Hydroxyethyl Starch Improves the Prognosis of Rats with Traumatic Shock via Activation of the ERK Signaling Pathway in Lymphocytes.

OBJECTIVE: Severe traumatic shock is one of the leading causes of death in young adults. A large number of studies have shown that effective volumetry resuscitation on the basis of controlled injury can not only increase the success rate of early resuscitation but also reduce systemic inflammatory response and improve the cure rate of severe traumatic shock. The study explored the effects of hydroxyethyl starch (HES) on the survival rate, lymphocyte function and proliferation of rats with traumatic shock, and the potential mechanisms. METHODS: Traumatic shock was constructed in rats as experimental model, and liquid resuscitation was performed using HES and lactated Ringer's (LR). 24-h mortality was recorded, and lymphocytes were isolated. The expressions of signaling pathway factors was detected by qPCR and Western blot. ELISA was performed to determine the expression of interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) in cell supernatant. RESULTS: HES for fluid resuscitation augmented the survival of traumatic shock rats, upregulated the expressions of MEK and ERK1/2, and downregulated the expressions of IL-6 and TNF-α. However, inhibition of ERK signaling pathway reversed the effect of HES on the immune improvement and the 24-h survival rate of the traumatic shock rats (P < 0.05). CONCLUSION: HES could exert the anti-inflammatory effects on lymphocytes by mediating the phosphorylation of proteins of the ERK signaling pathway. HSE demonstrated a high efficacy in effectively treating traumatic shock, thus could be used in clinical practice.

The Effects of Genetic 3-Mercaptopyruvate Sulfurtransferase Deficiency in Murine Traumatic-Hemorrhagic Shock.

INTRODUCTION: Hemorrhagic shock is a major cause of death after trauma. An additional blunt chest trauma independently contributes to mortality upon the development of an acute lung injury (ALI) by aggravating pathophysiological consequences of hemorrhagic shock. The maintenance of hydrogen sulfide availability is known to play an important role during hemorrhage and ALI. We therefore tested the impact of a genetic 3-mercaptopyruvate sulfurtransferase mutation (Δ3-MST) in a resuscitated murine model of traumatic-hemorrhagic shock. METHODS: Anesthetized wild-type (WT) and Δ3-MST mice underwent hemorrhagic shock with/without blunt chest trauma. Hemorrhagic shock was implemented for 1 h followed by retransfusion of shed blood and intensive care therapy for 4 h, including lung-protective mechanical ventilation, fluid resuscitation, and noradrenaline titrated to maintain a mean arterial pressure at least 50 mmHg. Systemic hemodynamics, metabolism, and acid-base status were assessed together with lung mechanics and gas exchange. Postmortem tissue samples were analyzed for immunohistological protein expression and mitochondrial oxygen consumption. RESULTS: 3-MST-deficient mice showed similar results in parameters of hemodynamics, gas exchange, metabolism, acid base status, and survival compared with the respective WT controls. Renal albumin extravasation was increased in Δ3-MST mice during hemorrhagic shock, together with a decrease of LEAK respiration in heart tissue. In contrast, mitochondrial oxygen consumption in the uncoupled state was increased in kidney and liver tissue of Δ3-MST mice subjected to the combined trauma. CONCLUSIONS: In summary, in a resuscitated murine model of traumatic-hemorrhagic shock, 3-MST deficiency had no physiologically relevant impact on hemodynamics and metabolism, which ultimately lead to unchanged mortality regardless of an additional blunt chest trauma.

NF-κB mediates early blood-brain barrier disruption in a rat model of traumatic shock.

