Effect of different resuscitation strategies on neutrophil activation in a swine model of hemorrhagic shock (original) (raw)
Related papers
2004
We have previously shown that lung injury following fluid resuscitation either with hypertonic saline (HS) or lactated Ringer's (LR) plus pentoxifylline (PTX) attenuated acute lung injury when compared with LR resuscitation. The objective of the present study is to determine whether our previous observations are accompanied by changes in polymorphonuclear leukocyte (PMN) behavior. To study this, PMN-endothelial cell interactions, microcirculatory blood flow, lung histology, lung PMN infiltration (MPO, Myeloperoxidase), and lung intracellular adhesion molecule-1 (ICAM-1) expression were assessed in a controlled hemorrhagic shock model followed by LR, HS, and LR+PTX resuscitation in rodents. Rats (240-300 g) were bled to a mean arterial pressure (MAP) of 35 mm Hg for 1 hr and then randomized into three groups: HS (7.5% NaCl, 4 ml/kg); LR (33 shed blood); and LR+PTX (25 mg/kg). Additionally, total shed blood was reinfused. A sham group underwent no shock and no treatment. The internal spermatic fascia was exteriorized and the microcirculation was observed by closed-circuit TV coupled to a microscope, 2 and 6 hrs after treatment. The number of leukocytes sticking to the venular endothelium was determined 2 hrs after fluid resuscitation. Microcirculatory blood flow was measured by an optical Doppler velocimeter. Lung histology and lung MPO immunostaining were assessed at 6 hrs, and lung ICAM-1 expression was determined by immunostaining at 2 hrs following fluid resuscitation. Two hours after treatment, HS (1.4 6 0.4), LR+PTX (1.7 6 0.3), and sham (0.4 6 0.2) groups presented significant reductions in leukocyte adherence (cells/100 lm venule length), compared with the LR group (4.0 6 0.9, P , 0.05). No differences were observed 6 hrs after treatment on leukocyte adherence and microcirculatory blood flow. ICAM-1 expression was significantly higher in LRtreated animals compared with the HS, LR+PTX, and sham groups (P , 0.01). PMN infiltration and overall lung injury were significantly attenuated by HS and LR+PTX. These results support earlier studies that indicated the potential application of HS and PTX in shock therapy and the increase in PMNendothelial cell interaction and lung injury after LR resuscitation.
Transfusion and Apheresis Science, 2012
Article history: a b s t r a c t Background: Recent publications have reported the severe adverse events associated with blood products but have not considered the effect of the volume and composition of the resuscitative fluids infused with the blood products. Methods: Injury leads to cellular reaction characterized by insulin resistance during which glucose cannot enter muscle and fat cells. In all cells, mitochondrial pyruvate dehydrogenase activity is decreased during insulin deficiency leaving cells deficient in substrates needed to power the Krebs cycle and make ATP. Results: D-b-Hydroxybutyrate, a normal ketone body metabolite, enters cells on the monocarboxylate transport mimicking the action of insulin and bypassing the enzymatic block at PDH. Metabolism of ketone bodies increases efficiency of mitochondrial energy production and cellular ATP level. Conclusion: Infusion of 250 ml of 600 mM Na D-b-hydroxybutyrate solution, with the same osmotic strength as the hypertonic NaCl solution currently being used, would correct insulin resistance, provide energy substrates for cells to produce ATP, correct the tendency of injured tissue to swell due to decreased energy of ionic gradients and correct acidosis observed in hemorrhage.
