摘要:

ObjectiveThe aim of this study was to investigate whether the methylxanthine-derivative pentoxifylline (PTX) affects bacterial clearance of the organism in states of hemorrhage and endotoxemia.DesignProspective, randomized, controlled trial.SettingExperimental laboratory in a university hospital.SubjectsFifty-four female chinchilla rabbits.InterventionsTo quantify the clearance process, defined numbers (107CFO) of Escherichia coli bacteria were injected intravenously into anesthetized rabbits, 60 mins after induction of hemorrhage (n = 9 + 3) or infusion of endotoxin (lipopolysaccharide [LPS]; 40 [micro sign]g/kg/hr; n = 9 + 3) and after saline infusion (control; n = 9), respectively. Hemorrhage was induced by bleeding, standardized by defined reduction of mean arterial pressure (30% of baseline value). To evaluate the potential effects of PTX on bacterial elimination and killing, in states of hemorrhage and endotoxemia, blood clearance of E. coli and colonization of different organs were investigated after pretreatment with PTX (30 mg/kg) as a bolus injection followed by continuous infusion of PTX (50 mg/kg/hr) in hemorrhagic (n = 9) and endotoxemic rabbits (n = 9). Three additional experiments were performed to evaluate the effects attributable to PTX itself.Measurements and Main ResultsParameters monitored were rates of bacterial and LPS elimination from the blood, arterial blood pressure, blood gases, and serum lactate concentrations. Additionally, flow cytometric analysis of respiratory burst activity was performed. Three hours after bacterial injection, the animals were killed, and tissue samples of liver, kidney, spleen, and lung were collected for bacteriologic examinations. Compared with the controls, hemorrhage and endotoxemia resulted in a significantly prolonged elimination of injected E. coli from the blood. The delayed blood clearance was associated with a significantly (p < .01) higher bacterial colonization of all organs, which was most pronounced in the lung. Pretreatment with PTX slightly enhanced blood clearance of E. coli as well as of LPS, and significantly reduced (p < .05) the colonization of lung and kidney after hemorrhage and endotoxemia. Furthermore, PTX suppressed polymorphonuclear neutrophil respiratory burst activity.ConclusionsHemorrhage and endotoxemia induce impaired bacterial clearance from blood and tissue. Treatment with PTX may reduce the risk of bacterial infections by attenuating bacterial colonization of organs in states of hemorrhage and endotoxemia. (Crit Care Med 1999; 27:756-763)

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo investigate the role of eicosanoid generation and neutrophilic infiltration in the protective effects of U74389F against ischemia/reperfusion injury in the small intestines of rats.DesignProspective, randomized, controlled study.SettingUniversity research laboratory.SubjectsAdult, male Sprague-Dawley rats weighing between 200 and 300 g.InterventionsGroups (5-8) of rats treated with U74389F or vehicle were subjected to a sham operation and 30 mins of ischemia by occlusion of the superior mesenteric artery or 30 mins of ischemia followed by 60 or 120 mins of reperfusion. U74389F (2.5 mg/kg Iv) or vehicle (citrate buffer) were slowly injected 2 mins before ischemia.Measurements and Main ResultsIschemia significantly (p < .05) increased mucosal injury (0 [normal] to 5) in both U74389F and untreated rats. In contrast, U74389F significantly (p < .05) attenuated the severity of injury after reperfusion. In vehicle-treated rats, ischemia/reperfusion significantly reduced villus height in both U74389F and untreated groups. However, the surface epithelial layer was intact in the U74389F but not in the vehicle-treated group. In addition, compared with the vehicle-treated group, U74389F significantly reduced neutrophil infiltration and prevented the increase in leukotriene B4and prostaglandin E2in response to ischemia and reperfusion.ConclusionsThis study demonstrates that the mechanism of U74389F against mesenteric ischemia/reperfusion includes a delay and reduction of neutrophilic infiltrate, an inhibition of leukotriene B4production, and a facilitation of mucosal restitution. (Crit Care Med 1999; 27:764-770)

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo determine whether cell-free hemoglobin augments the inflammatory cascade, as detected by production of tumor necrosis factor (TNF) elicited by bacterial endotoxin (lipopolysaccharide [LPS]).DesignIn vivo and ex vivo study, using a mouse model of sepsis.SettingAnimal research facilitySubjectsFemale Swiss Webster miceInterventionsFor the in vivo experiments, an LD50dose (500 [micro sign]g) of Escherichia coli LPS was injected intraperitoneally into mice. Cell-free crosslinked hemoglobin (60 mg/mouse) or saline was administered intravenously 10 hrs before or coincident with LPS. For the ex vivo experiments, hemoglobin (60 mg/mouse) or saline was administered intravenously to mice, and, 10 hrs later, hepatic Kupffer cells, peripheral blood mononuclear cells, or peritoneal macrophages were isolated.Measurements and Main ResultsIntravenous infusion of hemoglobin either 10 hrs before or coincident with intraperitoneal LPS resulted in a peak of plasma TNF that was greater than in control mice administered LPS only. Cultured Kupffer cells, isolated from mice that had received hemoglobin in vivo 10 hrs before cell collection, produced more TNF in response to LPS in vitro than cells from normal mice. A trend toward greater TNF production in vitro by peripheral blood mononuclear cells obtained from hemoglobin-treated mice also was observed. Enhanced sensitivity to LPS was not observed with cultured peritoneal macrophages from mice that had received hemoglobin.ConclusionsIntravenous hemoglobin increased the sensitivity of hepatic macrophages to subsequent stimulation by LPS. This effect may contribute to the increased mortality that we have observed in animals that have received both LPS and hemoglobin. (Crit Care Med 1999; 27:771-778)

