ARTERIAL BAROREFLEX FUNCTION IS IMPAIRED DURING THE RECOVERY FROM ACUTE LUNG INJURY IN A BLEOMYCIN-INDUCED RAT LUNG INJURY MODEL

Abstract

Objective: Acute lung injury (ALI) and its clinical correlate, the acute respiratory distress syndrome (ARDS), results due, in part, to disruption of the normal capillary endothelial barrier and invokes perturbations of ventilatory control. ALI is associated with autonomic dysfunction and cardiac arrhythmias. In a recent study we suggested that rats were susceptible to cardiac arrhythmia even during the recovery from ALI, in part, due to abnormalities in cardiac sympathetic ganglia. On the other hand, if arterial baroreflex function is altered during the recovery of ALI remains unknown. The primary goal of this study was to examine baroreflex function during the recovery stage from ALI in a bleomycin (Bleo)-induced rat ALI model. Design and method: ALI was induced in male SD rats (200-250g) using a single intra-tracheal injection of Bleo (2.5 mg/kg). 4 weeks post Bleo (n = 7) or saline (sham, n = 6), rats were anesthetized with urethane (800 mg/kg ip) and alpha-chloralose (40 mg/kg ip) to measure baroreflex sensitivity. Baroreflex curves were generated by measuring the heart rate (HR) and renal sympathetic nerve activity (RSNA) responses to decreases and increases in mean blood pressure (MAP) by intravenous administration of nitroglycerin (25 μg) followed by phenylephrine (10 μg). Differences between sham and Bleo rats were determined by one-way ANOVA followed by the Tukey post hoc test. Results: Compared to sham rats, there was a significant decrease in the RSNA (117.4±11.6 vs. 77.5±8.9 %baseline, P = 0.018) or HR (147.5±9.7 vs. 75.1±11.3 bpm, P<0.001) range in Bleo rats. Minimum RSNA or HR was also decreased in bleo rats compared to sham rats. There was no significant difference in either the slope coefficient or the blood pressure at the midpoint of the range (BP50) between the two groups. There was a significant decrease in peak slope [or maximum gain (Gainmax) in Bleo rats (MAP-RSNA Gainmax: 3.11±0.27 vs. 1.74±0.31, p = 0.017; MAP-HR Gainmax: 3.57±0.31 vs. 1.21±0.14, p<0.001). Conclusions: Our data demonstrate impaired baroreflex function during the recovery state from ALI. Autonomic dysfunction may also contribute to increased cardiovascular risk during the recovery stage from ALI.