摘要:

ObjectiveLower and upper inflection points on the quasi-static curve representing a composite of pressure/volume from the whole lung are hypothesized to represent initial alveolar recruitment and overdistension, respectively, and are currently utilized to adjust mechanical ventilation in patients with acute respiratory distress syndrome. However, alveoli have never been directly observed during the generation of a pressure/volume curve to confirm this hypothesis. In this study, we visualized the inflation of individual alveoli during the generation of a pressure/volume curve by direct visualization usingin vivomicroscopy in a surfactant deactivation model of lung injury in pigs.DesignProspective, observational, controlled study.SettingUniversity research laboratory.SubjectsEight adult pigs.InterventionsPigs were anesthetized and administered mechanical ventilation, underwent a left thoracotomy, and were separated into two groups: control pigs (n = 3) were subjected to surgical intervention, and Tween lavage pigs (n = 5) were subjected to surgical intervention plus surfactant deactivation by Tween lavage (1.5 mL/kg 5% solution of Tween in saline). The microscope was then attached to the lung, and the size of each was alveolus quantified by measuring the alveolar area by computer image analysis. Each alveolus in the microscopic field was assigned to one of three types, based on alveolar mechanics: type I, no visible change in alveolar size during ventilation; type II, alveoli visibly change size during ventilation but do not totally collapse at end expiration; and type III, alveoli visibly change size during tidal ventilation and completely collapse at end expiration. After alveolar classification, the animals were disconnected from the ventilator and attached to a super syringe filled with 100% oxygen. The lung was inflated from 0 to 220 mL in 20-mL increments with a 10-sec pause between increments for airway pressure and alveolar confirmation to stabilize. These data were utilized to generate both quasi-static pressure/volume curves and individual alveolar pressure/area curves.Measurements and Main ResultsThe normal lung quasi-static pressure/volume curve has a single lower inflection point, whereas the curve after Tween has an inflection point at 8 mm Hg and a second at 24 mm Hg. Normal alveoli in the control group are all type I and do not change size appreciably during generation of the quasi-static pressure/volume curve. Surfactant deactivation causes a heterogenous injury, with all three alveolar types present in the same microscopic field. The inflation pattern of each alveolar type after surfactant deactivation by Tween was notably different. Type I alveoli in either the control or Tween group demonstrated minimal change in alveolar area with lung inflation. Type I alveolar area was significantly (p< .05) larger in the control as compared with the Tween group. In the Tween group, type II alveoli increased significantly in area, with lung inflation from 0 mL (9666 ± 1340 &mgr;m2) to 40 mL (12,935 ± 1725 &mgr;m2) but did not increase further (220 mL, 14,058 ± 1740 &mgr;m2) with lung inflation. Type III alveoli initially recruited with a relatively small area (20 mL lung volume, 798 ± 797 &mgr;m2) and progressively increased in area throughout lung inflation (120 mL, 7302 ± 1405 &mgr;m2; 220 mL, 11,460 ± 1078 &mgr;m2)ConclusionThe normal lung does not increase in volume by simple isotropic (balloon-like) expansion of alveoli, as evidenced by the horizontal (no change in alveolar area with increases in airway pressure) pressure/area curve. After surfactant deactivation, the alveolar inflation pattern becomes very complex, with each alveolar type (I, II, and III) displaying a distinct pattern. None of the alveolar pressure/area curves directly parallel the quasi-static lung pressure/volume curve. Of the 16, only one type III atelectatic alveolus recruited at the first inflection point and only five recruited concomitant with the second inflation point, suggesting that neither inflection point was due to massive alveolar recruitment. Thus, the components responsible for the shape of the pressure/volume curve include all of the individual alveolar pressure/area curves, plus changes in alveolar duct and airway size, and the elastic forces in the pulmonary parenchyma and the chest wall.