大鼠烧伤早期肝功能及超微结构改变和药物保护作用的观察

为探讨烧伤及液体复苏后肝损害以及药物的保护作用,采用大鼠30%TBSAⅢ度烫伤模型,将126只 Wistar 大鼠随机分为正常对照组、早期复苏组、早期复苏 药物治疗组、延迟复苏组、延迟复苏 药物治疗组及不治疗组。观察烧伤后6,12,24及48小时血清 ALT、AST 含量变化,同时对肝细胞光镜及电镜下组织病理学改变进行了观察。结果表明:早期复苏及延迟复苏组血清 ALT、AST 及肝细胞形态均出现异常,ALT 在伤后6小时即显著升高,24小时达到峰值水平,AST 变化与 ALT 相似。病理检查显示肝细胞有不同程度损害。给予爱维治药物治疗后,上述损害均得到改善。结果提示:肝脏是烧伤早期易受损伤的器官之一,延迟复苏将进一步加重肝组织损伤;爱维治有益于保护肝细胞结构和功能。     

家兔吸入性损伤早期应用高氧平衡盐溶液的观察

目的探讨高氧平衡盐溶液在家兔吸入性损伤早期的治疗效果及其作用机制. 方法将77只家兔随机分为4组正常组(5只),不致伤;平衡盐溶液治疗组(24只),致伤后连续10 d补充平衡盐溶液;高氧液治疗组(24只),致伤后连续10 d补充高氧平衡盐溶液;对照组(24只),致伤后不治疗.致伤的3组家兔又于伤后1、2、3、5、7、10 d 6个时相点下观察,每时相点4只.观察各组兔呼吸情况及生存率,检测其动脉血气分析、白细胞及分类、肺湿干重比、肺组织丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性,观察肺组织的病理改变. 结果各致伤组兔伤后立即出现呼吸频率增快、张口呼吸、鼻翼扇动、咳嗽频繁,口、鼻腔分泌物增多,肺部可闻及干、湿性啰音.伤后10 d,对照组、平衡盐溶液治疗组、高氧液治疗组兔生存率分别为13.3%、27.8%、65.6%.血气分析结果均显示为代谢性酸中毒.各致伤组各时相点二氧化碳分压、白细胞、中性粒细胞、肺湿干重比、肺组织MDA等指标均较正常组升高,其顺序为对照组>平衡盐溶液治疗组>高氧液治疗组>正常组;而pH值、氧分压、SOD等指标均较正常组降低,其顺序为对照组<平衡盐溶液治疗组<高氧液治疗组<正常组(P<0.05).肺组织病理结果显示,家兔伤后肺体积明显增大,光镜下可见肺组织结构呈炎性改变,高氧液治疗组肺部损伤的范围及程度均较其他致伤组明显缩小或减轻. 结论早期应用高氧平衡盐溶液,对治疗吸入性损伤有明显的疗效.     

烧伤后早期应用不同液体复苏血钠和红细胞变化的临床研究

目的　观察烧伤后早期应用不同液体复苏患者血钠和红细胞的变化。方法　将 15 0例烧伤患者分为 3组 ,A组为中、小面积烧伤患者 5 0例 ,给予平衡盐溶液 (钠离子 130mmol/L)复苏 ;B组为大面积烧伤患者 5 0例 ,液体复苏方法同A组 ;C组为大面积烧伤患者 5 0例 ,给予高渗乳酸钠溶液 (钠离子 174mmol/L)复苏。观察伤后 1～ 3d患者的补液总量、血钠、红细胞数量及红细胞平均体积 (MCV)的变化。对A、B组患者的烧伤指数 (BI)与其伤后 1d的血钠值作相关性分析。　 结果　伤后 3d内A组患者补液总量、补钠量均低于其他两组 (P <0.0 1);C组补液总量低于B组 ,而补钠量多于B组 (P <0.0 1)。伤后 3d内B组血钠值接近正常值下限 ,C组血钠值接近正常值上限 ,前者明显低于后者 (P <0.0 5或 0 .0 1)。伤后 3d内B、C组的红细胞数量相近 (P >0.0 5 )。伤后 1dB、C组患者的MCV分别为 (95 .5± 5 .5 )、(92 .1± 4 .5 )fl,伤后 2d各为 (93.2± 6 .4 )、(90 .9± 5 .4 )fl,组间比较差异无显著性意义 (P >0.0 5 )。A、B组患者伤后 1d的血钠值与自身BI呈负相关 (r=- 0 84,P<0.0 1)。　 结论　大面积烧伤患者伤后早期采用高渗盐溶液复苏 ,血钠值平稳且红细胞的肿胀程度较轻     

