Ischaemic preconditioning and pharmacological preconditioning with dexmedetomidine in an equine model of small intestinal ischaemia-reperfusion

Abstract

<jats:title>Abstract</jats:title><jats:p>Small intestinal strangulation associated with ischaemia-reperfusion injury (IRI) is common in horses. In laboratory animals IRI can be ameliorated by ischaemic preconditioning (IPC) and pharmacological preconditioning (PPC) with dexmedetomidine. The aim of this study was to determine the effect of PPC with dexmedetomidine or IPC in an equine model of small intestinal ischaemia-reperfusion (IR).</jats:p><jats:p>In a randomized controlled experimental trial, 15 horses were assigned to three groups: control (C), IPC, and PPC with dexmedetomidine (DEX). All horses were placed under general anaesthesia and 90% jejunal ischaemia was induced for 90 minutes, followed 30 minutes of reperfusion. In group IPC, three short bouts of ischaemia and reperfusion were implemented, and group DEX received a continuous rate infusion of dexmedetomidine prior to the main ischaemia. Jejunal biopsies were collected before ischaemia (P), and at the end of ischaemia (I) and reperfusion (R). Mucosal injury was assessed by the Chiu-Score, inflammatory cells were stained by cytosolic calprotectin. The degree of apoptosis and cell necrosis was assessed by cleaved-caspase-3 and TUNEL.</jats:p><jats:p>Parametric data were analyzed by two-way ANOVA for repeated measurements followed by Dunnetts t-test. Non parametric data were compared between groups at the different time points by a Kruskal-Wallis-Test and a Wilcoxon-2-Sample-test.</jats:p><jats:p>The mucosal injury score increased during I in all groups. After reperfusion, IRI further progressed in group C, but not in IPC and DEX. In all groups the number of cleaved caspase-3 and TUNEL positive cells increased from P to I. The number of TUNEL positive cells were lower in group DEX compared to group C after I and R. Infiltration with calprotectin positive cells was less pronounced in group DEX compared to group C, whereas in group IPC more calprotectin positive cells were seen.</jats:p><jats:p>In conclusion, IPC and DEX exert protective effects in experimental small intestinal ischaemia in horses.</jats:p>

Anaesthesia management of transvenous implantation of a single‐chamber, rate‐adaptive pacemaker in a donkey with high‐grade second and third degree atrioventricular block

“…The use of medetomidine in isoflurane‐anaesthetised horses presents several advantages such as MAC reduction, limited cardiopulmonary effects and improvement of the recovery quality 20 . Additionally, dexmedetomidine, the active D‐enantiomer of medetomidine, has been shown to present pharmacological preconditioning ameliorating ischaemia‐reperfusion injury of different organs, including myocardium, in laboratory animal 22 and small intestines in laboratory animals and horses 23,24 . Adding a CRI of lidocaine produces further MAC reduction 25,26 and has antiarrhythmic effects 16 (especially interesting during intracardiac catheter advancement where arrhythmias can occur).…”

Preconditioning with lidocaine and xylazine in experimental equine jejunal ischaemia

“…A protective effect has also been described for the more selective alpha-2 agonist dexmedetomidine. 6 The use of xylazine for clinical cases may be more feasible, as this drug is licensed for horses and already part of many established anaesthetic regimens. Other alpha-2 agonists, like detomidine and .0 (0.9-13.8) 5.9 (5.5-11.9)…”

“…A historical control group consisting of five Warmblood horses, with an age range of 2-14 years (5.4 ± 4.9 years) and the weight between 464 and 610 kg (544 ± 53 kg), was used to limit the amount of horses needed. This control group was taken from our previous study evaluating the preconditioning effect of dexmedetomidine, 6 using the same experimental model, anaesthetic regime and sample preparation as the current study. The horses were acquired by the equine hospital for educational purposes and were subjected to euthanasia due to problems unrelated to the gastrointestinal tract, such as orthopaedic disease.…”

“…4,5 Moreover, a protective effect of dexmedetomidine was identified in an experimental model of equine small intestinal strangulation. 6 This beneficial effect may be due to its anti-inflammatory and antiapoptotic properties. 4 To the authors' knowledge, there are no reports on a preconditioning effect of xylazine, a more commonly used alpha-2 agonist in horses.…”

Atorvastatin Attenuates Radiotherapy-Induced Intestinal Damage through Activation of Autophagy and Antioxidant Effects

“…In addition, the villus/crypt (V/C) ratio was determined by dividing the villus height by the crypt depth; a lower ratio indicated severe damage [23,24]. Several investigators have also adopted Chiu's score or modified Chiu's injury score to assess mucosal injury of the small intestine from ischemia/reperfusion by histopathological evaluation [25,26]. Histopathological changes were evaluated by investigators (Cheng CH and Wen SU) in a double-blinded fashion under supervision by a certified pathologist (Lee YH).…”