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Simple Summary: Intestinal disease with disruption of blood flow (ischaemia) is associated with a relatively high mortality rate in horses. Many investigations have focused on treatment strategies that reduce tissue injury. The sedative drug dexmedetomidine was found to precondition intestines subjected to ischaemia, resulting in reduced injury in different species, including horses. However, it remains unknown what exactly mediates this effect. Therefore, the aim of this study was to determine the effect of dexmedetomidine preconditioning with and without the administration of a drug called vatinoxan, which antagonizes the action of dexmedetomidine on the peripheral alpha2 adrenoreceptor. In 12 horses under general anaesthesia, intestinal ischaemia was implemented, followed by tissue reperfusion. Six horses received dexmedetomidine only (group Dex), while the other six horses received both dexmedetomidine and vatinoxan (DexV). Intestinal samples were taken to evaluate the degree of tissue injury, followed by a comparison between the groups. There was no difference before and directly after the disruption of tissue blood flow. After reperfusion, group DexV showed less mucosal injury compared to group Dex. There were no significant differences in programmed cell death between the treatment groups. In conclusion, antagonizing the peripheral alpha2 adrenoreceptors did not negatively affect dexmedetomidine preconditioning. Pharmacological preconditioning with dexmedetomidine has been shown to ameliorate intestinal ischaemia reperfusion injury in different species, including horses. However, it remains unknown if this effect is related to alpha2 adrenoreceptor activity. Therefore, the aim of this study was to determine the effect of dexmedetomidine preconditioning with and without the administration of the peripheral alpha2 antagonist vatinoxan. This prospective randomized experimental trial included 12 horses equally divided between two treatment groups. Horses in group Dex received a bolus of dexmedetomidine followed by a continuous rate infusion (CRI), while group DexV additionally received vatinoxan as bolus and CRI. A median laparotomy was performed under general anaesthesia, and jejunal ischaemia was applied for 90 min, followed by 30 min of reperfusion. Mucosal damage was evaluated in full thickness biopsies by use of a semiquantitative mucosal injury score and by determining the apoptotic cell counts with immunohistochemical staining for cleaved caspase-3 and TUNEL. Comparisons between the groups and time points were performed using non-parametric tests (p < 0.05). During pre-ischaemia and ischaemia, no differences could be found in mucosal injury between the groups. After reperfusion, group DexV showed lower mucosal injury scores compared to group Dex. The apoptotic cell counts did not differ between the groups. In conclusion, antagonizing the peripheral alpha2 adrenoreceptors did not negatively affect dexmedetomidine preconditioning. [ABSTRACT FROM AUTHOR]

Simple Summary: Alpha-2 agonists are commonly used sedatives in horses. They are known for their inhibitive effects on gastrointestinal motility, which limits their use in horses with colic. Dexmedetomidine belongs to the α2 agonist drug class, and studies in human patients have reported that it may enhance gastrointestinal function instead of inhibiting it. Therefore, the aim of this study was to investigate the effect of dexmedetomidine on intestinal smooth muscle function in horses. To evaluate this in varying degrees of intestinal damage, tissue samples were taken from 12 horses prior to and during the disruption of small intestinal blood flow (pre-ischaemia and ischaemia), as well as following the reinstatement of blood supply (reperfusion). We found that the circular smooth muscle (CSM) contractility was not affected by ischaemia, whereas the longitudinal smooth muscle (LSM) showed an increase in both spontaneous and nerve mediated contractile activity. The addition of dexmedetomidine caused a decrease in the spontaneous contractile activity of CSM, but an increase in that of LSM. During ischaemia, dexmedetomidine also mildly increased the nerve mediated contractile activity. These results may indicate a stimulatory effect of dexmedetomidine on small intestinal contractility. However, the influence of dexmedetomidine administration on intestinal motility in vivo needs to be further investigated. α2 agonists are frequently used in horses with colic, even though they have been shown to inhibit gastrointestinal motility. The aim of this study was to determine the effect of dexmedetomidine on small intestinal in vitro contractility during different phases of ischaemia. Experimental segmental jejunal ischaemia was induced in 12 horses under general anaesthesia, and intestinal samples were taken pre-ischaemia and following ischaemia and reperfusion. Spontaneous and electrically evoked contractile activity of the circular and longitudinal smooth muscles were determined in each sample with and without the addition of dexmedetomidine. During a second experiment, tetrodotoxin was added to determine if the effect was neurogenic. We found that the circular smooth muscle (CSM) contractility was not affected by ischaemia, whereas the longitudinal smooth muscle (LSM) showed an increase in both spontaneous and induced contractile activity. The addition of dexmedetomidine caused a decrease in the spontaneous contractile activity of CSM, but an increase in that of LSM, which was not mediated by the enteric nervous system. During ischaemia, dexmedetomidine also mildly increased the electrically induced contractile activity in LSM. These results may indicate a stimulatory effect of dexmedetomidine on small intestinal contractility. However, the influence of dexmedetomidine administration on intestinal motility in vivo needs to be further investigated. [ABSTRACT FROM AUTHOR]

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. 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. [ABSTRACT FROM AUTHOR]