Cardiopulmonary arrest and resuscitation in Landrace/Large White swine: a research model

Sudden cardiac death (SCD) is a field of continuous research. In order to answer various questions regarding SCD, several animal models have been developed. The aim of the present study is to describe our experimental model of inducing cardiac arrest in Landrace/Large White pigs, and then resuscitated according to the International Guidelines on resuscitation. Fifteen Landrace/Large White pigs were anaesthetized and intubated while spontaneously breathing. The left and right jugular veins, as well as the femoral and the carotid arteries, were surgically prepared. Induction of cardiac arrest was achieved by using an ordinary rechargeable lithium battery, through a pacemaker wire inserted into the right ventricle. The typical Advanced Life Support (ALS) protocol was followed, and in case of restoration of spontaneous circulation, the animals were further evaluated for 30 min. Seven animals were successfully resuscitated using this protocol, whereas eight failed resuscitation efforts. Successful resuscitation was contingent on the restoration of the levels of coronary perfusion pressure and PETCO(2) during chest compressions. Among the different ways of inducing cardiac arrest, the ordinary lithium battery is a simple, safe and valuable technique. Landrace/Large White pigs' baseline haemodynamics closely resemble human haemodynamics, making the breed a favourable model for resuscitation.     

Whole blood and plasma amino acid transfers across the portal drained viscera and liver of the pig.

Whole blood (WB) and plasma (P) amino acid transfers across the portal drained viscera and the liver were determined during 6 h of a constant p-aminohippuric acid infusion in three hourly-fed Landrace x Large-White pigs (30.5 kg, mean live weight) surgically prepared with chronically inserted catheters in a mesenteric vein (MV), the portal vein (PV), an hepatic vein (HV) and the carotid artery (CA). Plasma and WB amino acid concentrations were determined in the CA, PV and HV. The plasma/WB ratios showed no significant differences for vessels except for lysine and glutamate for which this ratio is significantly higher in the HV and in the PV for lysine. This suggests that the PV lysine and HV glutamate were preferentially transported in the plasma. In the PV, threonine, valine and alanine are transported by both plasma and red blood cells. These data show that the contribution of plasma and whole blood to amino acid transport can be different between amino acids and between individual tissues.     

Endovascular hypothermia improves post-resuscitation myocardial dysfunction by increasing mitochondrial biogenesis in a pig model of cardiac arrest

The aim of the study was to investigate the effects of endovascular hypothermia on mitochondrial biogenesis in a pig model of prolonged cardiac arrest (CA). Ventricular fibrillation was electrically induced, and animals were left untreated for 10 min; then after 6min of cardiopulmonary resuscitation (CPR), defibrillation was attempted. 25 animals that were successfully resuscitated were randomized into three groups: Sham group (SG, 5, no CA), normal temperature group (NTG, 5 for 12 h observation and 5 for 24 h observation), and endovascular hypothermia group (EHG, 5 for 12 h observation and 5 for 24 h observation). The core temperatures (T_c) in the EHG were maintained at 34 ± 0.5 °C for 6 h by an endovascular hypothermia device (Coolgard 3000), then actively increased at the speed of 0.5 °C per hour during the next 6 h to achieve a normal body temperature, while T_c were maintained at 37.5 ± 0.5 °C in the NTG. Cardiac and mitochondrial functions, the quantification of myocardial mitochondrial DNA (mtDNA), peroxisome proliferator-activated receptor coactivator-1α (PGC-1α), nuclear respiratory factor (NRF)-1, and NRF-2 were examined. Results showed that myocardial and mitochondrial injury and dysfunction increased significantly at 12 h and 24 h after CA. Endovascular hypothermia offered a method to rapidly achieve the target temperature and provide stable target temperature management (TTM). Cardiac outcomes were improved and myocardial injuries were alleviated with endovascular hypothermia. Compared with NTG, endovascular hypothermia significantly increased mitochondrial activity and biogenesis by amplifying mitochondrial biogenesis factors’ expressions, including PGC-1α, NRF-1, and NRF-2. In conclusions, endovascular hypothermia after CA alleviated myocardial and mitochondrial dysfunction, and was associated with increasing mitochondrial biogenesis.     

