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H J Sugerman

Publications and source records attributed to H J Sugerman.

At least 19 recordsLinked to original sources
PubMed1995

Sepsis-induced acute lung injury is attenuated by selectin blockade following the onset of sepsis.

OBJECTIVE: To determine the effect of infusion with a dual-binding antibody to E- and L-selectin, EL-246, in a postonset model of sepsis. DESIGN: Nonrandomized controlled study. STUDY SUBJECTS: Young Yorkshire swine. INTERVENTIONS: Three groups were studied. Controls (n = 8) received saline solution only. Untreated animals with sepsis (n = 8) received a 1-hour intravenous infusion of live Pseudomonas aeruginosa. Animals treated with EL-246 (n = 6) received the same bacterial infusion and a 2-mg/kg bolus of EL-246 at 30 minutes. OUTCOME MEASURES: Systemic and pulmonary hemodynamics, arterial blood gas determination, bronchoalveolar lavage protein and neutrophil content, neutrophil integrin and selectin expression, neutrophil oxidant burst, and organ myeloperoxidase content. RESULTS: Treatment with EL-246 significantly reduced lung injury, as indicated by improved bronchoalveolar lavage protein and neutrophil content, resulting in a significant improvement in arterial oxygenation. This reduction in lung injury was produced by a reduction in lung myeloperoxidase content. Treatment with EL-246 failed to prevent the development of pulmonary hypertension and systemic hypotension. Neutrophils from animals with sepsis exhibited significant activation and upregulation of CD18, shedding of L-selectin, and production of increased levels of oxidants compared with controls. CONCLUSION: Treatment of animals with EL-246 soon the onset of sepsis produced significant protection against acute lung injury but failed to attenuate hemodynamic derangements associated with sepsis.

Animals↗
PubMed1995

Tumor necrosis factor-alpha and interleukin-6 selectively regulate neutrophil function in vitro.

The neutrophil is an important effector cell of the host response to sepsis. Tumor necrosis factor-alpha (TNF-alpha), a cytokine mediator of the septic response, is rapidly released following endotoxemia or gram-negative bacteremia. Interleukin-6 (IL-6) is another cytokine mediator of the host response to sepsis whose role is less well understood than that of TNF-alpha. It is known to be elevated in gram-negative sepsis, where peak levels have been correlated with mortality. This study examined the effect of IL-6 alone and in combination with TNF-alpha on three neutrophil functions--CD18 adhesion receptor expression, phagocytosis, and superoxide anion generation. Neutrophils from human volunteers were incubated with amounts of IL-6 ranging from 10 to 1000 ng/ml. At a concentration of 1000 ng/ml, IL-6 increased neutrophil phagocytosis of opsonized bacteria (826 +/- 255 x 10(3) MESF vs 552 +/- 103 MESF, P < 0.05) and also increased neutrophil superoxide anion generation (18.41 +/- 1.86 vs 12.6 nmol O2-/10(6) PMN/10 min, P < 0.05). Lesser amounts of IL-6 had no effect on phagocytosis or superoxide generation. IL-6 did not increase neutrophil CD18 adhesion receptor expression. Combining IL-6 with TNF-alpha at doses of 100 ng/ml and 100 U/ml, respectively, neutrophil phagocytosis (221 +/- 455 MESF vs 552 +/- 103 MESF) and superoxide generation (23.18 +/- 1.86 vs 12.6 nmol O2-/10(6) PMN/10 min) were significantly (P < 0.05) increased above control by an amount similar to that seen with 1000 U/ml TNF-alpha alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Effect of NSAIDs on gallbladder bile composition.

Secretion of gallbladder mucin is an important step in gallstone pathogenesis. Previous studies have demonstrated that aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) can both inhibit gallbladder mucin secretion and prevent gallstone formation in animal models of cholesterol gallstone disease. The present study was performed to determine if chronic NSAID use was associated with a reduction in the mucin content or affected the lipid components of human gallbladder bile. Four groups of patients were identified retrospectively from a cohort of 230 morbidly obese patients who underwent gastric bypass surgery. The index group consisted of 18 patients who were found to have gallstones at gastric bypass surgery and had a history of chronic NSAID use. Three other patient groups were identified from the cohort by matching this index population for sex, race, and age according to the following criteria: (1) patients with gallstones who had not utilized NSAIDs, (2) patients without gallstones but with chronic NSAID use, and (3) patients without gallstones and without a history of NSAID use. Gallbladder bile was obtained from all patients by direct aspiration from the gallbladder at the time of surgery. Patients with gallstones had a significantly (P < 0.02) greater concentration of gallbladder mucin in their gallbladder bile compared to patients without gallstones (0.897 +/- 0.226 vs 0.173 +/- 0.039 mg/ml). Among gallstone patients, gallbladder mucin was reduced in those patients with a history of chronic NSAID use (1.18 +/- 0.43 vs 0.74 +/- 0.19 mg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

