Hypercapnia attenuates the endotoxin-induced tissue metabolic acidosis in esophageal mucosa

Objective

To assess the effects of hypercapnia on the tissue metabolic response to Escherichia coli endotoxemia in rabbits.

Design

Prospective, controlled experimental study.

Setting

University laboratory.

Subjects

Thirty-six rabbits of both sexes, anesthetized with pentobarbital and ventilated mechanically (normoventilation).

Interventions

Animals were assigned to one of four groups: a) endotoxemic control group (n = 9), receiving intravenous Escherichia coli endotoxin (20 mg/kg bolus) via a peripheral vein; b) hypercapnia control group (n = 9), receiving exogenous carbon dioxide to achieve mild hypercapnia 60–90 mmHg; c) hypercapnia treated group (n = 9), treated identically to endotoxemic controls, and additionally receiving exogenous carbon dioxide to achieve mild hypercapnia 60–90 mmHg; d) control group (n = 9), receiving neither endotoxin nor carbon dioxide.

Measurements

We compared hemodynamics, blood gases, WBC, rectal temperature and tonometric findings in esophageal mucosa obtained in each group. Endotoxin injection decreased mean arterial pressure from 79 ± 9 to 54 ± 17.5 mmHg, decreased bicarbonate level from 21.6 ± 3 to 17.6 ± 4 mmHg, decreased WBC from 7.9 ± 2 to 1.9 ± 0.7 G/l, increased rectal temperature from 37.7 ± 1 to 39.9 ± 1.5°C, and caused a marked, continuous decrease in regional pH (pHi) from 7.40 ± 0.08 to 7.12 ± 0.11 at the end of the experiment. Hypercapnia alone had a minimal effect on the parameters and findings. Both hypercapnia and endotoxemia had no significant effect on regional CO₂ (PrCO₂) compared with controls, indicating lack of significant mucosal blood flow abnormalities throughout the experiment. In the hypercapnia treated group we observed an initial decrease in regional pH (pHi) from 7.42 ± 0.13 to 7.13 ± 0.08, but the value of this parameter remained stable (7.07 ± 0.05 at the end of the experiment) and the statistical difference compared with hypercapnia controls was nonsignificant (P > 0.05).

Conclusions

1. Endotoxin injection caused marked tissue acidosis without disturbing esophageal mucosal blood flow, which indicates a metabolic character of acidosis and underlines the significance of intracellular abnormalities during endotoxemia. 2. We hypothesize that hypercapnia attenuates the endotoxin-induced tissue metabolic acidosis and may exert a cytoprotective effect.