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Updated: Aug 9, 2026

Pressure Controlled Ventilation to Induce Acute Lung Injury in Mice
Published on: May 5, 2011
Effect of rate and inspiratory flow on ventilator-induced lung injury
P B Rich1, C A Reickert, S Sawada
1Department of Surgery, University of Michigan Medical Center, Ann Arbor, USA.
Background:
We examined the effects of decreasing respiratory rate (RR) at variable inspiratory times (It) and reducing inspiratory flow on the development of ventilator-induced lung injury.
Methods:
Forty sheep weighing 24.6+/-3.2 kg were ventilated for 6 hours with one of five strategies (FIO2 = 1.0, positive end-expiratory pressure = 5 cm H2O): (1) pressure-controlled ventilation (PCV), RR = 15 breaths/min, peak inspiratory pressure (PIP) = 25 cm H2O, n = 8; (2) PCV, RR = 15 breaths/min, PIP = 50 cm H2O, n = 8; (3) PCV, RR = 5 breaths/min, PIP = 50 cm H2O, It = 6 seconds, n = 8; (4) PCV, RR = 5 breaths/min, PIP = 50 cm H2O, It = 2 seconds, n = 8; and (5) limited inspiratory flow volume-controlled ventilation, RR = 5 breaths/min, pressure-limit = 50 cm H2O, flow = 15 L/min, n = 8.
Results:
Decreasing RR at conventional flows did not reduce injury. However, limiting inspiratory flow rate (LIFR) maintained compliance and resulted in lower Qs/Qt (HiPIP = 38+/-18%, LIFR = 19+/-6%, p < 0.001), reduced histologic injury (HiPIP = 14+/-0.9, LIFR = 2.2+/-0.9, p < 0.05), decreased intra-alveolar neutrophils (HiPIP = 90+/-49, LIFR = 7.6+/-3.8,p = 0.001), and reduced wet-dry lung weight (HiPIP = 87.3+/-8.5%, LIFR = 40.8+/-17.4%,p < 0.001).
Conclusions:
High-pressure ventilation for 6 hours using conventional flow patterns produces severe lung injury, irrespective of RR or It. Reduction of inspiratory flow at similar PIP provides pulmonary protection.
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