Letson, Hayley L., Morris, Jodie L., Biros, Erik, and Dobson, Geoffrey P. (2022) ALM induces cellular quiescence in the surgical margin 3 d following liver resection, hemorrhage, and shock. Journal of Surgical Research, 275. pp. 16-28.

PDF (Published Version) - Published Version Restricted to Repository staff only

 

1

Abstract

Introduction: The liver has a remarkable capacity to regenerate but not the resected lobe. Our aim was to examine the expression of a number of key genes of metabolism, proliferation, survival, and reprogramming 5 mm inside the resected margin following resuscitation with adenosine, lidocaine, and Mg2  (ALM) therapy.

Materials and methods: Anesthetized adult male SpragueeDawley rats randomly assigned to ALM treatment (n = 10) or Saline controls (n = 10) underwent liver resection (60% left lateral lobe) and uncontrolled bleeding. After 15 min, 3% NaCl +/- ALM bolus was administered, and after 60 min, a 4 h 0.9% NaCl +/-ALM stabilization ‘drip’ was commenced. After 72 h monitoring (or high moribund score), histopathology, inflammatory mediators, and relative expression of key genes of tissue repair were measured in the remaining left lateral liver.

Results: ALM animals survived 72 h compared to 23 h for Saline controls (P   0.002). In the surgical margin, ALM therapy showed preservation of cellular architecture, whereas controls had increased inflammation and diffuse necrosis. Liver proinflammatory cytokines were also 2- to 4-fold higher in Saline controls. ALM therapy dramatically suppressed (~70%) gene expression of four adenosine receptors, metabolic signaling, autophagy, apoptosis, and cell proliferation compared to controls, including suppression of the Yamanaka factors by up to 85%.

Conclusions: We conclude ALM therapy preserved hepatocyte architecture with less inflammation and necrosis 3 d after resection, hemorrhage, and shock. In addition, ALM induced cellular quiescence in the surgical margin, which may be a strategy for improved barrier protection and healing. Further studies are required to address this question.

Actions (Repository Staff Only)

Item Control Page