Lamellar energy metabolism and perfusion in the euglycaemic hyperinsulinaemic clamp model of equine laminitis.

Abstract

Hyperinsulinaemia is associated with the development of endocrinopathic laminitis; however, the mechanisms remain unclear. Evaluate the effects of hyperinsulinaemia on lamellar energy metabolism and perfusion during laminitis development. In vivo experiment. Eight Standardbred horses were instrumented with a microdialysis probe in the lamellae of a forelimb. A 24hours baseline period (BASELINE) was followed by 48hours of a continuous euglycaemic hyperinsulinaemic clamp (EHC) from 24 to 72hours (CLAMP). Microdialysate was collected every 6hours 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. Archived microdialysis samples from six identically instrumented Standardbred horses served as controls (CON). Variables were compared over time and between EHC and CON horses using a mixed-effects linear regression model. Glucose concentration decreased during the CLAMP period in CON and EHC horses (P<.001), but there was no difference between CON and EHC (P>.9). Lactate concentration increased during the CLAMP period in CON and EHC horses (P<.001), however, the rate of increase was significantly higher in EHC horses relative to CON (P=.014). There was a relative increase in pyruvate concentration in EHC horses compared with CON during the CLAMP period (P=.03). L:P increased significantly in CON horses during the CLAMP period (P<.001) but not in EHC (P=.1). Urea clearance did not change in CON (P=.9) or EHC (P=.05) during the CLAMP, but did increase in EHC relative to CON (P=.02). The effects of microdialysis probe implantation on perfusion and metabolism remain unclear. The EHC model may not mimic natural endocrinopathic laminitis. Laminitis developed without evidence of lamellar hypoperfusion or energy stress. Therapies to improve perfusion are unlikely to affect the initial development of endocrinopathic laminitis.