Histopathological and Pulmonary Gene Expression Findings Associated with Isoflurane Exposure in a Rat Hydrochloric Acid/Lipopolysaccharide Double-hit Acute Lung Injury Model.

OBJECTIVE

We examined histopathological injury and pulmonary mRNA expression of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), and vascular endothelial growth factor (VEGF) associated with isoflurane exposure in a rat hydrochloric acid + lipopolysaccharide (HCl+LPS) double-hit acute lung injury model.

MATERIAL AND

METHODS

Thirty-two male Wistar rats were assigned to control, HCl+LPS, HCl+LPS+isoflurane (6-h), or HCl+LPS+isoflurane (48-h) groups. After intratracheal HCl and LPS, isoflurane groups underwent 4 h of chamber exposure (3% induction, 1.4% maintenance), whereas non-isoflurane groups received matched oxygen exposure. The control, HCl+LPS, and 6-h isoflurane groups were evaluated at 6-h; the 48-h isoflurane group was evaluated at 48-h. No untreated 48-h HCl+LPS group was included.

RESULTS

HCl+LPS produced marked histopathological injury. At 6-h, the isoflurane-exposed group had lower injury scores and lower TNF-α and IL-1β mRNA expression than the time-matched untreated group. The 48-h isoflurane group also had lower values than the untreated 6-h group; however, this comparison was not time-matched. IL-6 mRNA expression was markedly higher in both isoflurane groups; IL-10 levels were highest, and VEGF approached the control value at 48-h.

CONCLUSION

Isoflurane exposure was associated with histopathological and transcriptional differences. The absence of the untreated 48-h and isoflurane-only groups precludes drawing conclusions about sustained efficacy, temporal response, or the mechanism underlying the IL-6 increase. The data do not establish a definitive therapeutic effect or a specific molecular mechanism.