Enteral administration of a synthetic monoacetyldiglyceride improves survival in a murine model of abdominal sepsis.

BACKGROUND: A monoacetyldiglyceride (MADG) markedly improves survival in a murine model of abdominal sepsis. MADGs have been shown to stimulate hematopoiesis in vitro. We examined effects of MADG administration in setting of cecal ligation and puncture (CLP) and hypothesized that oral (p.o.) administration of MADG would result in alterations of cytokine and chemokine expression after CLP. METHODS: Four groups of 20 mice: sham group underwent celiotomy but not CLP; control group underwent CLP and administration of phosphate buffer solution; simultaneous treatment group had administration of 50 mg/kg MADG p.o. Immediately, before CLP and at 24, 48, and 72-hour post-CLP, posttreatment group had initial administration of MADG at 1-hour post-CLP, and at 24, 48, and 72-hour postoperative. We followed survival to 10-day postoperative. Serum and tissue levels of pro- and anti-inflammatory cytokines were measured. Serum levels of chemokines stromal cell-derived factor (SDF-1) and stem cell factor (SCF) were measured to ascertain if effects of MADG involve stimulation of bone marrow stromal and stem cells. Polymerase chain reaction was used to measure SDF and SCF mRNA expression in liver and lung. RESULTS: Administration of MADG (p.o.) significantly improved survival in mice after CLP with associated systemic alterations of a variety of cytokines. Increased levels of mRNA coding for SCF and SDF in lung and liver were found after CLP. CONCLUSIONS: Administration of MADG (p.o.) after CLP results in marked improvement in survival. Cytokine level changes demonstrate associated immunomodulatory effects. These effects may be mediated by bone marrow stromal and stem cell activation, evidenced by increases in SDF and SCF. Further study of behavior of bone marrow-derived stem cells in setting of sepsis is warranted. MADG may hold promise for use in treatment of sepsis.

Hepatic angioembolization in trauma patients: indications and complications.

BACKGROUND: Hepatic angiography (HA) and hepatic angioembolization (HAE) are increasingly used to diagnose and treat intrahepatic arterial injuries. This study was performed to review indications, outcomes, and complications of HA/HAE in blunt trauma patients who underwent HAE as adjunct management of hepatic injury. METHODS: A retrospective review of consecutive cases of HA/HAE at a Level I trauma center during an 8-year period. Data include demographics, physiologic condition, liver injury grade, HA/HAE indications, outcomes, morbidity, and mortality. RESULTS: Seventy-nine patients underwent diagnostic HA; 31 (39%) had subsequent HAE. Fifty-eight hemodynamically stable patients had computerized axial tomographic (CT) scan followed by HA. HA was performed for contrast blush on CT in 30 (52%) of 58 patients, high-grade liver injury in 4 (7%), subsequent hemodynamic instability in 15 (27%), and angiography planned for other purpose in 9 (17%). HA confirmed arterial injury and led to HAE in 50% of patients with contrast blush on CT or high-grade liver injury. HA was negative when performed for hemodynamic instability or for other primary purposes. Twenty-one hemodynamically unstable patients underwent emergent laparotomy followed by postoperative HA with 11 (50%) requiring HAE. Overall mortality in HAE group was 16%, and liver-related morbidity was 29% usually presenting as gallbladder or liver necrosis. CONCLUSION: HA/HAE should be used when CT scan suggests associated intrahepatic arterial or high-grade injury in the management of hepatic injuries and should also be considered after laparotomy and perihepatic packing to control inaccessible intrahepatic hemorrhage. Mortality related to HAE is uncommon, but morbidity occurs frequently.

Physicochemical properties of perfluorochemical liquids influence ventilatory requirements, pulmonary mechanics, and microvascular permeability during partial liquid ventilation following intestinal ischemia/reperfusion injury.

OBJECTIVE: To test the hypothesis that the physicochemical properties of perfluorochemical liquid used in partial liquid ventilation can influence ventilatory requirements, pulmonary mechanics, microvascular permeability, and vasoactive mediator release in the abnormal lung. DESIGN: Prospective, controlled animal study. SETTING: Research laboratory in a university setting. SUBJECTS Male Sprague-Dawley rats: sham and intestinal ischemia/reperfusion injury. INTERVENTIONS: Treatment with perfluorochemical partial liquid ventilation (PLV: PP-5 or H-130) or conventional mechanical ventilation (CMV) over 60 mins of superior mesenteric artery occlusion and 60 mins of reperfusion. MEASUREMENTS AND MAIN RESULTS: Gas exchange, ventilatory requirements, and pulmonary mechanics were measured in vivo. Subsequently, pulmonary vascular resistance, microvascular permeability, and thromboxane were measured by using the isolated perfused lung preparation. PLV with PP-5 required significantly (p <.05) higher positive end-expiratory pressure resulting in increased mean airway pressures and pulmonary vascular resistance in both sham and intestinal ischemia/reperfusion injured animals compared with those treated with CMV or PLV H-130. PLV PP-5 also resulted in significantly (p <.05) lower respiratory compliance and greater microvascular permeability compared with sham animals. Following intestinal ischemia/reperfusion injury, PLV H-130 treated animals had significantly higher (p <.05) respiratory compliance than those treated with PLV PP-5 and a significantly lower (p <.05) intestinal ischemia/reperfusion-mediated increase in microvascular permeability than those treated with CMV or PLV PP-5. Thromboxane levels were significantly higher (p <.01) in injured animals treated with CMV or PLV PP-5 compared with comparably treated shams, were significantly lower (p <.01) in both PLV groups than CMV, and were further attenuated (p <.01) by PLV H-130 compared with PLV PP-5 animals. CONCLUSION: We conclude that PLV with perfluorochemical liquids attenuates pulmonary sequelae resulting from remote organ injury and that the extent of lung protection depends on the physicochemical properties of the perfluorochemical liquids.