title: Adenosine triphosphate-dependent calcium signaling during ventilator-induced lung injury is amplified by hypercapnia.
abstract: Adenosine triphosphate (ATP) is released by alveolar epithelial cells during ventilator-induced lung injury (VILI) and regulates fluid transport across epithelia. High CO(2) levels are observed in patients with "permissive hypercapnia," which inhibits alveolar fluid reabsorption (AFR) in alveolar epithelial cells. The authors set out to determine whether VILI affects AFR and whether the purinergic pathway is modulated in cells exposed to hypercapnia. Control group was compared against VILI (tidal volume [Vt] = 35 mL/kg, zero positive end-expiratory pressure [PEEP]) and protective ventilation (Vt = 6 mL/kg, PEEP = 10 cm H(2)O) groups. Lung mechanics, histology, and AFR were evaluated. Alveolar epithelial cells (AECs) were loaded with Fura 2-AM to measure intracellular calcium in the presence ATP (10 μM) at 5% or 10% CO(2) as compared with baseline. High tidal volume ventilation impairs lung mechanics and AFR. Hypercapnia (HC) increases intracellular calcium levels in response to ATP stimulation. HC + ATP is the most detrimental combination decreasing AFR. Purinergic signaling in AECs is modulated by high CO(2) levels via increased cytosolic calcium. The authors reason that this modulation may play a role in the impairment of alveolar epithelial functions induced by hypercapnia.
authors.affiliation: Departamento de Fisiopatologia, Hospital de Clinicas, Montevideo, Uruguay. abriva@hc.edu.uy
authors.forename: Arturo
authors.initials: A
authors.lastname: Briva
authors.forename: Cristina
authors.initials: C
authors.lastname: Santos
authors.forename: Leonel
authors.initials: L
authors.lastname: Malacrida
authors.forename: Fabiana
authors.initials: F
authors.lastname: Rocchiccioli
authors.forename: Juan
authors.initials: J
authors.lastname: Soto
authors.forename: Martin
authors.initials: M
authors.lastname: Angulo
authors.forename: Carlos
authors.initials: C
authors.lastname: Batthyany
authors.forename: Ernesto
authors.initials: E
authors.lastname: Cairoli
authors.forename: Hector
authors.initials: H
authors.lastname: Piriz
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects*; D006935:Hypercapnia / Q000503:physiopathology*; D008297:Male; D011659:Pulmonary Gas Exchange; D051381:Rats; D011921:Rats, Inbred WKY; D012121:Respiration, Artificial / Q000009:adverse effects*; D015656:Respiratory Mechanics; D013990:Tidal Volume
chemical_list: D000255:Adenosine Triphosphate