Intravenous injection of mesenteric lymph produced during hemorrhagic shock decreases RBC deformability in the rat.

Objective: To test the hypothesis that gut-derived factors carried in trauma-hemorrhagic shock (T/HS) lymph are sufficient to induce red blood cells (RBC) injury, to investigate their potential mechanisms of action, and to define the time post-T/HS that these factors appear in the lymph.

Methods: Mesenteric lymph collected from T/HS or trauma-sham shock (T/SS) rats over different time periods was injected intravenously into male rats at a rate of 1 mL/h for 3 hours. RBC deformability was measured using laser-assisted ektacytometer to calculate the elongation index.

Estrogenic hormone modulation abrogates changes in red blood cell deformability and neutrophil activation in trauma hemorrhagic shock.

Background: Decreased red blood cell (RBC) deformability and activation of neutrophils (polymorphonuclear leukocytes [PMN]) after trauma-hemorrhagic shock (T/HS) have been implicated in the development of multiple organ dysfunction. Experimentally, female animals seemed to be protected from the effects of T/HS, at least in part, because of elevated estrogen levels. Thus, we examined the relative role of estrogen receptor (ER)-alpha and -beta in this protective response.

Trauma-hemorrhagic shock-induced red blood cell damage leads to decreased microcirculatory blood flow.

Objective: To test the hypothesis that trauma-hemorrhagic shock (T/HS)-induced changes in red blood cells (RBC) contribute to the reduction of blood flow in distant organs.

Design: Laboratory study.

Setting: Academic medical center laboratory.

Alteration of alpha-spectrin ubiquitination after hemorrhagic shock.

Background: RBC deformability after trauma and hemorrhagic shock (T/HS) leads to the microcirculatory dysfunction and clinical manifestations of organ failure. However, the cellular mechanism of this phenomenon remains unknown. Spectrins are important for the shape and physical properties of erythrocytes, such as deformability and resistance to mechanical stress.

Endotoxemia down-regulates bone marrow lymphopoiesis but stimulates myelopoiesis: the effect of G6PD deficiency.

Bone marrow (BM) dysfunction is an important component of immunomodulation. This study investigated alterations in cell content, apoptotic responses, and cell proliferation in BM, blood, and spleen in endotoxemic mice (LPS from Escherichia coli). As the decreased antioxidant status associated with glucose-6-phosphate dehydrogenase (G6PD) deficiency has been shown to modulate the innate immune response, we also tested whether a G6PD mutation (80% decrease in cellular enzyme activity) alters BM responses during endotoxemia.

Hormonally active women tolerate shock-trauma better than do men: a prospective study of over 4000 trauma patients.

Objective: To test the hypothesis that comparably injured women, especially those in the hormonally active age groups, would manifest a better preserved hemodynamic response and tissue perfusion after major trauma than do men.

Summary Background Data: The notion that premenopausal women are more resistant than men to shock and trauma has been shown in numerous preclinical models. However, human studies on the effects of gender on outcome after shock-trauma are less clear, and none has examined the effect of gender on the immediate postinjury response to major trauma.

Resistance of the female, as opposed to the male, intestine to I/R-mediated injury is associated with increased resistance to gut-induced distant organ injury.

We tested the hypothesis that the female intestine is more resistant to gut I/R injury than the male intestine by comparing the effects of the isolated pure gut I/R superior mesenteric artery occlusion (SMAO) model on gut morphology and whether SMAO-induced distant organ injury (lung, bone marrow [BM], neutrophils, and red blood cells [RBCs]) would differ between male and proestrus female rats. At 6 or 24 h after SMAO or sham SMAO, gut injury, lung permeability, pulmonary neutrophil sequestration, RBC deformability, and BM RBC and white blood cell progenitor growth were measured, as was the ability of the plasma from these rats to activate naive rat neutrophils. At both 6 and 24 h after SMAO, the female rats had significantly less intestinal injury and reduced gut-induced lung injury, BM suppression, RBC dysfunction, and neutrophil activation than male rats subjected to SMAO.

Augmented erythrocyte band-3 phosphorylation in septic mice.

Infection-induced RBC dysfunction has been shown to play a role in the modulation of host response to injury and infection. The underlying biochemical mechanisms are not known. This study investigated alterations in RBC band-3 phosphorylation status and its relationship to anion exchange activity in vitro as well as under in vivo septic conditions induced by cecal ligation and puncture (CLP) in mice.

Defining the research agenda for surgical infection: a consensus of experts using the Delphi approach.

Background: A substantial proportion of operative procedures are complicated by infections, either remote from or related to the surgical site. These infections account for substantive morbidity and health care costs. With limited research funds available to study interventions designed to either prevent or reduce the morbidity associated with infections in surgical patients, we developed a research agenda to develop priorities to aid in study design and to focus both human and capital resources more effectively.

Small volume resuscitation with hypertonic saline is more effective in ameliorating trauma-hemorrhagic shock-induced lung injury, neutrophil activation and red blood cell dysfunction than pancreatitic protease inhibition.

Background: Recognition of the limitations of standard crystalloid resuscitation has led to the search for alternative resuscitation strategies that might better limit the development of trauma-hemorrhage-induced organ dysfunction and systemic inflammation. Thus, the goal of this study was to compare the effects of two resuscitation strategies alone, and in combination, with those of standard resuscitation with Ringers lactate (RL). The two strategies were small volume resuscitation with hypertonic saline (HTS) and intraluminal inhibition of pancreatic proteases with the serine protease inhibitor nafamostat.

Amiloride combined with small-volume resuscitation with hypertonic saline is superior in ameliorating trauma-hemorrhagic shock-induced lung injury in rats to the administration of either agent alone.

