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

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 cells

PaCO₂ target 80–100 mmHg

HCA 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 cells

12%

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 cells

10%

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 lines

10, 15%

Hypercapnia inhibited p65 translocation and IκB degradation

Cummins et al. [13]

Endotoxin stimulated. In vitro six different cell lines

5, 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 macrophages

5, 9, 12.5, 20%

Hypercapnia reduced cytokine release (IL-6, TNF-α)