The influence of the type of resuscitation fluid on gut injury and distant organ injury in a rat model of trauma/hemorrhagic shock
ABSTRACT Recognition that resuscitation with Ringers lactate (RL) potentiates trauma-hemorrhagic shock (T/HS)-induced organ injury and systemic inflammation has led to a search for improved initial fluid resuscitation regimens. However, one relatively neglected component in the search for new and novel resuscitation strategies is a determination of what fluid resuscitation therapy (i.e., control group) the new experimental regimen of interest should be tested against. Thus, we tested the effects of three commonly used resuscitation strategies on trauma-shock-induced gut and lung injury, as well as neutrophil activation and red blood cell (RBC) function.
Male Sprague Dawley rats were subjected to a laparotomy (trauma) and 90 minutes of sham shock (trauma-sham shock [T/SS]) or a laparotomy plus hemorrhagic shock (T/HS), followed by a reperfusion period of 3 hours. The T/HS groups were resuscitated either with their shed blood (SB), or half the SB and 1.5 times the SB volume as RL (SB/RL), or 3 times the SB volume as RL (3RL). The T/SS groups received either no resuscitation or RL at 1.5 times the SB volume of the T/HS rats. Gut injury was quantified by measuring intestinal permeability to flourescein dextran (FD-4), as well as by histologic analysis of the terminal ileum. Lung injury was assessed histologically and by the magnitude of neutrophil sequestration as reflected in myeloperoxidase levels. Neutrophil activation was measured by quantitating the level of CD11b expression using flow cytometry. RBC injury was analyzed by measuring the RBC deformability.
As compared with the T/SS groups, all three T/HS resuscitation regimens were associated with morphologic evidence of gut and lung injury, increased gut permeability, pulmonary leukosequestration, systemic neutrophil activation, and decreased RBC deformability (p < 0.05). However, the effect of the resuscitation regimens varied based on the tissues and cells tested. Morphologically, gut and lung injury as well as pulmonary neutrophil sequestration was worse in the 3RL T/HS group than the other two T/HS groups. As compared with the other two T/HS resuscitation regimens, resuscitation with the SB/RL combination was associated with less of an increase in gut permeability, systemic neutrophil activation, and RBC rigidification (p < 0.05).
The type of resuscitation regimen used influenced the extent of organ injury and cellular activation or dysfunction observed after T/HS with different resuscitation regimens showing varying effects depending on the cell or organ tested. Thus, when testing novel fluid resuscitation regimen, attention must be paid to the control resuscitation regimen used.
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ABSTRACT: Gut is very sensitive to hypoperfusion and hypoxia, and deranged gastrointestinal barrier is implicated in systemic failure of various organs. We recently demonstrated that diphenyldihaloketone EF24 improves survival in a rat model of hemorrhagic shock. Here, we tested EF24 and it's another analog CLEFMA for their effect on intestinal barrier dysfunction in hypovolemic shock. Hypovolemia was induced in rats by withdrawing 50% of blood. EF24 or CLEFMA (0.4 mg/Kg) treatment was provided, without volume resuscitation, after 1 h of hemorrhage. Ileum was collected 5 h after the treatment for investigating the expression of tight junction proteins (zonula occludens, claudin, and occludin) and epithelial injury markers (myeloperoxidase, ileal lipid-binding protein (ILBP), CD163, and plasma citrulline). The ileal permeability for dextran-fluoroisothiocynate and Evan's blue dye was determined. EF24 and CLEFMA reduced the hypovolemia-induced plasma citrulline levels and the ileal expression of myeloperoxidase, ILBP, and CD163. The drugs also restored the basal expression of tight junction proteins which were substantially deranged by hypovolemia. In ischemic ileum, the expression of phospho(Tyrosine)- zonula occludens-1 was reduced which was reinstated by EF24 and CLEFMA. On the other hand, the drug treatments maintained the hypovolemia-induced expression of phospho(Threonine)-occludin, but reduced that of phospho(Tyrosine)-occludin. Both EF24 and CLEFMA treatments reduced the intestinal permeability enhanced by hypovolemia. EF24 and CLEFMA attenuate hypovolemic gut pathology and protect barrier function by restoring the status of tight junction proteins. These effects were observed in unresuscitated shock, implying the benefit of EF24 and CLEFMA in pre-hospital care of shock.Journal of Pharmacology and Experimental Therapeutics 09/2014; DOI:10.1124/jpet.114.217331 · 3.86 Impact Factor
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ABSTRACT: To discuss the current resuscitative strategies for trauma-induced hemorrhagic shock and acute traumatic coagulopathy (ATC). Hemorrhagic shock can be acutely fatal if not immediately and appropriately treated. The primary tenets of hemorrhagic shock resuscitation are to arrest hemorrhage and restore the effective circulating volume. Large volumes of isotonic crystalloids have been the resuscitative strategy of choice; however, data from experimental animal models and retrospective human analyses now recognize that large-volume fluid resuscitation in uncontrolled hemorrhage may be deleterious. The optimal resuscitative strategy has yet to be defined. In human trauma, implementing damage control resuscitation with damage control surgery for controlling ongoing hemorrhage, acidosis, and hypothermia; managing ATC; and restoring effective circulating volume is emerging as a more optimal resuscitative strategy. With hyperfibrinolysis playing an integral role in the manifestation of ATC, the use of antifibrinolytics (eg, tranexamic acid and aminocaproic acid) may also serve a beneficial role in the early posttraumatic period. Considering the sparse information regarding these resuscitative techniques in veterinary medicine, veterinarians are left with extrapolating information from human trials and experimental animal models. Viscoelastic tests integrated with predictive scoring systems may prove to be the most reliable methods for early detection of ATC as well as for guiding transfusion requirements. Hemorrhage accounts for up to 40% of human trauma-related deaths and remains the leading cause of preventable death in human trauma. The exact proportion of trauma-related deaths due to exsanguinations in veterinary patients remains uncertain. Survivability depends upon achieving rapid definitive hemostasis, early attenuation of posttraumatic coagulopathy, and timely restoration of effective circulating volume. Early institution of damage control resuscitation in severely injured patients with uncontrolled hemorrhage has the ability to curtail posttraumatic coagulopathy and the exacerbation of metabolic acidosis and hypothermia and improve survival until definitive hemostasis is achieved.01/2014; DOI:10.1111/vec.12138
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ABSTRACT: Critically ill patients frequently display unexplained or incompletely explained features of gastrointestinal (GI) dysfunction, including gastric stasis, ileus, and diarrhea. This makes nutrition delivery challenging, and may contribute to poor outcomes. The typical bowel dysfunction seen in severely ill patients includes retarded gastric emptying, unsynchronized intestinal motility, and intestinal hyperpermeability. These functional changes appear similar to the corticotropin-releasing factor (CRF)-mediated bowel dysfunctions associated with stress of various types and some GI disorders and diseases. CRF has been shown to be present within the GI tract and its action on CRF receptors within the gut have been shown to reduce gastric emptying, alter intestinal motility, and increase intestinal permeability. However, the precise role of CRF in the GI dysfunction in critical illness remains unclear. In this short review, we provide an update on GI dysfunction during stress and review the possible role of CRF in the aetiology of gut dysfunction. We suggest that activation of CRF signaling pathways in critical illness might be key to understanding the mechanisms underlying the gut dysfunction that impairs enteral feeding in the intensive care unit.Nutrition 02/2013; 29(7-8). DOI:10.1016/j.nut.2012.12.023 · 3.05 Impact Factor