BACKGROUND: Blood-brain barrier (BBB) disruption is associated with a large number of central nervous system and systemic disorders. The aim of the present study was to investigate the dynamic change of BBB changes during traumatic shock and resuscitation as well as the mechanisms involved. METHODS: The experiments were performed on male Sprague-Dawley rats anesthetized with pentobarbital sodium. To produce traumatic shock, the rats were subjected to bilateral femoral traumatic fracture and blood withdrawal from the femoral artery to decrease mean arterial pressure (MAP) to 35 mm Hg. Hypovolemic status (at a MAP of 35 to 40 mm Hg) was sustained for 1 hour followed by fluid resuscitation with shed blood and 20 mL/kg of lactated Ringer's solution. RESULTS: The rats were sacrificed at 1 hour, 2 hours, or 6 hours after fluid resuscitation. Blood-brain barrier permeability studies showed that traumatic shock significantly increased brain water contents and sodium fluorescein leakage, which was aggravated by fluid resuscitation. Real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses revealed that Na-K-Cl cotransporter-1 and vascular endothelial growth factor (VEGF) expression were upregulated in cortical brain tissue of traumatic shock rats, and this change was accompanied by downregulation of occludin and claudin-5. Traumatic shock also significantly increased the protein levels of NF-κB-p65 subunit. Of note, administration of NF-κB inhibitor PDTC effectively attenuated augmentation of the above changes. CONCLUSION: Our results suggest that traumatic shock is associated with early BBB disruption, and inhibition of NF-κB may be an effective therapeutic strategy in protecting the BBB under traumatic shock conditions.

Poor microcirculatory flow dynamics are associated with endothelial cell damage and glycocalyx shedding after traumatic hemorrhagic shock.

BACKGROUND: Endothelial cell damage and glycocalyx shedding after trauma can increase the risk of inflammation, coagulopathy, vascular permeability, and death. Bedside sublingual video-microscopy may detect worse flow and perfusion associated with this endotheliopathy. We compared markers of endotheliopathy with physical flow dynamics after traumatic hemorrhagic shock. METHODS: Sublingual incident dark field video-microscopy was performed at three time points after injury (<10 hours, 10-30 hours, and 30-50 hours). Values for microcirculatory flow index (MFI), Point Of carE Microcirculation assessment (POEM) score, proportion of perfused vessels (PPV), microcirculatory heterogeneity index (MHI), perfused vessel density (PVD), and total vessel density (TVD) were obtained. ELISAs were performed to measure concentrations of thrombomodulin and syndecan-1 as biomarkers of endothelial cell damage and glycocalyx shedding respectively. Flow parameters were dichotomized to above and below average, and biomarkers compared between groups; below average MFI, POEM, PPV, PVD, and TVD, and above average MHI were considered poor microcirculatory flow dynamics. RESULTS: A total of 155 sublingual video-microscopy clips corresponding to 39 time points from 17 trauma patients were analyzed. Median age was 35 (IQR 25-52); 16/17 were men. Within 10 hours of injury, syndecan-1 concentrations were significantly higher compared to 17 age- and sex-matched healthy controls (30 [IQR 20-44] ng/mL) for worse TVD (78 [IQR 63-417] ng/mL), PVD (156 [IQR 63-590] ng/mL), PPV (249 [IQR 64-578] ng/mL), MFI (249 [IQR 64-578] ng/mL), MHI (45 [IQR] 38-68) ng/mL), and POEM scores (108 [IQR 44-462] ng/mL) (all p < 0.01). Thrombomodulin was also raised within 10 hours of injury when compared to healthy controls (2.9 [IQR 2.2-3.4] ng/mL) for worse PPV (4.1 [IQR 3.4-6.2] ng/mL) and MFI (4.1 [IQR 3.4-6.2] ng/mL) (both p < 0.05). CONCLUSIONS: Endothelial cell damage and glycocalyx shedding are associated with worse flow, density, and heterogeneity within microvessels after traumatic hemorrhagic shock. The clinical utility of these biomarkers and flow parameters at the bedside are yet to be elucidated. LEVEL OF EVIDENCE: Prognostic study, level III.

Sugar or salt? The relative roles of the glucocorticoid and mineralocorticoid axes in traumatic shock.

