The immune response to systemically administered endotoxin in the murine intestinal microcirculation under pentobarbital versus isoflurane anesthesia

Clin Hemorheol Microcirc. 2024;86(4):457-465. doi: 10.3233/CH-231989.

Abstract

Background: Pentobarbital and isoflurane are commonly used veterinary anesthetics. Due to the dangers of overdose by repeat-bolus regimen of pentobarbital, isoflurane has been recommended. However, literature suggests isoflurane-induced inhibition of cytokine and adhesion molecule release, impacting leukocyte adhesion.

Objective: This study aims to characterize the impacts of pentobarbital versus isoflurane on leukocyte interactions within the intestinal microcirculation with and without endotoxin challenge.

Methods: Female BALB/c mice were subjected to pentobarbital or isoflurane (N = 20) and challenged with endotoxin or saline by intraperitoneal injection. The mice were kept under anesthesia for 2 hours. Fluorochromes, rhodamine-6 G and fluorescein isothiocyanate, were injected intravenously. To visualize leukocyte adhesion within the intestinal microcirculation, laparotomy and intravital microscopy was performed. Leukocyte rolling and adhesion was quantified offline in a blinded fashion.

Results: Within collecting venules, leukocyte rolling and adhesion showed no significant differences between pentobarbital and isoflurane anesthesia under basal conditions. Endotoxin challenge caused a similar response in both anesthetic groups. Within postcapillary venules, no statistical differences between the two anesthetics were found for adhering leukocytes under basal conditions or following endotoxin challenge either. However, leukocyte rolling after LPS-challenge was significantly decreased in postcapillary venules during isoflurane anesthesia compared to pentobarbital anesthesia.

Conclusions: Isoflurane anesthesia showed only minor differences in the immune response to endotoxin within the intestinal microcirculation compared to pentobarbital anesthesia. Due to the superior safety profile of volatile anesthetics, immunological studies may choose isoflurane over pentobarbital as the veterinary anesthetic of choice.

Keywords: Intravital microscopy; isoflurane; leukocytes; microcirculation; pentobarbital.

MeSH terms

  • Anesthesia / methods
  • Anesthetics, Inhalation / pharmacology
  • Animals
  • Cell Adhesion / drug effects
  • Endotoxins* / pharmacology
  • Female
  • Intestines* / blood supply
  • Intestines* / drug effects
  • Isoflurane* / pharmacology
  • Leukocyte Rolling / drug effects
  • Leukocytes / drug effects
  • Mice
  • Mice, Inbred BALB C*
  • Microcirculation* / drug effects
  • Pentobarbital* / pharmacology

Substances

  • Isoflurane
  • Endotoxins
  • Pentobarbital
  • Anesthetics, Inhalation