title: Effects of hypercapnia and hypercapnic acidosis on attenuation of ventilator-associated lung injury.
abstract: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with impaired gas exchange, severe inflammation and alveolar damage including cell death. Patients with ALI or ARDS typically experience respiratory failure and thus require mechanical ventilation for support, which itself can aggravate lung injury. Recent developments in this field have revealed several therapeutic strategies that improve gas exchange, increase survival and minimize the deleterious effects of mechanical ventilation. Among those strategies is the reduction in tidal volume and allowing hypercapnia to develop during ventilation, or actively inducing hypercapnia. Here, we provide an overview of hypercapnia and the hypercapnic acidosis that typically follows, as well as the therapeutic effects of hypercapnia and acidosis in clinical studies and experimental models of ALI. Specifically, we review the effects of hypercapnia and acidosis on the attenuation of pulmonary inflammation, reduction of apoptosis in alveolar epithelial cells, improvement in sepsis-induced ALI and the therapeutic effects on other organ systems, as well as the potentially harmful effects of these strategies. The clinical implications of hypercapnia and hypercapnic acidosis are still not entirely clear. However, future research should focus on the intracellular signaling pathways that mediate ALI development, potentially focusing on the role of reactive biological species in ALI pathogenesis. Future research can also elucidate how such pathways may be targeted by hypercapnia and hypercapnic acidosis to attenuate lung injury.
authors.affiliation: Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada.
authors.forename: N M
authors.initials: NM
authors.lastname: Ismaiel
authors.forename: D
authors.initials: D
authors.lastname: Henzler
mesh_terms: D000142:Acidosis, Respiratory / Q000150:complications / Q000628:therapy*; D055371:Acute Lung Injury / Q000209:etiology / Q000628:therapy; D002245:Carbon Dioxide / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006935:Hypercapnia / Q000150:complications / Q000628:therapy*; D007249:Inflammation / Q000209:etiology / Q000628:therapy; D053717:Pneumonia, Ventilator-Associated / Q000628:therapy*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology; D011654:Pulmonary Edema / Q000473:pathology; D011661:Pulmonary Stretch Receptors / Q000502:physiology; D012128:Respiratory Distress Syndrome / Q000628:therapy; D018805:Sepsis / Q000150:complications; D013990:Tidal Volume
chemical_list: D002245:Carbon Dioxide