Cerebral Tissue Oxidative Ischemia-Reperfusion Injury in Connection with Experimental Cardiac Arrest and Cardiopulmonary Resuscitation: Effect of Mild Hypothermia and Methylene Blue

The present investigation is an expansion of previous studies which all share a basic experimental protocol of a porcine-induced cardiac arrest (CA) of 12 min followed by 8 min of cardiopulmonary resuscitation (CPR), different experimental treatments (immediate as well as postponed induced mild hypothermia and administration of much or less cool intravenous fluids), and a follow-up period of 3 h after which the animals were sacrificed. Another group of animals was studied according to the same protocol after 12-min CA and “standard CPR.” After death (within 1 min), the brains were harvested and frozen in liquid nitrogen awaiting analysis. Control brains of animals were collected in the same way after short periods of untreated CA (0 min, 5 min, and 15–30 min). Previous studies concerning chiefly neuropathological changes were now expanded with analyses of different tissue indicators (glutathione, luminol, leucigenin, malonialdehyde, and myeloperoxidase) of cerebral oxidative injury. The results indicate that a great part of oxidative injury occurs within the first 5 min after CA. Immediate cooling by administration of much intravenous fluid results in less cerebral oxidative injury compared to less intravenous fluid administration. A 30-min postponement of induction of hypothermia results in a cerebral oxidative injury comparable to that of “standard CPR” or the oxidative injury found after 5 min of untreated CA. Intravenous administration of methylene blue (MB) during and immediately after CPR in combination with postponed cooling resulted in no statistical difference in any of the indicators of oxidative injury, except myeloperoxidase, and glutathione, when this treatment was compared with the negative controls, i.e., animals subjected to anesthesia alone.     

Prevention of post-ischemic brain lipid conjugated diene production and neurological injury by hydroxyethyl starch-conjugated deferoxamine.

Hydroxyethyl starch conjugated deferoxamine (DFO) was administered to rats following resuscitation from 6.5 min cardiac arrest (CA) in an attempt to prevent the iron-catalyzed production of oxygen free radicals which may lead to neurologic injury and ultimately death following restoration of spontaneous circulation (ROSC). Brain conjugated dienes were analyzed spectrophotometrically 4 and 24 hr following ROSC, and were found to be significantly elevated when compared to non-ischemic controls. Hydroxyethyl starch-DFO treated rats demonstrated no increased conjugated diene production at either period. Neurologic injury was significantly less in drug treated rats surviving 24 or 72 hours when compared to controls. While mortality was similar in drug treated or control rats for the first 24 hours following ROSC, delayed mortality (days 1-10) was significantly less in drug treated animals, presumably as a result of neurologic protection afforded by post-ischemic drug administration. Administration of DFO conjugated to hydroxyethyl starch appears to modulate the neurologic injury which occurs during brain ischemia and reperfusion.     

Polyuria and impaired renal blood flow after asphyxia in preterm fetal sheep

Renal impairment is common in preterm infants, often after exposure to hypoxia/asphyxia or other circulatory disturbances. We examined the hypothesis that this association is mediated by reduced renal blood flow (RBF), using a model of asphyxia induced by complete umbilical cord occlusion for 25 min (n = 13) or sham occlusion (n = 6) in chronically instrumented preterm fetal sheep (104 days, term is 147 days). During asphyxia there was a significant fall in RBF and urine output (UO). After asphyxia, RBF transiently recovered, followed within 30 min by a secondary period of hypoperfusion (P < 0.05). This was mediated by increased renal vascular resistance (RVR, P < 0.05); arterial blood pressure was mildly increased in the first 24 h (P < 0.05). RBF relatively normalized between 3 and 24 h, but hypoperfusion developed again from 24 to 60 h (P < 0.05, analysis of covariance). UO significantly increased to a peak of 249% of baseline between 3 and 12 h (P < 0.05), with increased fractional excretion of sodium, peak 10.5 +/- 1.4 vs. 2.6 +/- 0.6% (P < 0.001). Creatinine clearance returned to normal after 2 h; there was a transient reduction at 48 h to 0.32 +/- 0.02 ml.min(-1).g(-1) (vs. 0.45 +/- 0.04, P < 0.05) corresponding with the time of maximal depression of RBF. No renal injury was seen on histological examination at 72 h. In conclusion, severe asphyxia in the preterm fetus was associated with evolving renal tubular dysfunction, as shown by transient polyuria and natriuresis. Despite a prolonged increase in RVR, there was only a modest effect on glomerular function.     

