Hypercapnia induces injury to alveolar epithelial cells via a nitric oxide-dependent pathway (original) (raw)
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Hypercapnia via Reduced Rate and Tidal Volume Contributes to Lipopolysaccharide-induced Lung Injury
2004
Appreciating that CO 2 modifies the chemical reactivity of nitric oxide (NO)-derived inflammatory oxidants, we investigated whether hypercapnia would modulate pulmonary inflammatory responses. Rabbits (n ϭ 72) were ventilated with approximately 7-ml/kg tidal volume for 6 hours. Animals were randomized to one of the following conditions: eucapnia (Pa CO 2 at approximately 35-40 mm Hg), eucapnia ϩ lipopolysaccharide (LPS), eucapnia ϩ LPS ϩ inhaled NO (iNO delivered at approximately 20 ppm), hypercapnia (Pa CO 2 at approximately 60 mm Hg), hypercapnia ϩ LPS, and hypercapnia ϩ LPS ϩ iNO. The hypercapnia ϩ LPS groups compared with groups exposed to eucapnia ϩ LPS displayed significantly increased bronchoalveolar lavage fluid protein concentrations (p Ͻ 0.05), lung wet-to-dry ratios (p Ͻ 0.05), bronchoalveolar lavage fluid cell counts (p Ͻ 0.05), and lung histologic alterations consistent with greater injury. Furthermore, expression of inducible nitric oxide synthase (p Ͻ 0.05), tissue myeloperoxidase content (p Ͻ 0.05), and formation of lung protein 3-nitrotyrosine derivatives (p Ͻ 0.05) was greatest under conditions of hypercapnia ϩ LPS. Groups exposed to hypercapnic conditions without LPS did not manifest these changes.
Hypercapnic acidosis in ventilator-induced lung injury
Intensive Care Medicine, 2010
Rationale: Permissive hypercapnia is established in lung injury management. Therapeutic hypercapnia causes benefit or harm, depending on the context. Ventilatorassociated lung injury has a wide spectrum of candidate mechanisms, affording multiple opportunities for intervention such as hypercapnia to exert benefit or harm. Objectives: To confirm (1) that hypercapnia attenuates in vivo ventilator-induced lung injury (VILI);
Respiratory Physiology & Neurobiology, 2015
We investigated the effects of acute hypercapnic acidosis and buffered hypercapnia on lung inflammation and apoptosis in experimental acute lung injury (ALI). Twenty-four hours after paraquat injection, 28 Wistar rats were randomized into four groups (n = 7/group): (1) normocapnia (NC, PaCO 2 = 35-45 mmHg), ventilated with 0.03%CO 2 + 21%O 2 + balanced N 2 ; (2) hypercapnic acidosis (HC, PaCO 2 = 60-70 mmHg), ventilated with 5%CO 2 + 21%O 2 + balanced N 2 ; and (3) buffered hypercapnic acidosis (BHC), ventilated with 5%CO 2 + 21%O 2 + balanced N 2 and treated with sodium bicarbonate (8.4%). The remaining seven animals were not mechanically ventilated (NV). The mRNA expression of interleukin (IL)-6 (p = 0.003), IL-1 (p < 0.001), and type III procollagen (PCIII) (p = 0.001) in lung tissue was more reduced in the HC group in comparison with NC, with no significant differences between HC and BHC. Lung and kidney cell apoptosis was reduced in HC and BHC in comparison with NC and NV. In conclusion, in this experimental ALI model, hypercapnia, regardless of acidosis, reduced lung inflammation and lung and kidney cell apoptosis.
Hypercapnia: is it protective in lung injury?
Medical Gas Research, 2013
Hypercapnic acidosis has been regarded as a tolerated side effect of protective lung ventilation strategies. Various in vivo and ex vivo animal studies have shown beneficial effects in acute lung injury setting, but some recent work raised concerns about its anti-inflammatory properties. This mini-review article aims to expand the potential clinical spectrum of hypercapnic acidosis in critically ill patients with lung injury. Despite the proven benefits of hypercapnic acidosis, further safety studies including dose-effect, level-and-onset of anti-inflammatory effect, and safe applicability period need to be performed in various models of lung injury in animals and humans to further elucidate its protective role.