A multicenter, placebo-controlled, randomized, double-blind, prospective trial of prophylactic ursodiol for the prevention of gallstone formation following gastric-bypass-induced rapid weight loss.

BACKGROUND: Previous studies have documented a high incidence of gallstone formation following gastric-bypass (GBP)-induced rapid weight loss in morbidly obese patients. This study was designed to determine if a 6-month regimen of prophylactic ursodiol might prevent the development of gallstones. METHODS: A multicenter, randomized, double-blind, prospective trial evaluated 3 oral doses of ursodiol: 300, 600, and 1,200 mg versus placebo beginning within 10 days after surgery and continuing for 6 months or until gallstone development, for patients with a body mass index (BMI) > or = 40 kg/m2. All patients had normal intraoperative gallbladder sonography. Transabdominal sonography was obtained at 2, 4, and 6 months following surgery, or until gallstone formation. RESULTS: Of 233 patients with at least one postoperative sonogram, 56 were randomized to placebo, 53 to 300 mg ursodiol, 61 to 600 mg ursodiol, and 63 to 1,200 mg ursodiol. Preoperative age, sex, race, weight, BMI, and postoperative weight loss were not significantly different between groups. Gallstone formation occurred at 6 months in 32%, 13%, 2%, and 6% of the patients on the respective doses. Gallstones were significantly (P < 0.001) less frequent with ursodiol 600 and 1,200 mg than with placebo. CONCLUSION: A daily dose of 600 mg ursodiol is effective prophylaxis for gallstone formation following GBP-induced rapid weight loss.

Adolescent↗
PubMed1995

Beneficial effects of a bradykinin antagonist in a model of gram-negative sepsis.

UNLABELLED: Activation of the kallikrein-kinin system in sepsis has long been recognized, but its role, beneficial or pathologic, has not been determined. Recently, however, specific bradykinin (BK) antagonists have become available and we sought to determine the effects of a BK antagonist, NPC17731, in a model of sepsis-induced acute lung injury (ALI). METHODS: Anesthetized swine were studied for 5 hours, receiving a 1-hour infusion of saline (Controls) or live Pseudomonas aeruginosa (Septic untreated). Treatment groups received a 5 mg/kg bolus of NPC17731 followed by a 1 mg/kg bolus hourly commencing either just before sepsis (Pretreatment) or 30 minutes following the onset of sepsis (Posttreatment). RESULTS: Septic untreated animals showed a rapid, progressive decline in arterial PaO2 compared to controls, and this was significantly improved in both treatment groups. Bronchoalveolar lavage at 5 hours in both treatment groups also showed significant decreases in neutrophil (PMN) counts and protein content compared to untreated septic animals, indicating decreased PMN migration and alveolar-capillary membrane damage. Both treatment groups also showed reduced PMN sequestration in the lung compared to untreated animals, although PMNs did exhibit significant upregulation of PMN CD18 receptor expression and superoxide generation. CONCLUSIONS: These data imply a significant role for BK in the pathogenesis of sepsis-induced ALI. Use of a competitive BK antagonist significantly attenuated the development of ALI without inhibiting PMN activation. BK antagonists may be a useful adjunct in the armamentarium against sepsis-induced ALI.

Animals↗
PubMed1995

Cardiopulmonary effects of raised intra-abdominal pressure before and after intravascular volume expansion.

The cardiopulmonary effects of acutely elevated intra-abdominal pressure (IAP) were studied in a porcine model to help define more clearly IAP effects in patients with trauma. IAP was increased in six anesthetized swine by intra-abdominal instillation of isotonic ethylene glycol up to an IAP of 25 mm Hg above baseline. Systemic and pulmonary hemodynamic parameters were measured, as well as the effects on bladder pressure, pleural pressure, and pulmonary function. At IAP of 25 mm Hg above baseline, intravascular volume expansion with saline was administered to return the cardiac index (CI) to baseline. Raising IAP correlated with measured bladder pressures (r = 0.9, p = 0.001). At IAP of 25 mm Hg, CI was significantly decreased (p < 0.05, analysis of variance (ANOVA); 3.6 +/- 0.3 vs. 2.2 +/- 0.3 L/min/m2); whereas wedge, pulmonary arterial, and pleural pressures were all elevated (p < 0.05, ANOVA). However, transarterial wedge pressure (wedge--pleural pressure) declined nonsignificantly with increasing IAP. Raised IAP caused impaired pulmonary function with a decreased (p < 0.05, ANOVA) PaO2 and increased (p < 0.05, ANOVA) PaCO2. Despite the elevated wedge pressure, fluid resuscitation returned CI to baseline. These data clarify the hemodynamic changes associated with raised IAP and indicate that care must be taken in interpreting hemodynamic measurements to determine intravascular fluid status in patients with elevated IAP.

Abdomen↗
PubMed1995

Treatment of increasing intracranial pressure secondary to the acute abdominal compartment syndrome in a patient with combined abdominal and head trauma.

Acute abdominal compartment syndrome has recently been shown to raise intracranial pressure (ICP). This may increase the risk of ischemic neuronal damage by decreasing cerebral perfusion pressure. We report the successful management of a patient with severe multisystem injury in whom abdominal decompression dramatically reduced high ICP unresponsive to medical measures.

Abdomen↗
PubMed1995

Circulating ICAM-1 is increased in septic shock.

Adhesion molecules play a critical role in the interaction of circulating neutrophils with vascular endothelium during inflammation. Increased quantities of soluble, circulating intercellular adhesion molecule-1 (cICAM-1) are present in various inflammatory conditions. The purpose of this investigation was to measure cICAM-1 levels in septic adults, as well as to examine the relationship between this potential marker of endothelial-cell activation and the consequences of sepsis (i.e., multiple organ failure and death). Using a sandwich-type enzyme-linked immunosorbent assay (ELISA), we measured cICAM-1 in blood samples obtained within 12 h of admission to an intensive care unit (ICU) for sepsis and other conditions. We found cICAM-1 levels to be increased in 25 septic patients (1,259 +/- 159 ng/ml, mean +/- SEM) as compared with 12 healthy volunteers (355 +/- 41 ng/ml, p < 0.0001) and four ICU patients without systemic inflammatory response syndrome (SIRS) (585 +/- 76 ng/ml, p < 0.001). Twenty-five patients with SIRS but no evidence of causative infection also had elevated levels of cICAM-1 (937 +/- 144 ng/ml, p = 0.12 versus sepsis). Serial measurements over the first week of sepsis demonstrated persistent elevation in most patients. Day 1 cICAM-1 levels were higher (p = 0.017, ANOVA) in 16 patients with septic shock than in seven with severe sepsis and two with sepsis but without hypotension or hypoperfusion. There was a positive correlation (r = 0.50, p = 0.009) between Day-1 cICAM-1 measurements and severity of shock as determined by the presence of hypotension and vasopressor use.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

A dual-binding antibody to E- and L-selectin attenuates sepsis-induced lung injury.

Many studies indicate a pivotal role for neutrophil adhesion in sepsis-associated lung injury. Neutrophil adhesion to endothelium depends on activation and expression of selectin and integrin adhesion receptors. We studied the effects of pretreatment with a dual-binding porcine anti-E- and anti-L-selectin monoclonal antibody (EL-246) on a porcine model of sepsis-induced lung injury. Four groups were studied for 5 h. Group 1 (control animals) received intravenous saline only. Group 2 (septic) received a 1-h infusion of Pseudomonas aeruginosa. Group 3 (EL-246 pretreatment) received EL-246 (1 mg/kg) prior to Pseudomonas infusion. Group 4 (EL-246 controls) received EL-246 infusion only. Group 2 animals showed rapid, significant decline in arterial pH and oxygen tension whereas, in Group 3, physiologic deterioration was significantly attenuated. Bronchoalveolar lavage at 5 h showed a significant increase in neutrophil count and protein content in Group 2. Group 3, however, showed no significant differences in these parameters compared with control animals. Despite severe neutropenia, lung myeloperoxidase content at 5 h was significantly reduced in Group 3 compared with Group 2. There was no significant difference in pulmonary and systemic hemodynamics between Groups 2 and 3. Group 4 animals exhibited a transient neutropenia, but otherwise no other differences in measured parameters were found compared with Group 1 control animals. In conclusion, EL-246 significantly reduced neutrophil accumulation in lung and attenuated sepsis-induced lung injury, but failed to attenuate deranged pulmonary and systemic hemodynamics.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Effects of surgically induced weight loss on idiopathic intracranial hypertension in morbid obesity.

BACKGROUND: The effect on CSF pressures and symptoms of weight loss induced by gastric surgery was studied in morbidly obese patients with idiopathic intracranial hypertension (IIH). METHODS: Gastric weight reduction surgery was performed in eight morbidly obese women (49 +/- 3 kg/m2 body mass index) who had IIH and elevated CSF pressures. Each had been treated medically for IIH. Two had ventriculoperitoneal shunts, with occlusion in both and hemorrhage and hemiparesis in one. Post--weight-reduction measurement of CSF pressures, signs and symptoms of IIH, and obesity co-morbidity were evaluated. RESULTS: CSF pressures decreased in all eight patients, from a mean of 353 +/- 35 to a mean of 168 +/- 12 mm H2O (p < 0.001), following mean weight loss of 57 +/- 5 kg (p < 0.001) when measured at 34 +/- 8 months after surgery. At follow-up no patient had papilledema, all eight patients had resolution or marked reduction of headache, and resolution of tinnitus occurred in all six patients with this symptom. Neuroimaging was unchanged at 27 +/- 6 months after surgery in six patients. There was also resolution or clinical improvement of additional obesity-related co-morbidity, including diabetes, hypertension, sleep apnea, obesity hypoventilation, joint pains, stress urinary incontinence, and gastroesophageal reflux. CONCLUSIONS: Although several complications occurred following obesity surgery over the 11 years of this study, the current low morbidity and mortality with gastric bypass make this a primary option in the severely obese patient with IIH.

Adult↗
PubMed1994

Delayed tumor necrosis factor alpha blockade attenuates pulmonary dysfunction and metabolic acidosis associated with experimental gram-negative sepsis.

OBJECTIVE: To ascertain the effect of delayed tumor necrosis factor alpha (TNF-alpha) on the evolution of systemic and pulmonary injury after the onset of sepsis. DESIGN: Prospective controlled trial. INTERVENTION: Anesthetized swine were made septic with a 1-hour infusion of live Pseudomonas aeruginosa, following which a treatment group received an infusion of anti-TNF-alpha monoclonal antibody (5 mg/kg). Control animals received 0.9% saline. RESULTS: Delayed anti-TNF-alpha treatment had no effect on septic pulmonary hypertension or decline in cardiac output. Late recovery in systemic arterial hypotension was associated with a reversal of arterial acidosis (P < .05 by t test and analysis of variance with Tukey's Studentized Range Test) compared with unprotected septic animals. Septic animals had a significant increase in mean (+/- SEM) plasma lactate levels at 5 hours compared with baseline values (3.8 +/- 0.7 vs 2 +/- 0.4, P < .05), but remained unchanged from baseline following anti-TNF-alpha treatment (1.5 +/- 0.1 vs 1.6 +/- 0.2, not significant). Characteristic septic neutropenia was dramatically reversed by anti-TNF-alpha treatment and was associated with downregulation (P < .05 by t test and analysis of variance) of polymorphonuclear neutrophil (PMN) leukocyte CD18 adhesion receptors and reduction (P < .05 by t test and analysis of variance) in lung PMN sequestration measured by myeloperoxidase activity. The mean (+/- SEM) decrease in bronchoalveolar lavage protein indicated an attenuated permeability injury in anti-TNF-alpha animals (septic animals at 5 hours compared with baseline value, 1044 +/- 270 vs 149 +/- 28 micrograms/mL; control animals at 5 hours compared with baseline value, 217 +/- 83 vs 129 +/- 19 micrograms/mL; P < .05 by t test and analysis of variance). CONCLUSIONS: These data show that delayed anti-TNF-alpha treatment reversed metabolic acidosis associated with sepsis. Furthermore, anti-TNF-alpha treatment reversed septic neutropenia, reduced PMN sequestration, and was associated with attenuated lung injury in a model of fulminant sepsis. This supports evidence of PMN-mediated tissue injury in sepsis and suggests mechanisms for potential therapeutic benefit of anti-TNF-alpha treatment in clinical practice.

Acidosis, Lactic↗
PubMed1994

Beneficial cardiopulmonary effects of pentoxifylline in experimental sepsis are lost once septic shock is established.

OBJECTIVE: To determine the effects of pretreatment and posttreatment with pentoxifylline in a porcine model of gram-negative sepsis. DESIGN: Nonrandomized controlled trial. STUDY SUBJECTS: Young Yorkshire swine. INTERVENTIONS: Six groups of ventilated swine were studied for 5 hours. Group 1 swine (control, n = 8) received saline solution only. Group 2 swine (sepsis, n = 8) received a 1-hour infusion of Pseudomonas aeruginosa. Groups 3, 4, and 5 swine received the P aeruginosa infusion and a 20 mg/kg bolus followed by a 6 mg/kg per hour infusion of pentoxifylline. Group 3 swine (n = 6) received pentoxifylline prior to the onset of sepsis; group 4 swine (n = 6) received pentoxifylline at 1 hour and group 5 swine (n = 4) at 2 hours after the onset of the P aeruginosa infusion. Group 6 swine (control pentoxifylline, n = 3) received pentoxifylline only. OUTCOME MEASURES: Hemodynamic variables, neutrophil counts and CD18 expression, tumor necrosis factor activity, and arterial blood gases were measured hourly. Bronchoalveolar lavage was performed at 0 and 5 hours to measure neutrophil and protein content. RESULTS: All variables remained unchanged in the control and control pentoxifylline groups. Both pretreatment and posttreatment with pentoxifylline significantly attenuated lung injury and improved arterial PaO2. The cardiac index was significantly improved by administration of pentoxifylline in groups 3 and 4. Administration of pentoxifylline to group 5 animals in established septic shock caused uncontrolled, fatal systemic hypotension in two of the four animals. Plasma tumor necrosis factor activity, blood polymorphonuclear leukocyte counts, and CD18 expression were unaffected by the administration of pentoxifylline. CONCLUSIONS: Pentoxifylline protects against pulmonary and systemic hemodynamic derangements in fulminant sepsis and protects against pulmonary dysfunction. Pentoxifylline has a "therapeutic window" when given in established sepsis; if administration is delayed until overt septic shock occurs, it may then have deleterious effects.

Animals↗
PubMed1994

Multi-agent therapy in the treatment of sepsis-induced microvascular injury.

Cyclo-oxygenase inhibition (with ibuprofen) combined with histamine (H1, H2) receptor antagonism (with diphenhydramine and cimetidine) attenuates microvascular leak injury in sepsis syndromes. Ibuprofen reduces microvascular injury by limiting oxygen radical production by neutrophils. Histamine is known to inhibit this oxygen radical production, an effect antagonized by cimetidine. In the present study neutrophils isolated from pigs made septic with Pseudomonas organisms exhibited a significant (P < 0.05) increase in the production of the oxygen radicals, superoxide anion (O2-, 133 per cent) and hypochlorous acid (HOCl, 38 per cent). Ibuprofen used alone attenuated this sepsis-stimulated overproduction. Addition of the antihistamines cimetidine and diphenhydramine produced a significant increase in oxygen radical production (P < 0.05), by 122 per cent (O2-) and 47 per cent (HOCl), equivalent to that in untreated septic animals. This coincided with a significant deterioration in pulmonary compliance (P < 0.05) compared with that found in control animals and those treated with ibuprofen alone, and a significant accumulation of extravascular lung water (P < 0.05) at 240 and 300 min versus baseline. Histamine receptor antagonism may inadvertently enhance microvascular injury in sepsis.

Animals↗
PubMed1994

Monoclonal antibody to tumor necrosis factor-alpha attenuates plasma interleukin-6 levels in porcine gram-negative sepsis.

