The role of prostaglandin E2 in immune suppression following injury.

It has been thought for some time that prostaglandin E2 (PGE2) released from activated monocytes/macrophages may contribute to the suppression of immunity seen after burns and major injury because PGE2 inhibits the activation of T lymphocytes. To clarify this issue, we studied 15 patients with total body surface area burns of 20% to 90% (mean, 48%). Peripheral blood mononuclear cells (PBMC) were obtained from these patients one to two times each week for 1 month after burn and were stimulated with the T-cell mitogen phytohemagglutinin (PHA). On 14 occasions the PBMCs from eight patients were significantly suppressed (30% or more) in their response to PHA (suppressed [sup] burn) as compared with PBMCs from normal controls. In 38 instances PBMCs from 12 patients were not significantly suppressed in PHA (nonsuppressed [nonsup] burn). Sup burn PBMCs and control PBMCs were cultured with or without the addition of the cyclooxygenase (CO) inhibitor indomethacin (Indo, 1 microgram/mL) and studied for PHA response and the production of the stimulatory cytokine interleukin-2 (IL-2). Indo partially restored the PHA response of sup burn PBMCs to normal. Sup burn PBMCs also were deficient in production of IL-2. Indo increased IL-2 production by sup burn PBMCs significantly more (160% +/- 20%, p less than 0.005) than control (57% +/- 5%) and nonsup PBMCs (67% +/- 8%). Next inhibition of the PHA response of PBMCs from 12 burn patients and 17 controls was studied by exogenous PGE2. At all time periods after burn injury, patients' PBMCs were significantly more sensitive to inhibition by PGE2 (50% inhibition at 10(-8) mol/L [molar] PGE2) than PBMCs from normal controls (50% inhibition at 10(-6) mol/L PGE2) with maximum sensitivity occurring 8 to 14 days after injury. Peripheral blood mononuclear cells from patients with more than 40% burns were significantly (p less than 0.05) more sensitive to PGE2 than those from patients with lesser burns. Interleukin-2 was added to cultures of sup burn PBMC, nonsup burn PBMC, and controls containing 10(-7) mol/L PGE2. Interleukin-2 totally reversed PGE2 inhibition of the PHA response in PBMC from both controls and burn patients. Because endotoxin leak from the gut has been implicated as a trigger for a number of the metabolic and immunologic abnormalities following injury, the authors looked for the effect of a bolus infusion of Escherichia coli endotoxin (Endo, 4 ng/kg) in seven normal healthy volunteers on the response of PBMC to PHA and on the production of PGE2 and IL-2.(ABSTRACT TRUNCATED AT 400 WORDS)     

Suppressor T-cell levels are unreliable indicators of the impaired immune response following thermal injury.

The presence of increased levels of suppressor T cells after thermal injury and their relevance remain controversial. It is unclear whether suppressor T cells are the cause or result of sepsis complicating thermal injury. Spleen cells from a standardized murine burn model and sham burn controls were studied and the relationship between the levels of suppressor cytotoxic T cells (CD8, Lyt-2+), helper T cells (CD4, L3T4+), response to concanavalin A (ConA) and to phytohemagglutinin (PHA) and interleukin-2 (IL-2) production was examined. Mortality following infection via cecal ligation and puncture (CLP) of matched controls was also studied. At day 7 postburn, mean ConA (70 +/- 12% of control) and PHA response (58% +/- 5.2% of controls) and IL-2 production (43% +/- 5.4%) were significantly less than sham burn values (100%; p less than 0.05). However, the mean percentage of cells staining with anti-Lyt-2 and anti-L3T4 (9.1 +/- 0.59 and 13.9 +/- 0.65) was similar to the mean percentage in sham burn animals (9.4 +/- 0.65 and 16.6 +/- 1.1). Furthermore, no significant differences were observed between burned mice and controls in helper (17.3% +/- 1.8% burn vs. 21.2% +/- 1.7% sham) or suppressor cell levels (7.8% +/- 1.2% burn vs. 8.6% +/- 0.7% sham) or helper-suppressor ratios on day 10 postburn. Mortality of 20 litter-matched controls subjected to CLP on day 10 postburn was 90%, which was significantly greater than the sham burn mortality of 20%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Depressed immune response in burn patients: use of monoclonal antibodies and functional assays to define the role of suppressor cells.