Fluid resuscitation with 0.9% saline alters haemostasis in an ovine model of endotoxemic shock
Thrombosis Research
Introduction: Fluid resuscitation is a cornerstone of severe sepsis management, however there are many uncertainties surrounding the type and volume of fluid that is administered. The entire spectrum of coagulopathies can be seen in sepsis, from asymptomatic aberrations to fulminant disseminated intravascular coagulation (DIC). The aim of this study was to determine if fluid resuscitation with saline contributes to the haemostatic derangements in an ovine model of endotoxemic shock. Materials and Methods: Twenty-one adult female sheep were randomly divided into no endotoxemia (n=5) or endotoxemia groups (n=16) with an escalating dose of lipopolysaccharide (LPS) up to 4 µg/kg/hr administered to achieve a mean arterial pressure below 60mmHg. Endotoxemia sheep received either no bolus fluid resuscitation (n=8) or a 0.9% saline bolus (40 mL/kg over 60 minutes) (n=8). No endotoxemia, saline only animals (n=5) underwent fluid resuscitation with a 0.9% bolus of saline as detailed above. Hemodynamic support with vasopressors was initiated if needed, to maintain a mean arterial pressure (MAP) of 60-65mmHg in all the groups. Results: Rotational thromboelastometry (ROTEM®) and conventional coagulation biomarker tests demonstrated sepsis induced derangements to secondary haemostasis. This effect was exacerbated by saline fluid resuscitation, with low pH (p = 0.036), delayed clot initiation and formation together with deficiencies in naturally occurring anti-coagulants antithrombin (p = 0.027) and Protein C (p = 0.001).
2020
Background: To investigate the effect of fluid resuscitation on glycocalyx shedding, and extravascular lung water index (ELWI), mean arterial pressure (MAP) and oxygen delivery (DO 2) changes. Methods: Male domestic piglets (Sus scrofa) 6-10 weeks old anesthetized and bled until mean arterial pressure drop to 20% of baseline and resuscitated with normal saline as much as blood drowned, followed with 40 mL/kg of normal saline after 30 minutes. Cardiac index (CI), ELWI, systemic vascular resistance index (SVRI), MAP, atrial natriuretic peptide (ANP) and syndecan-1 were measured before and after each fluid resuscitations. Results: Serum ANP was increased after normal volume fluid resuscitation (p= 0.043) and return its baseline value after hypervolemia fluid resuscitation. Serum Syndecan-1 levels did not increase. A small increase in ELWI only found 60 minutes after fluid resuscitation (p= 0.021). SVRI undergo a gradual decrease, until the lowest value at hypervolemia volume resuscitation. There was no difference between the MAP of the two groups (p= 0.105). Hemoglobin concentration significantly decreased from normal to hypervolemia volume resuscitation (p= 0.009). Oxygen delivery in hypervolemia resuscitation is higher than in normal volume resuscitation (p= 0.012), due to a significant increase in CI at hypervolemia volume resuscitation (p<0.001). Conclusions: Hypervolemia fluid resuscitation in the animal hemorrhage model is not induced glycocalyx shedding. Small increase ELWI was found in 60 minutes after fluid resuscitation. DO 2 is maintained by increasing CI in spite of decreasing hemoglobin level due to hemodilution. Increasing CI is balanced by reducing SVRI to sustain stable MAP.
Journal of Trauma and Acute Care Surgery, 2014
BACKGROUND: Severe hemorrhage is associated with the disruption of the endothelial glycocalyx (EG), a key component of the endothelium. The effects of blood components on the EG are unknown. The present study furthers our investigations into the effects of resuscitation with blood products on the skeletal muscle microcirculation of hemorrhaged rats, focusing on packed red blood cells (PRBCs) or fresh whole blood (FWB). METHODS: Rats were bled 40% of total blood volume and resuscitated with 1:1 PRBC/lactated Ringer's solution (LR), 1:1 washed PRBC (wPRBC)/LR, FWB or LR only. Sham animals were subjected to all procedures except hemorrhage and resuscitation. EG thickness, blood flow, and microvascular permeability were studied using intravital microscopy. Hemodynamics and coagulation tests (rotational thromboelastometry) were performed. RESULTS: After severe hemorrhage, EG and permeability were restored to sham levels in the PRBC/LR and FWB groups, but not in the wPRBC/ LR or LR groups. Clotting time was longer and clot elasticity and firmness were reduced in wPRBC/LR and LR, but not in FWB or PRBC/LR groups when compared with sham. CONCLUSION: Resuscitation with FWB or PRBC/LR was superior in reversing coagulopathy, restoring EG and permeability changes following hemorrhage, compared with wPRBC/LR or LR alone. As wPRBC/LR did not improve EG and permeability, these data suggest that the removal of residual plasma protein from wPRBC or resuscitation with a protein-free solution (LR) is not able to improve microcirculation and coagulation functions in this severe hemorrhage model.