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectivesTo determine whether transient, moderate hypothermia is beneficial after traumatic brain injury in fentanyl-anesthetized rats.DesignProspective, randomized study.SettingUniversity-based animal research facility.SubjectsAdult male Sprague-Dawley rats.InterventionsAll rats were intubated, mechanically ventilated, and anesthetized with fentanyl (10 &mgr;g/kg intravenous bolus and then 50 &mgr;g·kg−1·hr−1infusion). Controlled cortical impact was performed to the left parietal cortex, followed immediately by 1 hr of either normothermia (brain temperature 37 ± 0.5°C) or hypothermia (brain temperature 32 ± 0.5°C). Hypothermic rats were rewarmed gradually over 1 hr. Fentanyl anesthesia and mechanical ventilation were continued in both groups until the end of rewarming (2 hrs after traumatic brain injury).Measurements and Main ResultsHistologic assessment performed 72 hrs after traumatic brain injury was the primary outcome variable. Secondary outcome variables were physiologic variables monitored during the first 2 hrs after traumatic brain injury and plasma catecholamine and serum fentanyl concentrations measured at the end of both hypothermia and rewarming (1 and 2 hrs after traumatic brain injury). Contusion volume was larger in hypothermic vs. normothermic rats (44.3 ± 4.2 vs. 28.6 ± 4.0 mm,p< .05), but hippocampal neuronal survival did not differ between groups. Physiologic variables did not differ between groups. Plasma dopamine and norepinephrine concentrations were increased at the end of hypothermia in hypothermic (vs. normothermic) rats (p< .05), indicating that hypothermia augmented the systemic stress response. Similarly, serum fentanyl concentrations were higher in hypothermic (vs. normothermic) rats at the end of both hypothermia and rewarming (p< .05), demonstrating that hypothermia reduced the clearance and/or metabolism of fentanyl.ConclusionsModerate hypothermia was detrimental after experimental traumatic brain injury in fentanyl-anesthetized rats. Since treatment with hypothermia has provided reliable benefit in experimental traumatic brain injury with inhalational anesthetics, these results indicate that the choice of anesthesia/analgesia after traumatic brain injury may dramatically influence response to other therapeutic interventions, such as hypothermia. Given that narcotics commonly are administered to patients after severe traumatic brain injury, this study may have clinical implications.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveTo characterize the dose-related effects of dobutamine on pulmonary vascular tone and associated changes in right ventricular afterload in canine microembolic lung injury.DesignProspective, interventional study.SettingUniversity laboratory.SubjectsTen anesthetized and ventilated dogs.InterventionsRight heart catheterization for the measurement of pulmonary vascular resistance by multipoint mean pulmonary artery pressure (Ppa)/cardiac output (Q) plots, partitioning of pulmonary vascular resistance by the occlusion method, and determination of pulmonary arterial input impedance from spectral analysis of Ppa and Q waves, in ten anesthetized and ventilated dogs, before and after induction of acute microembolic lung injury, and without or with 5, 10, 15, and 20 &mgr;g·kg−1·min−1dobutamine.Measurements and Main ResultsMicroembolic pulmonary hypertension was associated with a shift of Ppa/Q plots to higher pressures, a slight decrease in the arterial component of pulmonary vascular resistance, a decrease in characteristic impedance, and an increase in the pulsatile component of right ventricular hydraulic load. At baseline, dobutamine had no effect on Ppa/Q plots at 5 and 10 &mgr;g·kg−1·min−1but increased Ppa at 15 and 20 &mgr;g·kg−1·min−1. In microembolic pulmonary hypertension, the only effect of dobutamine on Ppa/Q plots was a decrease in Ppa at 20 &mgr;g·kg−1·min−1. Dobutamine had no effect on the partitioning of pulmonary vascular resistance or on pulmonary arterial input impedance spectrum.ConclusionsDobutamine at doses up to 10 &mgr;g·kg−1·min−1has no flow-independent effect on the normal or the acutely hypertensive pulmonary circulation. Higher doses may be constricting or dilating depending on preexisting tone.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveGabexate mesilate, a synthetic protease inhibitor, has been shown to reduce endotoxin-induced pulmonary vascular injury in an animal model of sepsis by inhibiting leukocyte activation. We examined whether gabexate mesilate inhibits tumor necrosis factor-&agr;-induced expression of leukocyte adhesion molecules in cultured endothelial cells.DesignProspective, randomized, controlled study.SettingResearch laboratory at a university medical centerSubjectsCultured human umbilical vein endothelial cell (HUVECs).InterventionsHUVECs were stimulated with tumor necrosis factor-&agr; or lipopolysaccharide in the presence or absence of gabexate mesilate. Expression of E-selectin and intercellular adhesion molecule-1 was measured by cellular enzyme-linked immunosorbent assay. Messenger RNA levels of E-selectin and intercellular adhesion molecule-1 were determined by reverse transcription-polymerase chain reaction. DNA-binding activity of p65 in the nuclear extracts was evaluated by enzyme-linked immunosorbent