Recent experimental evidence has suggested that circulating suppressor leukocytes play an important role in mediating the suppression of immunity seen in burn patients. In order to shed further light on the relationship between suppressor cells and depressed cellular immunity 22 patients were studied (mean age 37) who had suffered severe burns of greater than 30% body surface area. Simultaneous studies were performed on 14 control laboratory personnel (mean age 32). Monoclonal antibodies were used to identify T-lymphocyte subsets known to have suppressor/cytotoxic (OKT8) and helper/inducer (OKT4) function, respectively. In addition, serial measurements were made of the response of circulating lymphocytes to the T-cell mitogen phytohemagglutinin (PHA). An inversion of the normal ratio between suppressor/cytotoxic and helper/inducer subsets (normal 0.55:1, postburn 1.4:1; p less than 0.001) occurred soon after burn injury, reached a peak in five to seven days and then returned gradually to normal levels by 14 days. A diminished response of patients' lymphocytes to PHA (57 +/- 10% SD suppression as compared with normal controls at five to seven days) corresponded with high suppressor to helper cell ratios and returned to normal at the same time. Functional assays, which recognize only high levels of activity, demonstrated circulating suppressor cells in nine patients during this same period but became negative by 14 days. These early immunologic modulations were not predictive of morbidity or mortality. Later in the postburn course, systemic sepsis in eight patients was associated with a return of increased suppressor to helper cell ratios and decreased mitogen (PHA) responsiveness. At this time functional assays demonstrated circulating suppressor cells in six patients. Five of these six patients died of sepsis. It was concluded that severe burn injury regularly induces an early transient increase in circulating suppressor cells accompanied by a depression of lymphocyte activation. A later (greater than 14 days postburn) increase in suppressor cells to levels detectable by functional assays is closely correlated with mortality from sepsis.     

Temporal correlation of impaired immune response after thermal injury with susceptibility to infection in a murine model

Suppression of cellular immunity and increased susceptibility to sepsis frequently accompany thermal injury. However, a convincing association between the two has been difficult to establish in human beings. Therefore we chose to investigate the relationship of impaired cell-mediated immunity with susceptibility to sepsis in an animal model. We studied the response to phytohemagglutinin (PHA) and interleukin-2 (IL-2) production by splenocytes from mice subjected to a standard 25% scald burn and killed at intervals of 3, 5, 7, 10, 14, and 25 days after thermal injury. Burned mice were compared in all instances to sham-burn animals (i.e., animals that had been anesthetized and shaved but not burned). We also studied mortality after cecal ligation and puncture (CLP), as a septic challenge, in burned and control animals at the same postburn intervals. We found maximal suppression (50% to 55%) of the PHA response at 10 to 14 days after injury and maximum suppression (68%) of IL-2 production at 7 days. Both of these parameters returned to normal by postinjury day 28. Mortality after CLP increased gradually from control levels after thermal injury up to a maximum of 88% on postburn day 10 and also returned to control levels after 28 days after burn. Significant correlations were found between mortality after CLP in the postburn period and suppression of the PHA response, on the one hand, and the suppression of IL-2 production, on the other (r = 0.89 and 0.91, respectively; p less than 0.05). This result implies a causal relationship between impaired cell-mediated immunity and susceptibility to sepsis after burn injury.     

A comparison of conservative versus early excision. Therapies in severely burned patients.