This study examined the kinetics of IL-6 release into the systemic circulation in a porcine model of bacterial sepsis induced by infusion of live Pseudomonas aeruginosa. Three groups of animals were studied. Group I (n = 12) animals received a 1 hr infusion of live P. aeruginosa. Group II (n = 6) animals received monoclonal antibody to tumor necrosis factor-alpha (TNF-alpha) (15 mg/kg) prior to induction of sepsis. Group III (n = 7) animals received sterile saline only. TNF-alpha and interleukin-6 (IL-6) levels rose sharply, in group I following pseudomonas infusion. Following a peak at 120 min after the bacterial infusion (4.8 +/- 0.7 U/ml at 120 min vs 0.4 +/- 0.2 U/ml at 0 min), TNF-alpha levels subsequently declined prior to the end of the experiment. In contrast, IL-6 levels rose sharply, subsequent to TNF-alpha, peaked at 180 min, and remained significantly elevated throughout the study period (5.3 +/- 0.9 ng/ml vs 0.05 +/- 0.01 ng/ml, 0 min). In animals pretreated with monoclonal antibody to TNF-alpha, no increase in TNF-alpha activity was detected at any time during the period of study. IL-6 levels in antibody-treated animals, although greatly attenuated, still rose significantly above baseline (2.02 +/- 0.8 ng/ml at 180 min vs 0.05 +/- 0.01 ng/ml at 0 min) and above levels in control animals. We conclude that although TNF-alpha plays an important role in synthesis and release of IL-6, there is a TNF-alpha-independent pathway for release of IL-6 in sepsis.

Animals↗
PubMed1994

Stapled ileoanal anastomosis without a temporary ileostomy.

Stapled J-pouch ileoanal operations were performed in 75 patients (35 men, 40 women; 72 with ulcerative colitis, 3 with familial polyposis) without an ileostomy in 68 (43 taking prednisone, 12 emergent surgery, 8 completion proctectomy with ileostomy takedown). The seven primary ileostomies were due to technical difficulties in two patients and toxic colitis in four patients. No patients were lost to follow-up. Of patients followed for more than 1 month, 96% had perfect daytime control, 86% had no nocturnal accidents, and 73% had no nocturnal spotting. Mucosa between the dentate line and the anastomosis averaged 1.1 +/- 1.0 cm, with the anastomosis at, or below, the dentate line in 16 patients, of whom 14 had excellent continence. Stools in 24 hours averaged 6.9 +/- 0.3, of which 1.8 +/- 0.2 were at night. Stool frequency was unrelated to gender, anastomotic distance from the dentate line, or age; however, patients 50 years of age or older had more problems with nocturnal fecal control than those younger than 50 years of age. Anastomotic leaks (four), cuff abscess (one), pouch leaks (two), and pelvic abscesses (three) were treated with drainage in all patients and ileostomy in five. Pouchitis occurred in 31% of patients and responded to oral antibiotic therapy. Acute complications were fewer, functional pouches greater, stool control better, and overall hospitalization shorter (all p < 0.01) than those in our 63 patients with a mucosectomy and handsewn ileoanal anastomosis.

Adenomatous Polyposis Coli↗
PubMed1994

Differential activation of alveolar, pulmonary arterial, and systemic arterial neutrophils demonstrates the existence of distinct neutrophil subpopulations in experimental sepsis.

Neutrophils (PMNs) are considered key cellular mediators of sepsis induced acute lung injury. PMN activation is manifest by increased beta 2 integrin expression and enhanced superoxide radical (O2-) generation. What is unclear is at which anatomical sites PMNs are activated and at which sites they release O2- and mediate lung injury. In this study we compared alveolar (ALV), systemic arterial (SA), and pulmonary arterial (PA) PMNs CD18 receptor expression, measured by fluorescent immunophenotyping and, O2- generation, measured by reduction of ferricytochrome C, in septic swine. Swine were anesthetized and ventilated, and given a 1-h infusion of live Pseudomonas aeruginosa. PA, SA, and ALV PMNs were isolated at 0 and 5 h. ALV PMNs O2- was reduced compared to SA blood PMNs O2- at 5 h, (AIV 5 h 23.6 +/- 3 vs. SA 0 h 34.3 +/- 5, p < .05). SA PMNs O2- generation was also significantly reduced compared to PA PMNs at 5 h (PA 5 h 21 +/- 2.5 vs. SA 5 h 16.9 +/- 2.6, p < .05). Alv PMNs expressed significantly greater CD18 receptor levels than SA blood PMNs at 5 h (AIV PMNs 5 h, 76 +/- 6 vs. SA PMNs 5 h 51 +/- 3, p < .05), however, PA PMNs CD18 receptor levels were not significantly different from SA PMNs levels at 5 h. These data corroborate a dissociation between two PMN functions in sepsis. O2- generation was reduced across the lung and following migration. However, alveolar PMNs had significantly upregulated CD18 expression compared to PMNs in PA and SA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