DOI: 10.5061/dryad.xpnvx0knv
title: Dexmedetomidine preconditioning reduces ischemia-reperfusion injury in equine model of large colon volvulus

description: Background: Large colon volvulus is a common cause of colic in horses with
 high morbidity and mortality when not promptly resolved surgically. More
 treatment options are needed to improve the outcome of these cases by
 ameliorating the damage caused by ischemia and reperfusion injury to the
 large colon. Objective: To determine the effect of preconditioning with
 dexmedetomidine prior to induction of ischemia-reperfusion (IR) injury in
 a large colon volvulus model in the horse. Study Design: Randomized
 prospective experimental blinded study. Methods: Horses received either a
 dexmedetomidine (DEX) or saline (CON) constant rate infusion (CRI)
 immediately following induction of anesthesia. Venous, arterial, and
 transmural occlusion of a section of the large colon was then performed
 for three hours, after which the ligatures and clamps were removed to
 allow for reperfusion for further three hours. Full thickness biopsies of
 the large colon were taken at baseline, 1 and 3 hours of ischemia, and at
 1 and 3 hours of reperfusion for histological analysis. Results: The
 severity of crypt epithelial loss (DEX= 2.1 (0.8-2.8), CON= 3.1(2.5-4), p
 = 0.03) and mucosal hemorrhage was decreased (DEX= 2.1 (1.3-3), CON=
 3.5(2.5-4), p = 0.03) in group DEX compared to group CON. Crypt length
 remained longer (DEX= 369.5±91.7 µm, CON= 238.5±72.6 µm, p = 0.02) and
 interstitium to crypt (I:C) ratio remained lower (DEX= 1.4 (1-1.7), CON=
 2.6 (1.8-5.9), p = 0.03) in group DEX compared to group CON during
 reperfusion. Main Limitations: Clinical applicability of pharmacologic
 preconditioning is limited.
description: Horses were anesthetized and prepared for aseptic celiotomy, and
 a 20-cm ventral midline incision was made. The large colon was
 exteriorized and placed on a plastic drape.  Approximately 15-20 minutes
 following induction of anesthesia, a 1- cm full thickness wedge biopsy of
 the antimesenteric border of either the dorsal or ventral colon (randomly
 assigned) was obtained as a baseline sample and the biopsy site was
 closed. A 40-cm area of dorsal and ventral colon centered over the pelvic
 flexure was then subjected to ischemia using Payr intestinal clamps to
 create transmural compression and arterial and venous ligation.  The
 colon, the colonic vasculature, and the associated mesentery was then
 surgically divided at the pelvic flexure so that the two ends no longer
 communicated to avoid the possibility of biopsy acquisition during
 ischemia affecting the reperfused tissue.  Each colonic
 segment was assigned randomly to either ischemic sampling or reperfusion
 sampling groups. A similar biopsy was obtained from the ischemic sampling
 portion of colon after one and three hours of ischemia. The colon was
 returned to the abdomen and the body wall temporarily closed with towel
 clamps between each biopsy.  After 3 hours of ischemia
 the ligatures and clamps were removed from the reperfusion assigned
 colonic segment to allow for reperfusion. Sampling took place similarly
 after one and three hours of reperfusion from the portion of colon
 assigned to reperfusion sampling. Biopsy sites were closed in two layers.
 The animals were humanely euthanized under general anesthesia after the
 final sample was collected. Biopsy samples were fixed
 in 10% formalin, prior to routine trimming in a plane parallel to the
 outer longitudinal muscularis, followed by histoprocessing, microtomy and
 staining with hematoxylin-eosin (H&E). The samples were
 histologically analyzed using brightfield microscopy by a board-certified
 pathologist who was blinded to the treatment. To
 incorporate a broad range of morphologic characteristics that may be
 associated with colon viability following IR injury, the specimens were
 analyzed and scored using the quantitative and semi-quantitative scoring
 system.
