Protective effects of dexmedetomidine on small intestinal ischaemia‐reperfusion injury in horses

Abstract

Background Strangulating small intestinal lesions in the horse have increased morbidity and mortality compared to nonstrangulating obstructions due to mucosal barrier disruption and subsequent endotoxaemia. Objectives To investigate protective effects of dexmedetomidine on small intestinal ischaemia‐reperfusion injury in the horse. Study design Randomised, controlled, experimental study. Methods Eighteen systemically healthy horses were randomly assigned to three groups: control, preconditioning, and post‐conditioning. During isoflurane anaesthesia, complete ischaemia was induced in a 1‐m segment of jejunum for 90 minutes. Horses in the preconditioning and post‐conditioning groups received dexmedetomidine (3.5 µg/kg followed by 7 µg/kg/h) before (preconditioning) or after beginning ischaemia (post‐conditioning), and during reperfusion. Jejunal biopsies were collected before ischaemia (baseline‐1), at the end of the ischaemic period (ischaemia), and 30 minutes after reperfusion (reperfusion‐1). Additional biopsies were taken 24 hours after reperfusion from ischaemia‐reperfusion‐injured jejunum (reperfusion‐2). Epithelial injury was scored histologically, and morphometric analyses were used to calculate villus surface area (VSA) denuded of epithelium. Data were analysed using analysis of variance, Kruskal‐Wallis and Wilcoxon two‐sample tests. Results In the control group, epithelial injury scores and percentage of VSA denudation for ischaemia‐reperfusion‐injured jejunum were higher compared to baseline‐1 at all time points. The ischaemia and both reperfusion samples from the pre‐ and post‐conditioning groups had lower epithelial injury scores and percentage of VSA epithelial denudation compared to the control group, with no difference from baseline‐1 at any time point for the preconditioning group. Main limitations Preconditioning has limited application in the clinical setting with naturally occurring strangulating small intestinal lesions. Conclusions Dexmedetomidine was protective for small intestinal ischaemia‐reperfusion injury in the horse when administered before or during ischaemia.

Adaptive mechanisms in no flow vs. low flow ischemia in equine jejunum epithelium: Different paths to the same destination

“…The intestinal epithelium is most sensitive to IRI ( 9 , 10 ) and thus its integrity is decisive for the fate of the patient. As the barrier between the gut lumen and the rest of the organism, it is a critical factor for the systemic health of the whole organism and thus the outcome of intestinal IRI.…”

Low Flow versus No Flow: Ischaemia Reperfusion Injury Following Different Experimental Models in the Equine Small Intestine

“…In small intestinal ischaemia models, segmental jejunal ischaemia has been created by occluding the mesenteric vessels with ligatures [ 3 , 4 , 5 , 6 , 7 ] or haemostatic clamps [ 8 , 9 , 10 , 11 ]. For the duration of ischaemia, 90 to 120 min has frequently been elected [ 5 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. However, reperfusion times vary markedly between the different studies, and sequential measurements during ischaemia and reperfusion are lacking.…”

“…Differing degrees of vascular occlusion have been used, as it remains unclear what type of ischaemia most accurately represents the clinical situation. Consequently, ischaemia models with a complete elimination of intestinal blood flow (no flow, NF), and models with varying degrees of blood flow reduction (low flow, LF) have been implemented [ 3 , 4 , 8 , 10 , 11 , 12 , 14 , 16 , 17 , 18 , 19 , 20 ].…”

“…Due to the variation in the type of experimental ischaemia applied, the comparability of the results between different studies is limited, and inconsistent results have been reported. One point of discussion is the occurrence of reperfusion injury, with conflicting results regarding mucosal deterioration [ 3 , 5 , 8 , 9 , 15 ] or the increase in apoptotic cells [ 7 , 11 , 15 ] following LF or NF ischaemia during reperfusion. These discrepancies complicate the interpretation and hinder the extrapolation to the clinical patient.…”

Protective effects of dexmedetomidine in vital organ injury: crucial roles of autophagy

“…Since DEX is a highly selective α2 adrenoceptor agonist, it may mediate a broad spectrum of pharmacodynamic actions on these organs. In numerous animal studies [ 18 , 38 , 39 ], DEX appears to alleviate the inflammation responses and the I/R injury of multiple organs, i.e., the brain, liver, and intestines. More importantly, although α2 adrenoceptor is not found in the myocardium, a large body of previous studies suggest that DEX plays a protective role on myocardial I/R injury [ 40 , 41 ].…”