Small volume albumin administration protects against hemorrhagic shock-induced bone marrow dysfunction

BACKGROUND: Unexpected immunomodulatory effects of colloids and crystalloids prompted an investigation of albumin's ability to prevent bone marrow (BM) suppression following trauma/hemorrhagic shock (T/HS: laparotomy + MAP 30 for 90 mins). METHODS: In vitro: Normal rat BM was plated for granulocyte-macrophage (CFU-GM) and erythrocyte colony forming units (BFU-E) with 2% v/v plasma from sham (T/SS) or T/HS rats and albumin (2-8 mg/mL). In vivo: Male rats (n = 4/group) were subjected to T/SS or T/HS and resuscitated with shed blood and twice the volume as Lactated Ringer's (LR) or blood and 1, 2, or 3 mL of albumin (50 mg/mL). Bone marrow harvested 3 hours post-resuscitation was plated for CFU-GM and BFU-E. RESULTS: In vitro: T/HS plasma decreased both CFU-GM and BFU-E growth as compared with T/SS, whereas increasing doses of albumin showed dose-dependent improvement in progenitor growth (p < 0.05). In vivo: The suppression of BM red and white cell progenitor growth seen in T/HS+LR rats as compared with T/SS was fully prevented by as little as 1 mL of albumin (p < 0.05). CONCLUSIONS: Small doses of albumin fully restore CFU-GM and BFU-E to sham values. We postulate that the binding of circulating toxic factors by albumin may play a role in this prevention of T/HS-induced BM suppression.     

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. Red blood cell deformability was measured by laser ektacytometry and erythrocyte shape was evaluated by scanning electron microscopy. RESULTS: Burn-induced RBC deformability changes (decrease in elongation index) and shape alterations (increase in the percentage of reversibly and irreversibly changed cells) were less severe in proestrus females than in diestrus females or males. Ovariectomized rats demonstrated more severe RBC changes than non-ovariectomized ones. The degree of RBC damage was the same in castrated and non-castrated males. CONCLUSIONS: Removal of female sex hormones increases the severity of burn-induced RBC, indicating that female sex hormones protect against burn-induced RBC dysfunction. In contrast, male sex hormones do not appear to modulate burn-induced RBC dysfunction.     

Factors in intestinal lymph after shock increase neutrophil adhesion molecule expression and pulmonary leukosequestration

BACKGROUND: Because the ischemic gut may produce factors that initiate systemic inflammation, we tested the hypothesis that factors released from the gut into the mesenteric lymphatics increase neutrophil (PMN) adhesion molecule expression after trauma and shock. METHODS: At 1 and 4 hours after hemorrhagic shock (30 mm Hg x 90 minutes) plus trauma (laparotomy) (T/HS) or sham-shock (T/SS), with or without mesenteric lymph duct ligation, PMN CD11b and CD18 expression was assessed in male rats. In additional rats, mesenteric lymph samples were tested for their ability to increase PMN CD11b expression in vitro. Lastly, at 4 hours after T/SS or T/HS with or without lymph duct ligation, pulmonary PMN sequestration was measured. RESULTS: Compared with T/SS rats, T/HS was associated with up-regulation of PMN CD11b and CD18 expression, which was largely prevented by ligation of the mesenteric lymph duct (p < 0.01). Lymph duct ligation also prevented T/HS-induced pulmonary leukocyte sequestration (p < 0.01). In addition, mesenteric lymph from rats subjected to T/HS but not T/SS increased CD11b expression (p < 0.01). CONCLUSION: Factors produced or released by the postischemic intestine and carried in the mesenteric lymph appear responsible for PMN activation and pulmonary PMN sequestration after an episode of T/HS.     

Gut injury and gut-induced lung injury after trauma hemorrhagic shock is gender and estrus cycle specific in the rat

BACKGROUND: The purpose of this study was to test the hypothesis that trauma-hemorrhagic shock (T/HS)-induced gut and lung injury is modulated by gender and the stage of the estrus cycle at the time of injury. METHODS: We compared the incidence and magnitude of gut and lung injury in male and female rats subjected to a laparotomy (trauma) followed by 90 minutes of shock (mean arterial pressure, 30 mm Hg) (T/HS) or sham shock. RESULTS: Lung injury and pulmonary neutrophil sequestration as well as gut injury were increased after T/HS in the diestrus female and the male rats, but not in the estrus or proestrus female rats. Although T/HS caused gut and lung injury in the male and the female diestrus rats, the magnitude of injury was less in the female diestrus than in the male rats (p < 0.05). A strong correlation was found between intestinal villous injury and lung injury as well as between gut injury and pulmonary leukosequestration in the female rats subjected to T/HS (p < 0.0001). Plasma nitric oxide levels were approximately two- to threefold higher in the male and the diestrus female rats subjected to T/HS than in other groups (p < 0.05), and a high degree of correlation (r2 = 0.68, p < 0.0001) was found between villous injury and plasma nitric oxide levels. Ileal constitutive nitric oxide synthase (NOS) and inducible NOS (iNOS) activity was measured. Ileal constitutive NOS activity was similar between the groups, but iNOS activity was three- to fourfold higher in the T/HS male rats than in the sham shock or the T/HS proestrus groups (p < 0.01). CONCLUSION: Gender and estrus cycle stage influence susceptibility to T/HS-induced gut and lung injury. This difference in susceptibility to organ injury was associated with increased plasma nitric oxide levels and increased ileal iNOS activity.     