Objective: Recognition of the limitations of standard crystalloid resuscitation has led to exploration for alternative resuscitation strategies that might better prevent the development of trauma-hemorrhage-induced organ dysfunction and systemic inflammation. Thus, the goal of this study was to compare the effects of two resuscitation strategies alone and in combination with that of standard resuscitation with Ringer's lactate. These two strategies were intravenous injection of amiloride, an inhibitor of Na/H exchange and epithelial Na channels, and resuscitation with hypertonic saline.

Mesenteric lymph duct ligation decreases red blood cell alterations caused by acute pancreatitis.

Background: Both experimental and clinical studies have shown that acute pancreatitis (AP) causes a significant decrease in red blood cell (RBC) deformability. The mechanisms by which AP induces RBC injury are unknown. The purpose of this study was to test the hypothesis that factors carried in the mesenteric lymph after an attack of AP significantly contribute to the RBC injury observed in AP.

Pancreatic duct ligation reduces lung injury following trauma and hemorrhagic shock.

Objective: To determine whether pancreatic digestive enzymes released into the ischemic gut during an episode of T/HS are involved in the generation of distant organ injury. This hypothesis was tested by examining the effect of PDL on T/HS-induced intestinal injury, lung injury, and RBC deformability.

Summary Background Data: The effect of pancreatic duct ligation (PDL) on distant organ injury following trauma/hemorrhagic shock (T/HS) was examined.

Alterations of red blood cell shape in patients with severe trauma.

Background: Trauma is accompanied by a decrease in red blood cell (RBC) deformability, which may manifest itself earlier than secondary septic complications. The mechanisms of this phenomenon are not clear. The aim of this study is to determine when the alterations of RBC shape appear in trauma patients.

Albumin protects against gut-induced lung injury in vitro and in vivo.

Objective: Since albumin has the ability to detoxify, we assessed whether low-dose albumin could protect against trauma/hemorrhagic shock (T/HS)-induced endothelial cell, lung, gut, and red blood cell (RBC) injury in vivo and endothelial cell injury in vitro.

Summary Background Data: T/HS cause ischemic insult to the gut, resulting in the release of biologically active factors into the mesenteric lymph, which then cause injury to multiple distant organs.

Methods: In vitro experiments tested the ability of albumin to reduce the cytotoxicity of mesenteric lymph from male rats subjected to T/HS (laparotomy + MAP 30 mm Hg for 90 minutes) for human umbilical vein endothelial cell (HUVEC).

Red blood cell damage after trauma-hemorrhage is modulated by gender.

Background: Previous studies have shown that trauma-hemorrhagic shock (T/HS) causes significant alterations in red blood cell (RBC) deformability and shape. Gender is becoming well recognized as a modulating factor in the pathophysiologic response to trauma. We hypothesize that female subjects are more resistant to adverse effects of T/HS on RBC deformability and shape than male subjects because of estrogen protection.

Female sex hormones protect red blood cells from damage after trauma-hemorrhagic shock.

Background: Trauma/hemorrhagic shock (T/HS) is known to cause changes in red blood cell (RBC) deformability and resting shape. Our previous studies have shown that proestrus female rats are more protected from shock-induced RBC damage than diestrus females or males. However, it is unclear whether female or male sex hormones can influence the severity of these alterations.

Red blood cell dysfunction in septic glucose-6-phosphate dehydrogenase-deficient mice.

Glucose-6-phosphate dehydrogenase (G-6-PDH) deficiency is the most common known human genetic polymorphism. This study tested the hypothesis that G-6-PDH deficiency worsens sepsis-induced erythrocyte dysfunction. Sepsis (24 h) was induced by cecal ligation and puncture in wild-type (WT) and G-6-PDH-deficient (G-6-PDH activity 15% of WT) mice.

Burn-induced red blood cell deformability and shape changes are modulated by sex hormones.

Background: Burns are known to cause changes in red blood cell (RBC) deformability and resting shape. However, it is unclear whether sex and sex hormones can influence the severity of these alterations.

Methods: Red blood cell deformability and shape were examined in proestrus and diestrus female rats, ovariectomized female rats, as well as castrated and non-castrated male rats (6 animals per group) subjected to scald burn.

Appearance of an erythrocyte population with decreased deformability and hemoglobin content following sepsis.

With the use of the cecal ligation and puncture model in mice, this study tested whether sepsis-induced decreased erythrocyte deformability is restricted to a subpopulation of cells. Erythrocyte subpopulations were isolated by centrifugal elutriation. Lineweaver-Burk conversion of deformability-response curves to shear stress was used to determine the shear stress at half-maximal cell elongation (K(EI)) and maximal cell elongation (EI(max)).

Effect of trauma-hemorrhagic shock on red blood cell deformability and shape.

Previous work in our laboratory has demonstrated a decrease in red blood cell (RBC) deformability in sepsis. This has not been studied following hemorrhagic shock. We tested the hypotheses that hemorrhagic shock, associated with soft tissue trauma, leads to decreased RBC deformability and that this is related to alterations in the resting shape of the RBC.

Mesenteric lymph duct ligation prevents shock-induced RBC deformability and shape changes.

Objectives: The exact mechanisms that lead to RBC deformability and shape changes after trauma/hemorrhagic shock remain unknown. We hypothesize that RBC injury is caused in part by gut injury and is mediated by gut-derived factors carried in the intestinal lymph.

Materials And Methods: RBC deformability was measured by a laser-assisted ektacytometer before and after trauma/hemorrhagic shock (T/HS) in 6 rats whose mesenteric lymph duct had been ligated and in 10 rats subjected to T/HS without duct ligation.