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Biomedical subjects

W L Biffl

Publications and source records attributed to W L Biffl.

At least 19 recordsLinked to original sources
PubMed2002

Routine preoperative laboratory analyses are unnecessary before elective laparoscopic cholecystectomy.

BACKGROUND: We formulated a clinical pathway (CP) for elective laparoscopic cholecystectomy (LC), which included the following preoperative evaluation: history and physical (H&P), right upper quadrant ultrasound (US), and liver function tests (LFTs). We hypothesized that routine LFTs did not alter management beyond that dictated by H&P and US, and could be excluded from the CP. METHODS: The study involved 387 consecutive patients undergoing elective LC. Abnormalities in the preoperative evaluation were compared with the finding of choledocholithiasis or other unexpected outcomes. RESULTS: In 187 (48%) patients, abnormalities were found by H&P (n = 7), US (n = 13), and LFTs (n = 177). Seven patients (2%) had documented choledocholithiasis; two had abnormal H & P; three had abnormal US; and four had abnormal LFTs. No patient with choledocholithiasis had abnormal LFTs but normal H&P and US. CONCLUSIONS: Routine LFTs before elective LC are not cost effective. Before LC H&P and US are warranted, but LFTs do not add any useful information and should not be routinely measured.

Adult↗
PubMed2001

Avoidance of abdominal compartment syndrome in damage-control laparotomy after trauma.

HYPOTHESIS: Abdominal compartment syndrome (ACS) is a morbid complication of damage-control laparotomy. Moreover, the technique of abdominal closure influences the frequency of ACS. DESIGN: Retrospective cohort study. SETTING: Urban level I trauma center. PATIENTS: We studied 52 patients with trauma who required damage-control laparotomy during the 5 years ending December 31, 1999, and who survived longer than 48 hours. MAIN OUTCOME MEASURES: Abdominal compartment syndrome, acute respiratory distress syndrome (ARDS), and multiple organ failure (MOF). RESULTS: Mean (+/- SD) age was 33 +/- 2 years; 38 (73%) were male. Mechanism of injury was blunt in 29 patients (56%), and mean (+/- SD) Injury Severity Score was 28 +/- 2. Development of ARDS and/or MOF was seen in 23 patients (44%); ARDS and MOF increased mortality from 12% (3/26) to 42% (11/26). Abdominal compartment syndrome was a common complication (17/52), and was associated with an increase in ARDS and/or MOF (12 patients [71%] vs 11 patients [31%] without ACS; P =.02, chi(2) test) and death (6 [35%] vs 8 patients [23%] without ACS). Primary fascial closure (n = 10) at the initial laparotomy was associated with ACS in 8 (80%) (P =.001, chi(2) test) and ARDS and/or MOF in 9 (90%) (P =.01, chi(2) test); skin closure (n = 25), with ACS in 6 (24%) and ARDS/MOF in 9 (36%); and Bogotá bag closure (n = 17), with ACS in 3 (18%) and ARDS/MOF in 8 (47%). CONCLUSIONS: Damage-control laparotomy is associated with frequent complications. In particular, ACS is a serious complication that increases ARDS and/or MOF and mortality. Avoiding primary fascial closure at the initial laparotomy can minimize the risk for ACS.

Abdomen↗
PubMed2001

Blunt carotid and vertebral arterial injuries.

Blunt carotid and vertebral arterial injuries are uncommon but have the potential for devastating consequences. The classic presentation is a neurologic deficit unexplained by computed tomographic scan findings. Screening patients based on injury mechanisms and patterns allows the diagnosis and treatment of injuries while they are still asymptomatic, potentially improving neurologic outcomes. The development of a grading scale may help refine treatment guidelines. Accessible grade II, III, and V carotid injuries should be repaired surgically. Anticoagulation should be considered first-line therapy for grade I and IV, and inaccessible grade II and III carotid lesions, and grade I-IV vertebral injuries. Grade V and persistent grade III lesions may be best treated employing endovascular techniques.

Carotid Artery Injuries↗
PubMed2001

Is breast cancer in young Latinas a different disease?