assay. Nuclear translocation of nuclear factor-&kgr;B induced by tumor necrosis factor-&agr; was evaluated by immunocytostaining and Western blot analysis. Degradation and phosphorylation of inhibitor of nuclear factor-&kgr;B (I&kgr;B) induced by tumor necrosis factor-&agr; were evaluated by Western blot analysis.Measurements and Main ResultsGabexate mesilate inhibited the tumor necrosis factor-&agr;-induced increases in the endothelial expression of E-selectin and intercellular adhesion molecule-1 by inhibiting the transcription. Tumor necrosis factor-&agr;-induced increase in DNA binding of p65 was inhibited by gabexate mesilate through inhibition of the nuclear translocation of p65. Gabexate mesilate inhibited the tumor necrosis factor-&agr;-induced degradation of I&kgr;B&agr;, an inhibitor of nuclear factor-&kgr;B, by inhibiting phosphorylation of I&kgr;B&agr; in HUVECs.ConclusionsGabexate mesilate inhibited the expression of leukocyte adhesion molecules by inhibiting the nuclear factor-&kgr;B-mediated transcription in HUVECs. Inhibition of nuclear factor-&kgr;B activation by gabexate mesilate could be explained by inhibition of degradation of I&kgr;B. Gabexate mesilate might reduce lipopolysaccharide-induced pulmonary vascular injury not only by inhibiting monocytic tumor necrosis factor-&agr; production but by inhibiting the expression of endothelial leukocyte adhesion molecules.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveTo determine the effect of chronic exposure to endotoxin (lipopolysaccharide) and Staphylococcal enterotoxin B on hepatic injury and function.DesignProspective, controlled trial.SettingResearch laboratory in a university hospital.SubjectsMale Sprague-Dawley rats weighing 325–350 g with chronic vascular and bile catheters.InterventionsChronically catheterized rats were treated daily with saline, 50 &mgr;g/kg Staphylococcal enterotoxin B alone, 1000 &mgr;g/kg lipopolysaccharide alone, 1000 &mgr;g/kg lipopolysaccharide with 50 &mgr;g/kg Staphylococcal enterotoxin B, or 100 &mgr;g/kg lipopolysaccharide with 50 &mgr;g/kg Staphylococcal enterotoxin B for 10 days. Serum and biliary measures of hepatic injury and dysfunction were measured before and then 6 hrs and 1, 2, 3, 7, and 10 days after the start of treatment. The animals were killed at 10 days and the livers examined histologically.Measurements and Main ResultsMean rates of bile flow, biliary indocyanine green excretion, and bile acid flux were significantly decreased immediately after treatment (6 hr, 1 and 2 days) and then at 10 days. Increases in biliary and serum &ggr;-glutamyltransferase and serum bile acids also occurred in a similar bimodal pattern. Animals treated with lipopolysaccharide or Staphylococcal enterotoxin B alone became tolerant and did not develop the bimodal pattern of hepatic dysfunction. Histologic examination of the liver at 10 days revealed periportal inflammation and fibrosis.ConclusionsThe combination of lipopolysaccharide and Staphylococcal enterotoxin B leads to late liver injury, whereas either toxin alone does not. These data may explain the frequent development of liver dysfunction in patients exposed to multiple bacterial toxins such as in sepsis, multiple-system organ failure, and other diseases with altered intestinal permeability.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveEpinephrine is widely used for treatment of life-threatening hypotension, although new vasopressor drugs may merit evaluation. The purpose of this study was to determine the effects of vasopressin vs. epinephrine vs. saline placebo on hemodynamic variables, regional blood flow, and short-term survival in an animal model of uncontrolled hemorrhagic shock and delayed fluid resuscitation.DesignProspective, randomized, laboratory investigation that used a porcine model for measurement of hemodynamic variables and regional abdominal organ blood flow.SettingUniversity hospital laboratory.SubjectsA total of 21 pigs weighing 32 ± 3 kg.InterventionsThe anesthetized pigs were subjected to a penetrating liver injury, which resulted in a mean ± sem loss of 40% ± 5% of estimated whole blood volume within 30 mins and mean arterial pressures of <20 mm Hg. When heart rate declined progressively, pigs randomly received a bolus dose and continuous infusion of either vasopressin (0.4 units/kg and 0.04 units·kg−1·min−1, n = 7), or epinephrine (45 &mgr;g/kg and 5 &mgr;g·kg−1·min−1, n = 7), or an equal volume of saline placebo (n = 7), respectively. At 30 mins after drug administration, all surviving animals were fluid resuscitated while bleeding was surgically controlled.Measurements and Main ResultsMean ± sem arterial blood pressure at 2.5 and 10 mins was significantly (p< .001) higher after vasopressin vs. epinephrine vs. saline placebo (82 ± 14 vs. 23 ± 4 vs. 11 ± 3 mm Hg, and 42 ± 4 vs. 10 ± 5 