Aquaporin channels may modulate ventilator-induced lung injury.
Adult Respiratory Distress Syndrome is a disease with functional lung heterogeneity and thus a ventilator-delivered breath may over-distend non-involved areas. In rats we examined ventilator-delivered tidal volume (TV) breaths of 7 and 20 ml/kg on lung water as evidence of lung injury. We examined the role of aquaporins on ventilator-induced lung injury (VILI) by infusing HgCl(2) which inhibits aquaporins by binding cysteine. Wet to dry lung weight ratio (W/D) as evidence of lung water was 4.47+/-0.1 SEM in controls, 4.6+/-0.1 and 5.5+/-0.2 (P<0.05) in rats ventilated at 7 and 20 ml/kg, respectively. Pulmonary artery pressure (PAP) rose from 23+/-1 to 26+/-1 mmHg (P<0.05, n=7) and cardiac output fell from 104+/-2 to 67+/-3 ml/min (P<0.05) in rats ventilated at 20 ml/kg. Left ventricular end diastolic pressure (n=3) was unchanged. Evans Blue dye, an albumin marker, increased from a control 37+/-11 to 97+/-41 mg/g wet lung in TV 20 rats (P<0.05). HgCl(2) infused slowly by tail vein did not significantly raise PAP, but did increase W/D to 6+/-0.2 (P<0.05) in rats ventilated at 20 ml/kg but not at 7 ml/kg. Equimolar cysteine infusions prevented the HgCl(2) from increasing the W/D above that seen with TV 20 ml/kg. Thus ventilation with TV of 20 ml/kg produced a protein-rich lung edema. Aquaporin channels may have a protective effect in VILI.
Hales
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CA
Department of Medicine (Pulmonary and Critical Care), Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. chales@partners.org
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Volokhov
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Mourfarrej
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Quinn
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D000818:Animals; D020346:Aquaporins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003545:Cysteine / Q000494:pharmacology; D005070:Evans Blue; D015633:Extravascular Lung Water / Q000737:chemistry / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury; D008627:Mercuric Chloride / Q000494:pharmacology; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D011654:Pulmonary Edema / Q000139:chemically induced; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000009:adverse effects; D013990:Tidal Volume; D013997:Time Factors; D012122:Ventilators, Mechanical / Q000009:adverse effects*; D014867:Water / Q000032:analysis
D020346:Aquaporins; D014867:Water; D005070:Evans Blue; D008627:Mercuric Chloride; D003545:Cysteine