Protective Effects Of Therapeutic Hypercapnia On Acute Lung Injury Rabbits And Influence Of Buffering Hypercapnic Acidosis

Objective To investigate whether deliberate elevation of PaCO₂ (therapeutic hypercapnia) protects against acute lung injury (ALI) rabbits and the effects of buffering hypercapnic acidosis, and illuminate the protection mechanism of therapeutic hypercapnia in ALI.Methods Twenty-four anesthetized, paralyzed New Zealand rabbits received the same ventilation strategy (tidal volume, 10 ml/kg; rate, 30 breaths/min; positive end-expiratory pressure, 1 cmH₂O). Animals were randomized into Group I (control); Group II (normocapnia);Group III(therapeutic hypercapnic acidosis,)and Group IV (therapeutic hypercapnia with buffering acidosis). Animals in Group II, III, IV were injected with oleic acid (0.08ml/kg) to produce ALI. Some pathologic and physiological indexes were collected and analyzed for four hours afterALI. Pulmonary water content, bronchoalveolar lavage fluid protein concentrations, TNF-α concentration in BAL, and the activity changes of NF-κB from the frozen lung tissue were measured.Results Lung tissue was pink , without hyperemia and edema in the normal group, but in the Group II and IV, lung tissue was obviously hyperemia and edema, and hemorrhagic spots were found on the surface. Lung tissue was lightly hyperemia and edema in the Group III. Histologic damage in Group II and IV was significantly severer than that in Group III. Group III experienced a significantly lower peak inspiratory pressure (16.2±2.0 cmH₂O), plateau inspiratory pressure (12.3±1.5 cmH₂O), and greater dynamic compliance(1.54±0.24 ml/cmH₂O), static compliance(2.06±0.30 ml/cmH₂O), PaO₂/ FiO₂ (271±28 mmHg) than did either Group II(20.2±2.6 cmH₂O; 17.0±1.9 cmH₂O; 1.14±0.18 ml/cmH₂O; 1.37±0.22 ml/cmH₂O; 164±46 mmHg) or Group IV(19.2±1.3 cmH₂O; 15.7±1.2 cmH₂O; 1.25±0.19 ml/cmH₂O; 1.55±0.26 ml/cmH₂O; 214±61 mmHg). The Group III compared with Group II and IV displayed significantly decreased bronchoalveolar lavage fluid protein concentrations (5.8±2.1g/L, 9.1±2.4g/L, 8.5±1.9g/L) and pulmonary water content (85.8±1.5%, 89.4±1.1%, 88.0±1.5%). TNF- α concentrations in BAL in Group II increased more significantly than that in Group III (P < 0.05) . TNF- α concentrations in Group III decreasedmore significantly than that in Group IV. Activity of NF-κB from the frozen lung tissue in the Group II, III and IV enhanced more obviously than that in the Group I (P < 0.05) . There was no significant in the Group II, III and IV with activity of NF-κB from the frozen lung tissueConclusion Therapeutic hypercapnia had protective effects on ALI rabbits induced by oleic acid and buffering hypercapnic acidosis attenuated its protection.