Early excision and grafting of small burn wounds is a generally accepted treatment. Early excision of burn injuries greater than 30% total body surface area (TBSA) in adults, however, has not been universally accepted. In this study, 85 patients whose ages ranged from 17 to 55 years with greater than 30% total body surface area (TBSA) burns were randomly assigned to either early excision or topical antimicrobial therapy and skin grafting after spontaneous eschar separation. Mortality from burns without inhalation injury was significantly decreased by early excision from 45% to 9% in patients who were 17 to 30 years of age (p less than 0.025). No differences in mortality could be demonstrated between therapies in adult patients older than 30 years of age or with a concomitant inhalation injury. Children (n = 259) with similar large burns treated by early excision showed a significant increase in mortality with increasing burn size and with concomitant inhalation injury (p less than 0.05). The mean length of hospital stay of survivors was less than one day per per cent of TBSA burn in both children and adults.     

Changes in circulating levels of interleukin 6 in burned patients

Interleukin 6 (IL-6) levels in serial serum samples of 10 burned patients were analyzed. The total body surface areas (TBSA) of the burn injury varied from 30 to 85%. Among these 10 patients, five recovered and the other five, who were septic, expired. A significant difference in serum IL-6 values on admission (5-13 h postburn) was found (p < 0.05) between patients who survived or died from burn injury as analyzed by the Wilcoxon's rank sum test. In addition, a significant difference in serum IL-6 on admission was also found (p < 0.05) between patients with TBSA of greater or less than 50%. Afterwards, an initial peak serum IL-6 response was detected within 4 days postburn. Significant differences in the peak serum IL-6 levels were not found between patients with TBSA of greater or less than 50% and patients who survived or expired from burn injury. In the survivors, serum IL-6 remained low, while IL-6 increased markedly starting at about one to two weeks postburn in four of the five nonsurvivors with proven sepsis. Except for the patient who expired 42 days postburn, the maximum serum IL-6 values of the other four nonsurvivors were all greater than those of the five survivors from burn injury. Significant correlation (p < 0.05) relating the change in serum IL-6 and body temperature was observed in only two (one survivor and one nonsurvivor) of the ten patients. Changes in serum IL-6 were also compared with changes in circulating TNF-alpha and IL-8 determined previously. A similar pattern in the dynamic changes of circulating TNF-alpha, IL-8 and IL-6 was observed in the individual burned patient. An increase in serum levels of all three cytokines was detected postburn. Serum levels of three cytokines were significantly higher in the septic patients, who all died. It was considered that all three cytokines analyzed may play a significant role in the pathophysiology of sepsis in burned patients.     

Burn depth affects dermal interstitial fluid pressure, free radical production, and serum histamine levels in rats

BACKGROUND: We measured the amount of edema and the free radical production in burn-injured skin and the serum histamine levels, as well as changes in dermal interstitial fluid pressure. METHODS: Thirty-six Wistar rats with 20% total body surface area burns of different depth were resuscitated by lactated Ringer's solution intravenously. The rats were divided into a deep burn (DB) group (n = 12), a superficial dermal burn (SDB) group (n = 12), and a sham burn (Sham) group (n = 12). Dermal interstitial fluid hydrostatic pressure (Pif), total skin water and xanthine oxidase activity, and serum histamine levels were measured until 60 minutes postburn. RESULTS: In the DB group, dermal Pif significantly fell to -35.9 +/- 11.0 and -40.9 +/- 7.0 mm Hg at 10 and 15 minutes postburn, respectively (p < 0.05); it returned to preburn values at 50 minutes postburn. In the SDB group, dermal Pif was slightly negative but did not markedly change. Total skin water was significantly higher than that of the DB and the Sham groups; however, in the SDB group, serum histamine and dermal xanthine oxidase were significantly higher than in the DB group at 15, 30, and 45 minutes postburn (p < 0.05). CONCLUSION: The fluid-resuscitated DB produced a more negative dermal Pif than the SDB, but less dermal edema. In contrast, the SDB appeared to mainly generate dermal edema formation by wound free radical production and serum histamine release. The dermal Pif is one of the factors associated with edema formation immediately after deep burns. However, an increase in vascular permeability associated with oxygen radical production plays a more important role in dermal edema formation than does dermal Pif.     

Changes in T lymphocyte subsets following injury. Assessment by flow cytometry and relationship to sepsis.

