sGC and PDE5 are elevated in lambs with increased pulmonary blood flow and pulmonary hypertension

Utilizing aortopulmonary vascular graft placement, we established a lamb model of pulmonary hypertension that mimics congenital heart disease with increased pulmonary blood flow. We previously demonstrated that endothelial nitric oxide synthase (eNOS) is increased in lambs at age 4 wk. However, these lambs display a selective impairment of endothelium-dependent pulmonary vasodilation that is suggestive of a derangement downstream of NO release. Thus our objective was to characterize potential alterations in the expression and activity of soluble guanylate cyclase (sGC) and phosphodiesterase type 5 (PDE5) induced by increased pulmonary blood flow and pulmonary hypertension. Late-gestational fetal lambs (n = 10) underwent in utero placement of an aortopulmonary vascular graft (shunt). Western blotting analysis on lung tissue from 4-wk-old shunted lambs and age-matched controls showed that protein for both subunits of sGC was increased in shunted lamb lungs compared with age-matched controls. Similarly, cGMP levels were increased in shunted lamb lungs compared with age-matched controls. However, PDE5 expression and activity were also increased in shunted lambs. Thus although cGMP generation was increased, concomitant upregulation of PDE5 expression and activity may have (at least partially) limited and accounted for the impairment of endothelium-dependent pulmonary vasodilation in shunted lambs.     

Direct demonstration of 25- and 50-microm arteriovenous pathways in healthy human and baboon lungs

Postmortem microsphere studies in adult human lungs have demonstrated the existence of intrapulmonary arteriovenous pathways using nonphysiological conditions. The aim of the current study was to determine whether large diameter (>25 and 50 microm) intrapulmonary arteriovenous pathways are functional in human and baboon lungs under physiological perfusion and ventilation pressures. We used fresh healthy human donor lungs obtained for transplantation and fresh lungs from baboons (Papio c. anubis). Lungs were ventilated with room air by using a peak inflation pressure of 15 cm H(2)O and a positive end-expiratory pressure of 5 cm H(2)O. Lungs were perfused between 10 and 20 cm H(2)O by using a phosphate-buffered saline solution with 5% albumin. We infused a mixture of 25- and 50-microm microspheres (0.5 and 1 million total for baboons and human studies, respectively) into the pulmonary artery and collected the entire pulmonary venous outflow. Under these conditions, evidence of intrapulmonary arteriovenous anastomoses was found in baboon (n = 3/4) and human (n = 4/6) lungs. In those lungs showing evidence of arteriovenous pathways, 50-microm microspheres were always able to traverse the pulmonary circulation, and the fraction of transpulmonary passage ranged from 0.0003 to 0.42%. These data show that intrapulmonary arteriovenous pathways >50 microm in diameter are functional under physiological ventilation and perfusion pressures in the isolated lung. These pathways provide an alternative conduit for pulmonary blood flow that likely bypasses the areas of gas exchange at the capillary-alveolar interface that could compromise both gas exchange and the ability of the lung to filter out microemboli.     

SPF级新生大鼠高氧肺损伤模型的建立

目的建立一种操作简便、性能稳定的新生大鼠高氧肺损伤动物模型。方法①设计制造能自动控制氧浓度的高氧动物饲养舱。②将孕期满21 d出生的SPF级新生大鼠随机分成4组,即：高氧组Ⅰ（入高氧舱中饲养1～7 d）,高氧组Ⅱ（入高氧舱中饲养14 d）,以及相应的空气对照组Ⅰ、Ⅱ,每组14只。舱内氧浓度≥90%,每天23 h。计算肺系数,HE染色与病理学观察。结果高氧组与相应的对照组比较：高氧组大鼠体重轻,肺系数大,HE染色显示部分肺泡萎缩、肺间质及肺泡腔有水肿、出血,中性粒细胞浸润;肺泡发育明显滞后,辐射状肺泡计数明显少。结论本动物饲养舱性能稳定,操作简便;复制的新生大鼠的肺病理变化符合高氧肺损伤的改变。     

Expression of VEGF and its receptors Flt-1 and Flk-1/KDR is altered in lambs with increased pulmonary blood flow and pulmonary hypertension

Utilizing in utero aortopulmonary vascular graft placement, we developed a lamb model of congenital heart disease and increased pulmonary blood flow. We showed previously that these lambs have increased pulmonary vessel number at 4 wk of age. To determine whether this was associated with alterations in VEGF signaling, we investigated vascular changes in expression of VEGF and its receptors, Flt-1 and KDR/Flk-1, in the lungs of shunted and age-matched control lambs during the first 8 wk of life. Western blot analysis demonstrated that VEGF, Flt-1, and KDR/Flk-1 expression was higher in shunted lambs. VEGF and Flt-1 expression was increased at 4 and 8 wk of age (P <0.05). However, KDR/Flk-1 expression was higher in shunted lambs only at 1 and 4 wk of age (P <0.05). Immunohistochemical analysis demonstrated that, in control and shunted lambs, VEGF localized to the smooth muscle layer of vessels and airways and to the pulmonary epithelium while increased VEGF expression was localized to the smooth muscle layer of thickened media in remodeled vessels in shunted lambs. VEGF receptors were localized exclusively in the endothelium of pulmonary vessels. Flt-1 was increased in the endothelium of small pulmonary arteries in shunted animals at 4 and 8 wk of age, whereas KDR/Flk-1 was increased in small pulmonary arteries at 1 and 4 wk of age. Our data suggest that increased pulmonary blood flow upregulates expression of VEGF and its receptors, and this may be important in development of the vascular remodeling in shunted lambs.     