The American Journal of Surgery, 2009
BACKGROUND: Recently, studies have been conducted examining the efficacy of 3% hypertonic saline solution (HS) for the treatment of traumatic brain injury; however, few studies have analyzed the effects of 3% hemorrhagic shock during hemorrhagic shock. The aim of this study was to test the potential immunomodulatory benefits of 3% hemorrhagic shock resuscitation over standard fluid resuscitation. METHODS: Wistar rats were bled to a mean arterial pressure of 35 mm Hg and then randomized into 3 groups: those treated with lactated Ringer's solution (LR; 33 mL/kg, n ϭ 7), 3% HS (10 mL/kg, n ϭ 7), and 7.5% HS (4 mL/kg, n ϭ 7). Half of the extracted blood was reinfused after fluid resuscitation. Animals that did not undergo shock served as controls (n ϭ 5). Four hours after hemorrhagic shock, blood was collected for the evaluation of tumor necrosis factor-␣ and interleukin-6 by enzyme immunoassay. Lung and intestinal samples were obtained for histopathologic analysis. RESULTS: Animals in the HS groups had significantly higher mean arterial pressure than those in the LR group 1 hour after treatment. Osmolarity and sodium levels were markedly elevated in the HS groups. Tumor necrosis factor-␣ and interleukin-6 levels were similar between the control and HS groups but significantly higher in the LR group (P Ͻ .05). The lung injury score was significantly higher in the LR group compared with the 7.5% HS and 3% HS groups (5.7 Ϯ 0.7, 2.1 Ϯ 0.4, and 2.7 Ϯ 0.5, respectively). Intestinal injury was attenuated in the 7.5% HS and 3% HS groups compared with the LR group (2.0 Ϯ 0.6, 2.3 Ϯ 0.4, and 5.9 Ϯ 0.6, respectively). CONCLUSIONS: A small-volume resuscitation strategy modulates the inflammatory response and decreases end-organ damage after HS. Three percent HS provides immunomodulatory and metabolic effects similar to those observed with conventional concentrations of HS.
Shock, 2006
HBOC-201, a hemoglobin-based oxygen carrier, improved physiologic parameters and survival in hemorrhagic shock (HS) animal models. However, resuscitation from HS and the properties of different fluids influence immune responses. The aim of this study was to determine if HBOC-201 significantly alters immune function in traumatic HS. Anesthetized pigs underwent soft tissue injury, controlled hemorrhage of 40% of blood volume, and resuscitation with HBOC-201 or Hextend, or no resuscitation. Sequential whole-blood samples were collected for analyses of leukocyte differential (hematology analyzer), T-lymphocyte subsets (CD3 + , CD4 + , and CD8 +) (FACS), lymphocyte adhesion marker CD49d (a 4-integrin) expression (FACS), plasma cytokines-tumor necrosis factor (TNF)-a, interleukin (IL)-6, and IL-10-(ELISA), and lymphocyte apoptosis (annexin-V/propidium iodide staining) (FACS). Statistical analyses were performed by the mixed procedure. Total WBC counts decreased posthemorrhage in both resuscitation groups. Lymphocyte percentages decreased and PMN percentages increased around 4 h posthemorrhage in all groups. CD3 cells decreased in all groups, but CD4 and CD8 cells decreased only in the resuscitation groups. TNF-a levels were not detectable in any groups. IL-6 levels were similar across treatment groups (P > 0.05); however, IL-10 levels were higher in the HBOC group, as early as 1 h posthemorrhage (P = 0.04). Increases in lymphocytic CD49d expression levels and apoptosis occurred only in nonresuscitation and Hextend groups, respectively (P # 0.01). In comparison with Hextend, HBOC-201 had no significant adverse or beneficial effects on immune function in this model of moderately severe HS in swine, suggesting that it may be safe as a resuscitation fluid in HS patients.