Experimental Hemorrhagic Shock Protocol in Swine Models: The Effects of 21-Aminosteroid on the Small Intestine

Abstract

BackgroundThe protective potential of lazaroids has been reported in previous studies on ischemia/reperfusion and induced hemorrhagic shock protocols.ObjectivesThe present study is the first experimental protocol on the effects of the antioxidant factor U-74389G on the small intestine of swine models in a hemorrhagic shock protocol and resuscitation with 3 different types of fluids.MethodsThe study included 49 Landrace breed swine that were divided into groups of 7 each. Hemorrhage was provoked 45 minutes after starting the surgical protocol (0 minutes), followed by resuscitation starting 30 minutes after haemorrhage ceased by using 3 different fluids. Three groups (Group A, resuscitation using blood; Group B, resuscitation with Ringer’s lactate solution; and Group C, resuscitation with hypertonic saline solution) underwent resuscitation with fluid alone, and another 3 groups (named A', B,' and C') were administered lazaroid U-74389G in addition to fluid. Control Group S underwent all the surgical procedures without hemorrhagic shock. Vital signs, complete blood count, and biochemical markers were analyzed, and tissue samples of the small intestine were collected from all animals. Further, malondialdehyde, tumor necrosis factor-α, and levels of inflammation in the tissue sample were measured.ResultsIn Group S-A-A' and Group S-C-C', the analysis did not show statistically significant differences in the percentage changes of histopathology, malondialdehyde, and tumor necrosis factor-α through time. In Group S-B-B', the malondialdehyde levels in the small intestine were reduced in both the B and B' groups, without lazaroid (Group B) (P = 0.038) and lazaroid (Group B') (P = 0.011), compared with Group S (control), but the group without lazaroid (Group B) had greater reduction in malondialdehyde levels than the group treated with lazaroid (Group B'). With regard to the biochemistry results, 24% reduction was observed for alkaline phosphatase (P = 0.022) in Group A' treated with lazaroid compared with that in the untreated group. Lastly, for the complete blood count parameters, a 14% reduction in white blood cells was observed in Group B', which was treated with lazaroid in all phases (P = 0.015) (absolute value = 6.23) compared with Group B (absolute value = 13.74).ConclusionsDespite few initial findings of this study suggesting that administration of lazaroid U-74389G may have some potential in attenuation of the effects of hemorrhagic shock in the small intestine of swine models, no differences remained after correction for multiple comparisons was made. Therefore, further research is required to investigate this result thoroughly.

Atezolizumab alleviates the immunosuppression induced by PD‑L1‑positive neutrophils and improves the survival of mice during sepsis

“…Histopathology was assessed according to the Chiu grading system, and histopathological scores (0-5 scale) were calculated following observation by light microscopy at ×200 magnification. The Chiu scoring standard of the ileal mucosa is divided into six levels according to the severity of injury: i) 0, the intestinal mucosal epithelium is normal without injury; ii) 1, the intestinal mucosal subepithelial space is widened and the capillaries have hyperemia; iii) 2, the intestinal mucosal subepithelial space is further extended and elevated, and separation of the epithelium and lamina propria occurs; iv) 3, part of the villous epithelium of the intestinal mucosa falls off; v) 4, the intestinal mucosal villous epithelium completely falls off, and capillary hemorrhages can be observed; and vi) 5, the intestinal mucosal lamina propria disintegrates, and mucosal bleeding ulcer occurs ( 21 , 22 ).…”

Experimental isolation and preservation of solid organs before transplantation: effects of pretreatment using four different molecules

“…The MDA concentration (nmol/g wet tissue) was calculated based on the third-order derivative peak height at 532 nm, which refers to the slope and intercept data of the computed least-squares fit using the standard calibration curve. 26 MDA levels were measured at baseline, immediately before organ retrieval, immediately after organ retrieval, and at 8 and 24 hours after organ retrieval.…”

Lazaroid U‑74389G in liver ischemia‑reperfusion injury: A swine model

“…A pre-medication injection with midazolam (0.5 mg/kg) and ketamine 15 mg/kg was administered intramuscularly (IM). Atropine (0.045 mg/kg) was administered IM in the neck at 10 min prior to intubation (22)(23)(24)(25)(26). Two polyethylene intravenous catheters (18G) were inserted into two peripheral veins in both ears for infusion of crystalloids and anesthetic drugs.…”

“…General anesthesia was maintained with continuous infusion of propofol at 6-8 mg/kg/h, as well as fentanyl (0.012 mg/kg; Janssen-Cilag International NV; Beerse, Belgium) and cisatracurium (0.5 mg/kg; GlaxoSmithKline Manufacturing SpA, Verona, Italy) and the animals were mechanically ventilated. The femoral vein was also catheterized for blood collection (23,25,26). During the experiment, the animals were continuously monitored by electrocardiography, pulse oximetry and measurement of arterial blood pressure.…”

“…Conversely, a recent study using an experimental protocol to induce hemorrhagic shock in swine revealed no protective effect of U-74389G in the small intestine according to the tissue MDA and serum alkaline phosphatase levels. Three groups underwent resuscitation with fluid alone, and in another 3 groups, the lazaroid U-74389G was administered in addition to fluid, while the control group underwent all the surgical procedures without hemorrhagic shock (23).…”