Alterations in TGF-beta1 expression in lambs with increased pulmonary blood flow and pulmonary hypertension

The mechanisms responsible for pulmonary vascular remodeling in congenital heart disease with increased pulmonary blood flow remain unclear. We developed a lamb model of congenital heart disease and increased pulmonary blood flow utilizing an in utero placed aortopulmonary vascular graft (shunted lambs). Morphometric analysis of barium-injected pulmonary arteries indicated that by 4 wk of age, shunts had twice the pulmonary arterial density of controls (P < 0.05), and their pulmonary vessels showed increased muscularization and medial thickness at both 4 and 8 wk of age (P < 0.05). To determine the potential role of TGF-beta1 in this vascular remodeling, we investigated vascular changes in expression and localization of TGF-beta1 and its receptors TbetaRI, ALK-1, and TbetaRII in lungs of shunted and control lambs at 1 day and 1, 4, and 8 wk of life. Western blots demonstrated that TGF-beta1 and ALK-1 expression was elevated in shunts compared with control at 1 and 4 wk of age (P < 0.05). In contrast, the antiangiogenic signaling receptor TbetaRI was decreased at 4 wk of age (P < 0.05). Immunohistochemistry demonstrated shunts had increased TGF-beta1 and TbetaRI expression in smooth muscle layer and increased TGF-beta1 and ALK-1 in endothelium of small pulmonary arteries at 1 and 4 wk of age. Moreover, TbetaRI expression was significantly reduced in endothelium of pulmonary arteries in the shunt at 1 and 4 wk. Our data suggest that increased pulmonary blood flow dysregulates TGF-beta1 signaling, producing imbalance between pro- and antiangiogenic signaling that may be important in vascular remodeling in shunted lambs.     

Animal models of acute lung injury

Acute lung injury in humans is characterized histopathologically by neutrophilic alveolitis, injury of the alveolar epithelium and endothelium, hyaline membrane formation, and microvascular thrombi. Different animal models of experimental lung injury have been used to investigate mechanisms of lung injury. Most are based on reproducing in animals known risk factors for ARDS, such as sepsis, lipid embolism secondary to bone fracture, acid aspiration, ischemia-reperfusion of pulmonary or distal vascular beds, and other clinical risks. However, none of these models fully reproduces the features of human lung injury. The goal of this review is to summarize the strengths and weaknesses of existing models of lung injury. We review the specific features of human ARDS that should be modeled in experimental lung injury and then discuss specific characteristics of animal species that may affect the pulmonary host response to noxious stimuli. We emphasize those models of lung injury that are based on reproducing risk factors for human ARDS in animals and discuss the advantages and disadvantages of each model and the extent to which each model reproduces human ARDS. The present review will help guide investigators in the design and interpretation of animal studies of acute lung injury.     

Membrane attack complex contributes to destruction of vascular integrity in acute lung allograft rejection

The lung is known to be particularly susceptible to complement-mediated injury. Both C5a and the membrane attack complex (MAC), which is formed by the terminal components of complement (C5b-C9), can cause acute pulmonary distress in nontransplanted lungs. We used C6-deficient rats to investigate whether MAC causes injury to lung allografts. PVG.R8 lungs were transplanted orthotopically to MHC class I-incompatible PVG.1U recipients. Allografts from C6-sufficient (C6(+)) donors to C6(+) recipients were rejected with an intense vascular infiltration and diffuse alveolar hemorrhage 7 days after transplantation (n = 5). Ab and complement (C3d) deposition was accompanied by extensive vascular endothelial injury and intravascular release of von Willebrand factor. In contrast, lung allografts from C6-deficient (C6(-)) donors to C6(-) recipients survived 13-17 days (n = 5). In the absence of C6, perivascular mononuclear infiltrates of ED1(+) macrophages and CD8(+) T lymphocytes were present 7 days after transplantation, but vascular endothelial cells were quiescent, with minimal von Willebrand factor release and no evidence of alveolar hemorrhage or edema. Lung allografts were performed from C6(-) donors to C6(+) recipients (n = 5) and from C6(+) donors to C6(-) recipients (n = 5) to separate the effects of systemic and local C6 production. Lungs transplanted from C6(+) donors to C6(-) recipients had increased alveolar macrophages and capillary injury. C6 production by lung allografts was demonstrated at the mRNA and protein levels. These results demonstrate that MAC causes vascular injury in lung allografts and that the location of injury is dependent on the source of C6.     