BACKGROUND: Breast cancer appears to be more aggressive in young women (< or =35 years). Race/ethnicity may further influence prognosis. The purpose of this review is to determine whether breast cancer in young Latinas differs from that in other women. METHODS: Our institutional (1977-2000) and state (1988-2000) tumor registries were reviewed and breast cancer cases analyzed. Data are expressed as mean +/- SEM. RESULTS: At our institution, 56 (7%) of 748 breast cancer patients were < or =35 years old; 32 (57%) were Latina. Compared with non-Latinas, Latinas presented at a younger age (P <0.05) and had more stage III/IV disease (38% versus 29%; P >0.05) and bilaterality (22% versus 8%; P >0.05), and worse 5-year survival (63% versus 83%; P >0.05). Statewide data were consistent with our institutional data. CONCLUSIONS: Latinas comprise a disproportionate share of our young breast cancer population, and may suffer more aggressive disease than other young women. Young Latinas may benefit from more vigilant screening and should be considered for novel therapeutic protocols.

Adult↗
PubMed2001

Secondary abdominal compartment syndrome is a highly lethal event.

BACKGROUND: Recent reports have described resuscitation-induced, "secondary" abdominal compartment syndrome (ACS) in trauma patients without intra-abdominal injuries. We have diagnosed secondary ACS in a variety of nontrauma as well as trauma patients. The purpose of this review is to characterize patients who develop secondary ACS. METHODS: Our prospective ACS database was reviewed for cases of secondary ACS. Physiologic parameters and outcomes were recorded. Data are expressed as mean +/- SEM. RESULTS: Fourteen patients (13 male, aged 45 +/- 5 years) developed ACS 11.6 +/- 2.2 hours following resuscitation from shock. Eleven (79%) had required vasopressors; the worst base deficit was 14.1 +/- 1.9. Resuscitation included 16.7 +/- 3.0 L crystalloid and 13.3 +/- 2.9 red blood cell units. Decompressive laparotomy improved intra-abdominal, systolic, and peak airway pressures, as well as urine output; however, mortality was 38% among trauma and 100% among nontrauma patients. CONCLUSIONS: Secondary ACS may be encountered by general surgeons in a variety of clinical scenarios; resuscitation from severe shock appears to be the critical factor. Early identification and abdominal decompression are essential. Unfortunately, in our experience, this is a highly lethal event.

Abdomen↗
PubMed2001

The abdominal compartment syndrome is a morbid complication of postinjury damage control surgery.

BACKGROUND: The abdominal compartment syndrome (ACS) is a recognized complication of damage control surgery (DCS). The purposes of this study were to (1) determine the effect of ACS on outcome after DCS, (2) identify patients at high risk for the development of ACS, and (3) determine whether ACS can be prevented by preemptive intravenous bag closure during DCS. METHODS: Patients requiring postinjury DCS at our institution from January 1996 to June 2000 were divided into groups depending on whether or not they developed ACS. ACS was defined as an intra-abdominal pressure (IAP) greater than 20 mm Hg in association with increased airway pressure or impaired renal function. RESULTS: ACS developed in 36% of the 77 patients who underwent DCS with a mean IAP prior to decompression of 26 +/- 1 mm Hg. The ACS versus non-ACS groups were not significantly different in patient demographics, Injury Severity Score, emergency department vital signs, or intensive care unit admission indices (blood pressure, temperature, base deficit, cardiac index, lactate, international normalized ratio, partial thromboplastin time, and 24-hour fluid). The initial peak airway pressure after DCS was higher in those patients who went on to develop ACS. The development of ACS after DCS was associated with increased ICU stays, days of ventilation, complications, multiorgan failure, and mortality. CONCLUSIONS: ACS after postinjury DCS worsens outcome. With the exception of early elevation in peak airway pressure, we could not identify patients at higher risk for ACS; moreover, preemptive abdominal bag closure during initial DCS did not prevent this highly morbid complication.

Abdomen↗
PubMed2001

Routine intraoperative laparoscopic ultrasonography with selective cholangiography reduces bile duct complications during laparoscopic cholecystectomy.

