension, hypoxaemia and membrane hyaline formation. AST, ALT, IL-6, MIP-2 serum and BAL fluid concentrations, as well as VEGF BAL fluid concentration, were increased in rats ventilated with high VT. Lung injury score was elevated. Aortic vascular responses to acetylcholine and norepinephrine, and microvascular responses to acetylcholine, were impaired. These changes resolved by 24-72 h.


CONCLUSIONS
Injurious ventilation is associated with respiratory and vascular dysfunction, accompanied by pulmonary and systemic inflammation. The survival rate was about 50%. In survivors, most induced changes completely normalized by 24-72 h after the insult.
Nin
Nicolás
N
Servicio de Cuidados Intensivos and CIBER de Enfermedades Respiratorias CB06/06/0044, Instituto de Salud Carlos III, Hospital Universitario de Getafe, Carretera de Toledo, Km. 12,500, 28905 Madrid, Spain.
Lorente
José A
JA
de Paula
Marta
M
El Assar
Mariam
M
Vallejo
Susana
S
Peñuelas
Oscar
O
Fernández-Segoviano
Pilar
P
Ferruelo
Antonio
A
Sánchez-Ferrer
Alberto
A
Esteban
Andrés
A
D000818:Animals; D001011:Aorta / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D006439:Hemodynamics; D007249:Inflammation / Q000209:etiology / Q000401:mortality / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply / Q000473:pathology; D008297:Male; D008833:Microcirculation; D011175:Positive-Pressure Respiration / Q000009:adverse effects* / Q000379:methods; D011659:Pulmonary Gas Exchange; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000401:mortality / Q000503:physiopathology*; D015656:Respiratory Mechanics; D016019:Survival Analysis
D015415:Biomarkers