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo investigate in a rat model of ventilation-induced lung injury whether metabolic changes in the lung are reflected by an increased purine concentration (adenosine, inosine, hypoxanthine, xanthine, and urate; an index of adenosine-triphosphate breakdown) of the bronchoalveolar lavage fluid and whether purine can, thus, indirectly serve as a marker of ventilation-induced lung injury.DesignProspective, randomized, controlled trial.SettingResearch laboratory.SubjectsForty-two male Sprague-Dawley rats.InterventionsFive groups of Sprague-Dawley rats were subjected to 6 mins of mechanical ventilation. One group was ventilated at a peak inspiratory pressure of 7 cm H2O and a positive end-expiratory pressure of 0 cm H2O. A second group was ventilated at a peak inspiratory pressure of 45 cm H2O and a positive end-expiratory pressure of 10 cm H2O. Three groups of Sprague-Dawley rats were ventilated at a peak inspiratory pressure of 45 cm H2O without positive end-expiratory pressure. Before mechanical ventilation, two of these groups received intratracheal administration of saline or exogenous surfactant at a dose of 100 mg/kg and one group received no intratracheal administration. A sixth group served as the nonventilated controls.Measurements and Main ResultsBronchoalveolar lavage fluid was collected in which both purine concentration ([micro sign]M; mean +/- SD) and protein concentration (mg/mL; mean +/- SD) were determined. Statistical differences were analyzed using the one-way analysis of variance (ANOVA) with a Student-Newman-Keul's post hoc test. Purine and protein concentrations were different between groups (ANOVA p value for purine and protein, <.0001). Both purine and protein concentrations in bronchoalveolar lavage fluid were increased in Group 45/0 (3.2 +/- 1.9 and 4.2 +/- 1.6, respectively) compared with Group 7/0 (0.4 +/- 0.1 [p < .05] and 0.4 +/- 0.2 [p < .001]) and controls (0.2 +/- 0.2 [p < .01] and 0.2 +/- 0.1 [p < .001]) and in Group 45/Na (5.8 +/- 2.5 and 4.2 +/- 0.5) compared with Group 7/0 (purine and protein, p < .001) and the controls (purine and protein, p < .001). Positive end-expiratory pressure prevented an increase in purine and protein concentrations in bronchoalveolar lavage fluid (0.4 +/- 0.3 and 0.4 +/- 0.2, respectively) compared with Group 45/0 (purine, p < .01; protein, p < .001) and Group 45/Na (purine and protein, p < .001). Surfactant instillation preceding lung overinflation reduced purine and protein concentration in bronchoalveolar lavage fluid (2.1 +/- 1.6 and 2.7 +/- 1.0) compared with Group 45/Na (purine, p < .001; protein (p < .01). Surfactant instillation reduced protein concentration compared with Group 45/0 (p < .01).ConclusionsThis study shows that metabolic changes in the lung as a result of ventilation-induced lung injury are reflected by an increased level of purine in the bronchoalveolar lavage fluid and that purine may, thus, serve as an early marker for ventilation-induced lung injury. Moreover, the study shows that both exogenous surfactant and positive end-expiratory pressure reduce protein infiltration and that positive end-expiratory pressure decreases the purine level in bronchoalveolar lavage fluid after lung overinflation. (Crit Care Med 1999; 27:779-783)

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveThe objective of this study was to test the hypothesis that cocaine-induced cerebral vasodilation in newborn sheep is mediated via beta-adrenergic receptor activation.DesignThe cerebral effects of a single intravenous injection of cocaine (4 mg/kg) given 30 mins after pretreatment with propranolol (1 mg/kg) were studied and compared with the results from a previous study using an identical cocaine protocol without propranolol pretreatment.SubjectsSeven chronically catheterized, unanesthetized newborn sheep (6 +/- 1 days old).MeasurementsCerebral blood flow using radiolabeled microspheres, mean arterial blood pressure (MAP), heart rate, and cerebral arterial and venous oxygen content were measured at baseline, after administration of propranolol, and 0.5, 5, 15, and 60 mins after cocaine injection. Cerebrovascular resistance was calculated as the MAP divided by the cerebral blood flow.Main ResultsPropranolol injection alone caused no systemic or cerebral physiologic changes other than an 11 +/- 2% (mean +/- SEM) decrease in heart rate, which was sustained after cocaine injection. In contrast to previous studies showing cerebral vasodilation (25% decrease in cerebrovascular resistance) and acute hypertension (57% Increase in MAP) 30 secs after cocaine injection, there were no changes in cerebrovascular resistance after cocaine injection and after propranolol pretreatment and there was only a 23 +/- 7% increase in MAP 30 secs after injection, with a return to baseline by 15 mins. Cocaine and norepinephrine levels were similar to those previously reported in the newborn sheep after an injection of 4 mg/kg cocaine.ConclusionPropranolol blocks cocaine-induced cerebral vasodilation and blunts the acute hypertension in newborn sheep, suggesting that cocaine's cerebrovascular effects in the developing brain are mediated, at least in part, by beta-adrenergic receptor activation. (Crit Care Med 1999;27:784-789)

