Dexmedetomidine preconditioning reduces ischemia-reperfusion injury in equine model of large colon volvulus
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Jan 31, 2024 version files 14.82 KB
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Public_data.xlsx
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README.md
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Abstract
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.
README: Dexmedetomidine preconditioning reduces ischemia-reperfusion injury in equine model of large colon volvulus
https://doi.org/10.5061/dryad.xpnvx0knv
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
Methods
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.