The effect of continuous digital hypothermia on lamellar energy metabolism and perfusion during laminitis development in two experimental models.

Abstract

BACKGROUND: Continuous digital hypothermia (CDH) prevents lamellar failure in the euglycaemic hyperinsulinaemic clamp (EHC) and oligofructose (OF) laminitis models, but the mechanisms remain unclear. OBJECTIVES: To evaluate the effects of CDH on lamellar energy metabolism and perfusion in healthy horses and during EHC and OF laminitis models. STUDY DESIGN: In vivo experiment. METHODS: Archived samples were used from Standardbred geldings that received no treatment (CON) (n&#xa0;=&#xa0;8) or underwent EHC (n&#xa0;=&#xa0;8) or OF (n&#xa0;=&#xa0;6) laminitis models. Both forelimbs were instrumented with a lamellar microdialysis system, and one forelimb was cooled (CDH) with the other maintained at ambient temperature (AMB). Microdialysate was collected every 6&#xa0;hours and analysed for glucose, lactate and pyruvate concentrations and lactate to pyruvate ratio (L:P). Microdialysis urea clearance was used to estimate lamellar tissue perfusion. Data were analysed using a mixed-effects linear regression model. RESULTS: Glucose did not change in CDH limbs relative to AMB in CON (P&#xa0;=&#xa0;.3), EHC (P&#xa0;=&#xa0;.3) or OF (P&#xa0;=&#xa0;.6) groups. There was a decrease in lactate (P&#xa0;<&#xa0;.001) and pyruvate (P&#xa0;<&#xa0;.01) in CDH limbs relative to AMB in all groups. L:P decreased in CON CDH relative to CON AMB (P&#xa0;<&#xa0;.001) but was not different in EHC (P&#xa0;=&#xa0;.6) and OF (P&#xa0;=&#xa0;.07) groups. Urea clearance decreased in CDH limbs relative to AMB in CON (P&#xa0;=&#xa0;.002) and EHC (P&#xa0;<&#xa0;.001), but not in OF (P&#xa0;=&#xa0;.4). MAIN LIMITATIONS: The EHC model may not mimic natural endocrinopathic laminitis. CONCLUSIONS: CDH caused a marked decrease in lamellar glucose metabolism (CON, EHC and OF) and perfusion (CON and EHC) without affecting lamellar glucose concentration. Although cellular energy failure is not a primary pathophysiological event in EHC and OF laminitis models, CDH may act by limiting energy supply to pathologic cellular processes whilst preserving those critical to lamellar homoeostasis.