BACKGROUND: Laparoscopic cholecystectomy (LC) is the preferred treatment for gallstone disease, even in many complicated cases. Perhaps the only downside to LC is a two- to threefold increase in common bile duct (CBD) injuries compared with open cholecystectomy (OC). Intraoperative cholangiography may prevent inj uries, but its routine use remains controversial. Our institution adopted a policy of selective intraoperative cholangiography in 1993. When intraoperative laparoscopic ultrasonography (IOUS) emerged as a viable diagnostic adjunct, it was hypothesized that the routine use of IOUS would facilitate dissection, detect occult choledocholithiasis, and prevent bile duct injuries during LC. STUDY DESIGN: The experience with LC at our university-affiliated teaching hospital was reviewed. Over a 4 1/2-year period (June 1, 1995, to January 31, 2000), two surgeons used IOUS routinely during LC (ultrasonography [US] group, n = 248); three other surgeons did not (non-US group, n = 594). We compared patient data and outcomes between the two groups. Continuous, data are expressed as mean +/- SEM. RESULTS: During the study period, 842 LCs were attempted. Patient age (37+/-1 years) and gender (85% female) did not differ between the groups. In the US group, more patients had acute cholecystitis (p < 0.05). More LCs were performed per year by non-US surgeons than US surgeons (45 versus 37). Despite this, all bile duct complications occurred in non-US cases (2.5% overall): five CBD injuries (0.8%), six bile leaks (1%), and four retained CBD stones (0.7%). In the subgroup of patients with acute cholecystitis, there were fewer conversions to OC in US compared with non-US cases (24% versus 36%, p = 0.09). CONCLUSIONS: IOUS is noninvasive, fast, repeatable, and can corroborate real-time visualization of the operative field. We have found that LC with IOUS is associated with fewer bile duct complications (CBD injuries, bile leaks, and retained CBD stones) than LC without adjunctive imaging. The success rate of LC in cases of acute cholecystitis is slightly higher when IOUS is used as an aid to dissection. In the absence of definitive prospective data, we recommend routine use of IOUS when performing LC, particularly in patients with acute cholecystitis.

Adult↗
PubMed2001

Hypertonic saline attenuation of the neutrophil cytotoxic response is reversed upon restoration of normotonicity and reestablished by repeated hypertonic challenge.

BACKGROUND: Hypertonic saline (HTS) resuscitation, in addition to enhancing hemodynamic recovery, modulates postinjury hyperinflammation in the critically injured. The polymorphonuclear neutrophil (PMN) cytotoxic response, a key element in the pathogenesis of postinjury organ dysfunction, is attenuated under hypertonic conditions. Although plasma Na(+) rises to 180 mmol/L after HTS infusion, baseline levels are reestablished within 24 hours. We hypothesized that HTS attenuation of the PMN cytotoxic response (beta2-integrin expression, elastase release, and O2- production) is reversed upon return to normotonicity, but can be reestablished by repeated HTS challenge. METHODS: Isolated human PMNs were incubated in HTS (Na(+) = 180 mmol/L) for 5 minutes at 37 degrees C then returned to normotonicity by centrifugation and resuspension in isotonic buffer. Stimulated (PAF) beta2-integrin expression was measured by flow cytometry. Stimulated (PAF/fMLP) elastase release and O2- production were measured by cleavage of N-methoxysuccinyl-Ala-Ala-Pro-Val p-nitroanilide and reduction of cytochrome c (Cyt c). Protein tyrosine phosphorylation in PMN cell lysates was assessed by Western blot. RESULTS: Clinically relevant levels of HTS induced tyrosine phosphorylation in resting PMNs and attenuated cytotoxic responses. Reestablishment of normotonicity returned these functions to baseline. A repeated HTS challenge after restoration of normotonicity also induced tyrosine phosphorylation and suppressed the cytotoxic response. CONCLUSIONS: HTS attenuation of the PMN cytotoxic response is reversible but can be reestablished by repeated HTS treatment. This phenomenon may provide the unique opportunity to selectively and temporarily decrease the postinjury inflammatory response when patients are at greatest risk for PMN-mediated tissue damage.

CD18 Antigens↗
PubMed2001

Phospholipase A(2)--derived neutral lipids from posthemorrhagic shock mesenteric lymph prime the neutrophil oxidative burst.