吸入性损伤早期应用高氧平衡盐溶液的临床疗效观察

目的观察吸入性损伤早期应用高氧平衡盐溶液的临床治疗效果,探讨液体给氧这一临床治疗新途径在烧伤早期的治疗作用. 方法随机选取烧伤总面积>30%TBSA、伴中度吸入性损伤的患者8例,设为治疗组;对照组选病情相似者4例.治疗组患者伤后每日静脉输入高氧平衡盐溶液1 500 ml,连续7 d,对照组静脉输入等量的单纯平衡盐溶液.观察两组患者的生命体征、血生化指标和血气分析. 结果与对照组相比,治疗组生命体征较平稳,血生化指标变化幅度轻,动脉氧分压高且差异有显著性意义(P<0.05). 结论吸入性损伤早期应用高氧平衡盐溶液有明确的疗效,这种液体给氧方式在烧伤早期救治中可能成为一种新的有效的治疗途径.     

抑制应激对严重烧伤大鼠炎症反应的影响

目的　观察冬眠药物对严重烧伤大鼠应激和炎症反应的影响。方法　SD大鼠 30 %TBSA深Ⅱ度烧伤 ,分为烧伤立即复苏组 (A组 ,30只 )、烧伤立即复苏冬眠合剂组 (B组 ,30只 )、烧伤延迟复苏组 (C组 ,30只 )、烧伤延迟复苏冬眠合剂组 (D组 ,2 5只 )、对照组 (假烧伤 ,E组 ,6只 )。高效液相色谱法检测伤后 3、6、12、2 4和 4 8h大鼠血浆中去甲肾上腺素 (NE)、肾上腺素 (E)和多巴胺 (DA)含量 ,ELISA和RIA法测定血浆IL 1α和PGE2 水平 ,激光共聚焦显微镜定位分析单个核细胞 (PBM Cs)中核因子 κB(NF κB)活性。　结果　血浆NE水平于伤后 6h达高峰 ,同一时相B组最低。血浆E水平亦于伤后 6h达高峰 ,B组峰值较其他组低。血浆DA水平在各组间和各时相点差异无统计学意义。伤后血浆IL 1α和PGE2 水平持续上升 ,同一时相B组低于A组 ,D组低于C组 ;同一时相B、D两组比较 ,B组低于D组。E组NF κB位于PBMCs胞浆中 ,A组伤后 6hNF κB以胞核浓度为高 ;B组胞浆和胞核中均有NF κB ,但以胞浆浓度为高 ;C或D组NF κB浓集于胞核内。　结论　冬眠药物能减少严重烧伤大鼠应激激素的分泌 ,可调节PBMCs的NF κB核移位和降低血浆炎症细胞因子水平     

TNF-α McAb对急性失血性休克大鼠肝脏的作用

目的探讨肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)在急性失血性休克大鼠肝损伤中的作用及TNF-α单克隆抗体的保护作用。方法将24只雄性SD大鼠随机均分为三组:对照组(A组)、休克+乳酸林格氏液复苏组(B组)和休克+TNF-α单克隆抗体复苏组(C组)。B和C组大鼠通过股动脉放血,制作急性失血性休克动物模型;B组用乳酸林格氏液复苏,C组用含TNF-α单克隆抗体(3mg/kg)的乳酸林格氏液复苏,而A组在同等条件下不进行失血。分别检测各组大鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、TNF-α水平和肝组织中MDA、SOD含量,并在光镜和电镜下观察各组大鼠肝组织的病理变化。结果 B、C组大鼠血清ALT、AST、TNF-α水平和肝组织中MDA含量较A组升高,SOD含量降低;C组ALT(343.63±35.61)U/L、AST(748.75±49.76)U/L、TNF-α(99.38±13.16)pg/mL、丙二醛(26.33±1.30)nmol/mgProt较B组ALT、AST、TNF-α、MDA含量降低,C组肝组织中SOD含量(510.14±47.44)U/mgProt较B组升高;在光镜、电镜下观察,C组肝组织损伤较B组减轻。结论 TNF-α可能是急性失血性休克肝损伤的重要因子之一,使用TNF-αMcAb复苏可以减轻失血性休克时大鼠肝损伤,具有一定的保护作用。     

一氧化氮/内皮素平衡关系与移植肝功能的相关研究

目的　研究大鼠肝移植术后早期一氧化氮 (NO ) /内皮素 (ET )平衡关系的改变 ,探讨其与肝功能的相关性 ,观察前列腺素E1 (PGE1 )的干预作用。方法　大鼠随机分为 4组 (各组n =8) :(1)正常对照组 (A组 ) ;(2 )手术对照组 (B组 ) ;(3 )实验组 (C组 ) ;(4 )PGE1 干预组 (D组 )。采用“双袖套法”建立肝移植模型。检测和比较受体术后 6h血液ALT ,AST ,NO和ET水平 ,观察肝脏组织学改变。结果　术后 6hB ,D组全部存活 (10 0 % ) ,C组存活 5只 (62 .5 % )。与C组比较 ,D组ALT ,AST ,ET明显降低 (P <0 .0 5 ) ,NO明显升高 (P <0 .0 5 )。NO ,ET及NO /ET值与ALT呈现明显的相关性 (依次为r =-0 .681,0 .793和 -0 .73 2 )。C组肝脏见明显的组织学损害 ,B ,D组组织结构基本保存完好。结论　肝移植术后早期血液NO ,ET水平及NO /ET比例关系 ,较好地反映了肝脏内皮细胞的功能状况。PGE1 可减轻肝血窦内皮细胞的损害 ,保护了移植肝功能。     

严重烧伤后早期肝细胞内外钠离子分布的研究

目的　深入了解严重烧伤后体内钠离子分布的特点 ,为进一步改良复苏方案、提高复苏疗效提供实验依据。方法　成年Sprague Dawley大鼠随机分为假伤组 (12只 )和烧伤组 (7只 ) ,烧伤组动物造成体表面积 4 0 %Ⅲ度烫伤 (以下称烧伤 ) ,按Parkland公式通过颈静脉插管进行液体复苏治疗。假伤组动物行颈静脉插管但不予补液 ,并用 37℃温水模拟烫伤过程。伤后 2 4h用2 3 Na 磁共振波谱技术在活体上直接检测肝细胞内区域和肝细胞外区域钠离子含量的变化 ,并通过测定2 3 Na 磁共振横向弛豫时间 (T2 )了解细胞内、外钠离子的存在状态。　结果　烧伤后 2 4h烧伤组大鼠肝细胞外的钠离子含量较假伤组减少 17%。烧伤组大鼠肝细胞外的2 3 Na 磁共振横向快弛豫时间 (T2f)不变 ,但在总横向弛豫时间中所占比值增加 ,提示细胞外基质中钠的结合位点相对增加 ;细胞内钠离子含量增加 5 7% ,但磁共振横向弛豫时间和快、慢T2 成分相对比值不变 ,提示细胞内分解代谢产物增加 ,以至细胞内基质中钠离子结合位点与钠离子含量成比率增长。　结论　严重烧伤早期 ,远隔部位肝脏器官的细胞外钠离子可因部分丢失于细胞内区域和钠离子结合位点增多而至相对不足     

高原烧伤大鼠脑损伤与丙二醛、超氧化物歧化酶含量变化

目的 观察高原严重烧伤延迟复苏后早期大鼠脑组织中丙二醛及超氧化物歧化酶含量变化及其与脑损伤的关系.方法 130只雄性Wistar大鼠设计高原(海拔3800 m)烧伤实验动物模型(TBSA 30%,Ⅲ度),并随机分4组:A组(高原烧伤即时复苏组)、B组(高原烧伤延迟复苏组)和C组(高原正常对照组),同时设D组(兰州地区正常对照组)(海拔1517 m).采用分光光度比色法检测脑组织中超氧化物歧化酶(SOD)的活性及丙二醛(MDA)的含量,采用干、湿重比重法测定脑组织含水量,运用末端脱氧核苷酸介导的X-dUTP缺口末端标记法(TUNEL)测定脑皮质细胞凋亡阳性细胞数.结果 A组大鼠脑组织中SOD活性于烧伤后24 h降至最低(90.45±14.78),B组大鼠腩组织中SOD活性除烧伤后12h外各时相点均低于A组(P<0.05).高原烧伤后大鼠脑组织中MDA含量即显著升高,于烧伤后12 h达最高峰(10.63±4.98),其后逐步降低至正常水平;B组大鼠脑组织中MDA含量变化趋势同A组,但于伤后7 d仍处于较高水平.脑组织含水量于伤后6 h开始升高,于24 h达高峰(71.70±2.32),于伤后7 d降至正常水平;B组变化趋势同A组.脑皮质TUNEL阳性细胞在伤后1 h即增多,于伤后24 h达高峰(233.33±16.22),于伤后7 d仍高于正常水平.结论 高原严重烧伤及延迟复苏后,脑组织中脂质过氧化物增加及超氧化物歧化酶耗竭,表明其可能参与了高原严重烧伤延迟复苏脑损伤的发生.     

高氧复方氯化钠溶液用于大鼠烧伤后休克的观察

目的观察并探讨高氧复方氯化钠溶液对烧伤休克的防治作用. 方法 (1)将Wistar大鼠分为6组,A组正常对照组;B组制作30%TBSAⅢ度烧伤模型,伤后1 h补充复方氯化钠溶液;C组致伤后6 h补充复方氯化钠溶液;D组伤后1 h补充高氧复方氯化钠溶液;E组伤后6 h补充高氧复方氯化钠溶液;F组致伤后不治疗.动态观察各组大鼠内毒素(LPS)、白细胞介素6(IL-6)、二胺氧化酶(DAO)活性、D-乳酸、丙二醛(MDA)的变化.(2)选择烧伤面积为50%～69%TBSA、伤后3 h内入院的患者,随机分为治疗组补充高氧复方氯化钠溶液;对照组补充复方氯化钠溶液.观察患者休克期变化、经皮氧分压、血红蛋白、血细胞比容及有无并发症等. 结果大鼠伤后各组监测指标水平均较A组显著升高,呈逐步上升趋势,F组更加明显,其顺序为F组>C组>B组>E组>D组(P＜0.05).烧伤患者治疗组较对照组休克期度过平稳,补液量减少,氧分压明显升高,并发症少,但血氧饱和度差异无显著性意义. 结论早期应用高氧复方氯化钠溶液,对防治烧伤休克有较好的疗效.     

Experimental study on early multiple organ failure after severe burns]

Forty-three male mongrel dogs (12.5 +/- 2.5 kg) were divided into normal control (n = 7), immediate infusion (n = 8), non-infusion (n = 13) and delayed infusion (n = 15) groups. A 50% TBSA third degree surface burn was produced by igniting 3% napalm for 30 seconds on the shaved back. Cardiac, pulmonary, hepatic, renal and gastrointestinal functions were monitored following the thermal injury. The findings of these studies showed that mean arterial pressure, cardiac index, left ventricular work, right ventricular work, ADP/O ratio and ATP were all significantly decreased (P less than 0.05). However pulmonary artery wedge pressure, pulmonary vascular resistance, systemic vascular resistance, P(A-a)O2, Beef, Cr, UN, ALT, LDH, TB, DB, and MDA were markedly increased (P less than 0.05). Severe shock occurred soon after burns. Thirteen dogs died within 12 hours in the non-infusion group. All the dogs were resuscitated when immediate infusion of lactic acid Ringers solution was given according to Parkland formula, and all of them tide over shock stage smoothly without obvious changes in visceral functions. However, dogs were not resuscitated when infusion was delayed 6 hours postburn. The changes in visceral were even more severe in this group than those in non-infusion group. These results demonstrated that delayed resuscitation was an important factor of MOF in the early postburn stage. The marked increase in MDA in the myocardiac, lung, liver, renal and gastrointestinal tissues indicated that lipoperoxidation by free oxygen radicals was closely related with visceral damages.(ABSTRACT TRUNCATED AT 250 WORDS)     

早期手术对烧伤大鼠肝血流量的影响

目的通过测定 TBSA30％Ⅲ度烧伤大鼠早期手术后肝血流量的变化,了解早期手术对肝脏血液灌流的影响。方法 Wistar 雄性大鼠34只,分为4组:烧伤组(A 组),输液组(B 组),早期手术组(C 组),正常对照组(D 组)。输液组经股静脉插管输入乳酸林格氏液;早期手术组于立即补液的同时行切痂同种异体植皮术。各组于伤后0,0.5,1,2,3,6,12和24小时,应用氢清除法测定肝血流量。结果 A 组与 B 组伤后均出现肝血流量显著下降,B 组直至伤后24小时肝血流量才恢复正常,而 C 组伤后肝血流量保持相对稳定,与正常对照组比较无显著意义。结论严重烧伤后立即液体复苏尚不足以维持有效的肝脏血流灌流,烧伤后早期手术尽早地去除焦痂组织,对改善肝血流量具有重要作用。     

犬烧伤休克延迟复苏的实验研究

目的探讨应用林格液进行烧伤休克延迟复苏的效果.方法12只犬随机分为对照组(S组,6只)和治疗组(LR组,6只).LR组采用35%TBSAⅢ度烧伤模型,伤后6h以乳酸林格液进行复苏,并以尿量为1.0ml@kg-1@h-1及心输出量为伤前值的70%～80%来调整输液速度及输入量,观察其在伤后第一个24h复苏中的容量负荷、平均动脉压(MAP)、左心室收缩压(LVSP)、左室内压最大上升/下降速率(±dp/dtmax)、心脏排血指数(CI)、氧供给(DO2)及氧消耗(VO2)等的变化.结果乳酸林格液在烧伤休克延迟复苏后第一个24h的复苏中,每1%烧伤面积的输液量为(887±1.02)ml/kg,比采用Parkland公式复苏多1.2倍,其中在复苏后4h内的输液量为(3.63±0.99)ml/kg,为总入量的41%;MAP、LVSP、±dp/dtmax、CI、DO2及VO2等指标在复苏后2h即达到或接近对照组水平.结论乳酸林格液在烧伤休克延迟复苏中,比早期复苏需要更多的液体量才能满足需求,而血流动力学、心肌功能及氧动力学等在复苏后2h即有明显改善.     

巯基丙酰甘氨酸对严重烫伤延迟复苏大鼠氧自由基作用的观察

目的　观察严重烫伤大鼠延迟复苏后氧自由基的损伤及巯基丙酰甘氨酸 (硫普罗宁 )的保护作用。　方法　制作大鼠 30 %Ⅲ度烫伤模型 ,分为延迟复苏组、巯基丙酰甘氨酸治疗组 ,应用电子自旋共振仪 (ESR)检测技术和传统间接检测手段 ,观察伤后 2 4、4 8h血浆及烧伤水肿液中超氧化物歧化酶 (SOD)、丙二醛 (MDA)变化 ,同时观察心、肝、肾、小肠的病理形态变化 ,检测血生化指标。设不烫伤大鼠为正常对照组。　结果　延迟复苏组大鼠较正常对照组血浆SOD含量下降 ,血浆及水肿液MDA明显升高 ,各脏器病理形态及血生化指标明显改变。巯基丙酰甘氨酸治疗组大鼠较延迟复苏组SOD增高 (P <0 .0 1) ,血液及痂下水肿液MDA含量下降 (P <0 .0 5 ) ,脏器病理形态及血生化指标有所改善。　结论　严重烫伤大鼠延迟复苏后存在氧化应激损伤 ,应用巯基丙酰甘氨酸治疗有一定保护作用     

The effects of diaspirin cross-linked hemoglobin on hemodynamics, metabolic acidosis, and survival in burned rats

OBJECTIVE: Diaspirin cross-linked hemoglobin (DCLHb) is a vasoactive hemoglobin-based oxygen carrier or "blood substitute" that has been shown to improve base deficit in several experimental studies of hemorrhagic shock. Our objective was to determine if the addition of DCLHb to the resuscitation regimen would improve hemodynamic parameters, metabolic acidosis, and survival in our rat burn shock model compared with currently used resuscitation therapy. METHODS: This was a randomized, controlled, experimental rat study. Male Wistar rats, weighing 200 to 250 g, were surgically prepared for an acute study. After placement of indwelling catheters, baseline hemodynamic values (mean arterial pressure, cardiac output, systemic vascular resistance, stroke volume, and base excess) were obtained. Thirty-two rats were used in the study, and they were either subjected to a 30% scald burn (experimental group) or sham burned (control group). The experimental animals were immediately intravenously resuscitated and followed for 6 hours. The resuscitation was based on the Parkland formula (4 mL/kg for each 1% of total body surface area [TBSA] burn), with 50% of the calculated fluid amount to be administered at a constant rate during the first 8 hours after burn. The animals were resuscitated for 6 hours and received between 9.00 and 11.25 mL of fluid depending on weight. The experimental animals were randomly assigned to one of three treatment groups: group I, lactated Ringer's solution; group II, lactated Ringer's solution-human serum albumin; group III, lactated Ringer's solution-DCLHb. Group I (n = 8) received 4 mL/kg lactated Ringer's solution for each 1% of TBSA burn. Group II (n = 8) received 2 mL/kg lactated Ringer's solution and 2 mL/kg human serum albumin for each 1% of TBSA burn. Group III (n = 8) received 2 mL/kg lactated Ringer's solution and 2 mL/kg DCLHb for each 1% of TBSA burn. The sham group (n = 8) was not burned and was not resuscitated. Animals that survived up to 6 six hours were killed. RESULTS: We found that mean arterial pressure, cardiac output, stroke volume, and base excess were all improved in the DCLHb-lactated Ringer's solution-treated animals compared with the other experimental treatment groups. The 6-hour mortality rates were zero of eight (lactated Ringer's solution-DCLHb group), zero of eight (sham group), three of eight (lactated Ringer's solution-human serum albumin group), and six of eight (lactated Ringer's solution only group). CONCLUSION: Early resuscitation with DCLHb is superior to non-oxygen-carrying resuscitative fluids in improving hemodynamics and survival in this model of burn shock. DCLHb might improve general tissue perfusion in the acute postburn period, and it could be useful in the early management of patients with severe burns.     

Improvement of early postburn cardiac function by use of Panax notoginseng and immediate total eschar excision in one operation

Cardiac dysfunction development in the early stage postburn has been an important problem in burn treatment. However, no effective therapies are available for use in clinical practice. In this study, we sought to determine whether early total eschar excision (EEE) in one operation and the traditional Chinese herb Panax notoginseng (PNS) would be helpful in improving early postburn cardiac function. 160 Wistar rats were randomly divided into burn (burn group, n = 50), burn treated with EEE (EEE group, n = 50), burn treated with PNS (PNS group, n = 50) groups and normal controls (n = 10). All rats except the normal control were given a 30% TBSA full skin thickness burn and resuscitated with Ringer's lactate. EEE was performed immediately after the burn group received the first intraperitoneal injection of Ringer's lactate. The wound was covered with homoskin from normal rats. In the PNS group, two doses of PNS (200 mg/kg for each dose) were given intraperitoneally immediately and 4 h postburn. Cardiac contractile function and cardiac troponin T (TnT) were determined at 1, 3, 6, 12 and 24 h postburn. Results showed that cardiac contractile parameters including AOSP, AODP, LVSP and +dp/dt(max) all declined and were still significantly lower than the control values at 24 h postburn. Cardiac TnT was elevated markedly and reached a level 25 times higher than control at 12 h postburn. In EEE and PNS groups, the reduction of cardiac contractile function was limited as compared with that in the burn group. Levels of TnT in both EEE and PNS groups were significantly lower than in the burn group 6 h postburn later. The findings of this study demonstrated that both EEE and PNS were effective in improving early postburn cardiac function.     

Randomized trial of efficacy of crystalloid and colloid resuscitation on hemodynamic response and lung water following thermal injury

To assess the effects of crystalloid and colloid resuscitation on hemodynamic response and on lung water following thermal injury, 79 patients were assigned randomly to receive lactated Ringer's solution or 2.5% albumin-lactated Ringer's solution. Crystalloid-treated patients required more fluid for successful resuscitation than did those receiving colloid solutions (3.81 vs. 2.98 ml/kg body weight/% body surface burn, p less than 0.01). In study phase 1 (29 patients), cardiac index and myocardial contractility (ejection fraction and mean rate of internal fiber shortening, Vcf) were determined by echocardiography during the first 48 hours postburn. Cardiac index was lower in the 12- to 24-hour postburn interval in the crystalloid group, but this difference between treatment groups had disappeared by 48 hours postburn. Ejection fractions were normal throughout the entire study, while Vcf was supranormal (p less than 0.01 vs. normals) and equal in the two resuscitation groups. In study phase 2 (50 patients), extravascular lung water and cardiac index were measured by a standard rebreathing technique at least daily for the first postburn week. Lung water remained unchanged in the crystalloid-treated patients (p greater than 0.10), but progressively increased in the colloid-treated patients over the seven day study (p less than 0.0001). The measured lung water in each treatment group was significantly different from one another (p less than 0.001). Cardiac index increased progressively and identically in both treatment groups over the study period (p less than 0.01). These data refute the existence of myocardial depression during postburn resuscitation and document hypercontractile left ventricular performance. The addition of colloid to crystalloid resuscitation fluids produces no long lasting benefit on total body blood flow, and promotes accumulation of lung water when edema fluid is being reabsorbed from the burn wound.     

Resuscitation-induced pulmonary apoptosis and intracellular adhesion molecule-1 expression in rats are attenuated by the use of Ketone Ringer's solution

BACKGROUND: Resuscitation with Lactated Ringer's solution after hemorrhagic shock in rats has been shown to cause early cellular injury in the lung. We hypothesized that the use of energy substrates, such as ketone bodies, in the resuscitation fluids would protect against this injury. As markers of cellular injury we measured the induction of apoptotic cell death and the expression of Intracellular Adhesion Molecule-1 (ICAM-1). STUDY DESIGN: Male Sprague Dawley rats (n = 35) under inhaled isoflurane anesthesia had placement of femoral arterial and venous catheters. A three-stage hemorrhage model was used for this experiment. There was an initial hemorrhage of 27 mL/kg for 10 minutes. During the next 75 minutes another 8 mL/kg of blood was withdrawn at a steady rate. The resuscitation fluids were then infused for 45 minutes during which the third continuous hemorrhage of 8 mL/kg was performed. The animals were randomized to five groups: 1) sham hemorrhage (n = 6); 2) sham resuscitation (n = 7); 3) Lactated Ringer's resuscitation, three times the volume of shed blood (n = 8); 4) Ketone Ringer's (containing 28 mEq/L of beta-hydroxybutyrate) resuscitation, three times the volume of shed blood (n = 7); and 5) plasma resuscitation, volume equal to shed blood (n = 7). The animals were sacrificed 1 hour after resuscitation and lungs were harvested. Western blot technique was used for the determination of proapoptotic protein (bax), antiapoptotic protein (bcl-2), apoptotic fragments of poly ADP-ribose polymerase, and ICAM-1. Sections of lung were also subjected to immunostaining using antibodies to bax and ICAM-1 proteins (reported as number of positive cells/mm2). RESULTS: Lactated Ringer's resuscitation caused a significant increase in pulmonary apoptosis and ICAM-1 expression compared with the sham hemorrhage group. Animals resuscitated with Ketone Ringer's solution and plasma did not show this injury pattern. CONCLUSIONS: Substitution of lactate with ketone bodies in the resuscitation fluid attenuates the expression of cellular injury markers in the lung.