The Role of Carotid Body Chemoreceptor Afferents in Mediating Abnormal Ventilation in Acute Lung Injury

Abstract

Background‐ Acute lung injury (ALI) induces inflammation that disrupts the normal alveolar‐capillary endothelial barrier which impairs gas exchange to induce hypoxemia that reflexively increases respiration. Increased respiratory rate (RR) usually develops within a few hours to a few days after ALI. This disorder of acute respiratory failure affects approximately 200,000 new cases each year in the US alone and has high morbidity and mortality. The neural mechanisms underlying the respiratory dysfunction after ALI are not fully understood. The purpose of this study involved investigating the role of carotid body chemoreceptor afferents in mediating abnormal ventilation in ALI. Methods and Results‐ ALI was induced in male SD rats (200‐250g) using a single intra‐tracheal injection of bleomycin (Bleo) (day 0) and respiratory variables‐ RR, TV (Tidal Volume), and MV (Minute Ventilation) in response to 10% hypoxia (10% O2, 0% CO2) and 5% hypercapnia (21% O2, 5% CO2) were measured weekly from W1‐W4 using whole‐ body plethysmography (WBP). MV at 21% O2 increased from baseline (W0) to W1 and W2 in bleo treated rats (p≤0.01 compared to saline treated sham rats). Changes in MV were due to a significant increase in RR while TV showed no changes. Chemoreflex was assessed by measuring the absolute difference between 21% O2 and hypoxia (10% O2, 0% CO2) & hypercapnia (21% O2, 5% CO2). Chemoreflex activation is a fundamental protective reflex that maintains oxygen homeostasis. Our data indicated a blunted chemoreflex at W1 and a sensitized chemoreflex in W3‐W4 during hypoxia and hypercapnia. We hypothesized that the blunted chemoreflex in W1 could be due to maximal pre‐activation of chemoreceptors, called the ‘ceiling effect’. To test this possibility, 90% hyperoxia (90% O2, 0% CO2) was given to bleo treated rats to inhibit the chemoreflex and our results showed no changes in RR, suggesting absence of the tonic activity at W1 post‐ALI. Conclusions‐ These data suggest that chemoreflex activation in response to hypoxia and hypercapnia is blunted at acute stage of lung injury but became sensitized at the recovery stage.