Dexmedetomidine Has Differential Effects on the Contractility of Equine Jejunal Smooth Muscle Layers In Vitro

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. ABSTRACT: 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.