Direct analysis of bacterial viability in endotracheal tube biofilm from a pig model of methicillin-resistant Staphylococcus aureus pneumonia following antimicrobial therapy

Confocal laser scanning microscopy (CLSM) helps to observe the biofilms formed in the endotracheal tube (ETT) of ventilated subjects and to determine its structure and bacterial viability using specific dyes. We compared the effect of three different treatments (placebo, linezolid, and vancomycin) on the bacterial biofilm viability captured by CLSM. Eight pigs with pneumonia induced by methicillin-resistant Staphylococcus aureus (MRSA) were ventilated up to 96?h and treated with linezolid, vancomycin, or placebo (controls). ETT images were microscopically examined after staining with the live/dead(?) BacLight(?) Kit (Invitrogen, Barcelona, Spain) with a confocal laser scanning microscope. We analyzed 127 images obtained by CLSM. The median ratio of live/dead bacteria was 0.51, 0.74, and 1 for the linezolid, vancomycin, and control groups, respectively (P?=?0.002 for the three groups); this ratio was significantly lower for the linezolid group, compared with the control group (P?=?0.001). Images showed bacterial biofilm attached and non-attached to the ETT surface but growing within secretions accumulated inside ETT. Systemic treatment with linezolid is associated with a higher proportion of dead bacteria in the ETT biofilm of animals with MRSA pneumonia. Biofilm clusters not necessarily attach to the ETT surface.     

Examination of Physiological Function and Biochemical Disorders in a Rat Model of Prolonged Asphyxia-Induced Cardiac Arrest followed by Cardio Pulmonary Bypass Resuscitation

Background

Cardiac arrest induces whole body ischemia, which causes damage to multiple organs particularly the heart and the brain. There is clinical and preclinical evidence that neurological injury is responsible for high mortality and morbidity of patients even after successful cardiopulmonary resuscitation. A better understanding of the metabolic alterations in the brain during ischemia will enable the development of better targeted resuscitation protocols that repair the ischemic damage and minimize the additional damage caused by reperfusion.

Method

A validated whole body model of rodent arrest followed by resuscitation was utilized; animals were randomized into three groups: control, 30 minute asphyxial arrest, or 30 minutes asphyxial arrest followed by 60 min cardiopulmonary bypass (CPB) resuscitation. Blood gases and hemodynamics were monitored during the procedures. An untargeted metabolic survey of heart and brain tissues following cardiac arrest and after CPB resuscitation was conducted to better define the alterations associated with each condition.

Results

After 30 min cardiac arrest and 60 min CPB, the rats exhibited no observable brain function and weakened heart function in a physiological assessment. Heart and brain tissues harvested following 30 min ischemia had significant changes in the concentration of metabolites in lipid and carbohydrate metabolism. In addition, the brain had increased lysophospholipid content. CPB resuscitation significantly normalized metabolite concentrations in the heart tissue, but not in the brain tissue.

Conclusion

The observation that metabolic alterations are seen primarily during cardiac arrest suggests that the events of ischemia are the major cause of neurological damage in our rat model of asphyxia-CPB resuscitation. Impaired glycolysis and increased lysophospholipids observed only in the brain suggest that altered energy metabolism and phospholipid degradation may be a central mechanism in unresuscitatable brain damage.     

影响心脏骤停患者心肺复苏成功率的因素分析

目的:分析我院心脏骤停患者心肺复苏的成功率,并探讨其影响因素。方法:选取198名行心肺复苏的心脏骤停患者为研究对象,实施心肺复苏,并记录患者一般情况、复苏开始时间和地点、复苏过程和复苏结局等多项指标,统计分析复苏效果。结果:1198名患者,72例取得最终复苏成功,心肺复苏成功率为36.4%;2不同年龄(=15.380,P0.001)、基础性疾病(x~2=11.465,P=0.043)、复苏开始时间(x~2=57.968,P0.001)、地点(x~2=61.384,P0.001)患者心肺复苏成功率差异有统计学意义,年龄16~60岁、非心血管疾病、心脏骤停5分钟内、院内开始心肺复苏者成功率较高;3复苏成功者和失败者复苏持续时间(t=-5.961,P0.001)和气道建立时间(t=-4.045,P=0.004)的差异具有统计学意义,成功者复苏持续时间要短于失败者,而气道建立时间要早于失败者。结论:快速建立人工气道,不盲目延长心肺复苏时间,提高心脏骤停患者心肺复苏的成功率。     

Impact of Rescue-Thrombolysis during Cardiopulmonary Resuscitation in Patients with Pulmonary Embolism

Background

Cardiac arrest in patients with pulmonary embolism (PE) is associated with high morbidity and mortality. Thrombolysis is expected to improve the outcome in these patients. However studies evaluating rescue-thrombolysis in patients with PE are missing, mainly due to the difficulties of clinical diagnosis of PE. We aimed to determine the success influencing factors of thrombolysis during resuscitation in patients with PE.