vs. 6 ± 3 mm Hg, respectively). Although portal vein blood flow was temporarily impaired by vasopressin, it was subsequently restored and significantly (p< .01) higher when compared with epinephrine or saline placebo (9 ± 5 vs. 121 ± 3 vs. 54 ± 22 mL/min and 150 ± 20 vs. 31 ± 17 vs. 0 ± 0 mL/min, respectively). Hepatic and renal artery blood flow was significantly higher throughout the study in the vasopressin group; however, no further bleeding was observed. Despite a second bolus dose, all epinephrine- and saline placebo–treated animals died within 15 mins after drug administration. By contrast, seven of seven vasopressin-treated animals survived until fluid replacement, and 60 mins thereafter, without further vasopressor therapy (p< .01). Moreover, blood flow to liver, gut, and kidney returned to normal values in the postshock phase.ConclusionsVasopressin, but not epinephrine or saline placebo, improved short-term survival in a porcine model of uncontrolled hemorrhagic shock after liver injury when surgical intervention and fluid replacement was delayed.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveTo investigate the beneficial effects of exogenous surfactant supplementation (ESS) and partial liquid ventilation (PLV) in treating acute lung injury induced by wood smoke inhalation.DesignA prospective, randomized, controlled, multigroup study.SettingAn animal research laboratory at a medical center.SubjectsNewborn piglets (n = 29; 1.80 ± 0.06 kg) of either sex.InterventionsAnimals were ventilated with a tidal volume of 15 mL/kg, a rate of 30 breaths/min, a positive end-expiratory pressure of 5 cm H2O, and an Fio2of 1.0. After the induction of acute lung injury by wood smoke inhalation, animals were randomly assigned to receive either conventional mechanical ventilation (CMV) or PLV with or without ESS pretreatment. Animals were grouped as CMV, ESS-CMV, PLV, and ESS-PLV.Measurements and Main ResultsArterial blood gases, cardiovascular hemodynamics, dynamic lung compliance, and total lung injury scores were measured. After smoke inhalation, all four groups displayed similar high arterial carboxyhemoglobin levels, low Pao2(<150 mm Hg), and low dynamic lung compliance (<66% of its baseline). In the CMV group, these deleterious conditions remained during the 4-hr observation period, and severe lung injury was noted histologically. All treatment groups demonstrated a significant increase in Pao2compared with the CMV group. In addition, both the PLV and ESS-PLV groups displayed significant improvements in dynamic lung compliance and in their histologic outcomes. Nevertheless, none of the variables measured in the PLV group differed from those measured in the ESS-PLV group.ConclusionsIn a newborn piglet model of smoke inhalation injury, PLV or ESS improved oxygenation. PLV compared favorably with ESS in its greater improvements in lung compliance and lung pathology. However, the combined therapy of ESS and PLV was not clearly superior to PLV alone during the observation period.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveTo measure patients’ risk for acquiring antibiotic-resistant microorganisms associated with intensive care unit admission.DesignProspective, observational study.SettingTen public hospitals including one university medical center.PatientsConsecutive patients admitted to ten intensive care units.InterventionsSerial patient surveillance cultures were screened for vancomycin-resistant enterococci, methicillin-resistantStaphylococcus aureus(MRSA), ceftazidime-resistant Gram-negative bacilli (CR-GNB), Acute Physiology and Chronic Health Evaluation II score, and antibiotic and medical device exposures.Measurements and Main ResultsA total of 1,697 patient admissions in ten intensive care units were enrolled. The overall carriage rate of antibiotic-resistant bacteria at intensive care unit entry was 12.1% for MRSA, 14% for CR-GNB and 4.7% for both. At discharge from the intensive care unit, new carriage of MRSA, CR-GNB, and both was found in 11.1%, 14.2%, and 2.4% of the patients, respectively. The acquisition rates in the individual units correlated highly and positively with proportion of patients with carriage at intensive care unit entry for both MRSA (n = 10, Pearson’sr= .89,p< 0.001) and CR-GNB (n = 10, Pearson’sr= .92,p< 0.001). By logistic regression, severity of illness (odds ratio, 1.4), length of stay (odds ratio, 1.7), use of penicillins (odds ratio, 1.9), and number of antibiotics (odds ratio, 1.2) and medical devices (odds ratio, 1.2) were independently associated with intensive care unit acquisition of MRSA. In comparison, variables independently associated with intensive care unit acquisition of CR-GNB were Acute Physiology and Chronic Health Evaluation II score (odds ratio, 1.5), number of antibiotics (odds ratio, 1.1), and artificial airway (odds ratio, 1.5).ConclusionsThese data suggest that hospitalization in the intensive care unit introduces significant risk to patients in terms of transmission of MRSA and/or CR-GNB. This risk seems to be influenced strongly by the proportion of patients with colonization at intensive care unit admission and is associated with severity of illness, length of stay, and exposures to antibiotics and medical devices.