Bench-to-bedside review: Permissive hypercapnia

Nevner veldig mye rundt hva hyperkapni kan brukes til i klinisk sammenheng, men spesielt interessant er kapittelet om hvordan det reduserer oksidativt stress, som forklarer godt og omfattende dette prinsippet.

Effects on free radical generation and activity

Hypercapnic acidosis appears to attenuate free radical production and modulate free radical induced tissue damage. In common with most biological enzymes, the enzymes that produce these oxidizing agents function optimally at neutral physiological pH levels. Oxidant generation by both basal and stimulated neutrophils appears to be regulated by ambient carbon dioxide levels, with oxidant generation reduced by hypercapnia and increased by hypocapnia [54]. The production of superoxide by stimulated neutrophils in vitro is decreased at acidic pH [6567]. In the brain, hypercapnic acidosis attenuates glutathione depletion and lipid peroxidation, which are indices of oxidant stress [39]. In the lung, hypercapnic acidosis has been demonstrated to reduce free radical tissue injury following pulmonary ischaemia/ reperfusion [27]. Hypercapnic acidosis appears to attenuate the production of higher oxides of nitric oxide, such as nitrite and nitrate, following both ventilator-induced [26] and endotoxin-induced [29] ALI. Hypercapnic acidosis inhibits ALI mediated by xanthine oxidase, a complex enzyme system produced in increased amounts during periods of tissue injury, which is a potent source of free radicals [68] in the isolated lung [24]. In in vitro studies the enzymatic activity of xanthine oxidase was potently decreased by acidosis, particularly hypercapnic acidosis [24,25].

Concerns exist regarding the potential for hypercapnia to potentiate tissue nitration by peroxynitrite, a potent free radical. Peroxynitrite is produced in vivo largely by the reaction of nitric oxide with superoxide radical, and causes tissue damage by oxidizing a variety of biomolecules and by nitrating phenolic amino acid residues in proteins [6973]. The potential for hypercapnia to promote the formation of nitration products from peroxynitrite has been clearly demonstrated in recent in vitroexperiments [45,51]. However, the potential for hypercapnia to promote nitration of lung tissue in vivoappears to depend on the injury process. Hypercapnic acidosis decreased tissue nitration following pulmonary ischaemia/reperfusion-induced ALI [27], but it increased nitration following endotoxin-induced lung injury [29].


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