Methodology/Principal Findings

We analyzed retrospectively the outcome of 104 consecutive patients with confirmed (n = 63) or highly suspected (n = 41) PE and monitored cardiac arrest. In all patients rtPA was administrated for thrombolysis during cardiopulmonary resuscitation. In 40 of the 104 patients (38.5%) a return of spontaneous circulation (ROSC) could be achieved successfully. Patients with ROSC received thrombolysis significantly earlier after CPR onset compared to patients without ROSC (13.6±1.2 min versus 24.6±0.8 min; p<0.001). 19 patients (47.5%) out of the 40 patients with initially successful resuscitation survived to hospital discharge. In patients with hospital discharge thrombolysis therapy was begun with a significantly shorter delay after cardiac arrest compared to all other patients (11.0±1.3 vs. 22.5±0.9 min; p<0.001).

Conclusion

Rescue-thrombolysis should be considered and started in patients with PE and cardiac arrest, as soon as possible after cardiac arrest onset.     

Up-regulation of cerebral carbonic anhydrase by anoxic stress in piglets

The resuscitation of asphyxiated babies is associated with changes in cerebral protein synthesis that can influence the neurological outcome. Insufficient gas exchange results in rapid shifts in extracellular and intracellular pH. Carbonic anhydrase (CA) plays an important role in buffering acute changes in pH in the brain. We investigated whether asphyxia/re-ventilation influences the expression of cerebral CA isoforms (CA-II, CA-III and CA-IV) in anaesthetized newborn pigs. The cerebral cortex, hippocampus, cerebellum and retina were sampled, and prepared for either CA immunohistochemistry or CA immunoblotting from piglets subjected to asphyxia (10 min) followed by 2-4 h of re-ventilation, and also from normoxic controls. The CA immunoreactivity (IR) of all the isoforms studied was weak in the controls, apart from staining of a few oligodendrocytes in the subcortical white matter, some astrocytes in the superficial layer of the cerebral cortex, the cerebellar Purkinje cells and the retinal Müller cells that possessed moderate CA-II IR. However, asphyxia induced a marked increase in the CA IR of all isoforms in all the cerebral regions investigated and the retina after 4 h of survival. The pyramidal cells of the frontal cortex and hippocampus displayed the most conspicuous increase in CA IR. Immunoblotting confirmed increased levels of all the CA isoenzymes. We conclude that raised CA levels after asphyxia may contribute to the compensatory mechanisms that protect against the pathological changes in the neonatal CNS.     

Nitrite therapy is neuroprotective and safe in cardiac arrest survivors

Cardiac arrest results in significant mortality after initial resuscitation due in most cases to ischemia-reperfusion induced brain injury and to a lesser degree myocardial dysfunction. Nitrite has previously been shown to protect against reperfusion injury in animal models of focal cerebral and heart ischemia. Nitrite therapy after murine cardiac arrest improved 22 h survival through improvements in myocardial contractility. These improvements accompanied transient mitochondrial inhibition which reduced oxidative injury to the heart. Based on preliminary evidence that nitrite may also protect against ischemic brain injury, we sought to test this hypothesis in a rat model of asphyxia cardiac arrest with prolonged survival (7d). Cardiac arrest resulted in hippocampal CA1 delayed neuronal death well characterized in this and other cardiac arrest models. Nitrite therapy did not alter post-arrest hemodynamics but did result in significant (75%) increases in CA1 neuron survival. This was associated with increases in hippocampal nitrite and S-nitrosothiol levels but not cGMP shortly after therapy. Mitochondrial function 1h after resuscitation trended towards improvement with nitrite therapy. Based on promising preclinical data, the first ever phase I trial of nitrite infusions in human cardiac arrest survivors has been undertaken. We present preliminary data showing low dose nitrite infusion did not result in hypotension or cause methemoglobinemia. Nitrite thus appears safe and effective for clinical translation as a promising therapy against cardiac arrest mediated heart and brain injury.     

