Novel Mechanism of Neural Control of Breathing in Acute Lung Injury (ALI)

Abstract

Increased respiratory rate (RR) usually develops within a few hours to a few days after ALI. However, the neural mechanisms underlying the breathing dysfunction after ALI are not fully understood. The purpose involved investigating the role of chemoreceptor afferents and pulmonary spinal afferents in the control of breathing in ALI. ALI was induced in male SD rats (200-250g) using intra-tracheal injections of bleomycin (Bleo) (day 0) and measured RR, TV (Tidal Volume), and MV (Minute Ventilation) weekly from W1-W4 using whole body plethysmography (WBP). Chemoreflex was assessed by measuring the absolute difference between 21% O2 and hypoxia (10% O2) & hypercapnia (5% CO2 and 7% CO2). MV at 21% O2 increased from baseline to W1 and W2. Changes in MV were due to significant increase in RR while TV showed no changes. Blunted chemoreflex was observed at W1 and W2 during hypoxia and hypercapnia which could be due to maximal pre-activation of chemoreceptors, called ceiling effect. Chemoreflex was inhibited in bleo-rats through 90% O2 (hyperoxia) which showed no changes in RR, suggesting absence of tonic activity. Other experiments included bleomycin on day 0, ablation of TRPV1-positive lung spinal afferents by bilaterally injecting 5μl of RTX (50 μg/ml) into the stellate ganglion (day 3) and measuring lung parameters (day 7). RTX ablation of pulmonary spinal afferents caused a significant reduction in RR in bleo-rats at W1. These data suggest that chemoreflex activation in response to hypoxia and hypercapnia is blunted whereas, pulmonary spinal afferent activation may play a major role in the increased RR in ALI.