Abstract
Surgical attenuation of a congenital portosystemic shunt (CPSS) results in increased portal vein perfusion, liver growth and clinical improvement. Portal lipopolysaccharide (LPS) is implicated in liver regeneration via toll-like receptor (TLR) 4 mediated cytokine activation. The aim of this study was to investigate factors associated with LPS in dogs with CPSS. Plasma LPS concentrations were measured in the peripheral and portal blood using a limulus amoebocyte lysate (LAL) assay.LPS concentration was significantly greater in the portal blood compared to peripheral blood in dogs with CPSS (P = 0.046) and control dogs (P = 0.002). LPS concentrations in the peripheral (P = 0.012) and portal (P = 0.005) blood of dogs with CPSS were significantly greater than those of control dogs. The relative mRNA expression of cytokines and TLRs was measured in liver biopsies from dogs with CPSS using quantitative PCR. TLR4 expression significantly increased following partial CPSS attenuation (P = 0.020). TLR4 expression was significantly greater in dogs that tolerated complete CPSS attenuation (P = 0.011) and those with good portal blood flow on pre-attenuation (P = 0.004) and post-attenuation (P = 0.015) portovenography. Serum interleukin (IL)-6 concentration was measured using a canine specific ELISA and significantly increased 24 h following CPSS attenuation (P < 0.001). Portal LPS was increased in dogs with CPSS, consistent with decreased hepatic clearance. TLR4 mRNA expression was significantly associated with portal blood flow and increased following surgery. These findings support the concept that portal LPS delivery is important in the hepatic response to surgical attenuation. Serum IL-6 significantly increased following surgery, consistent with LPS stimulation via TLR4, although this increase might be non-specific.
Highlights
A congenital portosystemic shunt (CPSS) is an abnormal vessel connecting the portal venous system to the systemic venous system (Payne et al, 1990)
TLR4 mRNA expression was significantly associated with portal blood flow and increased following surgery
We have previously shown that the hepatic expression of hepatocyte growth factor (HGF) and methionine adenosyltransferase 2 A, which are both markers of hepatocyte replication, are significantly increased following partial CPSS attenuation (Tivers et al, 2014a)
Summary
A congenital portosystemic shunt (CPSS) is an abnormal vessel connecting the portal venous system to the systemic venous system (Payne et al, 1990). Surgical CPSS attenuation is recommended to restore normal portal blood flow. Successful CPSS attenuation results in resolution of clinical signs, improvements in hepatic function and portal perfusion and increased liver volume (Hunt and Hughes, 1999; Kummeling et al, 2010; Lee et al, 2006; Stieger et al, 2007). These findings suggest that the return of normal hepatic size and function is achieved by liver regeneration. We have previously shown that markers of hepatocyte replication are associated with the degree of liver development and the response to surgery in dogs with CPSS, supporting a role for hepatic regeneration (Tivers et al, 2014a)
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