摘要:

ObjectiveTo determine the relationship of hypolipidemia to cytokine concentrations and clinical outcomes in critically ill surgical patients.DesignConsecutive, prospective case series.SettingSurgical intensive care unit of an urban university hospital.PatientsSubjects were 111 patients with a variety of critical illnesses, for whom serum lipid, lipoprotein, and cytokine concentrations were determined within 24 hrs of admission to a surgical intensive care unit. Controls were 32 healthy men and women for whom serum lipid, lipoprotein, and cytokine concentrations were determined.InterventionsBlood samples were drawn on admission to the intensive care unit. Predetermined clinical outcomes including death, infection subsequent to intensive care unit admission, length of intensive care unit stay, and magnitude of organ dysfunction were monitored prospectively.Measurements and Main ResultsMeasurements included total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoproteins A-I and B, phospholipid, triglyceride, interleukin-6, interleukin-10, soluble interleukin-2 receptor, tumor necrosis factor-&agr;, and soluble tumor necrosis factor receptors p55 and p75. Mean serum lipid concentrations were extremely low: total cholesterol, 127 ± 52 mg/dL; low-density lipoprotein cholesterol, 75 ± 41 mg/dL; high-density lipoprotein cholesterol, 29 ± 15 mg/dL. Total, low-density lipoprotein, and high-density lipoprotein cholesterol concentrations and apolipoprotein concentrations inversely correlated with interleukin-6, soluble interleukin-2 receptor, and interleukin-10 concentrations, whereas the triglyceride concentration correlated positively with tumor necrosis factor soluble receptors p55 and p75. Clinical outcomes were related to whether the admission cholesterol concentration was above (n = 56) or below (n = 55) the median concentration of 120 mg/dL. Each of the clinical end points occurred between 1.9- and 3.5-fold more frequently in the very low cholesterol (<120 mg/dL) group. Nine patients (8%) died during the hospitalization. Seven of the nine patients who died had total cholesterol concentrations below the median concentration of 120 mg/dL.ConclusionsLow cholesterol and lipoprotein concentrations found in critically ill surgical patients correlate with interleukin-6, soluble interleukin-2 receptor, and interleukin-10 concentrations and predict clinical outcomes.

ISSN:0090-3493    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo investigate whether rapid or slowly infused intravenous fat emulsions affect the ratio of prostaglandin I2/thromboxane A2in arterial blood, pulmonary hemodynamics, and gas exchange.DesignProspective, controlled, randomized, crossover study.SettingOperative intensive care unit of a university hospital.PatientsEighteen critically ill patients. Ten patients were stratified with severe sepsis, and eight patients had acute respiratory distress syndrome (ARDS).InterventionsPatients were assigned randomly to receive intravenous fat emulsions (0.4 × resting energy expenditure) over 6 hrs (rapid fat infusion) or 24 hrs (slow fat infusion) along with a routine parenteral nutrition regimen, by using a crossover study design.Measurements and Main ResultsSystemic and pulmonary hemodynamics as well as gas exchange measurements were recorded via respective indwelling catheters. Arterial thromboxane B2and 6-keto-prostaglandin-F1&agr;plasma concentrations were obtained by radioimmunoassay, and 6-keto-prostaglandin-F1&agr;/thromboxane B2ratios (P/T ratios) were calculated. Data were collected immediately before and 6, 12, 18, and 24 hrs after onset of fat infusion. In the ARDS group, P/T ratio increased by rapid fat infusion. Concomitantly, pulmonary shunt fraction, alveolar-arterial oxygen tension difference [P(a-a)o2]/Pao2, and cardiac index increased as well, whereas pulmonary vascular resistance and Pao2/Fio2declined. After slow fat infusion, a decreased P/T ratio was revealed. This was accompanied by decreased pulmonary shunt fraction, lowered P(a-a)o2/Pao2, and increased Pao2/Fio2. Correlations between plasma concentrations of 6-keto-prostaglandin-F1&agr;or thromboxane B2and measures of respiratory performance could be shown during rapid and slow fat infusion, respectively. In the sepsis group, the P/T ratio remained unchanged at either infusion rate, but pulmonary shunt fraction and P(a-a)o2/Pao2decreased after rapid fat infusion, whereas Pao2/Fio2increased.ConclusionPulmonary hemodynamics and gas exchange are related to changes of arterial prostanoid levels in ARDS patients, depending on the rate of fat infusion. In ARDS but not in sepsis patients clear of pulmonary organ failure, a changing balance of prostaglandin I2and thromboxane A2may modulate gas exchange, presumably via interference with hypoxic pulmonary vasoconstriction.

