• Carmen Menendez, Leticia Martinez-Caro, Laura Moreno, Nicolas Nin, Javier Moral-Sanz, Daniel Morales, Angel Cogolludo, Andres Esteban, Jose A Lorente, and Francisco Perez-Vizcaino.
• Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Madrid, Spain.
• Crit. Care Med.. 2013 Aug 1;41(8):e149-55.

ObjectivesAcute lung injury and acute respiratory distress syndrome are characterized by increased pulmonary artery pressure and ventilation-perfusion mismatch. We analyzed the changes in the pulmonary vascular function in a model of ventilator-induced acute lung injury.DesignControlled in vivo laboratory study.SettingAnimal research laboratory.SubjectsAnesthetized male Sprague-Dawley rats.InterventionsRats were ventilated for 120 minutes using low tidal volume ventilation (control group, tidal volume 9 mL/kg, positive end-expiratory pressure 5 cm H2O, n = 15), high tidal volume ventilation (high tidal volume group, tidal volume 25 mL/kg, zero positive end-expiratory pressure, n = 14), or high tidal volume ventilation plus the poly-(adenosine diphosphate-ribose) polymerase inhibitor 3-aminobenzamide (10 mg/kg IP, high tidal volume group + 3-aminobenzamide group, n = 7). Vascular rings from small pulmonary arteries were mounted in a myograph for isometric tension recording. Lung messenger RNA and protein expression were analyzed by reverse transcriptase-polymerase chain reaction and Western blot, respectively.Measurements And Main ResultsHigh tidal volume ventilation impaired phenylephrine- and acetylcholine-induced responses in pulmonary arteries in vitro, which were accompanied by induction of inducible nitric oxide synthase messenger RNA and protein. These effects, as well as hypoxemia and hypotension, were prevented by 3-aminobenzamide. Hypoxic pulmonary vasoconstriction and responses to exogenous sphingomyelinase were increased, whereas the responses to serotonin, Kv current density, and inhibition of Kv currents by hypoxia were unaffected by high tidal volume.ConclusionsHigh tidal volume ventilation-induced pulmonary vascular dysfunction was characterized by reduced alpha-adrenergic-induced vasoconstriction, reduced endothelium-dependent vasodilatation, and enhanced hypoxic pulmonary vasoconstriction.

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