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

Abstract

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.

Hypercapnic acidosis induces mitochondrial dysfunction and impairs the ability of mesenchymal stem cells to promote distal lung epithelial repair

“…Furthermore, although HPMECs are the most relevant cell type in the context of ARDS, in the study by Liu et al ., the in vitro results were corroborated by data in a rabbit model of LPS‐induced lung injury in which endothelial‐neutrophil responses were significantly increased during hypercapnia (5). These data contradict previous in vivo findings in the models of sepsis‐ and paraquat‐induced lung injury in rats, demonstrating an immunosuppressive effect of HC A (11, 12).…”

“…Attenuated neutrophilia in HCA has been demonstrated in numerous in vivo studies ( 11 , 12 , 48 ). Data from the current study suggest that the epithelium and endothelium contribute to this response by attenuating neutrophil chemoattraction and migration across the endothelial-epithelial barrier.…”

Inflammatory Mediators in Tracheal Aspirates of Preterm Infants Participating in a Randomized Trial of Permissive Hypercapnia

“…We neither observed effects on LTB 4 , IL-6, and NPY induced by moderate permissive hypercapnia nor on albumin concentrations, suggesting no difference in microvascular permeability between the study groups. In contrast to our results, hypercapnia reduced IL-6 and IL-1β expression in murine lung tissue of a paraquat-induced acute lung injury model accompanied by decreased numbers of neutrophils in lung tissue and inflammatory infiltration in alveolar septa compared to normoxia ( 59 ). However, results of this study were obtained after 1 h of mechanical ventilation and preclude assessment of long-term effects.…”

Protective effects of hypercapnic acidosis on Ischemia–reperfusion-induced retinal injury

“…In addition, our study indicated that HCA induction suppressed inflammation by the downregulation of NF-κB signaling in vitro and in vivo. This protective potential of HCA has been shown in various experimental models: Nardelli et al indicated that HCA decreased lung and kidney cell apoptosis [42], and Masterson et al observed that HCA reduced inflammation and lung injury in vivo and reduced NF-κB activation predominantly by inhibiting the activation and intrinsic activity of IκB kinase-β [33]. Our study is the first to demonstrate that HCA induction after I/R injury can provide retinal protection in a well-known animal model.…”