Hypercapnic Acidosis Is Protective in an In Vivo Model of Ventilator-induced Lung Injury
American Journal of Respiratory and Critical Care Medicine, 2002
To investigate whether hypercapnic acidosis protects against ventilator-induced lung injury (VILI) in vivo , we subjected 12 anesthetized, paralyzed rabbits to high tidal volume ventilation (25 cc/kg) at 32 breaths per minute and zero positive end-expiratory pressure for 4 hours. Each rabbit was randomized to receive either an F I CO2 to achieve eucapnia (Pa CO 2 ف 40 mm Hg; n ϭ 6) or hypercapnic acidosis (Pa CO 2 80-100 mm Hg; n ϭ 6). Injury was assessed by measuring differences between the two groups' respiratory mechanics, gas exchange, wet:dry weight, bronchoalveolar lavage fluid protein concentration and cell count, and injury score. The eucapnic group showed significantly higher plateau pressures (27.0 Ϯ 2.5 versus 20.9 Ϯ 3.0; p ϭ 0.016), change in Pa O 2 (165.2 Ϯ 19.4 versus 77.3 Ϯ 87.9 mm Hg; p ϭ 0.02), wet:dry weight (9.7 Ϯ 2.3 versus 6.6 Ϯ 1.8; p ϭ 0.04), bronchoalveolar lavage protein concentration (1,350 Ϯ 228 versus 656 Ϯ 511 g/ml; p ϭ 0.03), cell count (6.86 ϫ 10 5 Ϯ 0.18 ϫ 10 5 versus 2.84 ϫ 10 5 Ϯ 0.28 ϫ 10 5 nucleated cells/ml; p ϭ 0.021), and injury score (7.0 Ϯ 3.3 versus 0.7 Ϯ 0.9; p Ͻ 0.0001). We conclude that hypercapnic acidosis is protective against VILI in this model.
Hypercapnia: A Nonpermissive Environment for the Lung
American Journal of Respiratory Cell and Molecular Biology, 2012
Patients with severe acute and chronic lung diseases develop derangements in gas exchange that may result in increased levels of CO 2 (hypercapnia), the effects of which on human health are incompletely understood. It has been proposed that hypercapnia may have beneficial effects in patients with acute lung injury, and the concepts of "permissive" and even "therapeutic" hypercapnia have emerged. However, recent work suggests that CO 2 can act as a signaling molecule via pH-independent mechanisms, resulting in deleterious effects in the lung. Here we review recent research on how elevated CO 2 is sensed by cells in the lung and the potential harmful effects of hypercapnia on epithelial and endothelial barrier, lung edema clearance, innate immunity, and host defense. In view of these findings, we raise concerns about the potentially deleterious effects hypercapnia may have in patients with acute and chronic lung diseases.
Hypercapnic Acidosis Is Protective in an In Vivo Model of Ventilator-induced Lung Injury
American Journal of Respiratory and Critical Care Medicine, 2002
To investigate whether hypercapnic acidosis protects against ventilator-induced lung injury (VILI) in vivo , we subjected 12 anesthetized, paralyzed rabbits to high tidal volume ventilation (25 cc/kg) at 32 breaths per minute and zero positive end-expiratory pressure for 4 hours. Each rabbit was randomized to receive either an F I CO2 to achieve eucapnia (Pa CO 2 ف 40 mm Hg; n ϭ 6) or hypercapnic acidosis (Pa CO 2 80-100 mm Hg; n ϭ 6). Injury was assessed by measuring differences between the two groups' respiratory mechanics, gas exchange, wet:dry weight, bronchoalveolar lavage fluid protein concentration and cell count, and injury score. The eucapnic group showed significantly higher plateau pressures (27.0 Ϯ 2.5 versus 20.9 Ϯ 3.0; p ϭ 0.016), change in Pa O 2 (165.2 Ϯ 19.4 versus 77.3 Ϯ 87.9 mm Hg; p ϭ 0.02), wet:dry weight (9.7 Ϯ 2.3 versus 6.6 Ϯ 1.8; p ϭ 0.04), bronchoalveolar lavage protein concentration (1,350 Ϯ 228 versus 656 Ϯ 511 g/ml; p ϭ 0.03), cell count (6.86 ϫ 10 5 Ϯ 0.18 ϫ 10 5 versus 2.84 ϫ 10 5 Ϯ 0.28 ϫ 10 5 nucleated cells/ml; p ϭ 0.021), and injury score (7.0 Ϯ 3.3 versus 0.7 Ϯ 0.9; p Ͻ 0.0001). We conclude that hypercapnic acidosis is protective against VILI in this model.
Archivos De Bronconeumologia, 2010
Acute lung injury is a disease with high mortality, which affects a large numbers of patients whose treatment continues to be debated. It has recently been postulated that hypercapnia can attenuate the inflammatory response during lung injury, which would assign it a specific role within lung protection strategies during mechanical ventilation. In this paper, we review current evidence on the role that high levels of CO 2 in the blood play in lung injury. We conclude that, although there are reports that show benefits, the most recent evidence suggests that hypercapnia can be harmful and can contribute to worsening lung damage.