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

SIMPLE SUMMARY: One of the main causes of colic in horses is the occlusion of the intestinal blood vessels after displacement or entrapment of the small intestine. In search of new therapies to treat this lethal disease, experimental models have been used to simulate the clinical situation. Both low flow (LF) models with partial blood flow occlusion as well as no flow (NF) models with complete occlusion have been implemented in different studies. This has led to conflicting results and comparative studies are lacking. The objective of this study was to characterize the development of intestinal injury over time in two different experimental models implementing either partial or complete vessel occlusion. Under general anaesthesia, local intestinal blood flow was reduced by 80% in seven horses (LF), and by 100% in another seven horses (NF). The LF group exhibited more bleeding in the intestinal wall and a relatively high variability in intestinal oxygen levels and tissue damage. The NF group showed lower oxygen levels and decreased barrier function of the intestinal wall. These results aid in the selection of the suitable experimental model for future studies. The high variability following LF suggests that an NF model may produce more consistent intestinal damage. ABSTRACT: In experimental studies investigating strangulating intestinal lesions in horses, different ischaemia models have been used with diverging results. Therefore, the aim was to comparatively describe ischaemia reperfusion injury (IRI) in a low flow (LF) and no flow (NF) model. Under general anaesthesia, 120 min of jejunal ischaemia followed by 120 min of reperfusion was induced in 14 warmbloods. During ischaemia, blood flow was reduced by 80% (LF, n = 7) or by 100% (NF, n = 7). Intestinal blood flow and oxygen saturation were measured by Laser Doppler fluxmetry and spectrophotometry. Clinical, histological, immunohistochemical and Ussing chamber analyses were performed on intestinal samples collected hourly. Tissue oxygen saturation was significantly lower in NF ischaemia. The LF group exhibited high variability in oxygen saturation and mucosal damage. Histologically, more haemorrhage was found in the LF group at all time points. Cleaved-caspase-3 and calprotectin-stained cells increased during reperfusion in both groups. After NF ischaemia, the tissue conductance was significantly higher during reperfusion. These results aid in the selection of suitable experimental models for future studies. Although the LF model has been suggested to be more representative for clinical strangulating small intestinal disease, the NF model produced more consistent IRI.