Blunt splenic trauma.

The treatment of blunt splenic injury has evolved over time from splenectomy in all patients to nonoperative management in stable patients with operation reserved for failures of NOM. While rates of OPSI remain low in trauma patients, splenic salvage in stable patients should be attempted. However, clinical evidence of ongoing blood loss or instability should be addressed with prompt splenectomy. Careful patient selection is of paramount importance in nonoperative management of blunt splenic injury.

Injury-enhanced calcium mobilization in circulating rat neutrophils models human PMN responses.

G-protein coupled (GPC) chemoattractants are important neutrophil (PMN) activators in human shock and sepsis, acting in part by increasing cytosolic calcium ([Ca2+]i). Rats are widely used as laboratory models of shock and sepsis, but reports of [Ca2+]i flux in circulating rat PMN are rare. Moreover, the [Ca2+]i values reported often differ markedly from human systems. We developed study methods where basal [Ca2+]i values in circulating rat PMN were comparable to human PMN, but rat PMN still mobilized calcium poorly after stimulation. Trauma (laparotomy) did not change rat PMN basal [Ca2+]i, but induced brisk [Ca2+]i responses to chemokine and lipid mediators that approximated human PMN responses. This was associated with marked loading of microsomal calcium stores. Formyl peptides still mobilized calcium less well in rat than human PMN. Normal rat PMN appear to circulate in a less mature or primed form than human PMN. A very limited injury rapidly converts rat PMN to a more activated phenotype. PMN thus activated act quite similar to human PMN in terms of GPC receptor-mediated calcium mobilization. Trauma enhances rat PMN responses to GPC agonists at least in part by loading cell calcium stores.

The immunomodulatory effects of damage control abdominal packing on local and systemic neutrophil activity.

BACKGROUND: Damage control laparotomy (DCL) with abdominal packing has become commonplace after major trauma, but the immune consequences of DCL are unknown. METHODS: We collected 37 fluid samples from laparotomy pads (LPF) removed from 28 patients 1 hour to 7 days after DCL. Samples from eight patients who underwent serial packing were assayed for their mediator content and effects on neutrophil (PMN) function. Respiratory burst (RB) to N-formyl-methionyl-leucyl-phenylalanine and phorbol myristate acetate (PMA), as well as PMN calcium ([Ca2+]i) mobilization by GRO-alpha and platelet-activating factor were studied using dihydrorhodamine and fura-2-acetoxymethyl ester fluorescence. Brief exposure to 20% LPF (LPF20) modeled LPF acting on peritoneal PMNs and 2% LPF (LPF2) modeled the systemic effects on PMNs. Endotoxin (ETX), GRO-alpha, and leukotriene B4 were assayed by enzyme-linked immunosorbent assay. Data analysis was by analysis of variance with Dunn's comparisons or the Mann-Whitney test when indicated. RESULTS: LPF increased N-formyl- methionyl-leucyl-phenylalanine-induced RB from 0.4 +/- 0.1 x 103 counts per second (control) to 0.7 +/- 0.1 (LPF2) to 1.3 +/- 0.3 (LPF20) (p < 0.05), with LPF2 increasingly active at later times after injury. PMA-elicited RB was primed only by LPF2 from < 24 hours. Both LPF2 and LPF20 markedly suppressed GRO-alpha [Ca2+]i flux. Suppression by LPF2 was maximal at < 24 hours, abating after 48 hours. Suppression of GRO-alpha response was dose dependent: 150 +/- 8 nmol/L in control PMNs, 97 +/- 19 after LPF2, and 59 +/- 4 after LPF20 (all p < 0.05). [Ca2+]i flux after 1 nmol/L platelet-activating factor was only suppressed (from 181 +/- 14 nmol/L to 149 +/- 15 nmol/L, p < 0.05) by LPF20. LPF contained ETX, GRO-alpha, and leukotriene B4 at 10- to 20-fold plasma concentration in trauma patients. CONCLUSION: DCL results in peritoneal ETX and mediator accumulation even when cultures are sterile. LPF exposure primes PMN RB elicited by nonreceptor- (PMA) or receptor-coupled agonists that resist receptor desensitization. Conversely, LPF suppresses PMN responses to agonists that undergo receptor desensitization at high mediator concentrations. PMN dysfunction in such circumstances probably reflects a concomitant priming of some cell functions (e.g., RB) and desensitization of other (receptor-dependent) functions after an exposure to concentrated mediators. Peritoneal mediator production after DCL may be ETX driven, and may contribute to systemic inflammatory response syndrome. DCL trades early hemostasis for later inflammation. This should be considered in planning management strategies.

Hematopoietic failure after hemorrhagic shock is mediated partially through mesenteric lymph.

OBJECTIVE: To determine whether hemorrhagic shock-induced bone marrow failure is mediated by the gut through the production of toxic mesenteric lymph and whether shock-induced bone marrow failure could be prevented by division of the mesenteric lymphatics. DESIGN: Prospective, controlled study. SETTING: University surgical research laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Rats were divided into five groups: unmanipulated controls (n = 12), hemorrhagic shock with laparotomy (n = 8), hemorrhagic shock with mesenteric lymph duct ligation (n = 10), sham shock with laparotomy (n = 6), and sham shock with mesenteric lymph duct ligation (n = 7). At either 3 or 6 hrs after resuscitation, bone marrow was obtained for determination of early (cobblestone forming cells) and late (granulocyte-macrophage colony forming unit and erythroid burst forming unit) hematopoietic progenitor cell growth. Parallel cultures were plated with plasma (1% and 2% v/v) from all groups to determine the effect of lymphatic ligation on hematopoiesis. MEASUREMENTS AND MAIN RESULTS: Bone marrow cellularity, cobblestone forming cells, granulocyte-macrophage colony forming unit, and erythroid burst forming unit growth in rats subjected to hemorrhagic with lymph duct ligation were similar to those observed in sham-treated animals and significantly greater than in rats subjected to shock and laparotomy without lymphatic duct ligation. Plasma from rats subjected to shock without lymph ligation was inhibitory to hematopoietic progenitor cell growth. In contrast, this shock-induced inhibition was not observed with plasma obtained from shocked rats that underwent mesenteric lymph ligation. CONCLUSIONS: Hemorrhagic shock suppresses bone marrow hematopoiesis as measured by a decrease in early and late progenitor cell growth. This suppression appears mediated through mesenteric lymph as the effect is abrogated by mesenteric lymph duct ligation. These data clearly demonstrate a link between the gut and bone marrow failure after hemorrhagic shock