The increased susceptibility of severely injured patients to infection and death from sepsis has been attributed to abnormalities in cell-mediated immunity. The authors therefore assessed the relative number of peripheral blood T helper cells and T suppressor/cytotoxic cells and total T lymphocytes identified by the monoclonal antibodies (McA) OKT4, OKT8, and OKT3, respectively, in 25 patients with burns from 5 to 85% total body surface area (TBSA) (mean: 40%) and 21 patients with nonthermal injuries (mean Injury Severity Score (ISS): 21.4). Patients were compared to 21 healthy controls. Cells reacting with the McA were detected by flow cytometry, which enabled the examination of a population of cells the size of T lymphocytes, excluding larger contaminating cells that might bind the McA. Patients with burns of 30% TBSA or greater had a significant reduction (p less than or equal to 0.05) in OKT3+ cells up to 50 days post-burn. Both septic and nonseptic burn patients had reduced numbers of OKT3+ cells, as did patients after nonthermal injury, suggesting that this reduction was due to the injury itself. Patients with smaller burns (less than 30% TBSA) as a group did not have reduced OKT4+ cells, whereas those with larger burns showed significant reductions in OKT4+ cells (P less than or equal to 0.05) at 0 to 5, 6 to 10, 11 to 20, 21 to 30, and 41 to 50 days post-burn. Seven burn patients who became septic 10 days post-burn or later had significantly lower OKT4+ cells within 10 days of injury (mean: 33.75% +/- 7.4 SEM) than 10 patients who remained free of sepsis (mean: 42.2% +/- 5.4, p = 0.004). Patients with uncomplicated nonthermal injuries failed to show any significant reduction in OKT4+ cells. Following thermal injury, a reduction in OKT8+ cells was observed up to 10 days in patients with burns less than 30% TBSA, and up to 20 days in patients with larger burns. In both groups, at no time were increased OKT8+ cells found to correlate with clinical events. In patients with nonthermal injury, OKT8+ cells generally remained near the normal range.     

Differential regulation of T- and B-lymphocyte activation in severely burned patients.

We studied the in vitro expression and regulation of the CD23 and CD25 (Tac) surface antigens by peripheral blood lymphocytes (PBL) from severely burned patients (burn injuries ranging from 25% to 72% TBSA) in order to evaluate T- and B-lymphocyte activation processes after thermal trauma. The spontaneous and cytokine (IL-4, IL-2)-induced expression of CD23 which represents a B-cell activation marker was significantly reduced during the second to fifth week postburn when compared to healthy donors. In contrast, CD25, which is expressed on activated T cells, showed a marked increase both spontaneously, indicating an in vivo activation, and after stimulation with IL-2 or PHA. Concomitantly, T-cell proliferation induced by PHA or Con A was suppressed. However, the number of T and B cells remained unchanged. The data demonstrate the impairment of early events in the lymphocyte program in severely burned patients. The activation of B cells is downregulated, since they become refractory to external helper signals. In addition, T cells are highly activated but fail to proceed to proliferation in response to mitogenic stimuli.     

Mechanism of prevention of postburn hypermetabolism and catabolism by early enteral feeding.

This study was performed to investigate the mechanism whereby immediate enteral feeding after burn injury reduces postburn hypermetabolism and hypercatabolism. Fifty-seven burned guinea pigs (30% TBSA) were divided into three groups: A (N = 19), given 175 kcal/kg/day beginning 2 hours after burn; B (N = 20), given 175 kcal/kg/day with an initial 72-hour adaptation period; and C (N = 18), given 200 kcal/kg/day with the same adaptation period as B. Resting metabolic expenditure (RME) on PBD 13 was lowest in group A (109% of preburn level), compared with group B (144%, p less than 0.001) and group C (137%, p less than 0.01). On PBD 1, group A had the greatest jejunal mucosal weight and thickness (p less than 0.001), and mucosal weight had negative correlations with plasma cortisol (r = 0.829, p less than 0.001) and glucagon (r = 0.888, p less than 0.001). Two weeks after burn, urinary vanillyl mandelic acid (VMA) excretion, plasma cortisol, and glucagon were lowest in group A (p less than 0.05 to p less than 0.01). These hormones also significantly correlated with RME (p less than 0.01 to p less than 0.001). These findings suggest that immediate postburn enteral feeding can prevent hypermetabolism via preservation of gut mucosal integrity and prevention of excessive secretion of catabolic hormones.     

Postburn immunosuppression in an animal model. IV. Improved resistance to septic challenge with immunomodulating drugs

We have previously demonstrated that certain pharmacologic agents administered to burned mice will restore cell-mediated immunity, as evidenced by measurement of delayed hypersensitivity responses and determination of splenic helper/suppressor lymphocyte ratios. These drugs are systemic cimetidine, ibuprofen, cyclophosphamide, and topical cerium nitrate. In the studies reported here we performed cecal ligation and puncture (CLP) in burned mice as a measure of resistance to infectious challenge. Survival after CLP with a 23-gauge needle used for puncture was markedly decreased when performed on the tenth postburn day (normal 63.7%, 10 days postburn 20.0%; p less than 0.001), but survival was not decreased when CLP was performed on the fifth (60.0%; p not significant) or twenty-first postburn day (65.3%; p not significant). Animals were then treated with the four agents in carefully defined dosage regimens, and survival was again determined on the tenth postburn day. Survival figures with p values compared to burned, untreated animals: burn plus cimetidine 62.2%, p less than 0.0005; burn plus: ibuprofen 64.7% p less than 0.0003; burn plus cyclophosphamide 68.2%, p less than 0.0001; burn plus cerium nitrate 54.1%, p less than 0.004. Specific pharmacologic therapy in burned mice in dosage regimens that have been shown to improve cell-mediated immunity is also able to significantly improve resistance to subsequent infectious challenge.     

Changes in levels of serum IL-8 in burned patients

Interleukin (IL)-8 levels in serial serum samples of 10 burned patients were analysed. The total body surface areas (TBSAs) of the burn injury ranged 30 to 85 per cent. Of these ten patients, five recovered and the other five, who were septic, died. On admission at about 5–13 h postburn, one of the five survivors and two of the non-survivors had serum IL-8 levels higher than 18.1 pg/ml, which is the detection limit of the IL-8 assay kit. The serum IL-8 values of six healthy laboratory personnel included in the present study were all less than 18.1 pg/ml. Afterwards, an initial peak serum IL-8 response was detected within 2–4.5 days postburn. Significant differences in the peak serum IL-8 levels were not found between patients with TBSAs of greater or less than 50 per cent and patients who survived or expired from burn injury. In the survivors, serum IL-8 remained low, whereas IL-8 increased markedly, starting at about one week postburn in four of the five non-survivors with confirmed sepsis. Significant differences in the maximum serum IL-8 levels were detected between patients who recovered vs. those who died from the thermal injury. In conclusion, the results showed that there was an increase in serum IL-8 postburn. Serum IL-8 was significantly higher in the septic patients, who all died. This cytokine may play a significant role in the pathophysiology of sepsis in burned patients.     

大鼠烧伤后心肌局部肾素—血管紧张素系统的改变

目的 观察烧伤早期心肌局部肾素－血管紧张素系统（RAS）变化及其对心肌肌浆网（SR）钙运转功能的影响,探讨烧伤早期心功能障碍的发病机制。方法 大鼠随机分为对照组（8只,不予致伤）,烧伤组（40只,致30％Ⅲ度烧伤）,治疗组（40只,Lisinopril灌胃3天后致30％Ⅲ度烧伤）,测定烧伤前（对照组）及烧伤后3,8,24h左心功能变化,心肌组织血管紧张素转换酶（ACE）活性,血管紧张素Ⅱ（AⅡ）及钙离子（Ca^2 ）含量变化,测定心肌SR Ca^2 -ATPase活性,及SR Ca^2 运转功能的变化。结果 烧伤组大鼠左心室内压变化最大速率（±dp/dtmax)明显降低,心肌组织ACE活性、AⅡ及Ca^2 含量显著增加,心肌SR Ca^2 -ATP活性降低,SR Ca^2 摄取减少。治疗组预防性给予ACE抑制剂Lisinopril可显著降低烧伤后心肌组织ACE活性,减少A Ⅱ产生,Ca^2 含量降低,增加SR Ca^2 -ATPase活性,SR Ca^2 摄取增加,左心室功能明显改善。结论 烧伤早期心肌局部RAS迅速激活,抑制SR Ca^2 运转,可能是心肌RAS促进烧伤早期心功能障碍的作用机制之一。     

p38丝裂原活化蛋白激酶信号转导通路在严重烧伤大鼠枯否细胞肿瘤坏死因子α和白细胞介素1β产生中的作用

目的 探讨p38丝裂原活化蛋白激酶(MAPK)信号转导通路在严重烧伤大鼠枯否细胞(KCs)促炎性细胞因子肿瘤坏死因子α(TNF-α)和白细胞介素1β(IL-1β)产生中的作用。方法 健康成年的雄性SD大鼠32只,随机分为：假烫组;假烫 SB203580组;烧伤对照组;烧伤 SB203580组,每组8只。假烫或烧伤24h后分离出肝脏KCs,培养18h后加入50ng／ml的LPS进行刺激,18h后取上清液,用酶联免疫吸附法(ELISA)测定TNF-α和IL-1β的含量,并收集KCs,实时逆转录聚合酶链反应检测KCs内TNF-α和IL-1β mRNA表达的改变,蛋白印迹(Western blot)法检测KCs中p38MAPK和JNK活性的变化。结果 烧伤大鼠分离出的KCs培养上清液中TNF-α和IL-1β含量、KCs中TNF-α和IL-1β mRNA的表达均较假烫组的明显增强,同时KCs中p38 MAPK活性和JNK活性升高,SB203580能显著抑制大鼠KCs上清液中TNF-α和IL-1β含量、KCs中TNF-α和IL-1β mRNA的表达和p38MAPK活性的升高,对JNK活性无影响。结论p38MAPK信号转导通路介导了严重烧伤大鼠KCs促炎性细胞因子TNF-α和IL-1β的产生。     

Postburn pancreatitis.

OBJECTIVE: The authors examined the prevalence and complications of pancreatitis in severely burned patients. Factors predictive for the development of pancreatitis after burns are considered. SUMMARY BACKGROUND DATA: Pancreatitis has been documented at necropsy after burns; however, it is not clinically recognized as a common complication of burn injury. Recent improvements in survival rates could yield previously unrecognized complications, such as pancreatitis, particularly in those patients who previously would have not survived. The hypothesis is that pancreatitis is a frequent complication after major burn injury and causes significant morbidity for patients with large burns. METHODS: This retrospective review of adult patients with large burns examines postburn pancreatitis using stepwise logistic regression analysis. RESULTS: Forty-nine of 121 (40%) patients developed hyperamylasemia or hyperlipasemia well after the admission period (23 +/- 3 days), and all enzyme abnormalities were temporally associated with emerging infections. Most of these patients (40/49, 82%) had symptoms of pancreatitis. Three patients (6%) had pancreatic pseudocysts or abscesses. Inhalation injury (p = 0.0001), associated trauma (p = 0.0311), and escharotomy (p = 0.0415) were risk factors for pancreatitis. Using Fischer's exact test, patients with pancreatitis had increased mortality and length of stay. Patients with high enzyme elevations and > or = 50% body surface area burned were at severe risk of pancreatic pseudocyst or abscess development (43%; 90% confidence interval of 23-77%). CONCLUSIONS: Pancreatitis is a frequent complication after large burn injuries. Patients at high risk for pancreatitis complications should receive surveillance examinations during their acute hospitalization.     

Low plasma fibronectin indicates septicaemia in major burns

Plasma fibronectin was measured by laser nephelometry in 23 patients with 20--85% burns. Control measurements were made in 118 healthy blood donors aged 18--60 years. The reference level was significantly higher in the 72 males (mean +/- SD = 377 +/- 70 mg/l) than in the 46 females (327 +/- 55 mg/l). In the burn-injured patients the mean fibronectin concentration was significantly lower than the reference values for one week after the injury. All the patients had low concentrations, about 70% of their respective reference means, in the first 24 hours after the injury. When burn treatment was successful, the fibronectin thereafter increased, gradually exceeding the reference level. Patients with septic complications, by contrast, showed further reduction of fibronectin levels. In the patients who died, the fibronectin concentration 6--10 days after burn injury was significantly less than in the patients who survived. On the basis of these results, repeated analysis of plasma fibronectin in the early postburn period is recommended. Persistent fibronectin deficiency then is an indicator of imminent septicaemia, vital organ failure and risk of fatal outcome.     

大鼠烧伤后心肌局部肾素-血管紧张素系统的改变

目的观察烧伤早期心肌局部肾素血管紧张素系统（ＲＡＳ）变化及其对心肌肌浆网（ＳＲ）钙运转功能的影响,探讨烧伤早期心功能障碍的发病机制。方法大鼠随机分为对照组（８只,不予致伤）,烧伤组（４０只,致３０％Ⅲ度烧伤）,治疗组（４０只,Ｌｉｓｉｎｏｐｒｉｌ灌胃３天后致３０％Ⅲ度烧伤）,测定烧伤前（对照组）及烧伤后３,８,２４ｈ左心功能变化,心肌组织血管紧张素转换酶（ＡＣＥ）活性,血管紧张素Ⅱ（ＡⅡ）及钙离子（Ｃａ２＋）含量变化,测定心肌ＳＲＣａ２＋ＡＴＰａｓｅ活性,及ＳＲＣａ２＋运转功能的变化。结果烧伤组大鼠左心室内压变化最大速率（±ｄｐ／ｄｔｍａｘ）明显降低,心肌组织ＡＣＥ活性、ＡⅡ及Ｃａ２＋含量显著增加,心肌ＳＲＣａ２＋ＡＴＰａｓｅ活性降低,ＳＲＣａ２＋摄取减少。治疗组预防性给予ＡＣＥ抑制剂Ｌｉｓｉｎｏｐｒｉｌ可显著降低烧伤后心肌组织ＡＣＥ活性,减少ＡⅡ产生,Ｃａ２＋含量降低,增加ＳＲＣａ２＋ＡＴＰａｓｅ活性,ＳＲＣａ２＋摄取增加,左心室功能明显改善。结论烧伤早期心肌局部ＲＡＳ迅速激活,抑制ＳＲＣａ２＋运转,可能是心肌ＲＡＳ促进烧伤早期心功能障碍的作用机制之一。     

Protein loss across burn wounds

One factor contributing to negative nitrogen balance in burned patients is protein loss through the burn wound. There is, however, little information on the amount and type of protein lost by this route. This study was designed to quantitate protein loss through burn wounds. Multiple full- and partial-thickness burns on 29 patients were studied. Sampled burn sites were dried and occlusive sponge dressings (2' X 2') were applied and left in place for 1 hour. The central 1 square-inch portion of the dressing was then removed, rinsed in distilled water, and total protein, albumin, and globulin were measured in the water wash. Considerable protein losses were measured. These losses were greatest in the first 3 postburn days, being somewhat greater in full-thickness burns (0.98 +/- 0.82 mg/cm2/hr) compared to partial-thickness burns (0.59 +/- 0.41 mg/cm2/hr) during this period mean +/- SD). Subsequent to the first 3 postburn days, protein loss in all burn types decreased to a relatively steady rate of loss of approximately 0.25 mg/cm2/hr. Based upon these data, average daily protein losses during the first postburn week can be estimated by the following equation: 24-hour protein loss through burn surface (gm) = 1.2 X body surface area (m2) X % burn (%). On subsequent days, protein is lost at approximately half this rate. These data demonstrate significant protein losses through burn wounds greater than recent studies have considered. It is possible that inadequate nutritional replacement of these protein losses is partly responsible for the marked negative nitrogen balance of the early postburn period.