BACKGROUND: Our previous work identified posthemorrhagic shock mesenteric lymph (PHSML) lipids as key elements in polymorphonuclear neutrophil (PMN)--provoked acute lung injury. We hypothesize that gut phospholipase A(2) (PLA(2)) is responsible for the generation of proinflammatory lipids in PHSML that primes circulating PMNs for enhanced oxidative burst. METHODS: Mesenteric lymph was collected from rats (n = 5) before (preshock), during the induction of hemorrhagic shock (mean arterial pressure, 40 mm Hg x 30 minutes), and at resuscitation (shed blood + 2x lactated Ringer's solution). PLA(2) inhibition (quinacrine, 10 mg/kg, intravenously) was given before shock was induced. Extracted lipids were separated by normal phase high-pressure liquid chromatography and resuspended in albumin. PMNs were exposed to a 5% vol:vol concentration of eluted lipids and activated with N-formyl-methionyl-leucyl-phenylalanine (1 micromol/L). Superoxide production was assessed by cytochrome C reduction. RESULTS: High-pressure liquid chromatography--extracted neutral lipids of lymph collected before hemorrhagic shock did not prime the PMN oxidase, whereas isolated neutral lipids of postshock lymph primed PMNs 2.6- +/- 0.32-fold above baseline (P <.05). PLA(2) inhibition returned PHSML neutral lipid priming to baseline levels. CONCLUSIONS: PLA(2) inhibition before hemorrhagic shock abrogates the neutrophil priming effects of PHSML through reduction of the accumulation of proinflammatory neutral lipids. Identification of these PLA(2)-dependent lipids provides a mechanistic link that may have therapeutic implications for postshock acute lung injury.

Animals↗
PubMed2001

Neutrophil apoptosis is delayed by trauma patients' plasma via a mechanism involving proinflammatory phospholipids and protein kinase C.

BACKGROUND: Delayed apoptosis of primed neutrophils (PMNs) may facilitate PMN-mediated tissue injury leading to multiple organ failure (MOF). We previously reported delayed apoptosis and priming of PMNs in severely injured patients at risk for MOF. Our in vitro and in vivo data have implicated phospholipids in PMN cytotoxicity following trauma and shock. The phospholipid signaling pathway remains to be elucidated, but may involve protein kinase C (PKC). We hypothesized that circulating platelet-activating factor (PAF) and PAF-like proinflammatory phospholipids mediate delayed postinjury PMN apoptosis and that PKC is integral to the signaling pathway. METHODS: Blood was drawn from severely injured patients (n = 6; mean injury severity score = 21 and transfusion = 10 units) at 6 h postinjury. The plasma fraction was isolated and incubated (5% CO(2), 37 degrees C, 24 h) with PMNs harvested from healthy volunteers. Some PMNs were preincubated with a PAF receptor antagonist (WEB 2170, 400 microM) or a PKC inhibitor (Bis I, 1 microM). Apoptotic index (% PMNs undergoing apoptosis) was assessed morphologically. RESULTS: Trauma patients' plasma delayed PMN apoptosis compared with plasma from controls. The PMN apoptotic index was not altered by WEB 2170 or Bis I alone; however, WEB 2170 or Bis I pretreatment abrogated delayed PMN apoptosis in response to trauma patients' plasma. CONCLUSION: Trauma patients' plasma delays apoptosis of PMNs. Our data implicate PAF-like phospholipids in this effect, and PKC appears to be integral in the signaling process. Further elucidation of specific lipids and signaling pathways may reveal clinically accessible therapeutic targets to prevent PMN-mediated hyperinflammation.

Adolescent↗
PubMed2001

Evolution of a multidisciplinary clinical pathway for the management of unstable patients with pelvic fractures.

OBJECTIVE: To determine whether the evolution of the authors' clinical pathway for the treatment of hemodynamically compromised patients with pelvic fractures was associated with improved patient outcome. SUMMARY BACKGROUND DATA: Hemodynamically compromised patients with pelvic fractures present a complex challenge. The multidisciplinary trauma team must control hemorrhage, restore hemodynamics, and rapidly identify and treat associated life-threatening injuries. The authors developed a clinical pathway consisting of five primary elements: immediate trauma attending surgeon's presence in the emergency department, early simultaneous transfusion of blood and coagulation factors, prompt diagnosis and management of associated life-threatening injuries, stabilization of the pelvic girdle, and timely insinuation of pelvic angiography and embolization. The addition of two orthopedic pelvic fracture specialists led to a revision of the pathway, emphasizing immediate emergency department presence of the orthopedic trauma attending to provide joint decision making with the trauma surgeon, closing the pelvic volume in the emergency department, and using alternatives to traditional external fixation devices. METHODS: Using trauma registry and blood bank records, the authors identified pelvic fracture patients receiving blood transfusions in the emergency department. They analyzed patients treated before versus after the May 1998 revision of the clinical pathway. RESULTS: A higher proportion of patients in the late period had blood pressure less than 90 mmHg (52% vs. 35%). In the late period, diagnostic peritoneal lavage was phased out in favor of torso ultrasound as a primary triage tool, and pelvic binding and C-clamp application largely replaced traditional external fixation devices. The overall death rate decreased from 31% in the early period to 15% in the later period, as did the rate of deaths from exsanguination (9% to 1%), multiple organ failure (12% to 1%), and death within 24 hours (16% to 5%). CONCLUSIONS: The evolution of a multidisciplinary clinical pathway, coordinating the resources of a level 1 trauma center and directed by joint decision making between trauma surgeons and orthopedic traumatologists, has resulted in improved patient survival. The primary benefits appear to be in reducing early deaths from exsanguination and late deaths from multiple organ failure.

