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Table 2 Humoral effects of hypercapnia: summary of in vivo and ex vivo experiments on the effects of hypercapnia

From: The role of hypercapnia in acute respiratory failure

StudyExperimental modelApplied CO2Humoral effects
Shibata et al. [7]Free-radical ex vivo (rabbit)25%HCA attenuated free-radical injury via inhibition of endogenous xanthine oxidase
Laffey et al. [6]Pulmonary IR ex vivo (rabbit)12%HCA reduced TNF-α, 8-isoprostane, nitrotyrosine generation in the lung tissue and reduced apoptosis
Yang et al. [20]VILI in vivo (rat) and in vitro alveolar epithelial cellsPaCO2 target 80–100 mmHgHCA reduced caspase-3 activation (apoptosis), MPO, MDA, via ASK-1-JNK/p38 pathway inhibition
Otulakowski et al. [15]VILI ex vivo (mouse) and in vitro alveolar epithelial cells12%Hypercapnia prevented activation of EGFR and p44/42 MAPK pathway in vitro. TNFR shedding (on ADAM-17 ligand induced by stretch injury) was reduced in vivo
Takeshita et al. [16]Endotoxin in vitro pulmonary endothelial cells10%Hypercapnia reduced cell injury and prevented IκB degradation. NF-κB-dependent cytokine production was reduced
O’Toole et al. [8]In vitro three cell respiratory lines10, 15%Hypercapnia inhibited p65 translocation and IκB degradation
Cummins et al. [13]Endotoxin stimulated. In vitro six different cell lines5, 10%CO2 reduced the expression of innate immune effectors IL-6 and TNF-α
Wang et al. [21]Endotoxin stimulation. In vitro human and mouse macrophages5, 9, 12.5, 20%Hypercapnia reduced cytokine release (IL-6, TNF-α)
  1. HCA hypercapnic acidosis, ADAM-17 ADAM metallopeptidase 17, ASK-1 apoptosis signal-regulating kinase-1, EGRF epidermal growth factor receptor, IkB inhibitory kappa B, IL-6 interleukin-6, IR ischemia-reperfusion, JNK c-Jun N-terminal kinase, MDA malondialdehyde, MPO myeloperoxidase, NF-kB nuclear factor kappa B, p44/42 MAPK p44/p42 mitogen-activated protein kinase, TNF-α tumor necrosis factor-α, TNFR tumor necrosis factor receptor, VILI ventilator-induced lung injury