Evidence that Meishan and Large-White hybrid preovulatory follicles may differentially affect oocyte in vitro maturation and fertilization

Two experiments were carried out to test the hypothesis that follicles recovered from Meishan animals may provide a more favourable environment for oocyte maturation in vitro than follicles recovered from Large-White hybrid animals. In Experiment 1, all follicles ≥4 mm were recovered from six Meishan and seven Large-White hybrid gilts in the late follicular phase and healthy oocyte cumulus complexes recovered. Cumulus oocyte complexes were randomly divided into two groups, and each group cultured for 27 or 34 h (62 and 64; 56 and 56 for Meishan and Large-White hybrid, respectively) in defined medium in the presence of either of the two largest follicle shells per animal. Subsequent examination of oocyte nuclear maturation showed that although maturation did not differ significantly between the breeds after 27 h, more (P<0.01) Meishan oocytes co-cultured with Meishan follicles developed to metaphase II stage than Large-White hybrid oocytes co-cultured with Large-White hybrid follicles after 34 h. The next eight largest follicles per animal were cultured for 34 h to produce conditioned media. In Experiment 2, oocytes recovered from the slaughterhouse were matured for 46 h in the presence of conditioned media from Meishan (612 oocytes) or Large-White hybrid (731 oocytes) follicles, or in fresh medium in the presence of a follicle shell from slaughterhouse ovaries. Oocytes were then inseminated and 12 h later examined for penetration and male pronuclear formation. A higher (P<0.05) percentage of oocytes cultured in Meishan follicle conditioned medium underwent sperm penetration and male pronuclear formation than oocytes cultured in conditioned media from Large-White hybrid animals. Concentrations of oestradiol and progesterone in the conditioned media did not differ between the breeds (P>0.1). In conclusion, these results suggest that (1) Meishan oocytes have advanced maturational capacity when cultured with Meishan preovulatory follicle shells and (2) differences in follicle maturation in the Meishan compared to the Large-White hybrid pig may result in an improved ability of the follicles, via conditioned media, to support oocyte maturation and fertilization in vitro.     

Circulating levels of cytochrome c after resuscitation from cardiac arrest: a marker of mitochondrial injury and predictor of survival

Ca(2+) overload and reactive oxygen species can injure mitochondria during ischemia and reperfusion. We hypothesized that mitochondrial injury occurs during cardiac resuscitation, causing release of cytochrome c to the cytosol and bloodstream while activating apoptotic pathways. Plasma cytochrome c was measured using reverse-phase HPLC and Western immunoblotting in rats subjected to 4 or 8 min of untreated ventricular fibrillation and 8 min of closed-chest resuscitation followed by 240 min of postresuscitation hemodynamic observation. A sham group served as control. Plasma cytochrome c rose progressively to levels 10-fold higher than in sham rats 240 min after resuscitation (P < 0.01), despite reversal of whole body ischemia (decreases in arterial lactate). Cytochrome c levels were inversely correlated with left ventricular stroke work (r = -0.40, P = 0.02). Western immunoblotting of left ventricular tissue demonstrated increased levels of 17-kDa cleaved caspase-3 fragments in the cytosol. Plasma cytochrome c was then serially measured in 12 resuscitated rats until the rat died or cytochrome c returned to baseline. In three survivors, cytochrome c rose slightly to 相似文献   

猪CAST基因的单核苷酸多态性及其对肉质性状的效应

CAST基因作为肉质性状的主要候选基因.以80头外来猪和190头地方猪为材料,在CAST基因内含子24上检测到两个多态性位点(A916G 和C1633G ).在916位点上,长白猪和大白猪以A基因为优势基因,其频率分别为0.88和1.00;莱芜猪,大薄莲猪,沂蒙黑猪和里岔黑猪以B基因为优势基因,其频率分别为0.93, 0.97, 0.78和0.68.在1633位点上,长白猪和大白猪以C基因为优势基因,其频率分别为0.82和0.79:莱芜猪,大薄莲猪,沂蒙黑猪和里岔黑猪以D基因为优势基因,其频率分别为1.00, 1.00, 0.88, 0.78.在试验猪种中,共检测到6种单倍型(AACC,AACD,AADD,ABCC,BBCC,BBDD).单倍型分布的多重比较结果表明,外来猪种(长白猪和大白猪)与地方猪种(莱芜猪,大薄莲猪,沂蒙黑猪和里岔黑猪)比较差异极显著(P < 0.01).固定效应模型分析结果表明,嫩度,屠宰45 min后pH值和滴水损失单倍型间差异显著(P < 0.05).最小二乘分析结果表明,外来猪种与地方猪种在嫩度,屠宰45 min后pH值和滴水损失间差异显著(P < 0.05).BBDD单倍型个体与其它单倍型个体比较,嫩度及滴水损失差异显著(P < 0.05);AADD,BBCC,BBDD单倍型个体与其它单倍型个体比较,屠宰45 min后pH值差异显著(P < 0.05).因此,在育种过程中将CAST基因应用于标记辅助选择,将有利于改善猪肉品质,加快育种进程.     

纳洛酮对心搏骤停患者心肺复苏后氧化应激反应及缺血缺氧性脑病的影响

目的:探讨纳洛酮对心搏骤停患者心肺复苏(CPR)后氧化应激反应及缺血缺氧性脑病的影响。方法:将我院收治的78例骤停时间≤10 min的心搏骤停患者随机分为治疗组和对照组,每组各39例。两组均按照美国心脏学会心肺复苏指南进行标准的心肺复苏,治疗组在此基础上静脉注射纳洛酮2 mg,复苏后用纳洛酮0.4 mg/(kg·d)微量注射泵24h持续泵入。比较两组的CPR成功率、血浆丙二醛(MDA)含量和谷胱甘肽过氧化物酶(GSH-PX)、超氧化物歧化酶(SOD)活性,监测其不同时点脑氧摄取量(CEO2)的变化。结果:与对照组比较,治疗组自主循环恢复成功率、复苏后24 h存活率均显著升高(P<0.05)。自主循环恢复后,治疗组SOD、GSH-PX活性较对照组明显增加(P<0.05);复苏后24 h,两组MDA含量均显著升高,SOD、GSH-PX活性明显减弱,而治疗组各氧化应激指标明显优于对照组(P<0.05)。两组患者在复苏早期CEO2迅速升高,但在复苏后24 h开始下降,48~72 h处于相对稳定的水平,治疗组各时间点CEO2均明显高于对照组(P<0.05)。结论:纳洛酮可减轻心搏骤停患者CPR后体内氧化应激损伤和缺血缺氧性脑病,改善患者的预后。     

Relationships between ovulation rate and litter size in purebred Landrace and Yorkshire gilts

The aim of the present study was to investigate the ovulation rate and its relationship to number of total piglets born in purebred gilts under tropical climatic conditions. This study was conducted in two swine breeding herds (A and B) in the northeastern part of Thailand. The sources of swine genetic material originate from West Europe. Gilts were mated (AI) on the second or later observed estrus at a body weight of at least 130 kg. In most cases, they were mated at third estrus. One hundred and twenty-seven gilts, 24 Landrace and 24 Yorkshire from herd A, and 42 Landrace and 37 Yorkshire from herd B were used. Gilts were examined once by laparoscopy under general anesthesia between days 8 and 15 after mating. The ovaries were examined and the pathological findings were recorded. The number of corpora lutea was counted, and was assumed to equal the ovulation rate. Subsequent mating results and farrowing data were recorded. The data were analyzed with analysis of variance. Single or double unilateral cysts and par-ovarian cysts did not affect mating results. Landrace gilts were significantly younger at first mating than Yorkshire gilts (244 versus 249 days, P < 0.05). At first mating, Yorkshire gilts had a significantly higher ovulation rate compared to Landrace gilts (15.3 versus 13.8, P < 0.001). There was no difference in the number of total piglets born per litter between the two breeds, but the total prenatal loss from ovulation to farrowing was significantly higher in Yorkshire than in Landrace gilts. Both the low ovulation rate and the high prenatal loss contribute to the low litter size in gilts raised under tropical climatic conditions.     