ISSN:0090-3493    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo examine the efficacy of iontophoretic delivery of calcium to experimental hydrofluoric acid burns.DesignProspective, controlled study.SettingInstitutional laboratory.SubjectsMale nude rats.InterventionsFor thein vitroexperiment, a full-thickness skin from the back was set in a vertical flow-through diffusion cell. Calcium chloride was applied to the donor chamber, and transdermal transport of calcium was examined with or without a voltage gradient of 1.5 V. Either intact skin or skin whose stratum corneum was stripped with adhesive tapes was used. For thein vivoexperiment, hydrofluoric acid burns were induced by dispensing 50% hydrofluoric acid (50 &mgr;L) on the backs of the nude rats, who were under pentobarbital anesthesia. Rats were divided into four groups (n = 5 for each group): control group (burned but not treated); topical group (treated with calcium gluconate jelly); infiltration group (intradermal and subcutaneous injection of calcium gluconate); and iontophoresis group (treated with iontophoresis of calcium chloride at 1.5 V). Burn areas were measured and pathologic findings were classified microscopically into five stages at 1 wk: stage 1, epidermal burn; stage 2, superficial dermal burn; stage 3, deep dermal burn; stage 4, full-thickness burn; and stage 5, burn affecting the skeletal muscle.Measurements and Main ResultsIn thein vitroexperiment, calcium concentrations increased significantly only in stripped skins with a 1.5-V gradient. In thein vitroexperiment, burn areas were reduced significantly in the iontophoresis group compared with the other three groups. Pathologic findings were significantly improved in the iontophoresis group compared with the control group. This efficacy of iontophoresis was observed when it was initiated within 30 mins after hydrofluoric acid burn.ConclusionsThese results show that transdermal transport of calcium was enhanced in stripped skins by iontophoresis and that iontophoresis was more efficacious than topical or infiltration therapy for experimental hydrofluoric acid burns. Iontophoretic delivery of calcium seems to be easier than intra-arterial infusion and may be effective for the lesions where intra-arterial infusion is difficult.

ISSN:0090-3493    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo compare the effects of two different recruitment maneuvers repeated multiple times on gas exchange lung injury, hemodynamic, and lung mechanics.DesignRandomized prospective comparison.SettingsAnimal research laboratory.SubjectNineteen fasted Hampshire sheep.InterventionsIn 15 27-kg sheep with saline lavage lung injury, we compared the effects of two recruitment maneuvers: 40 cm H2O continuous positive airway pressure for 60 secs and 40 cm H2O positive end-expiratory pressure with 20 cm H2O pressure control, rate 10 breaths/min, inspiratory to expiratory ratio 1:1 for 2 mins. Each recruitment maneuver was repeated four times, every 30 mins after a 30-sec ventilator disconnection. An additional group received no recruitment maneuvers. Animals were assigned randomly to the three groups and ventilated with 20 cm H2O positive end-expiratory pressure, pressure control 15 cm H2O, rate 20 breaths/min, inspiratory to expiratory ratio 1:1, and Fio21.0 between recruitment maneuver periods.Measurements and Main ResultsSignificant and marked increases in Pao2were observed in the pressure control recruitment maneuver group but only after the second recruitment maneuver. In both the control group and continuous positive airway pressure groups, Pao2did not significantly increase after any recruitment maneuver compared with baseline injury. There was a significant decrease in cardiac output immediately after some continuous positive airway pressure recruitment maneuvers and a significant increase in mean pulmonary artery pressure in both continuous positive airway pressure and pressure control groups immediately after recruitment maneuvers, but these changes resolved within 10 mins. There were no marked histologic differences between groups and no volutrauma.ConclusionIn this model, maximal lung recruitment was obtained with 40 cm H2O positive end-expiratory pressure and 20 cm H2O pressure control applied repetitively every 30 mins for 2 mins without physiologic or histologic harm. Multiple recruitment maneuvers in some animals were required for maximum effect.

ISSN:0090-3493    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveThe intraosseous route is an emergency alternative for the administration of drugs and fluids if vascular access cannot be established. However, in hemorrhagic shock or after vasopressors are given during resuscitation, bone marrow blood flow may be decreased, thus impairing absorption of intraosseously administered drugs. In this study, we evaluated the effects of vasopressin vs. high-dose epinephrine in hemorrhagic shock and cardiac arrest on bone marrow blood flow.DesignProspective, randomized laboratory investigation that used an established porcine model for measurement of hemodynamic variables and organ blood flow.SettingUniversity hospital laboratory.SubjectsFourteen pigs weighing 30 ± 3 kg.InterventionsRadiolabeled microspheres were injected to measure bone marrow blood flow during a prearrest control period and during hypovolemic shock produced by rapid hemorrhage of 35% of the estimated blood volume. In the second part of the study, ventricular fibrillation was induced; after 4 mins of untreated cardiac arrest and 4 mins of standard cardiopulmonary resuscitation, a bolus dose of either 200 &mgr;g/kg epinephrine (n = 6) or 0.8 units/kg vasopressin (n = 6) was administered. Defibrillation was attempted 2.5 mins after drug administration, and blood flow was assessed again at 5 and 30 mins after successful resuscitation.Measurements and Main ResultsMean ± sem bone marrow blood flow decreased significantly during induction of hemorrhagic shock from 14.4 ± 4.1 to 3.7 ± 1.8 mL·100 g−1·min−1in the vasopressin group and from 18.2 ± 4.0 to 5.2 ± 1.0 mL·100 g−1·min−1in the epinephrine group (p= .025 in both groups). Five minutes after return of spontaneous circulation, mean ± sem bone marrow blood flow was 3.4 ± 1.1 mL·100 g−1·min−1after vasopressin and 0.1 ± 0.03 mL·100 g−1·min−1after epinephrine (p= .004 for vasopressin vs. epinephrine). At the same time, bone vascular resistance was significantly (p= .004) higher in the epinephrine group when compared with vasopressin (1455 ± 392 vs. 43 ± 19 mm Hg· mL−1·100 g·min, respectively).ConclusionsBone blood flow responds actively to both the physiologic stress response of hemorrhagic shock and vasopressors given during resuscitation after hypovolemic cardiac arrest. In this regard, bone marrow blood flow after successful resus-citation was nearly absent after high-dose epinephrine but was maintained after high-dose vasopressin. These findings emphasize the need for pressurized intraosseous infusion techniques, because bone marrow blood flow may not be predictable during hemorrhagic shock and drug therapy.

ISSN:0090-3493    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo determine whether elevations in pulmonary vascular pressure induced by mechanical ventilation are more injurious than elevations of pulmonary vascular pressure of similar magnitude occurring in the absence of mechanical ventilation.DesignProspective comparative laboratory investigation.SettingUniversity research laboratory.SubjectsMale New Zealand white rabbits.InterventionsThree groups of isolated, perfused rabbit lungs were exposed to cyclic elevation of pulmonary artery pressures arising from either intermittent positive pressure mechanical ventilation or from pulsatile perfusion of lungs held motionless by continuous positive airway pressure. Peak, mean, and nadir pulmonary artery pressures and mean airway pressure were matched between groups (35, 27.4 ± 0.74, and 20.8 ± 1.5 mm Hg, and 17.7 ± 0.22 cm H2O, respectively).Measurements and Main ResultsLungs exposed to elevated pulmonary artery pressures attributable to intermittent positive pressure mechanical ventilation formed more edema (6.8 ± 1.3 vs. 1.1 ± 0.9 g/g of lung), displayed more perivascular (61 ± 26 vs. 15 ± 13 vessels) and alveolar hemorrhage (76 ± 11% vs. 26 ± 18% of alveoli), and underwent larger fractional declines in static compliance (88 ± 4.4% vs. 48 ± 25.1% decline) than lungs exposed to similar peak and mean pulmonary artery pressures in the absence of tidal positive pressure ventilation.ConclusionsIsolated phasic elevations of pulmonary artery pressure may cause less damage than those occurring during intermittent positive pressure mechanical ventilation, suggesting that cyclic changes in perivascular pressure surrounding extra-alveolar vessels may be important in the genesis of ventilator-induced lung injury.

ISSN:0090-3493    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveAn enhanced formation of endogenous nitric oxide contributes to the circulatory failure caused by endotoxin (lipopolysaccharide). Many of the biological actions of nitric oxide are mediated by the guanylate cyclase/cyclic guanosine 3prime;,5′-monophosphate system. We recently discovered that two cell wall components, namely lipoteichoic acid and peptidoglycan of the Gram-positive bacteriumStaphylococcus aureus, synergize to cause shock and multiple organ dysfunction syndrome in the rat. Here we investigate the effects of a selective guanylate cyclase inhibitor, 1H-(1,2,4)oxadiazole(4,3-&agr;)quinoxaline-1-one (ODQ), on the circulatory failure and multiple organ dysfunction syndrome (kidney, liver, lung) caused by a) coadministration of lipoteichoic acid and peptidoglycan (Gram-positive shock) or b) lipopolysaccharide (Gram-negative shock) in the anesthetized rat. Furthermore, we investigated whether ODQ scavenges superoxide anions and/or hydroxyl radicals.DesignThein vivoportion of the study was a prospective, randomized, controlled animal study. Thein vitroportion included a) cultured ventricular myoblasts of the rat, H9c2(2-1) cells, and b) a cell free superoxide anion assay system.SettingUniversity-based research laboratory.SubjectsSeventy-five anesthetized, male Wistar rats were used for thein vivostudy.InterventionsFor thein vivoportion of the study, after surgical preparation, anesthetized rats were observed for 6 hrs. All rats were pretreated and received an intravenous infusion of saline (1.5 mL·kg−1·hr−1), which was maintained throughout the experiment. The rats were assigned to nine groups. Group 1 contained control rats (sham) subjected to 2 mL/kg saline intraperitoneally, 2 hrs before the experiment (n = 7). Group 2 contained control rats (sham) that received 2 mg/kg ODQ intraperitoneally, 2 hrs before the experiment (n = 9). Group 3 contained control rats (sham) that received 2 mL/kg dimethyl sulfoxide, 30% v/v in saline intraperitoneally, as a vehicle for ODQ, 2 hrs before the experiment (n = 6). In group 4 rats, Gram-positive shock was induced by coadministration of lipoteichoic acid (3 mg/kg intravenously) and peptidoglycan (10 mg/kg intravenously) (n = 10). In group 5, rats were pretreated with ODQ (as described previously) before lipoteichoic acid/peptidoglycan (n = 9). In group 6, rats were pretreated with dimethyl sulfoxide (as de- scribed previously) before lipoteichoic acid/peptidoglycan (n = 7). In group 7, Gram-negative shock was induced by lipopolysaccharide (6 mg/kg intravenously) (n = 11). In group 8, rats were pretreated with ODQ (as described previously) before lipopolysaccharide (n = 8). In group 9, rats were pretreated with dimethyl sulfoxide (as described previously) before lipopolysaccharide (n = 8).For thein vitroportion of the study, rat cells were preincubated with vehicle (saline and/or dimethyl sulfoxide) and ODQ (0.1 &mgr;M to 1 mM) for 2 hrs. The cells then were exposed to H2O2(1 mM) for 4 hrs at 37°C, after which time cell viability was determined by measuring the mitochondrial-dependent reduction of 3-(4,5-di-methyliazol-2-yl)-2,5-diphenyltetrazolium bromide to blue formazan. Next, an aqueous solution was incubated with ODQ (as described previously), and superoxide anions were produced by using a hypoxanthine/xanthine-oxidase assay. The chemiluminescence assay was used to evaluate any potential antioxidative effects of ODQ.Measurements and Main ResultsIn vivo,administration of lipoteichoic acid/peptidoglycan or lipopolysaccharide resulted within 6 hrs in hypotension, acute renal dysfunction, hepatocellular injury, and lung injury. Pretreatment of rats with ODQ attenuated the renal dysfunction, lung injury, and hepatocellular injury caused by lipoteichoic acid/peptidoglycan or lipopolysaccharide.In vitro,administration of H2O2(for 4 hrs) to rat cardiomyoblasts decreased mitochondrial respiration attributable to generation of hydroxyl radicals. Pretreatment of cells with ODQ did not abolish this cell injury. In addition, ODQ did not scavenge superoxide anions.ConclusionsThese results imply that ODQ, an inhibitor of guanylate cyclase, reduces the multiple organ injury and dysfunction caused by wall fragments of Gram-positive or Gram-negative bacteria in the anesthetized rat. The observed protective effects of ODQ are not attributable to the ability of ODQ to reduce the formation or the effects of superoxide anions or hydroxyl radicals.

ISSN:0090-3493    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo quantify the phenylephrine pressor responsiveness after severe brain injury combined with hypoxia-hypotension, and to study the respective roles of brain injury and hypoxia-hypotension in the observed alteration.DesignRandomized study.SettingAccredited animal laboratory.SubjectsAdult Sprague Dawley rats.InterventionsAnesthetized animals were assigned to control, brain injury, hypoxia-hypotension, and brain injury combined with hypoxia-hypotension groups. Brain injury was induced with an impact-acceleration device. During the 15-min hypoxia-hypotension, arterial oxygen pressure was decreased to 40 torr (5.3 kPa) and mean arterial pressure to 30 mm Hg. Thirty-six of the 53 included rats were alive at the end of hypoxia-hypotension (nine animals per group). In an additional group (Hypo, n = 8), mean arterial pressure was lowered to the level observed in brain injury combined with hypoxia-hypotension with pentobarbital infusion. Sixty minutes after injuries (T60), animals received 0.1, 1, and 10 &mgr;g/kg phenylephrine in a random order. Pressor responsiveness to phenylephrine was defined as maximal postinjection minus preinjection mean arterial pressure.Measurements and Main ResultsDuring hypoxia-hypotension, mortality was higher and residual restored blood volume was lower (p< .01) in the animals with brain injury and hypoxia-hypotension compared with hypoxia-hypotension alone. At T60, mean arterial pressure (mm Hg) was lower (p< .01) in the brain injury group (83 ± 22) compared with controls (110 ± 10) and in brain injury combined with hypoxia-hypotension (76 ± 18) compared with controls and hypoxia-hypotension (107 ± 14). Pressor responsiveness (mm Hg) to 1 and 10 &mgr;g/kg phenylephrine was less (p< .05) in brain injury combined with hypoxia-hypotension (15 ± 6 and 44 ± 8) and hypoxia-hypotension (15 ± 3 and 44 ± 8) compared with controls (26 ± 2 and 57 ± 11). No significant difference was observed for phenylephrine pressor responsiveness between controls and the Hypo group (25 ± 5 and 66 ± 7).ConclusionsCombination of brain injury and hypoxia-hypotension induces a severe hemodynamic alteration associated with a decreased pressor responsiveness to phenylephrine. Transient hypoxia-hypotension is responsible for the depressed &agr;-1 adrenergic reactivity.

ISSN:0090-3493    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo study the importance of endothelin-1-induced vasoconstriction in a model of acute and maintained low cardiac output, by investigating regional changes within the mesenteric and particularly the intestinal mucosal circulation.DesignProspective, controlled animal study.SettingUniversity-affiliated research laboratory.SubjectsThirteen fasted, anesthetized, mechanically ventilated landrace pigs.Measurements and Main ResultsCardiac output, portal venous blood flow, renal arterial flow, jejunal mucosal microcirculation by laser Doppler flowmetry, jejunal capnotonometry (Pco2gap), and jejunal mucosal oxygenation (tPo2) were monitored. Cardiac tamponade was established to reduce portal venous blood flow to a preset end point at two thirds of baseline. Measurements were made at baseline, after 90 mins of cardiac tamponade, and 90 mins after the administration of the combined endothelinA/endothelinBantagonist tezosentan at 1 mg·kg−1·hr−1during tamponade in seven animals. Six animals served as time controls and received only the vehicle. Cardiac tamponade decreased portal venous blood flow, renal arterial flow, and laser Doppler flowmetry, whereas the Pco2gap increased. The change in tPo2failed to gain statistical significance (p= .08). Administration of tezosentan during tamponade restored portal venous blood flow and laser Doppler flowmetry to baseline values, increased tPo2above baseline, and decreased Pco2gap. No effect on renal arterial flow was observed. Investigated variables remained unchanged in control animals after induction of cardiac tamponade.ConclusionsEndothelin-1 blockade in acute cardiac failure improves mesenteric, but not renal, perfusion, illustrating the regional importance of endothelin-1-induced vasoconstriction. Importantly, endothelin-1 blockade restored mucosal blood flow and oxygenation, which might be particularly interesting considering the implications for maintenance of mucosal barrier integrity in low output states.

ISSN:0090-3493    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo determine whether acid instillation augments tumor necrosis factor-&agr; and nitric oxide production by alveolar macrophages in rats, and to study the effects of treatment with pentoxifylline before acid instillation on the production of these inflammatory mediators.DesignControlled laboratory investigation on tumor necrosis factor-&agr; and nitric oxide production by alveolar macrophages of rats that had acid-induced lung injury.SettingUniversity research laboratory.SubjectAlveolar macrophages of rats.InterventionsAlveolar macrophages were recovered by bronchoalveolar lavage at 4, 10, 16, 24, and 72 hrs after unilateral hydrochloric acid (pH, 1.0; volume, 0.1 mL) instillation into the lungs of rats. Alveolar macrophages then were cultured with or without lipopolysaccharide. One group of rats was pretreated with pentoxifylline before acid instillation.Measurements and Main ResultsAlveolar macrophages from both acid-instilled and contralateral lungs, which had recovered 24 hrs after acid instillation, produced significantly greater tumor necrosis factor-&agr; and nitric oxide. Subsequent exposure to lipopolysaccharide, as a surrogate for bacterial infection, further promoted tumor necrosis factor-&agr; and nitric oxide release. Alveolar macrophages from rats pretreated with pentoxifylline before acid instillation produced significantly less tumor necrosis factor-&agr; and did not overproduce tumor necrosis factor-&agr; when exposed to lipopolysaccharide. In contrast, pretreatment with pentoxifylline had no effect on nitric oxide production by alveolar macrophages.ConclusionsAcid instillation stimulates alveolar macrophages to produce tumor necrosis factor-&agr; and nitric oxide. Pentoxifylline preserved innate production of tumor necrosis factor-&agr; to lipopolysaccharide and did not inhibit the production of bactericidal nitric oxide. This may partly explain why pentoxifylline reduces acid aspiration-induced lung injury while maintaining the host’s ability to combat bacterial infection after acid aspiration.

ISSN:0090-3493    

出版商:OVID    

年代:2001

数据来源: OVID