Influence of general anaesthesia on circulating biomarkers of glucose metabolism in pigs.

Pigs are widely used in metabolic research with procedures often requiring general anaesthesia. The aim was to investigate the effect of four different anaesthetic protocols: 1) isoflurane inhalation, 2) propofol infusion, 3) a mixture of tiletamine, zolazepam, medetomidine, ketamine and butorphanol (TZMKB)) and 4) ketamine combined with midazolam and xylazine (KMX)) on selected biomarkers during basal and glucose stimulated conditions. Eight domestic pigs were included in a cross-over design. Plasma concentrations of glucose, insulin, C-peptide, glucagon, cortisol, triglycerides, total cholesterol, aspartate amino transferase and alanine amino transferase, creatinine, urea, fructosamine, albumin, free fatty acids (FFAs) and glycerol were measured at baseline, during 2 h of anaesthesia and during 1 h of recovery. Intravenous glucose tolerance test (IVGTT, 0.5 g glucose/kg) was performed after 1 h of anaesthesia. Glucose disappearance rate and areas under the insulin, C-peptide and glucagon curves from the IVGTT were calculated. All four anaesthetic protocols affected glucose metabolism parameters significantly compared with un-anaesthetised pigs, which was particularly evident during IVGTT and for TZMKB and KMX anaesthesia. Propofol additionally influenced the plasma concentrations of triglycerides, FFAs and glycerol significantly. The remaining circulating biomarkers were largely unaffected by anaesthesia. These data underline the importance of considering the anaesthetic protocol in porcine studies of circulating metabolic biomarkers.

Hyperinsulinaemic hypoglycaemia in non-anaesthetized Göttingen minipigs induces a counter-regulatory endocrine response and electrocardiographic changes.

The potentially fatal cardiovascular effects of hypoglycaemia are not well understood and large animal models of the counter-regulatory responses and cardiovascular consequences of insulin-induced hypoglycaemia are needed to understand the mechanisms in humans. The aim of this study was to develop a human-like minipig model of hypoglycaemia including healthy and diabetic pigs to investigate endocrine, electrocardiographic and platelet effects. Hypoglycaemia was induced using a hyperinsulinaemic, hypoglycaemic clamp and an insulin bolus protocol. Plasma glucose, glucagon, C-peptide, insulin, epinephrine and platelet aggregation responses were measured before, during and after hypoglycaemia. Continuous electrocardiographic recordings were obtained. Hypoglycaemia at a plasma glucose concentration of 0.8-1.0 mM in the clamp induced 25-fold increase in epinephrine and sixfold and threefold increase in glucagon for healthy and diabetic pigs, respectively. The hypoglycaemic clamp induced QTc-interval prolongation and increase in cardiac arrhythmias. In the bolus approach, the non-diabetic group reached plasma glucose target of 1.5 mM and QTc-interval was prolonged after insulin injection, but before glucose nadir. The diabetic group did not reach hypoglycaemic target, but still demonstrated QTc-interval prolongation. These results demonstrate effects of hyperinsulinaemic hypoglycaemia closely resembling human physiology, indicating the minipig as a translational animal model of counter-regulatory endocrine and myocardial effects of hypoglycaemia.