BACKGROUND: Glucocorticoid deficiency (GD) has been proposed as a key contributor to shock states, but the presence and role of acute mineralocorticoid deficiency may be of equal or greater significance. We sought to analyze the incidence and degree of acute mineralocorticoid deficiency and GD in an animal model of severe hemorrhage and shock. METHODS: Fifty-seven swine underwent 35% volume-controlled hemorrhage followed by aortic cross-clamping for 50 minutes to induce truncal ischemia-reperfusion. Protocol-guided resuscitation was performed. Laboratory analysis included cortisol, aldosterone, and plasma renin activity. The aldosterone-to-renin ratio (ARR) was calculated at each time point, and changes were correlated to markers of perfusion. RESULTS: Mean baseline cortisol levels were 5.8 µg/dL. Following hemorrhage, there was a significant increase in mean cortisol to 9.2 µg/dL (p < 0.001). After 1 hour of reperfusion, there was no change in mean cortisol levels (9.8 µg/dL, p = 0.12). Mean baseline aldosterone was 13.3 pg/mL. Aldosterone levels before cross-clamp removal increased significantly to 115.1 pg/mL (p < 0.001) and then rapidly declined to 49.2 pg/mL (p < 0.001) after 1 hour of reperfusion. Conversely, baseline plasma renin activity was 0.75 ng/mL per hour and increased significantly before cross-clamp removal (1.8) and at 1 hour (8.9, both p < 0.001). The ARR at baseline was 96.1 and increased to 113.5 (p = 0.68) before cross-clamp removal but significantly declined following 1 hour of reperfusion to 7.6 (p < 0.001). Overall, this represented a 93% reduction in mean ARR following reperfusion. The degree of aldosterone deficiency correlated with degree of systemic shock as measured by arterial base deficit (r = 0.47, p = 0.04), while cortisol showed no correlation. CONCLUSION: Hemorrhagic shock with ischemia-reperfusion injury resulted in only modest impact on the glucocorticoid axis, but major dysfunction of the mineralocorticoid axis and severe hyperreninemic hypoaldosteronism. The degree of aldosterone deficiency may provide prognostic information or offer potential targets for pharmacologic intervention. LEVEL OF EVIDENCE: Diagnostic study, level III.

Organ failure in the obese adipocytes prime polymorphonuclear cell inflammation under stress conditions.

BACKGROUND: Obesity is associated with a higher risk of remote organ failure after shock and trauma. The mechanism(s) is poorly understood. Polymorphonuclear cell (PMN) inflammatory responses are important in the pathogenesis of organ injury following shock. Morbid obesity is a low-grade inflammatory state associated with proinflammatory mediator production from adipose tissue. We hypothesized that adipose tissue may modulate PMN inflammatory potential and is dependent on the magnitude of the injury-related stress response. This was studied in an in vitro model. METHODS: Adipose-derived stem cells (ADSCs) conditioned to behave as mature adipocytes were incubated with physiologic and stress concentrations of adrenaline for 12 hours, and cell culture supernatants were obtained. PMNs from normal human volunteers were cocultured with the ADSC supernatants (priming) followed by addition of 1-µM fMLP (activation). PMNs alone served as control. PMN activation was indexed by superoxide anion (O2) production, elastase release (%) and CD11b expression (mean fluorescent intensity). RESULTS: Physiologic and stress levels of adrenaline resulted in significantly increased PMN activation in the presence or absence of adipocytes. However, the largest increase was noted in PMNs exposed to ADSC culture supernatants that had been cocultured with stress levels of adrenaline for 12 hours, twofold increase in CD11b expression and fourfold increase in superoxide anion and percent elastase release. CONCLUSION: Adipocyte-derived mediators prime PMNs in vitro. There was a graded PMN response to adrenaline concentration with or without adipocytes in these experiments. The most profound increase in PMN inflammatory potential was noted with the adipocyte supernatant + stress adrenaline group. The clinical impact of obesity on remote organ injury is likely dependent on patient body mass index and the injury-related sympathetic responses. These data suggest a potential role for ß blockade in this patient population.

Corticotropin-releasing factor is present in intestinal tissue of patients with gastrointestinal dysfunction following shock and abdominal surgery.

OBJECTIVE: Corticotropin-releasing factor (CRF) is implicated in stress-related gastrointestinal dysfunction, possibly causing gut dysfunction following trauma and surgery. We investigated plasma and intestinal tissue CRF levels and gut function in patients with traumatic shock or those undergoing elective abdominal surgery. RESEARCH METHODS AND PROCEDURES: In a prospective, parallel, observational study in a university hospital surgical intensive care unit (ICU), 8 shocked patients (systolic blood pressure <90 mmHg and/or acidosis and/or urine output <1 mL/kg/hr and/or requiring >2 L of intravenous fluid resuscitation) undergoing small bowel resection during emergency laparotomy following abdominal injury and 17 stable patients undergoing elective hepatobiliary surgery were included if they required postoperative ICU management. Serial plasma and intestinal CRF was measured and postoperative gastric emptying and intestinal permeability were evaluated. RESULTS: Plasma CRF was significantly increased in the shocked patients compared with the elective surgery patients at all times. CRF peptide was quantified in intestinal tissue at similar levels in both groups. Intestinal permeability was increased and associated with shock and resuscitation fluid volume. Gastric emptying was retarded and correlated significantly with shock but not with plasma CRF. Delayed gastric emptying in shocked patients was associated with longer ICU stay. CONCLUSIONS: The novel finding is the presence of CRF in the small bowel of both elective and emergency gastrointestinal surgery patients with concomitant gastrointestinal dysfunction. Circulating CRF is associated with poor gastric emptying, which prolongs ICU stay, whereas shock significantly impairs gastric emptying and gut permeability.

Modulation of the unfolded protein response during hepatocyte and cardiomyocyte apoptosis in trauma/hemorrhagic shock.

Trauma with hemorrhagic shock (T/HS), has been shown to result in liver injury marked by hepatocyte apoptosis and heart failure marked by cardiomyocyte apoptosis, both of which we have shown to be prevented by IL-6 administration at resuscitation, and Stat3 largely mediated this. As specific mediators have not been delineated, we investigated the unfolded protein response (UPR), which, with marked activation, can lead to apoptosis. Prior studies of hepatic and cardiac injury examined limited repertoires of UPR elements, making it difficult to assess the role of the UPR in T/HS. This study describes the first global examination of the UPR transcriptome in the liver and heart following T/HS, demonstrating organ-specific UPR transcriptome changes. The non-canonical UPR chaperone, Hsp70, was most dysregulated following T/HS and may contribute to hepatocyte protection via an IL-6-mediated pathway, identifying a potential new therapeutic strategy to prevent hepatocyte death and organ dysfunction in T/HS.

Effect of carbachol on intestinal mucosal blood flow, activity of Na+-K+-ATPase, expression of aquaporin-1, and intestinal absorption rate during enteral resuscitation of burn shock in rats.

We investigated the effect of carbachol (CAR, a cholinergic agent) on intestinal mucosal blood flow (IMBF), activity of Na-K-ATPase, expression of aquaporin (AQP)-1, and intestinal absorption rate during enteral resuscitation of a 35%TBSA scald in rats with a glucose electrolyte solution (GES). One hundred male Wistar rats were randomly divided into five groups: sham scald (N group); scald without fluid resuscitation (S group); scald resuscitated with enteral GES alone (GES group); scald resuscitated with enteral CAR alone (CAR group); and scald resuscitated with enteral CAR plus GES (GES/CAR group). The rats were inflicted 35%TBSA third degree of scald injury on the back with boiling water (100 degrees C, 15 seconds) in all groups, except the sham scald group. A catheter was inserted into the proximal duodenum (5 cm distal to pylorus) and distal ileum (5 cm proximal to cecum), of each rats through laparotomy, thus a segment of intestine was virtually isolated to form a loop for inlet and outlet of introduced fluid. In N, GES, and GES/CAR groups, fluids were introduced 30 minutes after scald injury. The speed of fluid infusion was 4 ml/kg/1%TBSA for 4 hours. CAR (60 microg/kg) was injected into the intestinal lumen at 30-minute after injury in CAR and GES/CAR groups. At 2 and 4 hours after scald, intestinal absorption rate of water and Na, and IMBF were determined, respectively. Then, animals were killed, and specimens of intestinal tissue were obtained for the determination of the activity of Na-K-ATPase, hematoxylin-eosin coloring, and expression of AQP-1. The intestinal absorption rate was reduced markedly in GES group compared with sham scald group at 2 and 4 hours after scald, and absorption rate of small intestine in GES/CAR was significantly higher than that in GES group (P < .05). It was also found that there was significant decrease in IMBF, activity of Na-K-ATPase, and expression of AQP-1 in scald group compared with the sham group. However, in GES/CAR group, the levels of these parameters were significantly increased compared with scald groups (P < .05). The results indicate that CAR promotes intestinal absorption rate of water and Na by improving IMBF, ATPase activity, and AQP-1 expression in gut mucosa during resuscitation with enteral GES of burn shock in rats.

[Influence of trauma-hemorrhagic shock on endotoxin, tumor necrosis factor-alpha and interleukin-6 levels in mesenteric lymph and blood of rats].

OBJECTIVE: To investigate the influence of trauma-hemorrhagic shock on endotoxin (ET), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels in mesenteric lymph and blood of rats. METHODS: Mesenteric lymph from trauma-hemorrhagic shock rats were collected, levels of ET, TNF-alpha and IL-6 in mesenteric lymph were compared with those from blood samples. RESULTS: Levels of ET, TNF-alpha and IL-6 in mesenteric lymph were elevated during shock period (all P<0.05), and they were decreased to normal range after resuscitation, with an exception of high IL-6 level up to 2 hours following resuscitation. CONCLUSION: The bacterial translocation could occur during shock period via lymphatic pathway, thereby leading to the increase in TNF-alpha and IL-6 levels, as well as systemic inflammatory response syndrome.

[Effects of escharectomy during burn shock stage on the mRNA expression of IFN-gamma and IL-4 in spleen T lymphocytes in rats after thermal injury].

OBJECTIVE: To determine the serum level and mRNA expression of type-1/type-2 cytokines of T lymphocytes in spleens of rats after thermal injury and to investigate the effects of escharectomy during burn shock stage on IFN-gamma and IL-4. METHODS: One hundred and sixty male Wistar rats were randomized into four groups. In group A, animals were not subjected to escharectomy. In groups B, C and D, escharectomy and skin allograft were performed at 8, 24, 96 hours postburn (PB) respectively. At 4, 12, 24, 48, 96, 120 and 168 hours PB, animals were killed and blood and spleens samples were harvested. ELISA was applied to determine the concentration of IFN-gamma and IL-4 in serum. The expression pattern of IFN-gamma and IL-4 were observed at mRNA level in T lymphocytes isolated from spleen by RT-PCR. RESULTS: The serum level of IFN-gamma and IL-4 rose rapidly and significantly after scald injury, expression of IFN-gamma and IL-4 mRNA in rats' T lymphocyte were also up-regulated spontaneously. The serum level of IFN-gamma and its mRNA expression began to rise within 4 hours PB, peaking at 24 hours PB. Whereas IL-4 and its mRNA expression showed a persistent elevation. Thereby leading to a dominant tendency of Th2 cytokine response on 7 d PB. In group A all above parameters revealed most obvious changes compared with controls, then ranked in group D, B and C. CONCLUSION: Escharectomy during burn shock stage is helpful to decrease the harmful over expression of Th2-type lymphocyte after severe thermal injury.

Metabolic disturbances in shock, and the role of ATP-MgCl2 and sex steroids.

Hemorrhage following accidental injuries is a common cause of death in the industrialized world. Moreover, the impact of elective surgery and solid organ transplantation sometimes results in low flow conditions similar to those seen following hemorrhagic shock. A shortage in O(2) availability, or hypoxia, leads to sequential changes in cell metabolism and morphology, including inflammatory responses and the expression of hypoxia-inducible transcription factor-1, which controls the cellular adaptation to hypoxia. These endogenous adaptive responses show that O(2) deprivation is not an unforeseen event for cells. The purpose of this review article is to discuss the pathophysiologic principles of shock and the metabolic alterations that cells undergo during low flow conditions. Moreover, the rationale for therapeutic intervention by administering ATP-MgCl(2) and sex steroids following shock and trauma will also be discussed.

The gene expression of cytokines and chemokines induced by tourniquet shock in mice.

Traumatic shock is one of the major fields in forensic pathology, but its mechanism remains elusive from the pathophysiological aspects. Tourniquet shock has been established as one of the animal models of traumatic shock, and we examined the gene expression of cytokines and chemokines in the lung and liver in tourniquet shock using mice. Tourniquet was conducted by the application of elastic bands with five turns at both the thighs as high as possible for 2 h, followed by reperfusion. In this procedure, more than 90% mice died within 48 h after reperfusion. Serum hepatic transaminase and hematocrit values significantly increased at 2 h after reperfusion, and their elevation was still evident after 10 h. Histopathologically, hemorrhages, congestion and leukocyte recruitment were observed in the lung and liver specimens after 6 h of reperfusion. Immunohistochemical analysis with anti-myeloperoxidase antibody demonstrated a massive neutrophil infiltration in the lung and liver at 2 h or more after reperfusion. RT-PCR analyses demonstrated that the gene expression of interleukin-1beta, tumor necrosis factor-alpha, monocytes chemoattractant protein-1, macrophage inflammatory protein (MIP)-1alpha, MIP-2, KC and vascular endothelial adhesion molecule-1 was most enhanced in the lung and liver at 2 h after reperfusion. Thus, the gene expression of cytokines and chemokines is presumed to be closely related with the onset of tourniquet shock. From the forensic aspects, these cytokines and chemokines are considered to be useful markers for the early diagnosis of tourniquet shock.

[The effect of escharectomy during burn shock stage on the expression of ICAM-1 and TNF-alpha mRNA of rat pulmonary tissue].

OBJECTIVE: To study the rules of postburn expression of IGAM-1 and TNF-alpha and the rule of the change in the MPO activity in pulmonary tissue; to explore the influence of escharectomy on the changes in the above indices and to clarify the importance of escharectomy during shock stage. METHODS: One hundred and seventy six Wistar rats with 30% TBSA III degree back scald were used. RT-PCR was used in the examination of the expression of pulmonary tissue ICAM-1 and TNF-alpha mRNA and of the change in pulmonary MPO activity after escharectomy. RESULTS: The expressions of pulmonary ICAM-1 and TNF-alpha mRNA began to increase at 4 hour postburn and reached peak level at 12 and 24 hours postburn, respectively. Their expressions returned to near control level 96 hours postburn in rats undergone escharectomy during shock stage. On the contrary, they remained at a relative high level even on 7th postburn day in both non-operated rats and the rats receiving escharectomy 96 hours postburn. In addition, pulmonary tissue MPO activity fell to near control level in rats undergone escharectomy during shock stage, but it maintained a high level in rats in which escharectomy was not done during shock stage. CONCLUSION: These findings suggest that eschar could induce the production of endothelial adhesion molecules. Therefore escharectomy as early as possible is very important to prevent the expression and release of adhesion molecules and the development of SIRS.

Inhibition of nitric oxide synthesis aggravates hepatic oxidative stress and enhances superoxide dismutase inactivation in rats subjected to tourniquet shock.

The role of nitric oxide (NO) on liver oxidative stress and tissue injury in rats subjected to tourniquet shock was investigated. This shock model differs from others in that injury is a consequence of remote organ damage. Liver oxidative stress becomes evident after hind limb reperfusion, as evidenced by the loss of total tissue thiols; by increases in tissue oxidized glutathione (GSSG), lipid peroxidation (LPO), plasma aminotransferases (alanine aminotransferase (ALT) and (aspartate aminotransferase (AST)), and plasma nitrites; and by a 36% loss in total superoxide dismutase (SOD) activity. Portal blood flow is reduced by 54.1% after 2 h of hind limb reperfusion. Inhibition of NO synthesis with Nomega-nitro-L-arginine methyl ester or L-arginine methyl ester increased mean arterial blood pressure; further reduced portal blood flow; and aggravated liver injury as assessed by further loss in total thiols, increased LPO and GSSG content, and further increases in plasma ALT and AST. Total plasma nitrites were lower than in control animals, and total tissue SOD activity decreased by more than 80%. Treatment with the NO donor sodium nitroprusside reverted the decrease in portal blood flow and also reverted tissue thiol loss, LPO, and GSSG increases, as well as the loss of ALT and AST to plasma and of SOD activity to levels comparable to untreated control shock animals. As expected, plasma nitrites were greater than in tourniquet control animals. These data support the hypothesis that endogenous NO formation protects the rat liver from the consequences of oxidative stress elicited by hind limb reperfusion in rats subjected to tourniquet shock.

Pteridine and nitrite/nitrate formation in experimental septic and traumatic shock.

Bacterial lipopolysaccharides (LPS) induce the activity of guanosine triphosphate (GTP)-cyclohydrolase I (GTP-CHI), the first enzyme in the biosynthesis of tetrahydrobiopterin (H4bip) from GTP in endothelial cells and macrophages. In these and other cells, LPS also acts costimulatory with cytokines, i.e., mainly tumor necrosis factor-alpha (TNF-alpha). H4bip is the cofactor for nitric oxide synthase (NOS). We were interested in comparing the pteridine and nitrate levels in two baboon models: a hyperdynamic sepsis model and a hemorrhagic traumatic shock model. Our results show a similar response of pteridines (H4bip, neopterin) and nitrite/nitrate levels to an immune stimulus. LPS, which peaks rapidly, induces a sustained increase in pteridine levels in septic animals. Since hemorrhagic animals show very little response in terms of cytokine production, it was not possible to measure the induction of neopterin and nitrite/nitrate. This information could aid our understanding of the regulatory mechanisms in various forms of experimental shock.

[The injury of liver and kidney of rats sustaining delayed fluid resuscitation of burn shock].

Delayed fluid resuscitation of burn shock may lead to many harmful effects. We investigated the injury of liver and kidney of rats sustaining non-fluid perfusion, immediate perfusion, and delayed perfusion of burn shock. The electron spin reonance (ESR) was used to determine the existence of oxygen free radicals (OFR) successfully. We tested the activity of ATP enzyme in kidney, lactate dehydrogenase isoenzyme 5 (LDH5), GPT and GOT. We also tested the contents of malonaldehyde (MDA) and ATP in liver and kidney, urea nitrogen (BUN) and creatinine (Cr) in blood. We found that OFR plays an important role in the injury of liver and kidney sustaining delayed fluid resuscitation of burn shock. Immediate fluid perfusion can not protect the liver and kidney perfectely. And some OFR scavengers should be added to the fluid resuscitation of burn shock.

[The injury of heart of rats sustaining delayed fluid resuscitation after burn shock].

Delayed fluid resuscitation of burn shock may lead to many harmful effects. We investigated the injury of heart of burned rats having no fluid resuscitation, immediate and delayed fluid replacement. We used electron spin resonance (ESR) to determine the presence of oxygen free radicals (OFR). We also found significant increase in malondialdehyde (MDA) in delayed resuscitation group. The activity of lactate dehydrogenase isoenzyme (LDH) and creatine phosphokinase isoenzyme (CPK-MB) were increased in the latter group. Immediate fluid replacement can not protect the heart perfectly. Some new measure should be added to the fluid replacement in burn shock.

[The pharmacokinetics of ceftazidime in the burned patients].

Pharmacokinetic studies were carried out following systemic administration of ceftazidime in ten burn patients (TBSA 30%-60% and with full-thickness burn) and six healthy volunteers. Dynamic ceftazidime concentrations in blood, urine and blister fluid were analysed by HPLC. The results showed that the burned patients, especially during their shock phase, some pharmacokinetics parameters differed from that of normal volunteers, in that the volume of distribution (0.45 +/- 0.06 L/kg vs. 0.23 +/- 0.05 L/kg) and non-renal clearance of drug (30.54 +/- 21.97ml.min-1 vs. 11.08 +/- 4.91 ml.min-1) increased, but the elimination of half-life was prolonged. The result indicated that it was not necessary to increase the dosage of ceftazidime in extensive burns in the early period. Burn blister fluid concentrations were higher than MIC. Ranging from 1.004-21.62 micrograms/ml, indicating that systemic ceftazidime could penetrate second-degree burn tissue in the early postburn stage.