Hemodialysis and blood coagulation: the effect of hemodialysis on coagulation factor XIII and thrombin-antithrombin III complex.

Blood membrane interaction during hemodialysis (HD) regularly leads to stimulation of leukocyte function and related release of granular enzymes. The present study aimed to investigate the possible influence of an HD-induced release of granulocyte elastase on blood coagulation. Therefore a highly sensitive substrate of polymorphonuclear elastase, the plasma coagulation factor XIII and its subunits A and S were determined in the course of HD. Consumption of both subunit A and S have been previously shown to be due to proteolysis by elastase, whereas a decrease in subunit A will be typical for thrombin activation. Furthermore, the thrombin-antithrombin III complex (TAT) acting as a predisposition parameter for thrombotic events was measured during HD treatment. Apart from a virtual fall in factor XIII total activity simulated by heparin, no significant HD-induced consumption of factor XIII could be observed. There was also no indication of an elastase- or thrombin-related change in subunit concentrations. Predialysis values of the TAT complex were generally elevated in HD patients, but only patients with acute renal failure showed a constant increase of TAT during HD. These findings suggest that HD patients are exposed to a latent activation of coagulation resulting in an elevated thrombogenetic risk mainly due to the underlying disease. An additional coagulatory stimulation by the HD procedure seems to be restricted to cases of acute renal failure.     

Effects of intravascular volume expansion on cerebral blood flow in patients with ruptured cerebral aneurysms

To clarify the effect of intravascular volume expansion on cerebral blood flow (CBF) in patients after subarachnoid hemorrhage (SAH), we performed 55 pairs of regional CBF measurements using the xenon-133 inhalation method before and after volume expansion in 35 patients with ruptured cerebral aneurysms. CBF was calculated as the hemispheric mean value of the initial slope index. To accomplish volume expansion, we transfused 500 ml of 5% human serum albumin in half an hour. After volume expansion with albumin, the hemoglobin value decreased significantly (P less than 0.005). Volume expansion did not change the mean arterial blood pressure. During the first 2 weeks after SAH, CBF decreased significantly after volume expansion (P less than 0.005). During the 3rd week after SAH and subsequently to the 4th week after SAH, volume expansion produced no change in CBF. In patients with symptomatic vasospasm, CBF decreased significantly after volume expansion (P less than 0.005). In patients without symptomatic vasospasm, volume expansion produced no change in CBF. The results of this study suggest that increasing the intravascular volume above normal by volume expansion does not increase CBF or reverse symptomatic vasospasm.     

Effect of experimental common carotid arteriotomy on cerebral blood flow in rats

Cerebral blood flow (CBF) and its reactivity to alterations in arterial carbon dioxide tension were measured in 52 rats. Measurements were made in four groups of rats: 15 were controls, 14 had one carotid artery clamped, 11 had microvascular common carotid arteriotomies, and 12 had sham arteriotomies. Before carotid operation, a flow change of 1 ml/100 g of brain per minute per torr change in CO2 tension was demonstrated in the rats, a value for reactivity similar to that found in normal humans. After unilateral common carotid ligation, CBF was not significantly disturbed in either hemisphere, and reactivity was preserved. In rats subjected to arteriotomy, CBF fell by 30% from the control level in both hemispheres, and carbon dioxide reactivity was reduced by 80%. Very similar reductions in flow (38%) and reactivity (76%) were produced after sham arteriotomy, in which the common carotid artery was isolated between temporary clamps for 30 minutes, but the arteriotomy incision was not made. The observed flow reduction and carbon dioxide reactivity impairment must result from the reperfusion of the brain through the traumatized carotid artery, inasmuch as no impairment of either flow or reactivity followed extravascular dissection and permanent ligation of the vessel. These changes may be mediated by damage to the sympathetic plexus or the innervation of the carotid body chemoreceptors or by the release of histamine, prostaglandins, or other vasoactive substances from the incised vessel wall. If this finding is applicable to humans, it suggests that the entire cerebral circulation in patients with respiratory impairment may be precarious for some hours after a carotid endarterectomy and confirms the danger of hypercapnia during anesthesia for carotid surgery.     

Effects of xenon on cerebral blood flow and cerebral glucose utilization in rats

BACKGROUND: The effects of xenon inhalation on mean and local cerebral blood flow (CBF) and mean and local cerebral glucose utilization (CGU) were investigated using iodo-[14C]antipyrine and [14C]deoxyglucose autoradiography. METHODS: Rats were randomly assigned to the following groups: conscious controls (n = 12); 30% (n = 12) or 70% xenon (n = 12) for 45 min for the measurement of local CBF and CGU; or 70% xenon for 2 min (n = 6) or 5 min (n = 6) for the measurement of local CBF only. RESULTS: Compared with conscious controls, steady state inhalation of 30 or 70% xenon did not result in changes of either local or mean CBF. However, mean CBF increased by 48 and 37% after 2 and 5 min of 70% xenon short inhalation, which was entirely caused by an increased local CBF in cortical brain regions. Mean CGU determined during steady state 30 or 70% xenon inhalation remained unchanged, although local CGU decreased in 7 (30% xenon) and 18 (70% xenon) of the 40 examined brain regions. The correlation between CBF and CGU in 40 local brain structures was maintained during steady state inhalation of both 30 and 70% xenon inhalation, although at an increased slope at 70% xenon. CONCLUSION: Effects of 70% xenon inhalation on CBF in rats are time-dependent. During steady state xenon inhalation (45 min), mean values of CBF and CGU do not differ from control values, and the relation of regional CBF to CGU is maintained, although reset at a higher level.     

Rheological study on the development and growth of cerebral aneurysms using an experimental animal model]

To clarify the pathogenesis of saccular cerebral aneurysms, it is essential to study hemodynamic influences on the development and growth of these aneurysms. Up to now, a number of experimental flow studies have been done using a variety of glass models of cerebral arterial bifurcations with or without aneurysms. Blood flow at the bifurcation can be readily influenced even by subtle changes of the intraluminal geometry. But, it is quite difficult to obtain the accurate geometry of the lumen artificially. Using the bifurcation of animal model of the disease, this limitation can be overcome. In the present study, using cerebral arterial bifurcations in rats which were treated to induce experimental cerebral aneurysms, flow patterns were studied to elucidate the pathogenesis of cerebral aneurysms from the rheological point of view. (Experiment-1) Microscopic flow visualization at the bifurcation of major cerebral arteries in control rats was done. After perfusion and fixation, a right anterior cerebral and olfactory artery (ACA/OA) junction was extirpated from the base of the brain and served for laboratory preparation. A suspension of small latex particles in various sizes was subjected to constant flow rate through the preparation, recorded on videotapes and 16 mm cinefilms. The results of flow analysis were: 1) Small particles accumulated at the region just distal to the apical intimal pad on the side of daughter ACA, where the initial changes of aneurysm formation are known to occur. This finding indicates a flow stagnation. 2) The apical intimal pad, not the apex itself, acted as the flow divider. 3) Flow disturbances existed both in the daughter ACA and in the OA. (Experiment-2) Using ACA/OA bifurcations with shallow invaginations and small aneurysms, which were obtained from the rats treated to induce experimental aneurysms, flow patterns were obtained by the same methods as mentioned in (Experiment-1). Flow characteristics were: 1) Particles entering the dome from the proximal end of the aneurysmal orifice markedly decreased their flow velocity at that site. 2) Particles running along the luminal surface of the dome were in low flow velocity. This indicates a tendency of stagnation there. 3) The wall shear stress was highest at the distal end of the aneurysmal orifice, which may be responsible for the development of these lesions. (Experiment-3) A technique was developed to visualize the flow at the major cerebral arterial bifurcation in living rats which were prepared to induce experimental cerebral aneurysms.(ABSTRACT TRUNCATED AT 400 WORDS)     

The effect of cerebral anoxia on blood coagulation in the guinea-pig

Summary The effect of cerebral anoxia on the behaviour of the blood coagulation processes were investigated by means of a thrombelastograph. The experiments were carried out on 40 guinea-pigs (10 of which served as controls) under general ethyl urethan anaesthesia. The anoxia was induced by constriction of both carotid arteries. For these investigations, blood was taken from the jugular veins 10, 30 and 60 minutes after constriction of the arteries. Statistically significant disturbances in the blood coagulation processes were noted (a lengthening of section r) together with a deterioration in the elasticity of the clot (reduction of the ma value).

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Zusammenfassung Die Auswirkung zerebraler Anoxie auf das Verhalten der Blutgerinnungsvorgänge wurde mit Hilfe eines Thrombelastographen untersucht. Die Untersuchungen wurden an 40 Meerschweinchen, von denen 10 als Kontrollen dienten, unter allgemeiner Äthyl-Urethan-Narkose ausgeführt. Die Anoxie wurde durch Unterbindung beider Karotiden herbeigeführt. Es wurde zur Untersuchung Blut aus der Vena jugularis 10, 30 und 60 Minuten nach der Arterienunterbindung entnommen. Die Autoren fanden statistisch gesicherte Störungen des Blutgerinnungsvorganges (eine Verlängerung der Sektion r) zusammen mit einer Störung der Elastizität des Blutgerinsels (Verminderung des ma-Wertes).

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Resumen Las consecuencias de la anoxia cerebral sobre el desarrollo del mecanismo de la coagulación sanguínea han sido estudiados por medio de un trombelastografo. Las experiencias abarcan un lote de 40 cobayas, (de los cuales 10 sirvieron de testigos) y practicadas bajo anesteis general con etil metano. La anoxia era provocada por la compresión de las dos arterias carótidas. Se tomaba sangre de las venas yugulares, 10, 30 y 60 minutos después de la compresión de las arterias. Se observan las perturbaciones en el mecanismo de la coagulación sanguínea: alargamiento de la seción r asociado a la modificación de la elasticidad del coagulo (disminución de la valem na).

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Résumé Les conséquences de l'anoxie cérébrale sur le déroulement du mécanisme de la coagulation sanguine ont été étudiéesau moyen du throbélastograph. Les expériences portent sur un lot de 40 cobayes, (dont 10 servent de témoins) et pratiquées sous anesthésie générale à l'éthyl méthane. L'anoxie est provoquée par la compression des 2 artères carotides. On prélève le sang des veines jugulaires 10, 30, 60 minutes après la compression des artères. On note les perturbations dans le mécanisme de la coagulation sanguine: allongement de le section «r» associé à la modification de l'élasticité du caillot (diminution de la valeur «ma»).

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Riassunto Gli AA. hanno studiato l'effetto dell'anossia cerebrale sul comportamento della coagulazione sanguigna mediante il tromboelastografo. L'indagine fu effettuata su 40 cavie (di cui 10 impiegate per controllo) sotto anestesia generale con etiluretano. L'anossia venive provocata con la costrizione delle due carotidi. Il prelievo del sangue dalle giugulari fu effettuato 10, 30 e 80 minuti dopo la costrizione delle arterie.Gli AA. hanno osservato alterazioni di rilevanza statistica nel processo di coagulazione sanguigna (allungamento della sezione «r») insieme ad abbassamento della elasticità del grumo (riduzione del valore «ma»).

     

Effects of spironolactone on systolic blood pressure in experimental diabetic rats

BACKGROUND: Mineralocorticoid hormones, which maintain electrolyte balance and blood pressure, are thought to be associated not only with the expression of renal 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), but also with that of intracellular mineralocorticoid receptors (MRs). The present study was designed to test whether the mineralocorticoid action of glucocorticoid corticosterone on renal MR is involved in the development of diabetes-associated hypertension by measuring the alterations of renal 11beta-HSD2. METHOD: We measured the mean systolic blood pressure, renal 11beta-HSD1, and mRNA levels in streptozotocin (STZ)-induced diabetic rats that received spironolactone, insulin, or no treatment, and in nondiabetic controls that received spironolactone. RESULTS: Four weeks after an injection of STZ, the renal 11beta-HSD2 and mRNA levels were significantly lower in diabetic rats than in control rats, and the mean systolic blood pressure was 14.8% higher in diabetic rats than in controls. Subcutaneous injections of spironolactone into diabetic rats for three weeks partially reversed the decrease in renal 11beta-HSD2 activity and gene expression, and prevented the mean systolic blood pressure elevation. Spironolactone treatment for one week also resulted in a significant reduction in mean systolic blood pressure during the development of diabetic hypertension. However, treatment with STZ did not significantly decrease the renal 11beta-HSD1 activity and mRNA expression, and spironolactone treatment did not exert a significant effect on this enzyme in STZ-induced diabetic rats. CONCLUSION: In the development of diabetes-induced hypertension, the effect of spironolactone on mean systolic blood pressure may be associated with the mineralocorticoid effects of corticosterone on renal MR, as well as an alteration of renal 11beta-HSD2 activity and its mRNA expression in insulin-dependent diabetic rats.     

Alterations in cerebral vessels in experimental animals and their possible relationship to the development of aneurysms.

Aneurysmal changes were studied by light and electron microscopes in experimental monkeys to elucidate their pathogenesis. Early changes were found not at the medial defect but in one branch near the apex. Degeneration of the elastic lamina was always more than that of the media throughout the process of aneurysm formation. Endothelial injury was present even at the bifurcation without a bulge. The present study suggests that aneurysmal changes are initiated by degenerative changes in the endothelium, which are followed by alterations in the underlying elastic lamina and, in turn, in the medial layer.     

肝移植术患者术前应用重组活化入凝血因子Ⅶa的效果

目的 评价肝移植术患者术前应用重组活化入凝血因子Ⅶa(rFⅦa)的效果.方法 择期行原位肝移植术的终末期肝病患者20例,ASAⅡ或Ⅲ级,Child-Pugh分级B或C级,术前均存在凝血功能障碍,凝血酶原时间(PT)＞20 s.切皮前5 min静脉注射rFⅦa 40～80 μg·kg-1.分别于注药前即刻(T0)、注药后5(T1)、15(T2)、30(T3)、60(T4)、120 min(T5)、无肝期15 min(T6)及新肝期30 min(T7)取颈内静脉血4.5 ml,测定PT、凝血酶原活度(PTA)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、国际标准化比值(INR)、纤维蛋白原(Fib)、D-二聚体(DD)、血小板计数(PLT).结果 与T0比较,PT和INR在T1～6降低,PTA在T1-6增加,APTr在T2～5缩短,TT在T7延长(P＜0.05),各时间点nb、PLT、DD差异无统计学意义(P＞0.05).术中输注浓缩红细胞(11±6)U,出血总量600～4000 ml,其中使用rFⅦa后120min内出血量200～2 400 ml.给药期间未发生过敏反应,术后未发生静脉血栓等并发症.结论 肝移植术前应用rFⅦa可改善患者术中凝血功能,且无明显副作用.     

Effect of intravenous administration of coagulation factor XIII concentrate on persistent pleural air leak

We administered coagulation factor XIII concentrate intravenously to six patients suffering from persistent air leak with no evidence of bronchopleural fistulae They are those who had either failed to be healed in response to pleurodesis, intrapleural fibrin glue injection and surgery or had not received such treatment. Their blood coagulation factor XIII activity levels were less than 70% of the standard plasma level. In four of the six patients, air leak stopped within 10 days after the treatment begun. Because factor XIII plays an important role in wound healing, reduction in the activity level can be a cause of insufficient healing of pulmonary surface fistulae and may lead to persistent air leak. In such cases, intravenous administration of factor XIII concentrate increases the activity levels and may put an end to persistent air leak.     