Permeability of barriers to albumin flux in lungs of sheep resuscitated from hemorrhagic shock

We assessed pulmonary endothelial and epithelial permeability and lung lymph flow in nine adult sheep under base-line conditions and after resuscitation from profound hemorrhagic shock. Animals were mechanically ventilated and maintained on 1% halothane anesthesia while aortic pressure was held at 40 Torr for 3 h. Systemic heparin was not used. After reinfusion of shed blood, sheep recovered from anesthesia and we measured lung lymph flow (QL), lymph-to-plasma concentration ratio for proteins, and time taken to reach half-equilibrium concentration of intravenous tracer albumin in lymph (t1/2). Twenty-four hours after bolus injection of radio-albumin we lavaged subsegments of the right upper lobe and determined fractional equilibration of the tracer in the alveolar luminal-lining layer. In each sheep we had measured these parameters 7 days earlier under base-line conditions. Animals were killed, and the lungs were used for gravimetric determination of extravascular lung water (gravimetric extravascular lung water-to-dry weight ratio) 24 h after resuscitation from shock. Pulmonary endothelial injury after resuscitation was evidenced by marked increase in QL, without fall in lymph-to-plasma ratio. Time taken to reach half-equilibrium concentration fell from 169 +/- 47 (SD) min in base-line studies to 53 +/- 33 min after shock. There was no evidence of lung epithelial injury. Gravimetric extravascular lung water-to-dry weight ratio was significantly increased in these animals killed 24 h after resuscitation (4.94 +/- 0.29) compared with values in our laboratory controls (4.13 +/- 0.09, mean +/- SD). These data demonstrate a loss of lung endothelial integrity in sheep after resuscitation from profound hemorrhagic shock.     

在小鼠心跳骤停期间应用中度低温对复苏后抗氧化物酶活性的影响

目的：低温在许多小鼠心跳骤停后复苏模型的研究中被证实是有效的。心跳骤停后释放的氧自由基是产生继发性损伤的一个重要机制。本研究旨在探索心跳骤停期间应用中度低温对复苏后抗氧化物酶活性的影响。方法：用氯化钾诱导8min心跳骤停。此实验分为常温心跳骤停组（NCA）、低温心跳骤停组（HCA）TL对照组。HCA组在心跳骤停5min后开始降温使核心温度维持在（30．0±1．0）℃。应用胸部按压和肾上腺素来复苏。在心跳骤停两组各选择三个时间点：复苏后1h、4h和24h。测量超氧化物歧化酶（SOD）和过氧化氢酶（CAT）在心脏和肝脏的活性。结果：实验动物在HCA组比常NCA组生存率高。HCA组比NCA组复苏时间明显延长。与NCA组相比,HCA组复苏后24h的SOD活性在肝脏表达明显降低。与NCA组相比,HCA组复苏后4h的CAT活性在肝脏表达显著增高。结论：在心跳骤停过程中,与正常体温相比,应用中度低温能够提高生存率。与正常体温相比较,在心跳骤停中期间应用中度低温不影响心脏的SOD与CAT活性,应用中度低温在肝脏可延迟性抑制SOD的活性并且短暂提高CAT活性。     

Effects of a free radical scavenger N-tert-butyl-alpha-phenylnitrone (PBN) on short-term recovery of immature rats after status epilepticus

The present study examined the effects of a free radical scavenger, N-tert-butyl-alfa-phenylnitrone (PBN) on lithium-pilocarpine-induced status epilepticus (SE) and its short-term consequences in rats 12 (P12) or 25 (P25) days old. PBN (2 x 100 mg/kg i.p.) was injected according to the following schedules: 1) PBN-pretreated animals received the first dose 30 min prior to pilocarpine, the second dose was given 1 min after SE onset, and 2) PBN-treated animals received the first dose of PBN 1 min after SE onset and the second one 60 min later. Paraldehyde was administered to decrease mortality. Effects of PBN were highly age-dependent. In P25 group, PBN-pretreatment increased latency to SE onset and significantly suppressed the severity of motor manifestation of SE. Both PBN pretreatment and treatment improved recovery after SE. In contrast, administration of PBN in P12 animals did not affect SE pattern or recovery after SE. Administration of PBN had no effects on the motor performance of animals 3 and 6 days after SE. Neuronal damage was examined 24 h and 7 days after SE using Fluoro-Jade B staining. Mild neuroprotective effects of PBN in hippocampal fields CA1 and CA3 occurred in P25 rats in both experimental schedules. In contrast, administration of PBN aggravated neuronal injury in the hippocampus in P12 rats. Administration of PBN to intact rats did not induce neurodegeneration in either age group.