Role of the gut lymphatic system in multiple organ failure

The central concept of this review is that gut-derived factors contained primarily in the mesenteric lymph rather than the portal blood contribute to distant organ injury. This hypothesis is supported by recent studies indicating that division of the mesenteric lymphatic ducts prevents lung injury after hemorrhagic shock and significantly ameliorates lung injury after thermal injury. The mechanism of hemorrhagic shock-induced lung injury appears to be through mesenteric lymph-induced activation of neutrophils and activation/injury of endothelial cells. This notion is supported by in vitro studies indicating that mesenteric lymph, but not portal vein plasma, collected after a nonlethal episode of hemorrhagic shock activates neutrophils, increases endothelial cell monolayer permeability, and can even cause endothelial cell death. This concept that gut-derived factors contained primarily in the mesenteric lymph rather than the portal system potentiate the development of distant organ (lung) injury, if correct, would help clarify several important issues. First, because the lung is the first organ exposed to mesenteric lymph (i.e., mesenteric lymph enters the subclavian via the thoracic duct), it would help explain the clinical observation of why the lung is generally the first organ to fail in severely injured patients. Second, this gut lymphatic hypothesis would provide new information on the pathophysiology of gut-induced lung injury. Finally, it would help explain the discordant results between experimental and some clinical studies on the role of gut injury and loss of gut barrier function in the development of a systemic inflammatory state and distant organ injury.     

Prolonged QT interval and cardiac arrhythmias in two neonates: sudden infant death syndrome in one case

Two neonates with arrhythmias and the long QT syndrome are described. The arrhythmias were detected in utero and both infants were apparently well after birth. The first infant, although well, had a bradycardia for the first 9 days of life. A normal heart rate was documented at 10 days but a prolonged QT interval was not appreciated on the ECG. He was discharged from hospital but died suddenly and unexpectedly 3 days later. A post-mortem examination failed to find a cause for his death which therefore fell into the category of the sudden infant death syndrome (SIDS). A retrospective analysis of the perinatal electrocardiogram showed a probable junctional rhythm with 2:1 conduction to the ventricle; the QT interval was prolonged at 0.52 seconds (QTC = 0.63). The second infant had a QT interval of 0.52 seconds (QTC = 0.54) and frequent ventricular premature beats on a 24-hour electrocardiogram. She was treated with propranolol and remains well 2 years later. Sudden infant death has often been described in the siblings of children with the long QT syndrome and one other report described a case of SIDS which was said to have had a prolonged QT interval on the perinatal ECG. This report, however, provides unquestionable evidence, in one case, of an association between the long QT syndrome and SIDS.     

Excretory urography with iohexol: evaluation in children

A multicenter clinical study was conducted using iohexol, a second-generation nonionic contrast medium, for excretory urography performed in 130 children. Doses of iohexol (300 mg iodine/ml) ranged between 150 and 660 mgI/kg (0.5 and 2.2 ml/kg). Iohexol was tolerated well, and no significant adverse reactions occurred. Sixty-five iohexol urograms were evaluated to determine the minimum dose for adequate visualization of the kidneys and collecting systems. A dose greater than 300 mgI/kg (1.0 ml/kg) always resulted in a urogram of diagnostic quality, while visualization was insufficient for diagnosis in 10% of studies done with doses of 150-300 mgI/kg (0.5-1.0 ml/kg). Another 65 iohexol urograms were compared in a blinded manner with a similar number of studies performed using iothalamate meglumine at comparable iodine concentration and dose. Visualization of calyces and pelvoinfundibular structures achieved with iohexol was rated better with statistical significance, but there was no difference in visualization of the renal parenchyma or ureters. Use of iohexol in excretory urography may be advantageous in children who are at greatest risk for an adverse reaction to contrast media or in those most likely to benefit from use of a low osmolality contrast agent.     

Volumetric rendering techniques: applications for three-dimensional imaging of the hip

Volumetric rendering is a new approach to three-dimensional (3D) imaging that overcomes many of the drawbacks of currently available surface-rendering systems. Its application on the Pixar Imaging System in two cases of acetabular fracture was assessed to illustrate the features of the technique. The fast-computing architecture and large memory of this system allow rapid generation of a series of high-quality 3D images in each plane of rotation (x or spinal axis, z or somersaulting axis) that can be viewed as independent static images or as an animated real-time video loop. Editing to remove the normal contralateral hemipelvis enhances appreciation of acetabular abnormalities. Every pixel of computed tomographic data is preserved, allowing representation of both soft tissue and bone as translucent overlap. The presentation of data also allows detection of subtle abnormalities and features and minimizes the artifact generation common in surface-rendered images.     

Burn wound sepsis may be promoted by a failure of local antibacterial host defenses.

Little attention has been focused on the local burn wound environment, even though burn wound sepsis is a common cause of death in the burn victim. To characterize the effect of the local burn wound environment on neutrophil function and metabolism, the opsonic activity of blister fluid specimens against Pseudomonas aeruginosa was measured as was the effect of blister fluid on control neutrophil oxygen consumption using preopsonized zymosan and f-met-leu-phe (FMLP) as stimuli. Blister fluid did not support the killing of P. aeruginosa by normal neutrophils as well as normal serum. Additionally, blister fluid inhibited zymosan-stimulated, but not FMLP-stimulated, neutrophil oxygen consumption. The inhibitory effect of blister fluid on zymosan-stimulated oxygen consumption correlated with the extent of complement activation, measured as C3d or C3AI (p less than 0.01). That blister fluid did not inhibit the FMLP-mediated respiratory burst supports the concept that the blister fluid inhibitory effect on the zymosan-mediated respiratory burst was mediated through the complement receptor. These findings that blister fluid can affect the bactericidal and metabolic activity of normal neutrophils support the concept that cellular function can be altered by the microenvironment in which the cells are bathed. This potential impairment of host defenses within the burn wound could predispose the burn victim to burn wound sepsis.