Dexmedetomidine preconditioning reduces ischaemia–reperfusion injury in equine model of large colon volvulus

Abstract

AbstractBackgroundLarge colon volvulus is a cause of colic in horses with high morbidity and mortality when not promptly treated. More treatment options are needed to improve the outcome of these cases by protecting against the damage caused by ischaemia and reperfusion injury.ObjectivesTo determine the effect of preconditioning with dexmedetomidine prior to induction of ischaemia–reperfusion (IR) injury in a large colon volvulus model in the horse.Study designRandomised blinded in vivo experiments.MethodsHorses received either a dexmedetomidine (DEX) or saline (CON) constant rate infusion (CRI) immediately following induction of anaesthesia. Venous, arterial, and transmural occlusion of a section of the large colon was performed for 3 h, after which the ligatures and clamps were removed to allow for reperfusion for 3 h. Biopsies of the large colon were taken at baseline, 1 and 3 h of ischaemia, and at 1 and 3 h of reperfusion.ResultsThe severity of crypt epithelial loss (DEX = 2.1 [0.8–2.8], CON = 3.1 [2.5–4], p = 0.03) and mucosal haemorrhage was decreased (DEX = 2.1 [1.3–3], CON = 3.5 [2.5–4], p = 0.03) in group DEX compared to group CON when graded on a scale of 0–4. Crypt length remained longer (DEX = 369.5 ± 91.7 μm, CON = 238.5 ± 72.6 μm, p = 0.02) and interstitium to crypt (I:C) ratio remained lower (DEX = 1.4 (1–1.7), CON = 2.6 [1.8–5.9], p = 0.03) in group DEX compared to group CON during reperfusion.Main limitationsClinical applicability of pharmacologic preconditioning is limited.ConclusionPreconditioning with a dexmedetomidine CRI prior to IR injury demonstrated a protective effect histologically on the large colon in the horse. Further investigation into postconditioning with dexmedetomidine is warranted as a possible intervention in colic cases suspected of being large colon volvulus.