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo study differences in organ sensitivity during progressive endotoxin shock tissue levels of hypoxanthine, used as an indicator of adenosine triphosphate depletion and cellular energy failure, were monitored simultaneously in several organs by in vivo microdialysis.DesignProspective, controlled animal study.SettingUniversity research laboratory.SubjectsSeventeen landrace pigs.Measurements and Main ResultsTissue levels of hypoxanthine, assessed by in vivo microdialysis, were monitored (in the ileum, liver, lung, skeletal muscle, subcutaneous fat, and arterial blood) simultaneously in addition to central hemodynamics during endotoxin shock in ten pigs. Seven sham animals not receiving endotoxin served as controls. Marked changes were seen in central hemodynamic parameters in response to endotoxemia. Very prominent increases were seen in the ileum and liver, followed by the lung, whereas only limited changes were observed in subcutaneous fat. These results indicate a differentiated development of cellular energy failure in response to endotoxemia in different organs. By considering the high amounts of xanthine oxidase seen in the gut, the increases in hypoxanthine may provide an important substrate for reactive oxygen species formation in this organ. The limited changes seen in subcutaneous fat suggest that this tissue may provide limited sensitivity when monitoring the septic patient.ConclusionsThese findings support the concept of specific vulnerability of the gut during endotoxemia. (Crit Care Med 1999; 27:790-797)

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo determine if head-injured patients with premorbid nasal colonization with Staphylococcus aureus are at increased risk for S. aureus infection.Designor=to9, intensive care unit (ICU) admission, hospitalization in another hospital <24 hrs, no recent use of antibiotics.SettingAcute care trauma facility.PatientsAny patient sustaining acute, blunt, or penetrating injury and meeting the enrollement criteria were eligible.InterventionsSwab cultures of both internal nares were performed within 72 hrs of readmission and cultured for S. Aureus. Patients were prospectively monitored for S. Aureus infections until discharge.Measurements and Main ResultsAdmission nasal cultures were positive (NC+) for S. aureus in 144 of the 776 patients cultured. Forty of the 144 NC+ patients had isolated head (37) or high cervical spine (3) injury, and 11 of that group (27.5%) developed S. aureus infections. The remaining 104 patients positive for S. aureus on admission had no head injury (74) or head combined with torso and extremity injuries (30). S. aureus infection was diagnosed in 11 of the 104 patients (10.6%). The difference in incidence of infections is significant (p < .01), as is the difference in incidence of pneumonia (20% vs. 3.8%, respectively [p < .01]). Organisms causing pneumonia were often the same organisms isolated from the nares on admission.ConclusionsNasal colonization with S. aureus at the time of severe head injury increases the risk of S. aureus pneumonia during hospitalization. Prophylactic measures against S. aureus pneumonia may help reduce the length and cost of hospitalization.(Crit Care Med 1999; 27:798-801)

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo compare the amount of variability in ventilation during intrahospital transport of intubated pediatric patients ventilated either manually or with a transport ventilator.DesignProspective, randomized study.SettingTertiary, multidisciplinary, pediatric intensive care unit.PatientsForty-nine pediatric postoperative heart patients who required transport while still intubated.InterventionsPatients were randomized to receive either manual ventilation during transport or ventilation by a portable mechanical ventilator. Baseline ventilatory and hemodynamic parameters were recorded before and during transport. Before and after arterial blood gases were also obtained. All other aspects of care were identical.Measurements and Main ResultsThere was a statistically significant greater amount of variation in ventilation during transport with manual technique as opposed to the mechanical ventilator. A Student's t-test on pre- to post-blood gas differences showed a significantly lower PetCO2(p = .02) in the manually ventilated patients when compared with the mechanically ventilated patients. Values for PCO2were higher, but only marginally significant (p = .08). Repeated measures analysis of variance using these same pre- and post blood gas values confirmed the significant decrease in PetCO2(p = .05). Minute to minute variation in PetCO2during transport was greater and the mean values significantly lower in the manually ventilated group (p < .05). Hemodynamic data were remarkably stable when examined both before and after transport and on a minute to minute basis during transport.ConclusionsManual ventilation during intrahospital transport results in greater fluctuation of ventilatory parameters from an established baseline than does use of a transport ventilator. No clinically significant changes in status occurred during the brief period of transport studied. (Crit Care Med 1999; 27:802-806)

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID