摘要:

Inadequate splanchnic perfusnin, detected as a low gastric intramucosal pH (pHi), in the face of normal systemic perfusion predicts an increased risk for multiple organ failure after trauma. Although the exact etiology of this low pHi is unknown, angiotensin II is thought to be an important regulator of gut perfusion during and after resuscitation from shock. The purpose of this study is to determine whether enalaprilat, an angiotensin-converting enzyme inhibitor, improves gut perfusion in critically injured patients. To test this hypothesis, 18 trauma patients monitored with a nasogastric tonometer and a pulmonary artery catheter were enrolled in a prospective study. A single dose of enalaprilat, .625 mg, was given as an i.v. bolus or a 4 h infusion following systemic resuscitation. Pre- and postdrug tonometric and hemodynamic data, including cardiac index, mean arterial pressure, right ventricular end-diastolic volume index, systemic vascular resistance index, and oxygen transport variables were compared using the pairedttest. Results demonstrate that pHi was significantly improved after 4 h (7.13 ± .04 to 7.19 ± .03,p= .03) and after 24 h compared with baseline (7.14 ± .04 to 7.25 ± .04,p= .04). Overall, pHi increased in 12 of 18 patients. No significant differences were observed in any of the studied hemodynamic or systemic perfusion variables including mean arterial pressure (92 ± 4 to 87 ± 4,p= .24) and oxygen delivery (669 ± 33 to 675 ± 32,p= .82). In examining the determinants of pHi, the intramucosal-arterial Pco2difference was improved after enalaprilat administration (27 ± 6 to 17 ± 3 mmHg,p= .04) while no difference was observed in arterial bicarbonate (19.5 ± .7 to 19.7 ± .8,p= .90). Additionally, the change in pHi observed with enalaprilat correlated with predrug intramucosal-arterial Pco2difference (r = .74, r2= .55,p= .0005). These results demonstrate that enalaprilat improves gut perfusion as measured by gastric tonometry in critically injured patients, and that this effect appears to be independent of changes in systemic perfusion.

ISSN:1073-2322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

RBC deformability (RBCD) is decreased in critically ill patients. This is thought to impede the passage of the RBC through the microcirculation. The cell transit analyzer (CTA) provides an evaluation of RBCD. RBCD was examined in 16 patients admitted to the surgical intensive care unit. CTA analysis was conducted within 24 h of admission to the surgical intensive care unit or as soon as possible thereafter, and then repeated every 72 h. Counts per second (C/s) was the parameter used as an index of RBCD. Patients were classified as Septic/SIRS or nonseptic at the time of each blood collection by standard clinical criteria. There were 34 total specimens, 22 septic/SIRS and 12 nonseptic. The C/s for the SIRS samples (41.7 ± 3.4 was significantly (p< .05) lower than that of the non-SIRS samples (54.3 ± 5.3). Seventeen of the Septic/SIRS samples were obtained following blood transfusion. Pearson's test calculated for the C/s and the total number of packed RBC transfusions showed a positive correlation (r= .594) that was statistically significant (p< .02). CTA was also performed on 10 U of banked packed RBCin vitro. Deformability was maintained at a constant level until the very end of the storage period, at which time there was a statistically significant decrease in C/s (p< .0001). These data suggest that packed RBC transfusion is associated with a significant improvement in the abnormally low RBCD seen in critically ill patients. This may be due to replacement of previously rigidified cells by cells with a more normal RBCD.

ISSN:1073-2322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Tumor necrosis factor (TNF) may be a major endogenous mediator of sepsis-induced acute organ injury. We proposed that treatment of septic pigs with the combined agents ibuprofen, a cycloox-ygenase inhibitor, and histamine receptor antagonists, cimetidine (H2antagonist) and diphenhydramine (H1antagonist) would result in lower circulating levels of TNF and decreased parameters of sepsis-induced injury in these animals. To test this, plasma TNF activity, cardiac index, systemic and pulmonary arterial pressures, arterial Po2and bronchoalveolar lavage protein content were monitored for 300 min in four groups of anesthetized pigs: saline-infused control pigs (n = 4); pigs infused for 60 min withPseudomonas aeruginosa(5 x 1088organisms/mL, .3 mL/20 kg/min) (n = 5) and pigs infused for 60 min withP. aeruginosaplus ibuprofen (12.5 mg/kg) alone (n = 4) or ibuprofen plus cimetidine (150 mg) and diphenhydramine (30 mg/kg) at 0 and 120 min (CID, n = 4). Within 60 min, pigs infused withP. aeruginosaexhibited increased plasma TNF activity (>8-fold increase in ng/mL TNF; L929 cytolysis assay) and showed alterations in all hemodynamic and pulmonary parameters. Ibuprofen or CID administration in the septic pigs decreased peak TNF activity by 4.6 and 10.2 ng/mL, respectively, and CID treatment was correlated with better attenuation of certain sepsis-induced alterations. These results show that CID treatment attenuates sepsis-induced injury and that this is correlated with reduced plasma TNF activity in a porcine model of sepsis-induced acute organ injury.

ISSN:1073-2322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Loss of gut barrier function after burn injury can be important in the pathogenesis of systemic infections and organ dysfunction. The purpose of this study was to determine how rapidly impairment of gut barrier function occurs after burn injury and how long it persists. BALB/c mice were gavaged with 1010 111In-oxine-labeledEscherichia coli3 h before inflicting a 20% total body surface area burn. They were then killed at 5, 15, 30, 60, 120, or 240 min post-burn. Additional mice were given a 20% or 30% burn injury and were randomized into eight groups, which were killed at either 4 h or 1,2,4,7,14, or 21 days post-burn. Each mouse was gavaged with 1010 111In-oxine-labeledE. coli4 h before sacrifice to determine the magnitude of translocation. Gut barrier function was impaired as early as 5 min post-burn and was maximal by 4 h. Rapid improvement was observed by 24 h, followed by slow improvement, but with persistent abnormality through 21 days post-burn. Killing of translocated bacteria was impaired at 4 h and day 7 post-burn, according to the percentage of viableE. colithat remained alive in the tissues. The magnitude of gut dysfunction following burn injury is temporally related.

ISSN:1073-2322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

To test the effects of C1-esterase inhibitor in scald burns on bacterial translocation and intestinal damage, standardized deep partial-thickness burns were inflicted on domestic pigs, scalding 30% of the skin surface for 25 s with 75°C hot water. The animals (n = 17; weight 25–35 kg) were divided into three groups: I) the control group (n = 5) without scald burn; II) the group (n = 6) with scald burn; and III) the group with C1-inhibitor (n = 6): scald burn and treatment with C1-inhibitor (C1-INH; BERINERT®, Behring, Marburg, Germany). Parameters measured and compared in this model were activity of complement system, hemodynamics, body weight, pathological organ alterations including intestinal lesions, bacterial translocation, and skin damage. C1-INH administration significantly decreased the plasma levels of the specific soluble membrane attack complex (SC5b-9), bacterial translocation, and the degree of intestinal ischemia in the postburn period compared with untreated animals. Moreover, animals treated with C1-INH exhibited a minor degree of organ alterations including damage of the skin and development of edema. The favorable effects of C1-INH may be explained by the protection of the intestinal and dermal microcirculation in the acute phase of thermal injury.

ISSN:1073-2322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The role of nitric oxide (NO) in hepatic oxygen transport is unclear. We investigated the effects of aminoethyl-isothiourea (AE-ITU), a selective inhibitor of iNOS activity, on liver blood flow and oxygen consumption (Vo2H) in the pig. Endotoxin (lipopolysaccharide, LPS) was given intraportally (1.7 μg/kg/h), followed by AE-ITU (10 mg/kg) after 3 h (n = 7). LPS controls (n = 8) received LPS for 6 h. AE-ITU controls (n = 6) received saline/AE-ITU. LPS (treatment group) caused significant reductions at 3 h in cardiac output (CO) from 4.4 ± .4 to 2.7 ± .3 L/min, in hepatic artery flow (QHA) from 266 ± 53 to 127 ± 19 mL/min, and in portal venous flow (QPV) from 630 ± 50 to 323 ± 33 mL/min. Hepatic oxygen delivery (Do2H) was reduced from 93 ± 11 to 38 ± 5 mL/min (p< .05), while hepatic oxygen extraction ratio (ERo2H) increased, and Vo2H was maintained. Similar changes were observed in LPS controls. AE-ITU caused no changes in saline controls. After injection of AE-ITU during LPS infusion, CO was unchanged, while QHAincreased gradually from 127 ± 20 to 268 ± 40 mL/min over 3 h (p< .05) and Do2H from 38 ± 5 to 60 ± 5 mL/in (p< .05). ERo2H increased from .54 ± .04 to .69 ± .03 in 30 min, while Vo2H increased from 23 ± 4 to 35 ± 3 mL/in in 3 h (p< .05). Thus, AE-ITU restored hepatic arterial blood flow and increased hepatic oxygen consumption in pigs with endotoxemia.

ISSN:1073-2322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Ischemia and reperfusion causes tissue injury that can be partially prevented by mild hypothermia. In this study we postulated that hypothermic protection could occur if imposed only during reperfusion. Rabbit ears were partially amputated, the central artery occluded for 6 h followed by reperfusion at an ambient temperature of either 20 or 24°C resulting in ischemic ear temperatures of 22.5 vs. 24.7°C. Ear temperature of rabbits remaining in the 24°C room increased with reperfusion to 32.4°C whereas those moved to the 20°C room increased to 30.0°C by 2 h of reperfusion. Ear volume was used as a measure of tissue edema and was measured for 7 days after the ears were allowed to reperfuse. Normalized myeloperoxidase content (polymorphonuclear cell accumulation) was significantly greater in the 24°C ischemia-24°C reperfusion group compared with the other groups. Ear edema was significantly less in the two groups exposed to 20°C reperfusion compared with the 24°C ischemia-24°C reperfusion group. Peak ear volume was 5.0 times baseline for the 24°C ischemia-24°C reperfusion, 4.0 times baseline for the 20°C ischemia-24°C reperfusion, 3.4 times baseline for the 24°C ischemia-20°C reperfusion, and 3.3 times baseline for the 20°C ischemia-20°C group. We conclude that mild hypothermia reduces PMN accumulation and is more effective in preventing tissue injury when imposed during reperfusion compared with during ischemia.

ISSN:1073-2322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Transmucosal passage of bacteria across the intestine, the essential and prerequisite step for bacterial translocation, cannot be effectively studied usingin vivomodels of translocation. We have adapted the Ussing chamber into a fresh, sterile organ culture system that can facilitate the study of bacterial-epithelial interactions. Intestinal membranes were mounted in the Ussing chamber and perfused with a solution rich in putative mucosal micronutrients. The transmembrane potential difference was constantly monitored as a marker of intestinal integrity. Transmucosal passage of various bacteria across the normal intestinal epithelium was quantitated, and the mucosal membrane was examined by light and transmission electron microscopy. The addition of potassium cyanide to the mucosal perfusate resulted in an irreversible loss of potential difference. Oxygen deprivation also led to a precipitous drop in potential difference, but it was reversible with prompt reoxygenation. In contrast, intestinal membranes perfused with a solution consisting of Dulbecco's modified Eagle's medium + 20 mM glutamine maintained their potential difference for a sustained period (<180 min). Both the viability and structural integrity of the ileal intestinal membrane were maintained in cultureex vivousing this perfusate. Qualitative differences were observed in the mechanism of transmucosal passage of mild to moderately virulent bacteria such asEscherichia coliC-25 andProteus mirabilisM-13, which pass through the intestinal epithelium without causing overt damage to the mucosa, and more virulent organisms such asSalmonella typhimurium, which cause extensive mucosal damage by light and transmission electron microscopy. The Ussing system should provide a useful model of intact organ culture for the study of the mechanisms of bacterial translocation and the pathogenesis of enteric infections.

ISSN:1073-2322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Background: Neutrophils are of great importance for the host's defense against invading organisms. Granulocyte colony-stimulating factor (G-CSF) has been used to augment both the neutrophil number and function, and its prophylactic administration has proved beneficial in animal models of sepsis. However, pretreatment with G-CSF is not practical under clinical conditions. We therefore investigated the effect of recombinant human (rh)G-CSF, administered only after infection, on the survival rate as well as the hemodynamic and cytokine response of the animals. Methods: Chronically catheterized conscious pigs were challenged withPseudomonas aeruginosa(8 x 107colony-forming units kg-1· h-1for 120 h (control group, n = 10). Animals in the G-CSF group (n = 7) also received rhG-CSF (5 μg kg-1· day-1), the first dose being given 3 h after beginning bacterial infusion. Results: The mortality rate was 50% (5/10) and 29% (2/7) in the control and G-CSF groups, respectively (p= NS, control vs. G-CSF group). Fever, severe pulmonary hypertension, and a hyperdynamic response were recorded in all of the animals. In spite of a prompt and significant recovery from the initial leukopenia (p< .05 vs. control group), the animals of the G-CSF group showed no significant differences in the parameters investigated from those of the controls. Compared with the survivors, the interleukin-1 receptor antagonist was markedly elevated in all nonsurvivors after 6 h of sepsis (p< .05). Conclusions: These data suggest that treatment with rhG-CSF after the onset of bacterial sepsis might not significantly improve the chances of survival for non-neutropenic patients.

ISSN:1073-2322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

This study was designed to evaluate the decreased permselectivity of the capillary wall and the resultant higher permeability to macromolecular anionic albumin in septic rats, by quantitative estimation of Evans blue-albumin complexes in interstitial tissue. Septic peritonitis was induced by intraperitoneal injection ofEscherichia coli-06 KS H16. Twenty-four hours after induction of septic peritonitis, intact (healthy, noninoculated animals) and septic rats were perfused with 5 mL/Kg of a solution of Evans blue in normal saline (20 mg/mL in .9% NaCl). In septic rats, the interstitial concentration of Evans blue in mesentery, pancreas, and diaphragmatic muscle was significantly higher than that observed in intact animals. The present observations were made in the same experimental model of abdominal sepsis that showed a substantial reduction in the endothelial negative charge of the mesenteric, pancreatic, and diaphragmatic capillary beds. The evidence obtained from this experiment confirms that the loss of the permselective properties of capillary wall for macromolecular anionic albumin derives from a drastic reduction of its normally present and regularly distributed fixed electronegative charges.

ISSN:1073-2322    

出版商:OVID    

年代:1998

数据来源: OVID