Adult↗
PubMed2001

Hypertonic saline alteration of the PMN cytoskeleton: implications for signal transduction and the cytotoxic response.

BACKGROUND: Recognition that hypertonic saline (HTS) modulates the inflammatory response has renewed interest in this agent for postinjury resuscitation. Changes in extracellular tonicity alter cell shape and are accompanied by cytoskeletal reorganization. Recent evidence suggests that cytoskeletal reorganization is critical for receptor-mediated signal transduction. We hypothesized that HTS-induced changes in the cytoskeleton interfere with cytotoxic signal transduction. METHODS: Isolated neutrophils (PMNs) were incubated in HTS (Na+ = 180 mmol/L) and activated with N-formyl-methionyl-leucyl-phenylalanine (receptor-mediated) or phorbol myristate (receptor independent). Actin polymerization was assessed by digital image microscopy and flow cytometry. PMN superoxide anion (O2-) production and p38 MAPK activation was measured by reduction of cytochrome c and Western blot. Pretreatment with cytochalasin B was used to disrupt HTS-induced actin reorganization. RESULTS: HTS inhibited receptor-mediated cytoskeletal reorganization and attenuated p38 MAPK activation and O2- production. HTS had no effect on receptor-independent O2- production. Cytoskeletal disruption (cytochalasin B) prevented HTS attenuation of receptor-mediated p38 MAPK activation. CONCLUSION: HTS attenuates the PMN cytotoxic response by interfering with intracellular signal transduction. Changes in the actin cytoskeleton appear to modulate receptor-mediated p38 MAPK signaling.

Actins↗
PubMed2001

Plasma from aged stored red blood cells delays neutrophil apoptosis and primes for cytotoxicity: abrogation by poststorage washing but not prestorage leukoreduction.

BACKGROUND: Blood transfusion-particularly that of older stored red blood cells (RBCs)--is an independent risk factor for postinjury multiple organ failure. Immunomodulatory effects of RBC transfusion include neutrophil (PMN) priming for cytotoxicity, an effect exacerbated by longer RBC storage times. We have found that delayed PMN apoptosis in trauma patients is provoked by transfusion, independent of injury severity. We hypothesized that aged stored RBCs delay PMN apoptosis, but that prestorage leukodepletion or poststorage washing could abrogate the effect. METHODS: Healthy volunteers each donated 1 unit of blood. One half was leukodepleted, and RBC units were processed in the usual fashion and stored at 4 degrees C. Aliquots were removed on days 1, 14, 21, and 42 and the plasma fraction isolated. Selected aliquots were washed with normal saline before plasma isolation. PMNs harvested from healthy controls were incubated (5% CO2, 37 degrees C) with unmodified, leukoreduced, or washed RBC plasma (20% plasma/80% RPMI 1640), and apoptosis assessed by morphology after 24 hours. Apoptotic index (apoptotic PMNs/total PMNs) was compared. PMN priming for superoxide release was also assessed after plasma exposure. RESULTS: PMN apoptosis was delayed by RBCs stored for 21 or 42 days. Prestorage leukodepletion did not alter the effect. However, washing 42-day-old RBCs abrogated the effect. PMN priming for superoxide was provoked by stored packed RBCs in an identical pattern to delayed apoptosis. CONCLUSION: Plasma from stored RBCs-even if leukoreduced-delays apoptosis and primes PMNs. The effect becomes evident at 21 days and worsens through product outdate (42 days), but may be prevented by poststorage washing. Inflammatory agents contaminating stored blood likely mediate the effect. Modification of transfusion practices (e.g., giving fresher or washed RBCs or blood substitutes) may attenuate adverse immunomodulatory effects of transfusion in trauma patients.

Analysis of Variance↗
PubMed2001

Mesenteric lymph is responsible for post-hemorrhagic shock systemic neutrophil priming.