description: # Dexmedetomidine preconditioning reduces ischemia-reperfusion injury in
 equine model of large colon volvulus
 Colon tissue samples
 collected from experimental animals under general anesthesia. Full
 thickness biopsies of the large colon were taken at baseline, after 1 and
 3 hours of ischemia, and after 1 and 3 hours of reperfusion for
 histological analysis. Horses received during ischemia and reperfusion
 either dexmedetomidine (precon) or saline (control). ## Description of the
 data and file structure Biopsy samples were fixed in 10% formalin, prior
 to routine trimming in a plane parallel to the outer longitudinal
 muscularis, followed by histoprocessing, microtomy and staining with
 hematoxylin-eosin (H&E). The samples were histologically analyzed
 using brightfield microscopy by a board-certified pathologist who was
 blinded to the treatment. To incorporate a broad range of morphologic
 characteristics that may be associated with colon viability following IR
 injury, the specimens were analyzed and scored using the quantitative and
 semi-quantitative scoring system. Description of time points: H1-C1D:
 sample from the dorsal colon before ischemia H1-C1V: sample from the
 ventral colon before ischemia H1-I1: sample from the colon after one hour
 of ischemia H1-I2: sample from the colon after three hours of ischemia
 H1-R1: sample from the colon after one hour of reperfusion H1-R2: sample
 from the colon after three hours of reperfusion Description of samples Avg
 Crypt Length, Precon mean: mean value of the colon crypt length in the
 precon group           Avg Crypt Length, percon, sd: standard deviation of
 the colon crypt length in the precon group Avg Crypt Length, control,
 mean: mean value of the colon crypt length in the control group Avg Crypt
 Length, control, sd: standard deviation of the colon crypt length in the
 control group Avg I:C Ratio, precon, median: median interstitium (I) to
 crypt (C) ratio in the precon group Avg I:C Ratio, precon, upper limit:
 upper limit of the interstitium (I) to crypt (C) ratio in the precon group
 Avg I:C Ratio, precon, lower limit: lower limit of the interstitium (I) to
 crypt (C) ratio in the precon group Avg I:C Ratio, control, median :
 median interstitium (I) to crypt (C) ratio in the control group Avg I:C
 Ratio, control, upper limit: upper limit of the interstitium (I) to crypt
 (C) ratio in the control group Avg I:C Ratio, control, lower limit: lower
 limit of the interstitium (I) to crypt (C) ratio in the control group Avg
 %LE Loss Ratio, precon, median: median percent luminal epithelial loss in
 the precon group Avg %LE Loss Ratio, precon, upper limit: upper limit of
 the percent luminal epithelial loss in the precon group Avg %LE Loss
 Ratio, precon lower limit: lower limit of the percent luminal epithelial
 loss in the precon group Avg %LE Loss Ratio, control, median: median
 percent luminal epithelial loss in the control group Avg %LE Loss Ratio,
 control upper limit: upper limit of the percent luminal epithelial loss in
 the control group Avg %LE Loss Ratio, control, lower limit: lower limit of
 the percent luminal epithelial loss in the control group Avg %LG Loss
 Ratio, precon, median: median percent crypt epithelial loss in the precon
 group Avg %LG Loss Ratio, precon, upper limit: upper limit of the percent
 crypt epithelial loss in the precon group Avg %LG Loss Ratio, precon lower
 limit: lower limit of the percent crypt epithelial loss in the precon
 group Avg %LG Loss Ratio, control, median: median percent crypt epithelial
 loss in the control group Avg %LG Loss Ratio, control, upper limit: upper
 limit of the percent crypt epithelial loss in the control group Avg %LG
 Loss Ratio, control, lower limit: lower limit of the percent crypt
 epithelial loss in the control group Avg Muc Hem, precon, median: median
 amount of mucosal hemorrhage in the precon group Avg Muc Hem, precon,
 upper limit: upper limit of the amount of mucosal hemorrhage in the precon
 group Avg Muc Hem, precon, lower limit: lower limit of the amount of
 mucosal hemorrhage in the precon group Avg Muc Hem, control, median:
 median amount of mucosal hemorrhage in the control group Avg Muc Hem,
 control, upper limit: upper limit of the amount of mucosal hemorrhage in
 the control group Avg Muc Hem, control, lower limit: lower limit of the
 amount of mucosal hemorrhage in the control group