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveEpithelial Na+channels and Na+/K+-adenosine triphosphatase (ATPase) in alveolar epithelium have a very important role in the absorption of excessive fluid from the alveolar space. We examined whether single dexamethasone injection at therapeutic doses would modulate lung epithelial Na+channels and Na+/K+-ATPase and increase alveolar fluid clearance in adult rats.DesignControlled laboratory study.SettingUniversity research laboratory.SubjectsAdult male Sprague-Dawley rats (n = 138).InterventionsRats were intraperitoneally injected with dexamethasone at a dose ranging from 0.02 to 2.0 mg/kg, and allowed free access to food and water.Measurements and Main ResultsAlveolar fluid clearance was determined by measuring the increase in albumin concentration in the lung instillate solution. We discovered a significant increase in alveolar fluid clearance at 48 and 72 hrs after dexamethasone treatment. The effect of dexamethasone was dose dependent. In addition, increased alveolar fluid clearance was associated with a faster recover from hypoxemia, which was induced by filling the alveolar space with instillate solution. The dexamethasone-induced increase in alveolar fluid clearance was inhibited by amiloride and ouabain. Quantitative reverse transcriptase-polymerase chain reaction showed that dexamethasone treatment increased lung &bgr;-epithelial Na+channel mRNA levels. The expression of &ggr;-epithelial Na+channel mRNA was also increased slightly. In contrast, &agr;-epithelial Na+channel mRNA levels did not differ from control levels. There was no change in &agr;1- or &bgr;1-Na+/K+-ATPase mRNA levels over 72 hrs after dexamethasone treatment. However, we found that lung Na+/K+-ATPase hydrolytic activity, determined by monitoring the ouabain-sensitive ATPase hydrolysis, was increased at 48 and 72 hrs after dexamethasone treatment.ConclusionsSingle dexamethasone injection at therapeutic doses is capable of modulating lung epithelial Na+channels and Na+/K+-ATPase and increase alveolar fluid clearance, thereby accelerating recovery from pulmonary edema.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveBecause alveoli fill with perfluorocarbons during liquid ventilation, an uptake of perfluorocarbons by type II pneumocytes can be postulated that might affect synthesis and secretion of pulmonary surfactant. The study was performed to answer the following questions: Do isolated type II pneumocytes take up perfluorocarbons? Do perfluorocarbons affect lipid synthesis of type II cells? Do perfluorocarbons change surfactant secretion of type II pneumocytes?DesignControlled experiments that used isolated type II pneumocytes.SettingExperimental laboratory of a university hospital.SubjectsMale Wistar rats.InterventionsTo study perfluorocarbon uptake, isolated type II cells were incubated with fluorescence-labeled perfluorocarbons and examined with a laser scanning microscope. The effect of perfluorocarbons on biosynthesis of phospholipids and triglycerides was measured by incubating cells that were pulse-labeled with [H]-palmitic acid for 30 secs, with two different perfluorocarbons (PF 5080 or RM 101) for 10 mins. The effect of perfluorocarbon incubation on lipid secretion was studied by transmission electron microscopy. To quantify secretion, adherent type II pneumocytes (containing radioactively labeled phospholipids) were incubated with perfluorocarbons, and extra- and intracellular radioactivity was measured.Measurements and Main ResultsWe found a significant uptake of labeled perfluorocarbons into lamellar bodies within 10 mins. Both perfluorocarbon species significantly (p< .05) reduced the biosynthesis of phospholipids when compared with control. Perfluorocarbon incubation did not affect mitochondrial activity, tested by MitoTracker staining. Transmission electron microscopy revealed changes that suggest an increased secretion of surfactant by type II cells. Studies with radioactively labeled surfactant revealed a significantly (p< .01) higher amount of extracellular lipids after RM 101 and PF 5080 treatment (RM 101, 17 ± 7.9%; PF 5080, 9 ± 1.9%) compared with control (5.3 ± 1.9%).ConclusionsOur results suggest that perfluorocarbons are taken up by type II pneumocytes and cause an increased secretion of surfactant, despite a relative reduction in the synthesis of phospholipids.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID