The conservation of mitochondrial function by ischaemia – the ischaemia paradox

The aim of this study was to compare oxidative phosphorylation of rat heart mitochondria, isolated: (i) immediately after excision of the heart; (ii) after 60 min of low flow normoxic perfusion; (iii) after 60 min of high flow normoxic perfusion; (iv) after 30 min of no-flow ischaemia and (v) after 30 min ischaemia followed by 20 min reperfusion. The results, using a retrogradely perfused rat hart as a model, show that mitochondrial oxidative phosphorylation after 30 min of no-flow ischaemia showed no difference from oxidative phosphorylation measured on mitochondria isolated directly after excision of the heart. However, after 30 min no-flow ischaemia followed by 20 min of reperfusion, oxidative phosphorylation deteriorated in comparison with oxidative phosphorylation after 30 min of ischaemia only. Furthermore, oxidative phosphorylation after 60 min of non-ischaemic high flow perfusion (thus high coronary flow), compared better with oxidative phosphorylation after ischaemia-reperfusion than with oxidative phosphorylation after ischaemia alone.     

Haemostasis and antithrombin III in the full-term newborn foal

Thirty-three Standardbred foals received a physical examination and had blood drawn for anti-thrombin III (AT III), immunoglobulin G (IgG), and haemostasis evaluation between 24 and 72 h of age. Based on physical examination, a normal haemogram within reference intervals and serum IgG concentration >600 mg/dl, 19 foals remained in the study. AT III values for protein concentration (mg/dl) and activity (mg/dl and percentage thrombin inhibition) were determined by rocket immunoelectrophoresis and chromogenic substrate assay, respectively, and compared to the reference intervals for adults. In 19 healthy, full-term foals, the mean plasma AT III activity for percentage thrombin inhibition (75.9%), mean amount of active AT III (19.2 mg/dl) and the mean plasma AT III concentration (28.7 mg/dl) were significantly (P<0.05) lower than the reference interval of adult values. The mean active AT III concentration for both foals (19.2 mg/dl) and adults (24.6 mg/dl) was significantly (P<0.05) less than their AT III concentration, 28.7 and 44.3 mg/dl, respectively. Fibrinogen degradation products (FDPs) were increased in 100% of the foals, with 12 of 19 (63%) having FDPs >10 <40 g/dl). Platelet count, prothrombin time, activated partial thromboplastin time and fibrinogen did not differ significantly from those of adult values.These findings support the view that haemostasis in the full term foal is characterised as a hypercoagulable state by the significant decrease in plasma AT III activity and concentration and increase in split products of fibrin and fibrinogen.     

红花注射液对脂多糖诱导的兔弥散性血管内凝血的作用

 目的：研究红花注射液对脂多糖（LPS）诱导的兔弥散性血管内凝血（DIC）的作用。方法：兔耳缘静脉持续滴注LPS建立兔DIC模型。采用全自动凝血分析仪检测活化部分凝血活酶时间（APTT）和凝血酶原时间（PT）;凝固法测定纤维蛋白原含量;全自动血细胞分析仪进行血小板计数;发色底物法测定蛋白C及抗凝血酶Ⅲ的活性;全自动血浆分析仪测定丙氨酸氨基转移酶（ALT）和血尿素氮（BUN）;ELISA法检测血浆纤维蛋白（原）降解产物（FDP）和肿瘤坏死因子 α（TNF-α）含量。结果：DIC模型组APTT和PT进行性延长,ALT活性和BUN含量显著升高,蛋白C和抗凝血酶Ⅲ的活性显著降低,血小板计数进行性减少,血浆FDP和TNF-α含量显著升高。给予红花注射液后,DIC模型兔APTT和PT的延长明显缩短,血小板计数、纤维蛋白原含量、蛋白C及抗凝血酶Ⅲ活性均明显恢复,血浆ALT、BUN、FDP和TNF-α水平均明显降低。结论: 红花注射液对LPS诱导的兔DIC有较好的拮抗作用。     

Modulation of nitric oxide affects myocardial perfusion-contraction matching in anaesthetized dogs with recurrent no-flow ischaemia

Myocardial perfusion and contraction are closely coupled; however, the effect of recurrent no-flow ischaemia on perfusion-contraction matching remains to be established. In the present studies, we examined the influence of modulating nitric oxide availability on perfusion-contraction matching after recurrent no-flow ischaemia in acute open-chest, anaesthetized dogs. The following three groups were studied: (1) saline; (2) L-NAME (10 mg kg(-1) I.V.); and (3) enalaprilat (1.5 mg kg(-1) I.V.). Regional myocardial blood flow was measured with microspheres and contractile function with piezoelectric crystals to determine systolic wall thickening. Dogs underwent four cycles of 5 min acute ischaemia and 5 min coronary reperfusion; area at risk was similar for all groups. In all dogs, ischaemic zone contractile function was depressed after recurrent no-flow ischaemia despite increased myocardial blood flow during reperfusion; contractile function was further depressed during L-NAME and was partly restored with enalaprilat. Within the ischaemic region, blood flow in subendocardial and subepicardial layers increased significantly compared with baseline during each reperfusion period independently of treatment. Our findings suggest that reduced NO availability can significantly impair myocardial perfusion-contraction matching, which is partly restored by administration of an NO donor.     

血栓通注射液对LPS诱导的兔弥散性血管内凝血的拮抗作用

 目的：研究血栓通注射液对脂多糖（LPS）诱导的兔弥散性血管内凝血（DIC）的影响。方法：对兔耳缘静脉持续滴注LPS以建立兔DIC模型,记录各组动物在24 h后的生存率;全自动血浆分析仪测定丙氨酸氨基转移酶(ALT)和血尿素氮(BUN);用全自动凝血分析仪检测活化部分凝血活酶时间（APTT）和凝血酶原时间（PT）;用凝固法测定纤维蛋白原含量;全自动血细胞分析仪进行血小板计数;发色底物法测定蛋白C和抗凝血酶Ⅲ的活性;ELISA法检测血浆中肿瘤坏死因子α（TNF-α）的含量。结果：持续从兔耳缘静脉滴注LPS后,DIC模型组动物大量死亡,ALT和BUN显著升高,APTT和PT显著延长,蛋白C和抗凝血酶Ⅲ的活性明显降低,血小板计数明显减少,血浆中TNF-α的含量显著升高。注射血栓通注射液后,动物的死亡率明显下降,ALT和BUN明显下降,APTT和PT明显缩短,血小板计数明显上升,纤维蛋白原含量显著提高,蛋白C和抗凝血酶Ⅲ活性明显提升;血浆TNF-α的含量明显降低。结论：血栓通注射液对LPS所诱导的兔DIC有良好的拮抗作用。     

Investigation of Inflammatory and Hemostatic Parameters in Female Patients Undergoing Total Knee Arthroplasty Surgery

Tendency to hypercoagulation is a common phenomenon in primary osteoarthritis patients (POA) undergoing total knee arthroplasty (TKA) surgery, but the clinical implications of this condition are not clear. Therefore we aimed to evaluate the inflammatory and coagulation parameters in the patient group and find a possible explanation for the tendency to hypercoagulation occurring in plasma and synovia of inflamed joints. Of the evaluated factors involved in inflammation and coagulation, galectin-3, C reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, FVIIa:C, FXII:C, and platelet count increased, whereas tissue factor (TF) activity in synovia, PT, APTT and FVII:C in plasma and synovia were decreased. In conclusion, activation of inflammation and tendency to hypercoagulation is observed in preoperative plasma and synovia of patients undergoing TKA surgery.     

Disturbances of haemostasis in diabetes mellitus

Diabetes mellitus is associated with disturbances in haemostasis that could contribute to the development of thrombotic complications.The present study was undertaken to determine the behavior of coagulation variables and fibrinolytic system in diabetes mellitus. Forty five diabetic patients and forty five matched controls were evaluated by doing the following haemostatic parameter, prothrombin time, partial thromboplastin time, thrombin time, coagulation factors assay II, VII, IX, & plasma fibrinogen, ADP-induced platelet aggregation, protein C, alpha2- antiplasmin, PAI and FDPs. Generally diabetic patients have high levels of fibrinogen, alpha2- antiplasmin, & PAI and lower level of protein C. Other haemostatic parameters did not show statistically significant difference between diabetic patients and control group. Significantly elevated levels of PAI, alpha2- antiplasmin together with low protein C level in diabetic patients may result in the disturbance of haemostatic balance favoring thrombotic events. CONCLUSION: High levels of plasma fibrinogen, alpha2A- antiplasmin with low plasma protein C activity could lead to a prothrombotic tendency in insulin dependent diabetic patients. Moreover, in non-insulin dependent diabetic patients, the above mentioned parameters together with high levels of ADP-induced platelet aggregation and plasminogen activator inhibitor may increase the risk of thrombotic complications. Obesity can be considered as an additional risk factor for development of thrombosis in diabetic patients.     

In situ analysis of ischaemia/reperfusion injury in rat liver studied in three different models

Animal models of liver ischaemia and reperfusion are frequently used to study the consequences on liver cells of transient oxygen deprivation. In 3 different rat models we studied ischaemia/reperfusion effects on liver cell membrane integrity, cytoplasmic enzyme proteins and enzyme activities by in situ histochemical techniques. In vivo ischaemia, as well as no-flow hypoxia, or N₂-induced hypoxia in isolated perfused livers, reduced the activity of 5'-nucleotidase, a sensitive marker for plasma membrane damage in hepatocytes. As little as 2 minutes of reoxygenation in each model resulted in leakage of soluble enzymes from parenchymal and non-parenchymal liver cells, as shown by decreased protein level and activity of cytoplasmic enzymes. Whereas a multifocal decrease was observed after in vivo reperfusion, a decrease was found in all periportal and midzonal cells after blood-free reoxygenation. As judged by alkaline phosphatase activity and immunohistochemistry, an influx of inflammatory cells was not found in the in vivo model. Our findings indicate that reoxygenation itself, rather than restoration of flow, accounts for the loss of soluble enzymes from liver cells after a period of hypoxia. In situ detection of enzyme protein and activity proved useful for the examination of very early ischaemia/reperfusion effects on rat liver cells.     

Effects of a natural estrogen, estradiol, on hemostasis in guinea pigs

17-beta-estradiol was administered weekly to female guinea-pigs at the dosage of 2-3 mg/kg body weight during 4-6 weeks. Compared to a control population, no significant effect was observed on: recalcification time; thromboelastography; PTT; APTT; Quick one stage prothrombin time; antigenic and active plasma fibrinogen level; antithrombin III level; factor XI level; red and white blood cell count. A significant increase in levels of factor II (+25%), of factor V, of factor XII (+40%) and a decrease in levels of complex VII + X was observed. Values for AT III, factor XII, chronometric and immunologic fibrinogen plasma levels, unknown until now for the guinea-pig, were established.     

肢体缺血再灌注损伤对大鼠肠系膜微循环和血液流变性的变化及意义

目的研究大鼠肢体缺血再灌注损伤时肠系膜微循环和血液流变性的变化，并探讨其意义。方法用BI-2000医学图像分析系统对肢体缺血再灌注大鼠的肠系膜微循环进行观察，大鼠随机分为6组（每组10只），在肢体缺血前（Control组），缺血4h（Ⅰ组），再灌注20min（IP,．20组），再灌注60min（IR60组），再灌注120min（IR120组），再灌注200min（IR200组）时观察和记录肠系膜微循环改变，并测定血液流变学指标并于上述各时间点分别测定各组动物血液流变学指标及前列环素（Pros—tacyclin，PGI2）水平、血栓素A2（Thromboxane A2，TXA2）水平、前列环素／血栓素A2比值（PG12／TXA2）。结果①与Control组比较，IR20组、IR60组大鼠肠系膜微动脉和微静脉管径缩小（P〈0．01或P〈0．05）；IR120组、IR200组大鼠肠系膜微动脉和微静脉管径扩大（P〈0．01或P〈0．05）；Ⅰ组变化差异无显著性（P〉0．05）。②与Control组比较，IR20组、IR60组、IR120组、IR200组大鼠肠系膜微动脉和微静脉血流速度依次减慢（P〈0．01）；Ⅰ组变化差异无显著性（P〉0．05）。③再灌注期，白细胞黏附聚集、白微栓及管周出血增多；血浆黏度、全血低切还原黏度（1s^-1）、全血高切还原黏度（200s^-1）、红细胞比容、红细胞聚集指数、血沉方程K值、红细胞刚性指数等指标增高，红细胞变形指数降低。血浆中PGI2、TXA2含量均于再灌注期先升高后降低，但PGI2／TXA2比值减小。结论大鼠肢体IR损伤时存在肠系膜微循环障碍和血液流变性异常，其发生可能与血管内皮的功能受损，PGI2／TXA2水平的平衡失调有重要关系。     

PGI2对肾缺血再灌损伤兔肠系膜微循环和血液流变性的影响

目的：探讨前列腺素I2（PGI2）对兔肾缺血再灌注（IR）损伤时肠系膜微循环和血液流变性的影响。方法： 采用钳夹肾动脉的方法建立急性肾缺血再灌注损伤模型。日本大耳白兔36只，随机分为：假手术对照（sham）组、单纯缺血再灌注（IR）组和PGI2+IR（PGI2）组。运用微循环显微镜自动摄像分析系统，于肾缺血60 min和再灌注120 min时动态观察肠系膜微循环和测定血液流变学指标。结果： ①缺血期和再灌注期IR组的肠系膜微动、静脉管径减小，血流速度明显减慢，白细胞粘附聚集、白微栓及管周出血增多，全血粘度、血浆粘度、全血还原粘度、红细胞压积、红细胞聚集指数、血沉、血沉方程K值、纤维蛋白原含量增高，红细胞变形指数降低，与假手术对照组比较有显著差异（P＜0.01或P＜0.05）。②5-40 ng·kg-1·min-1PGI2可不同程度地影响肠系膜微循环和血液流变性，其中在10 ng·kg-1·min-1PGI2组，微血管管径和流速、白细胞粘附、白微栓、管周出血及上述各血液流变学指标与IR组比较显著差异（P＜0.01或P＜0.05），与假手术对照组比较微血管管径明显增大（P＜0.01），而其余指标无显著差异（P＞0.05）。结论： 肾IR损伤时肠系膜微循环和血液流变性异常，PGI2对其具有明显的预防作用，以10 ng·kg-1·min-1PGI2为最佳有效预防剂量。     

一个纤维蛋白原γ链Arg275His突变导致的遗传性异常纤维蛋白原血症家系

目的　对一个遗传性异常纤维蛋白原血症家系进行表型和基因型分析。方法　采集家系3代5人外周血,吸取上层血浆用血凝仪检测活化部分凝血酶原时间、凝血酶原时间、凝血酶时间、蛋白C活性、蛋白S活性和抗凝血酶活性,纤维蛋白原活性和抗原分别用Clauss法和免疫比浊法进行检测。以常规酚-氯仿法抽提家系所有成员外周血基因组DNA,PCR扩增纤维蛋白原基因FGA、FGB和FGG所有外显子及其侧翼序列,PCR产物纯化后直接测序以检测基因突变。结果　先证者活化部分凝血酶原时间、凝血酶原时间正常,凝血酶时间超出正常上限值2倍以上,纤维蛋白原活性明显下降,抗原也低于正常范围,且活性显著低于抗原;其母表型检测结果与之相似。基因分析显示先证者呈纤维蛋白原FGG基因第8外显子g.5 6 78G>A杂合碱基置换,导致Arg2 75 His错义突变,该突变来源于母系。结论　纤维蛋白原γ链Arg2 75 His杂合错义突变是引起该家系异常纤维蛋白原血症的原因。     

Disturbances of Haemostasis in Diabetes Mellitus

Diabetes mellitus is associated with disturbances in haemostasis that could contribute to the development of thrombotic complications.The present study was undertaken to determine the behavior of coagulation variables and fibrinolytic system in diabetes mellitus. Forty five diabetic patients and forty five matched controls were evaluated by doing the following haemostatic parameter, prothrombin time, partial thromboplastin time, thrombin time, coagulation factors assay II, VII, IX, & plasma fibrinogen, ADP-induced platelet aggregation, protein C, a₂- antiplasmin, PAI and FDPs. Generally diabetic patients have high levels of fibrinogen, a₂- antiplasmin, & PAI and lower level of protein C. Other haemostatic parameters did not show statistically significant difference between diabetic patients and control group. Significantally elevated levels of PAI, a₂- antiplasmin together with low protein C level in diabetic patients may result in the disturbance of haemostatic balance favoring thrombotic events. Conclusion: High levels of plasma fibrinogen, a₂A- antiplasmin with low plasma protein C activity could lead to a prothrombotic tendency in insulin dependent diabetic patients. Moreover, in non-insulin dependent diabetic patients, the above mentioned parameters together with high levels of ADP-induced platelet aggregation and plasminogen activator inhibitor may increase the risk of thrombotic complications. Obesity can be considered as an additional risk factor for development of thrombosis in diabetic patients.     

下肢骨折围手术期凝血-抗凝及纤溶指标动态变化的意义

目的：探讨下肢骨折患者围手术期凝血一抗凝及纤溶指标动态变化规律,指导临床有针对性预防下肢深静脉血栓形成。方法：选择下肢骨折需卧床治疗患者35例为实验组,选择上肢骨折患者30例为对照组。分别于术前、术后1d、术后3d及术后14d采集静脉血,检测血浆凝血酶原时间（PT）、活化部分凝血活酶时间（AFIT）、纤维蛋白原（FIB）、纤维蛋白（原）降解产物（FDP）、D．二聚体（D-D）、抗凝血酶活性（AT）。结果：FIB、FDP和D-D：实验组术后1d和术后14d与术前比较差异有非常显著性意义（P〈0．01）,对照组术后1d与术前比较差异有非常显著性意义（P〈0．01）;AT：实验组术后14d与术前比较差异有非常显著性意义（P〈0．01）。结论：下肢骨折患者术后局部血流减慢,FIB、FDP和D-D增高,AT降低,提示机体可能处于血栓前状态或有血栓形成。     

Validity of the microdialysis technique for experimental in vivo studies of myocardial energy metabolism

OBJECTIVES: The validity of the microdialysis technique for experimental in vivo studies of myocardial energy metabolism is not known. To address this question interstitial levels of energy-related metabolites (lactate, adenosine, inosine and hypoxanthine) obtained by the microdialysis technique were compared with corresponding metabolites from myocardial biopsies at given intervals in a porcine heart model using different protocols of ischaemia and reperfusion. METHODS: In an open chest porcine heart model, interstitial levels of energy-related metabolites were monitored using the microdialysis technique. All animals (n = 23) were subjected to 120-min pretreatment followed by 40 min of regional ischaemia and 120 min of reperfusion. Tissue biopsies were obtained in the beginning, middle and at the end of the 40-min ischaemic period and at the end of the reperfusion period. Pretreatment consisted of either rest (group 1, n = 7), or rest for 90 min and one ischaemia/reperfusion (10 + 20 min) cycle (group 2, n = 9), or four ischaemia/reperfusion cycles (10 + 20 min each) (group 3, n = 7). RESULTS: Interstitial levels of energy-related metabolites monitored by the microdialysis technique correlated with tissue biopsy levels of lactate (r = 0.90, P < 0.001), adenosine (r = 0.89, P < 0.001), inosine (r = 0.88, P < 0.001) and hypoxanthine (r = 0.91, P < 0.001), respectively, which were obtained by tissue biopsies at given time intervals. These significant correlations were valid regardless of the functional state of the myocardium. CONCLUSION: We observed significant correlations between microdialysis probe levels and tissue biopsy levels of energy-related metabolites in both ischaemic and non-ischaemic tissue. These data assess the validity of the microdialysis technique (in the current setting) for studying dynamic changes of myocardial energy metabolism.     

The influence of retrograde reperfusion on the ischaemia‐/ reperfusion injury after liver transplantation in the rat

Dysfunction of the graft after liver transplantation caused by ischaemia‐/reperfusion (I/R) injury is a serious clinical problem. The aim of this study was to evaluate the influence of different kinds of reperfusion on I/R injury in a rat model. Arterialized orthoptic rat liver treatment was performed on male LEWIS‐(RT¹)‐rats. Three groups (n = 7) were formed. Group I: antegrade reperfusion with a 6‐min delayed reperfusion via the hepatic artery. Group II: Antegrade reperfusion, simultaneously, via the portal vein and the hepatic artery. Group III: Retrograde reperfusion via the vena cava. Serum parameters were determined one, 24 and 48 h after operation. Furthermore, after 48 h, the liver was taken for histological assessment. After 48 h, rats of group III showed significantly lower aspartate amino transferase and alanine amino transferase serum levels compared with group I and group II rats. Forty‐eight hours after transplantation, glutamate dehydrogenase serum level was significantly lower in group III than in group II. In histology, group III livers showed significantly less necrotic spots than group I and group II livers. Maximum size of the necrotic spots was significantly lower in group III than in group I. Also, significantly more necrotic spots were seen in the ‘Rappaport′s zone’ 1 and 2 of group I than in group III. Our data suggested that the expression of I/R‐injury correlates with the type of reperfusion. Furthermore, under standard conditions, this study was able to demonstrate that in a rat model, the retrograde reperfusion leads to a lower expression of I/R‐injury than the antegrade reperfusion.     

复方丹参注射液抗脂多糖诱导的兔弥漫性血管内凝血

目的: 研究复方丹参注射液对脂多糖(LPS)诱导的兔弥漫性血管内凝血(DIC)的作用。方法: 用LPS诱导兔DIC模型。凝固法测定纤维蛋白原含量,全自动凝血分析仪检测活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)和纤维蛋白原含量;全自动血细胞分析仪进行血小板计数;全自动血浆分析仪测定谷丙转氨酶(ALT)以及血尿素氮(BUN);发色底物法测定蛋白C及抗凝血酶Ⅲ的活性。观察复方丹参注射液对LPS诱导的兔DIC的拮抗作用。结果: 兔耳缘静脉持续滴注LPS,观察到:APTT和PT显著延长;血小板计数和纤维蛋白原含量明显减少;ALT和BUN显著升高;蛋白C和抗凝血酶Ⅲ的活性明显降低。给予复方丹参注射液后,APTT和PT的延长明显缩短;血小板计数和纤维蛋白原的含量均明显恢复;ALT和BUN显著下降;蛋白C及抗凝血酶Ⅲ的活性显著改善。结论: 复方丹参注射液对LPS诱导的兔DIC有良好的拮抗作用。     

Cytotoxicity, blood compatibility and antimicrobial activity of two cyanoacrylate glues for surgical use

The biocompatibility of two cyanoacrylate surgical glues (Glubran and Glubran 2), supplied by General Enterprise Marketing, Viareggio, Lucca, Italy, was tested through cytotoxicity and blood compatibility tests and the evaluation of antimicrobial activity. Cytotoxicity and blood compatibility tests were performed on the polymerized glues. Using the neutral red uptake test, the extracts from Glubran and Glubran 2 after polymerization were non-toxic to L929 cells only when diluted 1: 10 with culture medium. Glubran and Glubran 2 induced a significant decrease of activated partial thromboplastin time (APTT), which is favourable with regard to the desired haemostasis. The APTT shortening determines a haemostatic effect and therefore contribute to the tissue adhesion induced by the glues. Otherwise, no significant variation of prothrombin activity, fibrinogen, platelet number, total and differential leukocyte count was induced by the glues, which, in addition, did not show haemolytic effect. There was no difference between Glubran and Glubran 2 regarding haemocompatibility. The antimicrobial ability of the unpolymerized glues was tested onto Bacillus subtilis var. niger for 3 weeks: neither Glubran nor Glubran 2 were found effective in this respect. In conclusion, we can assume that cytotoxicity was severe with the undiluted glues, but was acceptable when glues were diluted. On the contrary, blood compatibility was acceptable for the intended use of the glues. No difference was found between Glubran and Glubran 2 after polymerization.     

Splanchnic ischaemia–reperfusion injury: mechanistic insights provided by mutant mice

Reperfusion of ischaemic tissues often leads to microvascular dysfunction that is manifested as impaired endothelium‐dependent dilation of arterioles, enhanced fluid filtration and leucocyte plugging in capillaries, and the trafficking of leucocytes and plasma protein extravasation in postcapillary venules. Efforts to define the mechanisms that underlie these microvascular responses to ischaemia and reperfusion have largely relied on pharmacological agents and monoclonal antibodies. Gene‐targeting technology has been applied to the production of transgenic and knockout mice that are rapidly gaining acceptance as tools for mechanistic studies of ischaemia–reperfusion (I/R) injury that obviate some of the concerns (e.g. specificity) raised about previously employed experimental strategies. This review summarizes some of our efforts to apply gene‐targeted mice to the study of I/R injury in the splanchnic vascular bed. A role for endothelial cell adhesion molecules (CAMs) and reactive oxygen metabolites is supported by results from mutant mice. Low density lipoprotein receptor mice also reveal that the microvascular and inflammatory responses to I/R are greatly exaggerated during chronic hypercholesterolaemia. The wide variety of mutant mice that have been produced for inflammation‐related research makes this experimental strategy particularly promising for mechanistic investigations of the tissue responses to I/R.     

A model of disseminated intravascular blood clotting

Vascular-platelet and plasma hemostasis was studied in dogs after blood loss (40–45 ml/kg body weight) followed by hypervolemic (60–65 ml/kg body weight) transfusion of homologous (from three donors) plasma enriched with platelets and leukocytes. After a brief phase of hypercoagulation, hypocoagulation was discovered in all the experimental dogs, accompanied by a reduction in the platelet count and in the intensity of platelet aggregation, lengthening of the bleeding time, a decrease in the resistance of the capillary wall, a decrease in the plasma fibrinogen concentration and activity of factor XIII, and an increase in the fibrinolytic activity of the blood. The results are evidence of the development of an acute syndrome of disseminated intravascular blood clotting.Laboratory of Pathophysiology, Central Research Institute of Hematology and Blood Transfusion, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR N. A. Fedorov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 7, pp. 116–120, July, 1978.