Effects of Anesthesia on Ozone-Induced Lung and Systemic Inflammation

Miranda L Wilson,W Sandy Liang,Jarl A Thysell,Kristen K Baumann,Michelle A Erickson,Danny V Quaranta

doi:10.1007/s00408-022-00514-5

Abstract

PurposeAnesthetics are required for procedures that deliver drugs/biologics, infectious/inflammatory agents, and toxicants directly to the lungs. However, the possible confounding effects of anesthesia on lung inflammation and injury are underreported. Here, we evaluated the effects of two commonly used anesthetic regimens on lung inflammatory responses to ozone in mice.MethodsWe tested the effects of brief isoflurane (Iso) or ketamine/xylazine/atipamezole (K/X/A) anesthesia prior to ozone exposure (4 h, 3 ppm) on lung inflammatory responses in mice. Anesthesia regimens modeled those used for non-surgical intratracheal instillations and were administered 1–2 h or 24 h prior to initiating ozone exposure.ResultsWe found that Iso given 1–2 h prior to ozone inhibited inflammatory responses in the lung, and this effect was absent when Iso was given 23–24 h prior to ozone. In contrast, K/X/A given 1–2 h prior to ozone increased lung and systemic inflammation.ConclusionOur results highlight the need to comprehensively evaluate anesthesia as an experimental variable in the assessment of lung inflammation in response to ozone and other inflammatory stimuli.

Highlights

Ozone (O3) is a widespread air toxicant with well-established inflammatory effects in the lungs, but it affects other organs, such as the liver, spleen, and brain
Since drugs or other interventions to be administered intratracheally would ideally be given a short time before exposure to ozone to maximize their effects/minimize their metabolism, we evaluated anesthesia administration at 1–2 h prior to ozone exposure
The controls for ketamine were IP injected with saline, whereas Iso controls were not, we found that IP injections did not significantly influence the measured outcomes, and so we combined the Iso and Ketamine no anesthesia control groups for analysis. O3 significantly increased Whole-lung lavage (WLL) total cells, macrophages, and neutrophils except in the 1–2-h Iso group (Fig. 2A–C)

Summary

Introduction

Ozone (O3) is a widespread air toxicant with well-established inflammatory effects in the lungs, but it affects other organs, such as the liver, spleen, and brain. Approaches for selectively inhibiting lung inflammation may provide insight on the systemic effects of O3 and could involve direct delivery of substances to the lungs through the trachea prior to O3 exposure Volatile anesthetics such as isoflurane are frequently used for intratracheal instillations and other surgeries [1,2,3]. Isoflurane can have anti-inflammatory effects [4, 5], which may be most potent in the respiratory tract since it is the first site of exposure Injectable anesthetics such as ketamine/xylazine are used for intratracheal instillations [6], but may modulate inflammatory responses [7,8,9,10]. We found that Iso and K/X/A modify lung inflammation in response to O3

Methods

Results

Conclusion