Effects of three-dimensional angiography on the coiling of cerebral aneurysms

OBJECTIVE: To assess how information acquired with three-dimensional angiography (3DA) affects the endovascular management of cerebral aneurysms. METHODS: The role of 3DA in 50 aneurysm cases was assessed with respect to five predetermined factors, i.e., whether 3DA facilitated treatment, modified the coil embolization technique, made treatment unnecessary or unjustified by revealing new information, suggested a potential treatment failure or complication, or did not contribute to endovascular management. RESULTS: Findings for a total of 46 patients with 50 aneurysms who underwent 3DA in the course of their endovascular treatment were analyzed. Overall, 3DA facilitated coiling in 25 cases, modified the treatment technique in 11 cases, eliminated the need for treatment in 9 cases, and suggested a potential treatment complication in 5 cases. 3DA was deemed useful in the management of all cases, and in no case was its use associated with a complication. Specifically, 3DA facilitated treatment by delineating the optimal fluoroscopic tube angulation for coiling, modified treatment by revealing anatomic characteristics that would require balloon remodeling or stent assistance, obviated treatment by excluding the possibility of an aneurysm or by identifying unfavorable anatomic features, and predicted a treatment complication by revealing an associated vessel that was likely to be compromised with coiling of the aneurysm. CONCLUSION: 3DA enhances our ability to treat aneurysms endovascularly. Most importantly, aneurysm treatment may be facilitated, modified, or proven unnecessary because of vital information obtained with 3DA.     

Effects of basic fibroblast growth factor on experimental diabetic neuropathy in rats

Basic fibroblast growth factor (bFGF) stimulates angiogenesis and induces neural cell regeneration. We investigated the effects of bFGF on diabetic neuropathy in streptozotocin-induced diabetic rats. Diabetic rats were treated with human recombinant bFGF as follows: 1) intravenous administration, 2) intramuscular injection into thigh and soleus muscles with cross-linked gelatin hydrogel (CGH), and 3) intramuscular injection with saline. Ten or 30 days later, the motor nerve conduction velocity (MNCV) of the sciatic-tibial and caudal nerves, sensitivity to mechanical stimuli, sciatic nerve blood flow (SNBF), and retinal blood flow (RBF) were measured. Delayed MNCV in the sciatic-tibial and caudal nerves, hypoalgesia, and reduced SNBF in diabetic rats were all ameliorated by intravenous administration of bFGF after 10, but not 30, days. Intramuscular injection of bFGF with CGH also improved sciatic-tibial MNCV, hypoalgesia, and SNBF after 10 and 30 days, but caudal MNCV was not improved. However, intramuscular injection of bFGF with saline had no significant effects. bFGF did not significantly alter RBF in either normal or diabetic rats. These observations suggest that bFGF could have therapeutic value for diabetic neuropathy and that CGH could play important roles as a carrier of bFGF.     

血必净注射液对脓毒症大鼠单核细胞组织因子及凝血功能的影响

目的 观察血必净注射液对盲肠结扎穿孔术(CLP)所致脓毒症大鼠单核细胞组织因子及凝血功能的影响.方法 将104只Wistar大鼠随机分为正常组、假手术组、CLP组和血必净组,后3组按活杀时间再分为手术后12、24、48、72 h 4个亚组,每组8只.各组于相应时间点经腹主动脉取血,采用流式细胞仪检测单核细胞蛋白酶激活受体-1(PAR-1)的平均荧光强度,采用酶联免疫吸附试验(ELISA)检测血浆组织因子(TF)和肿瘤坏死因子(TNF)-α蛋白含量,并观察凝血活酶时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)的变化.结果 CLP组大鼠单核细胞PAR-1(24、48、72 h分别为21.87±1.08、24.23±0.70、29.70±0.40)、血浆TF[24、48、72 h分别为(505.24±82.82)、(695.43±138.89)、(342.86±16.29)ng/L]、TNF-α水平均较正常组、假手术组显著升高(P<0.05或P<0.01),血必净组町显著降低PAR-1(48、72 h分别为21.47±1.76、19.59±0.17,P<0.05或P<0.01)、TF[24、48、72 h分别为(266.67±9.29)、(280.71±41.25)、(253.93±15.31)ng/L,P<0.05或P<0.01]、TNF-α水平(P<0.05或P<0.01),并恢复PT、APTT、FIB至正常范围.结论 血必净注射液通过降低单核细胞PAR-1、TF水平改善脓毒症动物凝血功能紊乱.