Lipopolysaccharide and toll-like receptor 4 in dogs with congenital portosystemic shunts

Abstract

Plasma LPS concentrations were measured in the peripheral and portal blood 37 using a limulus amoebocyte lysate (LAL) assay. LPS concentration was significantly 38 greater in the portal blood compared to peripheral blood in dogs with CPSS (P = 39 0.046) and control dogs (P = 0.002). LPS concentrations in the peripheral (P = 0.012) 40and portal (P = 0.005) blood of dogs with CPSS were significantly greater than those 41 for control dogs. The relative mRNA expression of cytokines and TLRs was 42 measured in liver biopsies from dogs with CPSS using quantitative PCR. TLR4 43 expression significantly increased following partial CPSS attenuation (P = 0.020). 44 TLR4 expression was significantly greater in dogs that tolerated complete CPSS 45 attenuation (P = 0.011) and those with good portal blood flow on pre-attenuation (P = 46 0.004) and post-attenuation (P = 0.015) portovenography. Serum IL-6 concentration 47 was measured using a canine specific ELISA and significantly increased 24 h 48 following CPSS attenuation (P < 0.001). 49Portal LPS was increased in dogs with CPSS, consistent with decreased 50 hepatic clearance. TLR4 mRNA expression was significantly associated with portal 51 blood flow and increased following surgery. These findings support the concept that 52 portal LPS delivery is important in the hepatic response to surgical attenuation. Serum 53 IL-6 significantly increases following surgery, consistent with LPS stimulation via 54 TLR4, although this increase might be non-specific. 55 3

Clinical response in dogs with acute hemorrhagic diarrhea syndrome following randomized probiotic treatment or fecal microbiota transplant

“…In humans with sepsis, serum LPS increases, regardless of blood culture positivity ( 42 , 43 ). LPS increases in naturally occurring ( 42 – 46 ) and induced ( 47 ) GI hyperpermeability models or decreased systemic bacterial clearance ( 48 ) but has not been previously evaluated in AHDS dogs. While other GI permeability biomarkers have not correlated with AHDS outcomes ( 2 ), LPS correlated moderately with fecal scores and disease severity.…”

Clinical characteristics of, prognostic factors for, and long-term outcome of dogs with multiple acquired portosystemic shunts: 72 cases (2000–2018)

“…Although the condition is not entirely understood, it is believed to be secondary to circulating neurotoxins that can impair neuron and astrocyte function, cause an inflammatory response, and alter the permeability of the blood-brain barrier, impairing cerebral function. [43][44][45][46] Clinical signs associated with hepatic encephalopathy are variable and can range from excitatory activity, such as seizures, to inhibitory activity, such as lethargy, ataxia, and unresponsiveness. 3,11,24 Interestingly, dogs in the present study with more severe neurologic signs did not have an increased odds of death related to MAPSSs when compared to dogs with mild neurologic signs such as depressed mentation.…”

Haematology and coagulation profiles in cats with congenital portosystemic shunts

“…1,8,9,11 This leukocytosis in dogs is thought to be related to inflammation due to inadequate hepatic clearance of lipopolysaccharide and chronic stress. 11,40 A recent study showed evidence of reduced inflammation following CPSS attenuation in dogs in the form of reduction in neutrophil concentration, monocyte concentration and C-reactive protein. 11 It is unclear why cats with a CPSS do not demonstrate increased WBC counts similar to dogs.…”