Therapeutic hypercapnia enhances the inflammatory response to endotoxin in the lung of spontaneously breathing rats*

Norozian, Faraz M.; Leoncio, Michael; Torbati, Dan; Meyer, Keith; Raszynski, André; Totapally, Balagangadhar

doi:10.1097/ccm.0b013e31820ee1f2

Cited by 23 publications

(11 citation statements)

References 40 publications

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“…The alveolar septal thickness, 3-to 5-mm in 4 and 12 weeks, in the CD-fed rats without LPS was notably lower than that, 10 mm, of the control rats in Norozian et al's study [28]. The higher amount of vitamins E and D 3 for preventing oxidative rancidity of fat in both the CD and HFD than that of typical normal chow may contribute to thinner alveolar septal thickness at baseline in this rats [29].…”

Section: Discussionmentioning

confidence: 87%

Lard-based high-fat diet increases secretory leukocyte protease inhibitor expression and attenuates the inflammatory response of acute lung injury in endotoxemic rats

et al. 2015

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Section: Discussionmentioning

confidence: 87%

Lard-based high-fat diet increases secretory leukocyte protease inhibitor expression and attenuates the inflammatory response of acute lung injury in endotoxemic rats

et al. 2015

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“…Controversies remain as to the potential mechanisms underlying the effects of hypercapnia on lung neutrophilic infiltration, which depend on the level of PaCO 2 , the duration of hypercapnia, and the route of hypercapnia induction (inhalation or mechanical ventilation). Hypercapnic acidosis has been shown to reduce lung neutrophil infiltration in different ALI models, such as the ischemia-reperfusion model in rabbits (Laffey et al, 2000a), intratracheal instillation (Laffey et al, 2004) and intraperitoneal injection (Norozian et al, 2011) of endotoxin, and cecal ligation and puncture in rats. However, it is not clear whether the protective effects of hypercapnic acidosis in these models are neutrophil-dependent.…”

Section: Discussionmentioning

confidence: 99%

“…Acute hypercapnic acidosis has been suggested to attenuate lung injury in ischemic reperfusion (Laffey et al, 2000a), sepsis Higgins et al, 2009), and endotoxin (Norozian et al, 2011) models, raising the possibility of a potential therapeutic application of hypercapnia in acute lung injury (ALI) (therapeutic hypercapnia).…”

Section: Introductionmentioning

confidence: 99%

Effects of acute hypercapnia with and without acidosis on lung inflammation and apoptosis in experimental acute lung injury

Nardelli

Rzezinski

Silva

et al. 2015

Respiratory Physiology & Neurobiology

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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, PaCO2=35-45 mmHg), ventilated with 0.03%CO2+21%O2+balancedN2; (2) hypercapnic acidosis (HC, PaCO2=60-70 mmHg), ventilated with 5%CO2+21%O2+balancedN2; and (3) buffered hypercapnic acidosis (BHC), ventilated with 5%CO2+21%O2+balancedN2 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-1β (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.

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“…Putative mediators of lung injury shown to be attenuated by therapeutic hypercapnia in these models have included inflammatory cell influx (37,45,72), proinflammatory cytokines (14,38,72), and oxidative stress (31,38,52,72). However, several studies have also indicated the potential for hypercapnia to worsen lung injury (41,53,54) and to potentially cause an increase in inflammation in the noninjured lung (2,45), highlighting the need for further study. Our aim therefore was to examine effects of therapeutic hypercapnia in a new rat model with similarities to human BPD (47), secondary to bleomycin exposure.…”

mentioning

confidence: 99%

Therapeutic hypercapnia prevents bleomycin-induced pulmonary hypertension in neonatal rats by limiting macrophage-derived tumor necrosis factor-α

Sewing

Kantores

Ivanovska

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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Sewing AC, Kantores C, Ivanovska J, Lee AH, Masood A, Jain A, McNamara PJ, Tanswell AK, Jankov RP. Therapeutic hypercapnia prevents bleomycin-induced pulmonary hypertension in neonatal rats by limiting macrophage-derived tumor necrosis factor-␣. Am J Physiol Lung Cell Mol Physiol 303: L75-L87, 2012. First published May 11, 2012; doi:10.1152/ajplung.00072.2012.-Bleomycin-induced lung injury is characterized in the neonatal rat by inflammation, arrested lung growth, and pulmonary hypertension (PHT), as observed in human infants with severe bronchopulmonary dysplasia. Inhalation of CO2 (therapeutic hypercapnia) has been described to limit cytokine production and to have anti-inflammatory effects on the injured lung; we therefore hypothesized that therapeutic hypercapnia would prevent bleomycin-induced lung injury. Spontaneously breathing rat pups were treated with bleomycin (1 mg/kg/d ip) or saline vehicle from postnatal days 1-14 while being continuously exposed to 5% CO2 (PaCO 2 elevated by 15-20 mmHg), 7% CO2 (PaCO 2 elevated by 35 mmHg), or normocapnia. Bleomycin-treated animals exposed to 7%, but not 5%, CO2, had significantly attenuated lung tissue macrophage influx and PHT, as evidenced by normalized pulmonary vascular resistance and right ventricular systolic function, decreased right ventricular hypertrophy, and attenuated remodeling of pulmonary resistance arteries. The level of CO2 neither prevented increased tissue neutrophil influx nor led to improvements in decreased lung weight, septal thinning, impaired alveolarization, or decreased numbers of peripheral arteries. Bleomycin led to increased expression and content of lung tumor necrosis factor (TNF)-␣, which was found to colocalize with tissue macrophages and to be attenuated by exposure to 7% CO2. Inhibition of TNF-␣ signaling with the soluble TNF-2 receptor etanercept (0.4 mg/kg ip from days 1-14 on alternate days) prevented bleomycin-induced PHT without decreasing tissue macrophages and, similar to CO2, had no effect on arrested alveolar development. Our findings are consistent with a preventive effect of therapeutic hypercapnia with 7% CO2 on bleomycin-induced PHT via attenuation of macrophage-derived TNF-␣. Neither tissue macrophages nor TNF-␣ appeared to contribute to arrested lung development induced by bleomycin. That 7% CO2 normalized pulmonary vascular resistance and right ventricular function without improving inhibited airway and vascular development suggests that vascular hypoplasia does not contribute significantly to functional changes of PHT in this model. carbon dioxide; inflammation; neonatal lung injury BRONCHOPULMONARY DYSPLASIA (BPD) is a chronic pneumopathy affecting extremely premature infants who frequently require supplemental oxygen and/or mechanical ventilation. The incidence of BPD is inversely proportional to the gestational age at which infants are born, with an incidence approaching 60% in the smallest survivors (4). The cardinal feature of BPD, as observed in the current era, is an inhibition or arrest of alveolar and ...

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Therapeutic hypercapnia enhances the inflammatory response to endotoxin in the lung of spontaneously breathing rats*

Cited by 23 publications

References 40 publications

Lard-based high-fat diet increases secretory leukocyte protease inhibitor expression and attenuates the inflammatory response of acute lung injury in endotoxemic rats

Lard-based high-fat diet increases secretory leukocyte protease inhibitor expression and attenuates the inflammatory response of acute lung injury in endotoxemic rats

Effects of acute hypercapnia with and without acidosis on lung inflammation and apoptosis in experimental acute lung injury

Therapeutic hypercapnia prevents bleomycin-induced pulmonary hypertension in neonatal rats by limiting macrophage-derived tumor necrosis factor-α

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