Hypercapnic Acidosis Is Protective in an In Vivo Model of Ventilator-induced Lung Injury

Abstract

To investigate whether hypercapnic acidosis protects against ventilator-induced lung injury (VILI) in vivo, we subjected 12 anesthetized, paralyzed rabbits to high tidal volume ventilation (25 cc/kg) at 32 breaths per minute and zero positive end-expiratory pressure for 4 hours. Each rabbit was randomized to receive either an FI(CO(2)) to achieve eucapnia (Pa(CO(2)) approximately 40 mm Hg; n = 6) or hypercapnic acidosis (Pa(CO(2)) 80-100 mm Hg; n = 6). Injury was assessed by measuring differences between the two groups' respiratory mechanics, gas exchange, wet:dry weight, bronchoalveolar lavage fluid protein concentration and cell count, and injury score. The eucapnic group showed significantly higher plateau pressures (27.0 +/- 2.5 versus 20.9 +/- 3.0; p = 0.016), change in Pa(O(2)) (165.2 +/- 19.4 versus 77.3 +/- 87.9 mm Hg; p = 0.02), wet:dry weight (9.7 +/- 2.3 versus 6.6 +/- 1.8; p = 0.04), bronchoalveolar lavage protein concentration (1,350 +/- 228 versus 656 +/- 511 micro g/ml; p = 0.03), cell count (6.86 x 10(5) +/- 0.18 x 10(5) versus 2.84 x 10(5) +/- 0.28 x 10(5) nucleated cells/ml; p = 0.021), and injury score (7.0 +/- 3.3 versus 0.7 +/- 0.9; p < 0.0001). We conclude that hypercapnic acidosis is protective against VILI in this model.

Hypercapnic Acidosis Impairs Plasma Membrane Wound Resealing in Ventilator-injured Lungs

“…Our results confirm earlier reports from other injury models, that CO 2 influences vascular barrier function and thereby the mechanics of the injured lung (4)(5)(6)(7)(8)(9). However, we also show that CO 2 tension influences the probability that injured cells will repair plasma membrane defects.…”

“…Concern about detrimental effects of acidemia on renal and cardiovascular function have motivated attempts to enhance CO 2 removal by tracheal gas insufflation (2) and have led to unsubstantiated recommendations about the use of bicarbonate buffers in hypercapnic patients (3). More recent data suggest that hypercapnia may actually protect the lung from certain manifestations of ischemiareperfusion, endotoxin, and mechanical ventilation-related injury (4)(5)(6)(7)(8)(9). Hypocapnia, in contrast, and correction of acidemia may be harmful (10)(11)(12).…”

Hypercapnic acidosis confers antioxidant and anti-apoptosis effects against ventilator-induced lung injury

“…Although a lot of evidence suggests that hypercapnic acidosis has a valuable role in experimental models, 14,15,18,37,45 we also should pay attention to consider harmful effects of hypercapnia and/or acidosis on its potential clinical application. It is clear that hypercapnic acidosis may exert adverse hemodynamic effects in patients Histogram of early apoptosis and late apoptosis/necrosis in the three groups.…”

“…The overall histologic injury score (HIS) was evaluated according to a previous study. 14 Immunostaining with an antibody against activated caspase-3 (Cell Signaling Technology, USA) was used to quantify the apoptosis in the lung sections. 29 The number of cleaved-caspase-3-positive cells was counted at the surface of the airway epithelial cells in 10 fields using the  40 objective lens.…”

“…Subsequent studies have demonstrated hypercapnia's protective effects against VILI in both isolated perfused lungs and an animal model. [14][15][16] The mechanism by which hypercapnic acidosis affects acute lung injury, includes the attenuation of NF-kB activation, 17 the inhibition of endogenous xanthine oxidase 18 and oxygen radical formation, 19 and the reducing release of the cytokines. 12,20,21 However, it is still unclear whether hypercapnic acidosis may affect cell apoptosis and oxidative stress injury of the alveolar by MAPK pathways in VILI.…”