BACKGROUND: Hemorrhagic shock-induced splanchnic hypoperfusion has been implicated as a priming event in the two event model of multiple organ failure (MOF). We have previously shown that early postinjury neutrophil (PMN) priming identifies the injured patient at risk for MOF. Recent in vitro studies have demonstrated that postshock mesenteric lymph primes isolated human neutrophils. We hypothesize that lymphatic diversion before hemorrhagic shock abrogates systemic PMN priming and subsequent lung injury. METHODS: Sprague-Dawley rats (n >or= 5 per group) underwent hemorrhagic shock (MAP 40 mm Hg x 30 min) and resuscitation (shed blood + 2x crystalloid) with and without mesenteric lymphatic duct diversion. Sham animals underwent anesthesia and laparotomy. Whole blood was taken 2 hours after resuscitation, heparinized, and incubated for 5 min at 37 degrees C. Surface expression of CD11b (a marker for PMN priming) was determined by flow-cytometry compared with isotype controls. In addition, lung myeloperoxidase (MPO) was measured for PMN sequestration, and Evans blue lung leak was assessed in the bronchoalveolar lavage fluid in sham, and shock +/- lymph diversion animals. RESULTS: Hemorrhagic shock resulted in increased surface expression of PMN CD11b relative to sham (23.8 +/- 6.7 vs. 9.9 +/- 0.6). Mesenteric lymphatic diversion before hemorrhagic shock abrogated this effect (8.0 +/- 2.6). Lung PMN accumulation, as assessed by MPO, was greater in the lungs of nondiverted (113 +/- 14 MPO/mg lung) versus sham (55 +/- 4 MPO/mg lung, p < 0.05); lymph diversion reduced lung PMNs to control levels (71 +/- 6.5 MPO/mg lung, p < 0.05). Evans blue lung leak was 1.6 times sham in the hemorrhagic shock group; this was returned to sham levels after lymph diversion (p < 0.05). CONCLUSION: Post-hemorrhagic shock mesenteric lymph primes circulating PMNs, promotes lung PMN accumulation, and provokes acute lung injury. Lymphatic diversion abrogates these pathologic events. These observations further implicate the central role of mesenteric lymph in hemorrhagic shock-induced lung injury. Characterizing the PMN priming agents could provide insight into the pathogenesis of postinjury MOF and ultimately new therapeutic strategies.

Animals↗
PubMed2001

Post-hemorrhagic shock mesenteric lymph lipids prime neutrophils for enhanced cytotoxicity via phospholipase A2.

Hemorrhagic shock induced mesenteric hypoperfusion has long been implicated as a key event in the pathogenesis of the adult respiratory distress syndrome (ARDS) and multiple organ failure (MOF). Previous work links post-hemorrhagic shock mesenteric lymph (PHSML) lipids and neutrophil (PMN) priming in the pathogenesis of ARDS. We hypothesize that gut phospholipase A2 (PLA2) liberates proinflammatory lipids following hemorrhagic shock, which are responsible for enhanced PMN cytotoxicity. Mesenteric lymph was collected from rats (n > or = 5) before hemorrhagic shock, during hemorrhagic shock (MAP 40 mm Hg x 30 min), and after resuscitation (shed blood + 2x lactated Ringers). PMNs were incubated with physiologic concentrations (1-5%, v:v) of (a) buffer control, (b) sham (c) pre-shock lymph, (c) PHSML, (d) PHSML lipid extracts, (e) heat-denatured PSHML, and (f) PHSML harvested after i.v. pretreatment with a known PLA2 inhibitor (quinacrine, 10 mg/kg). PMNs were activated with fMLP (1 micromol), and the maximal rate of superoxide production measured by reduction of cytochrome c. Gut morphology was assessed histologically using hematoxalin and eosin (HE) staining. PHSML and PHSML lipid extracts (5%, v:v) primed for enhanced superoxide production compared to buffer controls (2.5-fold and 3.6-fold), sham (2.5-fold) and pre-shock lymph (2.0-fold). Lymph collected after systemic PLA2 inhibition, in contrast, abrogated the PMN priming response. Gut mucosal morphology, at end-resuscitation, was intact on HE staining both with and without PLA2 inhibition. Heat denaturing the PHSML (eliminating cytokines and complement), on the other hand, did not reduce PMN priming. Physiologic concentrations of PHSML lipids prime the PMN respiratory burst. Lymph priming is diminished with systemic PLA2 inhibition, implicating gut PLA2 as a source of proinflammatory lipids that may be central in the pathogenesis of hemorrhagic shock induced ARDS/MOF.

Animals↗