Systemic microvascular leak in an in vivo rat model of ventilator-induced lung injury.
Positive pressure mechanical ventilation has significant systemic effects, but the systemic effects associated with ventilator-induced lung injury (VILI) are unexplored. We hypothesized that VILI would cause systemic microvascular leak that is dependent on nitric oxide synthase (NOS) expression. Rats were ventilated with room air at 85 breaths/minute for 2 hours with either VT 7 or 20 ml/kg. Kidney microvascular leak, which was assessed by measuring 24-hour urine protein and Evans blue dye, was used as a marker of systemic microvascular leak. A significant microvascular leak occurred in both lung and kidney with large VT (20 ml/kg) ventilation. Injection of 0.9% NaCl corrected the hypotension and the decreased cardiac output related to large VT, but it did not attenuate microvascular leak of lung and kidney. Serum vascular endothelial growth factor was significantly elevated in large VT groups. Endothelial NOS expression significantly increased in the lung and kidney tissue with large VT ventilation but not inducible NOS. The NOS inhibitor, N-nitro-L-arginine methyl ester, attenuated the microvascular leak of lung and kidney and the proteinuria with large VT ventilation. Endothelial NOS may mediate the systemic microvascular leak of the present model of VILI.
Choi
Won-Il
WI
Department of Medicine, Pulmonary/Critical Care Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Quinn
Deborah A
DA
Park
Kwon Moo
KM
Moufarrej
Ramzi K
RK
Jafari
Behrouz
B
Syrkina
Olga
O
Bonventre
Joseph V
JV
Hales
Charles A
CA
D000818:Animals; D019559:Capillary Leak Syndrome / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D002199:Capillary Permeability / Q000187:drug effects; D003404:Creatinine / Q000378:metabolism; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000097:blood; D006439:Hemodynamics; D015151:Immunoblotting; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D007668:Kidney / Q000098:blood supply; D008168:Lung / Q000098:blood supply; D008222:Lymphokines / Q000097:blood; D008297:Male; D008657:Metabolic Clearance Rate; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D011507:Proteinuria / Q000209:etiology / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000009:adverse effects* / Q000379:methods; D012128:Respiratory Distress Syndrome / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D012965:Sodium Chloride / Q000494:pharmacology; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D012965:Sodium Chloride; D003404:Creatinine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester