海水浸泡对枪弹伤合并失血性休克大鼠血流动力学的影响及机制探讨

目的　研究海水浸泡对枪弹伤合并失血性休克大鼠血流动力学、心肌细胞线粒体功能及一些生化指标的影响 ,探讨海水浸泡对心肌功能的影响及可能的机制。方法　健康Wistar雄性大鼠 2 0只 ,右侧大腿肌肉丰满处应用射钉枪造成贯通伤 ,包扎伤口。右侧颈总动脉插管至左心室 ,接四道生理记录仪 ,记录心肌力学的改变。左侧股动脉快速放血使血压降至 50mmHg(1mmHg =0 .1 33kPa) ,维持低血压 1h后 ,随机分为 2组 :海水浸泡组和陆地对照组 ,测定海水浸泡 5h大鼠平均动脉压 (MAP)、心率 (HR)、左室内压最大变化速率 (±dp·dt- 1 ·max- 1 )、左室收缩压 (LVSP)、心肌细胞线粒体呼吸功能、膜流动性 ,心肌组织Na+ -K+ -ATP酶活性、丙二醛 (MDA)含量及血浆乳酸脱氢酶 (LDH)。结果　海水浸泡 5h ,枪弹伤合并失血性休克大鼠MAP、HR、±dp·dt- 1 ·max- 1 、LVSP显著低于陆地对照组 ,心肌细胞线粒体呼吸控制率 (RCR)显著下降 ,膜脂区微黏度显著升高 ,心肌组织Na+ -K+ -ATP酶活性显著下降 ,心肌MDA含量和血浆LDH活力显著升高。结论　海水浸泡可以严重影响枪弹伤合并失血性休克大鼠血流动力学状态 ,加重其心肌的损伤     

精子活动力与线粒体酶活性的相关性

目前对生殖组织线粒体功能失调的研究很少,仍缺乏生物化学上的依据来证实线粒体功能和精子活动力的关系。线粒体能量代谢的最后通路是电子传递链,它是由线粒体内膜上的两个转运载体（辅酶Q和细胞色素C）和四个多聚酶复合物（复合物Ⅰ、Ⅱ、Ⅲ、Ⅳ）组成,其中,复合物Ⅰ为NADH脱氢酶,复合物Ⅱ为琥珀酸脱氢酶,复合物Ⅰ＋Ⅲ为NADH细胞色素C还原酶,复合物Ⅱ＋Ⅲ为琥珀酸色素C还原酶,复合物Ⅳ为细胞色素C氧化酶,柠檬酸合酶（CS）为线粒体的一个可靠的酶标记物。这些呼吸链酶活性的改变通常和各种线粒体功能失调有关。本文的目的是…     

长期规律运动对老年大鼠心肌细胞线粒体功能的影响

目的：探讨运动对老年大鼠心肌线粒体功能的影响。方法：将２０只２４月龄ＳＤ大鼠平均分成两组，１组为对照组，２组进行有规律的游泳训练，９０ｍｉｎ／次，６次／周，８周后测定大鼠心肌线粒体呼吸功能和电子传递组分的变化。结果：２组运动后呼吸控制率，碳氧比值明显增加，电子传递组分的活性显著升高。结论：长时间有规律的游泳运动能明显提高老年大鼠心肌线粒体的功能，可能是运动改善了老年动物心脏功能的能量基础。     

银杏叶提取物对糖尿病大鼠心肌线粒体的保护作用

目的观察银杏叶提取物(EGb)对糖尿病大鼠心肌线粒体的保护作用。方法40只SD大鼠随机分为正常对照组、糖尿病组和EGb治疗组，观察各组大鼠心肌线粒体超微结构，检测心肌线粒体琥珀酸脱氢酶(SDH)、超氧化物歧化酶(SOD)、一氧化氮合酶(NOS)的活性，以及一氧化氮(NO)、丙二醛(MDA)的含量。结果糖尿病大鼠心肌线粒体主要表现为肿胀，嵴变短，空泡化；SDH、SOD活性下降，NOS活性及MDA、NO含量增高。EGb治疗组病变较糖尿病组明显减轻，心肌线粒体SDH、SOD活性升高，NOS活性及NO、MDA含量下降。结论EGb能保护自由基和过量一氧化氮对心肌线粒体的损伤，提高SDH活性，从而对糖尿病大鼠心肌起保护作用。     

衰老小鼠脑老化过程中线粒体结构功能与mtDNA缺失的生物学规律

目的：研究小鼠脑老化过程中线粒体的生物学变化规律，探讨衰老的机制。方法：实验于2002—01／2003—04在广州体育学院科学实验中心及中山大学医学院完成。利用电镜对线粒体进行观察计数，Clark氧电极法测定线粒体呼吸链细胞色素C氧化酶及NADH脱氢酶活性，分光光度法测定抗氧化酶活性，聚合酶链反应检测mtDNA 3866 bp片段缺失率。结果：与5月龄小鼠比较，20月龄的老年小鼠脑线粒体数量减少、体积增大，线粒体呼吸控制率减小，而ADP／O比值无显著性差异，呼吸链NADH脱氢酶、细胞色素C氧化酶活性下降，mtDNA 3866bp片段缺失率增加，而抗氧化酶活性却增大。通过各指标间的相关分析发现呼吸控制率与mtDNA缺失率显著相关(r=0．739，P&;lt;0．01)，NADH脱氢酶、细胞色素C氧化酶活性与mtDNA缺失率亦显著相关(r=0．582，P&;lt;0．05，r=0．810，P&;lt;0．01)，但抗氧化酶活性与mtDNA缺失率无相关性(r=0．256，P&;gt;0．05)。结论：推测衰老时mtDNA的损伤积累可引起呼吸链酶复合物活性下降，导致呼吸链功能减退致生物衰老。     

不同液体复苏对失血性休克大鼠心肌核因子-κB表达的影响

目的 观察失血性休克大鼠心肌病理和核转录因子-κB(NF-κB)活性的变化以及不同液体复苏对其影响.方法 将40只Wistar大鼠,随机分为五组:假手术(Sham)组、休克(Shock)组、乳酸林格液复苏(RL)组、羟乙基淀粉复苏(HES)组、自身血液复苏(BL)组,每组8只,建立失血性休克再复苏大鼠模型.采集心脏组织,观察病理变化,并用免疫组化法检测NF-κB的表达情况.结果 与Sham组相比,其余各组心肌组织中NF-κB的表达均明显增加(P<0.05或P<0.01),且心肌有不同程度的损伤;BL组心肌NF-κB的表达增加明显低于RL、HES组(P<0.05),心肌损伤的程度也较轻.结论 不同液体复苏均可使失血性休克大鼠心肌组织NF-κB的表达和损伤程度明显降低,且二者呈显著正相关.自身血液与乳酸林格液和羟乙基淀粉相比,是较理想的失血性休克的复苏液体.     

失血性休克-再灌流后期大鼠肝脏细胞色素P450的变化

目的：研究大鼠在失血性休克－再灌流后期大鼠肝脏中细胞色素P450的变化，探讨细胞色素P450与肝脏在再灌注后期损伤的关系。方法：建立失血性休克大鼠模型，随机分为休克再灌流组、对照组和假休克组，检测肝脏的P450和细胞色素b5的含量、氨基比林－N－去甲基酶的活性水平、丙二醛。结果：休克再灌注组中的细胞色素P450的含量和氨基比林－N－去甲基酶的活性水平明显高于对照组和假休克组，丙二醛也高于其他组，而细胞色素b5各组无差异。结论：细胞色素P450也参与了失血性休克－再灌流后期大鼠肝脏的损伤。     

高住低训模型大鼠心肌线粒体呼吸链酶复合物的活性:线粒体习服过程所需时间分析

背景:以往的研究发现,高原训练的有效时间为4～6周,而高住低训的有效训练时间、尤其是线粒体的习服所需要的时间还未见系统报道.目的:构建模拟"高住低训"训练法大鼠模型,观察低氧和高原训练刺激作用下,高住低训习服过程中模型大鼠心肌线粒体呼吸链酶复合物活性的动态变化,分析线粒体呼吸链酶复合物的高住低训习服过程所需时间.设计:分组对照动物实验.单位:辽宁师范大学体育学院运动生理实验室.材料:实验选用健康成年SD大鼠40只,雌雄不拘,由大连医科大学实验动物中心提供.实验动物的处置符合动物伦理学.实验用模型常压低氧环境所用低氧分压系统由美国Hypoxico公司制造,氧气监测仪为美国产TOXIBLAEPGM-36型.方法:随机将大鼠分为5组:常氧对照组,高住低训1,2,3,4周组,每组8只.高住低训组大鼠每天在低氧分压系统模拟的海拔2 500 m的高原环境生活,同时模拟海拔1300m环境下游泳运动1 h,每周训练6d.主要观察指标:采用可见分光光度法测定每组大鼠心肌线粒体呼吸链复合酶体Ⅰ-Ⅳ活性,用Bradford法进行线粒体蛋白定量检测.结果:①心肌线粒体呼吸链复合酶活性:高住低训1周大鼠心肌线粒体呼吸链酶复合物Ⅰ～Ⅳ活性较对照组显著降低,差异有显著性意义(P<0.05～0.01);高住低训2周时酶复合Ⅲ活性与对照组比较,差异无显著性意义(P>0.05),而其他酶复合物在高住低训3周时与对照组比较,差异无显著性意义(P>0.05).②线粒体蛋白含量:高住低训1,2周时与对照组比较,差异无显著性意义(P>0.05),高住低训3,4周时高于对照组,差异有显著性意义(P<0.05).结论:模型大鼠心肌线粒体呼吸链酶复合物Ⅰ～Ⅳ活性的高住低训习服过程需要3周.     

衰老小鼠脑老化过程中线粒体结构功能与mtDNA缺失的生物学规律

目的:研究小鼠脑老化过程中线粒体的生物学变化规律,探讨衰老的机制。方法:实验于2002-01/2003-04在广州体育学院科学实验中心及中山大学医学院完成。利用电镜对线粒体进行观察计数,Clark氧电极法测定线粒体呼吸链细胞色素C氧化酶及NADH脱氢酶活性,分光光度法测定抗氧化酶活性,聚合酶链反应检测mtDNA3866bp片段缺失率。结果:与5月龄小鼠比较,20月龄的老年小鼠脑线粒体数量减少、体积增大,线粒体呼吸控制率减小,而ADP/O比值无显著性差异,呼吸链NADH脱氢酶、细胞色素C氧化酶活性下降,mtDNA3866bp片段缺失率增加,而抗氧化酶活性却增大。通过各指标间的相关分析发现呼吸控制率与mtDNA缺失率显著相关(r=0.739,P<0.01),NADH脱氢酶、细胞色素C氧化酶活性与mtDNA缺失率亦显著相关(r=0.582,P<0.05,r=0.810,P<0.01),但抗氧化酶活性与mtDNA缺失率无相关性(r=0.256,P>0.05)。结论:推测衰老时mtDNA的损伤积累可引起呼吸链酶复合物活性下降,导致呼吸链功能减退致生物衰老。     

冬虫夏草提取液对糖尿病小鼠肝线粒体氧化损伤的保护效应

目的：从线粒体呼吸链角度分析中药冬虫夏草提取液对糖尿病引起的氧化损伤的保护作用。 方法：实验于1998-03／2000—07在中国科学院动物研究所生物膜与膜生物国家重点实验室完成。雄性昆明小白鼠32只，随机分为4组，每组8只。正常对照组不加任何处理因素，虫草组、维生素E组和糖尿病组小鼠用四氧嘧啶建立实验性糖尿病小鼠模型，分别给予口服虫草提取液（1mL／只）和皮下注射维生素E溶液（4mg／kg），糖尿病组不用任何保护作用药物。利用比色法从线粒体水平测定抗氧化酶活性，用铁氰化钾脉冲法测定线粒体呼吸活链Ⅱ＋Ⅲ电子传递与质子泵出偶联状况（H^＋／2e）。 结果：32只小鼠均进入结果分析。①小鼠谷胱甘肽含量，谷胱甘肽过氧化物酶活性、谷胱甘肽过氧化物酶活性和丙二醛含量比值：糖尿病组低于正常对照组，虫草组、维生素E组高于糖尿病组，差异有显著性意义（P＜0．05～0．001）。②丙二醛含量：糖尿病组高于正常对照组，虫草组、维生素E组低于糖尿病组（P＜0．001）。③糖尿病组线粒体呼吸链复合体Ⅱ＋Ⅲ电子传递与质子泵出总比值、净比值低于正常对照组，降低了24．76％，32.31％（P＜0．001）。虫草组、维生素E组线粒体呼吸链复合体Ⅱ＋Ⅲ电子传递与质子泵出总比值、净比值显著回升，高于糖尿病组（P＜0．001）。 结论：线粒体呼吸过程产生的自由基在糖尿病的肝损伤中可能具有重要的作用，其原因与电子漏增加、电子传递与质子泵出脱偶联有关；同时也证明了虫草提取液能有效的拮抗由糖尿病引起的肝线粒体的氧化损伤。     

Protective effect of urinary trypsin inhibitor on myocardial mitochondria during hemorrhagic shock and reperfusion

OBJECTIVE: To examine the mitochondrial function in the myocardium after hemorrhagic shock and reperfusion and to evaluate the protective effect of urinary trypsin inhibitor (UTI) on mitochondria. DESIGN: Animal experiment. SETTING: University research laboratory. SUBJECTS: Wistar rats receiving 50,000 units/kg/hr of UTI (n = 27; UTI group) and control rats (n = 26; control group). INTERVENTIONS: Rats were subjected to low-perfusion ischemia with the left ventricular systolic pressure maintained at 50 mm Hg for 60 mins by bleeding, followed by a 60-min reperfusion by transfusion of shed blood. UTI was infused continuously from 10 mins before bleeding. Cardiac function was measured before bleeding, after bleeding, and after transfusion; at each determination point, the myocardial contents of adenosine triphosphate (ATP), creatine phosphate (P-Cr), pyruvate (Pyr), and lactate (Lac) were measured enzymatically. The cytosolic phosphorylation potential (PP) as well as the redox potential of the oxidized form of nicotinamide adenine dinucleotide/reduced form of nicotinamide adenine dinucleotide couple in mitochondria (Eh(NAD+/NADH)) and change of Gibbs free energy in ATP hydrolysis (deltaG(ATP hydrolysis) energy) were calculated. MEASUREMENTS AND MAIN RESULTS: Cardiac function decreased during hemorrhagic shock but improved significantly in the UTI group after transfusion compared with the control group. Lac and the Lac/Pyr ratio were significantly lower in the UTI group than in the control group after transfusion. ATP and P-Cr were significantly higher in the UTI group than in the control group after transfusion. PP (x10(3) M-1), Eh(NAD+/NADH) (x - 1 mV), and deltaG(ATP hydrolysis) (x - 1 kcal/mol) were 1.9 +/- 0.4, 266 +/- 4, and 9.7 +/- 0.2, respectively, in the control group and 4.0 +/- 0.9, 274 +/- 5 and 13.0 +/- 0.2, respectively, in the UTI group after transfusion (p <.001, p <.001, and p <.001, respectively). CONCLUSIONS: In reperfusion after hemorrhagic shock, oxidative phosphorylation in myocardial mitochondria is impaired and energy production remains reduced, even after reperfusion. UTI contributed to the recovery of cardiac function after reperfusion, probably by reducing the severity of mitochondrial dysfunction during a state of shock and by maintaining energy production.     

不同补液温度对失血性休克兔二胺氧化酶和心肌酶变化的影响

目的 探讨失血性休克时适宜的抗休克补液温度。方法 将23只家兔按随机方法分为假手术 组(n=7)、液体复苏温热组(n=8)、常温组(n=7)和低温组(n=8)。温热组、常温组、低温组兔复制失血性休克 模型后,给予3倍失血量的平衡液及自体血复苏,液体温度分别控制在(39.5±1.3)℃、(20.6±1.3)℃和 (10.7±1.6)℃。选择休克前、休克模型成功后30 min及液体复苏后1、2和4 h 5个时间点取血,观察二胺氧 化酶(DAO)和心肌酶的变化。结果 温热溶液复苏DAO升高幅度较低;温热溶液复苏使肌酸激酶、肌酸激酶 同工酶和乳酸脱氢酶上升幅度较小。结论 温热液体治疗失血性休克对改善肠黏膜和心肌细胞缺血性损伤, 维持肠黏膜完整性有一定意义。     

Heat shock pretreatment prevents cardiac mitochondrial dysfunction during sepsis

The present study was designed to investigate the effect of previous heat shock treatment on the mitochondria function of the heart during a cecal ligation and puncture (CLP)-induced sepsis model. Rats of the heated group were heated by whole-body hyperthermia 24 h before the CLP operation. Cardiac mitochondria were freshly collected 9 and 18 h after CLP, indicating early and late sepsis, respectively. The expressions of heat shock protein 72 (Hsp72), glucose-regulated protein 75 (Grp75), and mitochondrial complexes I, II, III, and IV were evaluated by Western blot and immunochemical analysis. Enzyme activities of NADH cytochrome c reductase (NCCR), succinate cytochrome c reductase (SCCR), and cytochrome c oxidase (CCO) were measured after the reduction or oxidation of cytochrome c using a spectrophotometer. The results showed that the ATP content in the heart significantly declined during late sepsis, whereas heat shock treatment reversed this declination. The enzyme activities of NCCR, SCCR, and CCO were apparently suppressed during late stage of sepsis. The protein expressions of mitochondrial complex II and complex IV and Grp75 were also down-regulated during sepsis. Previously treated by heat shock, late-sepsis rats emerged with a high preservation of mitochondrial respiratory chain enzymes, both the protein amount and enzyme activity. Aspects of morphology were observed by electron microscopy, while heat shock treatment revealed the attenuation of cardiac mitochondrial damage induced by sepsis. In conclusion, structural deformity and the decrease of respiratory chain enzyme activity in mitochondria and its leading to a decline of ATP content are highly correlated with the deterioration of cardiac function during sepsis, and heat shock can reverse adverse effects, thus achieving a protective goal.     

A comparison of resuscitation with packed red blood cells and whole blood following hemorrhagic shock in canines

Resuscitation with crystalloid and packed red blood cells has for the most part replaced the use of plasma and whole blood in the initial treatment of hemorrhagic shock. The effects of such changes on cardiovascular function following hemorrhagic shock remain largely unexplored. We examined cardiovascular function in anesthetized canines subjected to severe hemorrhagic shock. Mongrel canines of either gender were anesthetized with isoflurane and instrumented for measurement of arterial pressure, cardiac output, coronary flow, and left ventricular pressure and volume for the determination of end systolic elastance (Ees). Following a 30-min stabilization period, blood was rapidly removed to induce fixed pressure (mean arterial pressure = 35 mmHg) hemorrhagic shock for 90 min or until an arterial lactate of 7.0 mM was achieved. Animals were then resuscitated with 2/3 of the shed volume as lactated Ringer's and an equal volume of either whole blood (WB, n = 8) or packed red blood cells (PRBC, n = 10) resuspended in lactated Ringer's (LR) solution to replace expressed plasma volume. PRBC resuscitated dogs showed lower values of mean arterial pressure, cardiac output, rates of ventricular contraction and relaxation and myocardial work. Increasing the maintenance infusion rate of LR (10 mL/kg/h) following PRBC infusion normalized mean arterial pressure, but not other indices of cardiovascular function. Thus, WB, but not PRBC resuscitation restores normal myocardial function during resuscitation from severe hemorrhagic shock.     

腹腔海水浸泡对失血性休克犬血浆电解质水平的影响

目的：研究腹腔海水浸泡对失血性休克犬血浆电解质水平的影响。方法：实验动物致伤后随机分为3组：失血性休克组、海水浸泡组、腹腔海水浸泡并失血性休克组，观察各组动物外周血钠、钾、氯水平及渗透压的变化。结果：海水浸泡组与腹腔海水浸泡并失血性休克组外周血钠、钾、氯水平及渗透压显著高于失血性休克组，而两组血钠、钾、氯水平及血浆渗透压均无显著差别。结论：腹腔海水浸泡可导致失血性休克犬高钠血症、高钾血症、高氯血症及高渗性脱水。     

不同液体复苏对颅脑外伤并发急性失血性休克大鼠脑保护作用比较

目的比较不同种类液体复苏对大鼠颅脑外伤并发急性失血性休克模型的局部脑血流（rCBF）、脑水肿和血脑屏障（BBB）的影响.方法SD大鼠60只随机分为5组：①假手术组（Ⅰ组）;②脑外伤＋休克组（Ⅱ组）;③生理盐水组（Ⅲ组）;④10%羟乙基淀粉（HES）组（Ⅳ组）;⑤小容量高晶体-高胶体渗透压混合液（HHS,7.5%NaCl与10%HES按1：1混合）（Ⅴ组）.记录外伤、休克和复苏前后平均动脉压（MAP）和rCBF的变化,测定复苏后3 h脑组织含水量以及脑组织伊文思蓝（EB）含量.结果在复苏后即刻,Ⅲ、Ⅳ、Ⅴ组MAP和rCBF均恢复正常,分别在15 min、30 min和45 min后开始下降,至120 min时,Ⅴ组显著高于Ⅲ、Ⅳ组（P＜0.05）.复苏后3 h,Ⅴ组脑组织含水量双侧正常,Ⅲ组双侧均显著高于Ⅰ、Ⅴ组（P＜0.05）;Ⅱ、Ⅲ组损伤侧脑组织EB含量显著高于Ⅳ、Ⅴ组（P＜0.05）.结论小容量HHS复苏能够有效、持久地恢复颅脑外伤并发失血性休克大鼠的MAP和rCBF,减轻脑水肿,改善BBB.NS恢复MAP和rCBF的时间较短,加重脑水肿和BBB破坏.10%HES的作用介于小容量HHS和NS之间.     

Intrinsic myocardial function in hemorrhagic shock

Hemorrhage is a stress on the cardiovascular system that results in decreased loading of the heart but also decreased blood pressure and thus decreased perfusion pressure for tissue blood flow. The heart's response to hemorrhage is governed by both an increase in sympathetic nervous system activation of the heart and decreased preload and afterload for the heart. Whether the heart can maintain normal contractile function and reserves under conditions of prolonged hemorrhagic shock is not clear. To assess the effects of hemorrhagic shock of different lengths on intrinsic cardiac contractile function, guinea pigs were surgically prepared for the measurement of blood pressure, heart rate, and cardiac output and blood samples were taken for the measurement of metabolic indices of cardiovascular stress. Fifty percent of the animals' blood volume was removed and then animals were followed for 1, 2, or 3 h of hemorrhagic shock. Hearts were then removed for measurement of intrinsic contractile function. Hearts from animals exposed to 1 or 2 h of shock exhibited normal ventricular function although hearts removed after 3 h exhibited changes in ventricular function. Maintenance of normal cardiac function through at least 2 h of shock must represent adequate physiologic modulation of coronary blood flow to deliver adequate oxygen to match the myocardial oxygen demands under conditions of severe blood loss. This balance may be disrupted by 3 h of shock thus resulting in loss of contractile reserve.     

Reversible blockade of electron transport during ischemia protects mitochondria and decreases myocardial injury following reperfusion

Cardiac mitochondria sustain damage during ischemia and reperfusion, contributing to cell death. The reversible blockade of electron transport during ischemia with amobarbital, an inhibitor at the rotenone site of complex I, protects mitochondria against ischemic damage. Amobarbital treatment immediately before ischemia was used to test the hypothesis that damage to mitochondrial respiration occurs mainly during ischemia and that protection of mitochondria during ischemia leads to decreased cardiac injury with reperfusion. Langendorff-perfused Fischer-344 rat hearts were treated with amobarbital (2.5 mM) or vehicle for 1 min immediately before 25 min of global ischemia. Both groups were reperfused for 30 min without additional treatment. Subsarcolemmal (SSM) and interfibrillar (IFM) populations of mitochondria were isolated after reperfusion. Ischemia and reperfusion decreased state 3 and increased state 4 respiration rate in both SSM and IFM. Amobarbital treatment protected oxidative phosphorylation measured following reperfusion and improved the coupling of respiration. Cytochrome c content measured in SSM and IFM following reperfusion decreased in untreated, but not in amobarbital-treated, hearts. H(2)O(2) release from SSM and IFM isolated from amobarbital-treated hearts during reperfusion was markedly decreased. Amobarbital treatment before ischemia improved recovery of contractile function (percentage of preischemic developed pressure: untreated 51 +/- 4%, n = 12; amobarbital 70 +/- 4%, n = 11, p < 0.01) and substantially reduced infarct size (untreated 32 +/- 2%, n = 7; amobarbital 13 +/- 2%, n = 7, p < 0.01). Thus, mitochondrial damage occurs mainly during ischemia rather than during reperfusion. Reperfusion in the setting of preserved mitochondrial respiratory function attenuates the mitochondrial release of reactive oxygen species, enhances contractile recovery, and decreases myocardial infarct size.     

Diaspirin-crosslinked hemoglobin reduces mortality of severe hemorrhagic shock in pigs with critical coronary stenosis

OBJECTIVE: To evaluate the effects of resuscitation with a 10% diaspirin-crosslinked hemoglobin (DCLHb) solution on global hemodynamic variables, systemic and myocardial oxygen transport and tissue oxygenation, and contractile function of the left ventricle in an experimental model of severe hemorrhagic shock and critical stenosis of the left anterior descending coronary artery (LAD). DESIGN: Prospective, placebo-controlled, randomized study. SETTING: Experimental animal laboratory. SUBJECTS: A total of 20 anesthetized pigs. INTERVENTIONS: After implementation of a permanent critical LAD stenosis (ie, maintenance of basal blood flow but absence of reactive hyperemia after a 10-sec complete vessel occlusion), hemorrhagic shock (target mean aortic pressure, 45 mm Hg) was induced within 15 mins by programmed withdrawal of blood and maintained for 60 mins. Subsequently, the volume of plasma lost during hemorrhage was replaced by either a balanced electrolyte solution containing 10 g/dL DCLHb (DCLHb group; n = 10) or an 8 g/dL human albumin solution (HSA) oncotically matched to DCLHb (HSA group; n = 10). Data were collected immediately after the infusion of the different solutions and again after 60 mins had elapsed. MEASUREMENTS AND MAIN RESULTS: Although five of ten HSA-treated animals died of acute left ventricular failure within the first 20 mins after complete fluid resuscitation, all of the DCLHb-treated animals survived the 60-min observation period after resuscitation (p < .05). This significant difference in mortality is explained by higher coronary perfusion pressure in DCLHb-treated animals (75 +/- 17 vs. 27 +/- 17 torr DCLHb vs. HSA group; p < .05) and persistence of subendocardial ischemia and hypoxia (radioactive microspheres method) in HSA-treated animals on resuscitation particularly affecting the LAD-supported myocardium (subendocardial oxygen delivery: 20 +/- 11 vs. 3 +/- 1 mL oxygen x g(-1) x min(-1), DCLHb vs. HSA group; p < .05). Except for enhanced myocardial contractility immediately on infusion of DCLHb (maximal left ventricular pressure increase: 2373 +/- 782 vs. 1730 +/- 543 torr x sec(-1) DCLHb vs. HSA group; p < .05), no differences were detected between groups concerning the variables of systemic oxygen transport, tissue oxygenation, and regional contractile function of the myocardium (determined with microsonometry). CONCLUSIONS: Fluid resuscitation with 10% DCLHb solution completely reverses hemorrhagic shock-induced subendocardial ischemia and hypoxia in the presence of compromised coronary circulation and thereby prevents early death after resuscitation.     

Depletion of myocardial glucose is observed during endotoxemic but not hemorrhagic shock in a porcine model

Introduction

Metabolic dysfunction is one of the hallmarks of sepsis yet little is known about local changes in key organs such as the heart. The aim of this study was to compare myocardial metabolic changes by direct measurements of substrates, such as glucose, lactate and pyruvate, using microdialysis (MD) in in-vivo porcine endotoxemic and hemorrhagic shock. To assess whether these changes were specific to the heart, we simultaneously investigated substrate levels in skeletal muscle.

Methods

Twenty-six female pigs were randomized to three groups: control (C) n = 8, endotoxemic shock (E) n = 9 and hemorrhagic shock (H) n = 9. Interstitial myocardial pyruvate, lactate and glucose were measured using MD. Skeletal muscle MD was also performed in all three groups.

Results

Marked decreases in myocardial glucose were observed in the E group but not in the H group compared to controls (mean difference (CI) in mmol/L: C versus E -1.5(-2.2 to -0.8), P <0.001; H versus E -1.1(-1.8 to -0.4), P = 0.004; C versus H -0.4(-1.1 to 0.3), P = 0.282). Up to four-fold increases in myocardial pyruvate and three-fold increases in lactate were seen in both shock groups with no differences between the two types of shock. There was no evidence of myocardial anaerobic metabolism, with normal lactate:pyruvate (L:P) ratios seen in all animals regardless of the type of shock.In skeletal muscle, decreases in glucose concentrations were observed in the E group only (mean difference: C versus E -0.8(-1.4 to -0.3), P = 0.007). Although skeletal muscle lactate increased in both shock groups, this was accompanied by increases in pyruvate in the E group only (mean difference: C versus E 121(46 to 195), P = 0.003; H versus E 77(7 to 147), P = 0.032; C versus H 43(-30 to 43), P = 0.229). The L:P ratio was increased in skeletal muscle in response to hemorrhagic, but not endotoxemic, shock.

Conclusions

Endotoxemia, but not hemorrhage, induces a rapid decrease of myocardial glucose levels. Despite the decrease in glucose, myocardial lactate and pyruvate concentrations were elevated and not different than in hemorrhagic shock. In skeletal muscle, substrate patterns during endotoxemic shock mimicked those seen in myocardium. During hemorrhagic shock the skeletal muscle response was characterized by a lack of increase in pyruvate and higher L:P ratios.Hence, metabolic patterns in the myocardium during endotoxemic shock are different than those seen during hemorrhagic shock. Skeletal muscle and myocardium displayed similar substrate patterns during endotoxemic shock but differed during hemorrhagic shock.