Progressive dysfunction of nitric oxide synthase in a lamb model of chronically increased pulmonary blood flow: a role for oxidative stress

Cardiac defects associated with increased pulmonary blood flow result in pulmonary vascular dysfunction that may relate to a decrease in bioavailable nitric oxide (NO). An 8-mm graft (shunt) was placed between the aorta and pulmonary artery in 30 late gestation fetal lambs; 27 fetal lambs underwent a sham procedure. Hemodynamic responses to ACh (1 microg/kg) and inhaled NO (40 ppm) were assessed at 2, 4, and 8 wk of age. Lung tissue nitric oxide synthase (NOS) activity, endothelial NOS (eNOS), neuronal NOS (nNOS), inducible NOS (iNOS), and heat shock protein 90 (HSP90), lung tissue and plasma nitrate and nitrite (NO(x)), and lung tissue superoxide anion and nitrated eNOS levels were determined. In shunted lambs, ACh decreased pulmonary artery pressure at 2 wk (P < 0.05) but not at 4 and 8 wk. Inhaled NO decreased pulmonary artery pressure at each age (P < 0.05). In control lambs, ACh and inhaled NO decreased pulmonary artery pressure at each age (P < 0.05). Total NOS activity did not change from 2 to 8 wk in control lambs but increased in shunted lambs (ANOVA, P < 0.05). Conversely, NO(x) levels relative to NOS activity were lower in shunted lambs than controls at 4 and 8 wk (P < 0.05). eNOS protein levels were greater in shunted lambs than controls at 4 wk of age (P < 0.05). Superoxide levels increased from 2 to 8 wk in control and shunted lambs (ANOVA, P < 0.05) and were greater in shunted lambs than controls at all ages (P < 0.05). Nitrated eNOS levels were greater in shunted lambs than controls at each age (P < 0.05). We conclude that increased pulmonary blood flow results in progressive impairment of basal and agonist-induced NOS function, in part secondary to oxidative stress that decreases bioavailable NO.     

Microvessel quantitation in intraductal and early invasive breast carcinomas

OBJECTIVE: To study the angiogenic process in intraductal carcinoma of the breast, with and without a small focus of stromal infiltration, and to compare the microvessel density between the in situ phase and the early infiltration phases of breast cancer. STUDY DESIGN: Microvessel density (number of microvessels per square millimeter of neoplasia) was quantitatively evaluated on anti-factor VIII-immunostained histologic sections obtained from 10 ductal carcinomas in situ (DCIS) (category A), 22 DCIS with a small focus of stromal infiltration (category B), 10 microinvasive carcinomas (category C), 12 T1a carcinomas (category D) and 20 T1b carcinomas (category E). RESULTS: The five categories of lesion had different values for microvessel density (P = .0017). Category A had microvessel density lower than category B (P = .0005). Category B had microvessel density higher than categories C, D and E (P = .0028, .0133 and .0033, respectively). CONCLUSION: Microvessel density seems to be a feature related to each crucial step in the early phases of neoplastic progression.     

Intrapulmonary shunting and pulmonary gas exchange during normoxic and hypoxic exercise in healthy humans.

Exercise-induced intrapulmonary arteriovenous shunting, as detected by saline contrast echocardiography, has been demonstrated in healthy humans. We have previously suggested that increases in both pulmonary pressures and blood flow associated with exercise are responsible for opening these intrapulmonary arteriovenous pathways. In the present study, we hypothesized that, although cardiac output and pulmonary pressures would be higher in hypoxia, the potent pulmonary vasoconstrictor effect of hypoxia would actually attenuate exercise-induced intrapulmonary shunting. Using saline contrast echocardiography, we examined nine healthy men during incremental (65 W + 30 W/2 min) cycle exercise to exhaustion in normoxia and hypoxia (fraction of inspired O(2) = 0.12). Contrast injections were made into a peripheral vein at rest and during exercise and recovery (3-5 min postexercise) with pulmonary gas exchange measured simultaneously. At rest, no subject demonstrated intrapulmonary shunting in normoxia [arterial Po(2) (Pa(O(2))) = 98 +/- 10 Torr], whereas in hypoxia (Pa(O(2)) = 47 +/- 5 Torr), intrapulmonary shunting developed in 3/9 subjects. During exercise, approximately 90% (8/9) of the subjects shunted during normoxia, whereas all subjects shunted during hypoxia. Four of the nine subjects shunted at a lower workload in hypoxia. Furthermore, all subjects continued to shunt at 3 min, and five subjects shunted at 5 min postexercise in hypoxia. Hypoxia has acute effects by inducing intrapulmonary arteriovenous shunt pathways at rest and during exercise and has long-term effects by maintaining patency of these vessels during recovery. Whether oxygen tension specifically regulates these novel pathways or opens them indirectly via effects on the conventional pulmonary vasculature remains unclear.     

Altered endothelium-dependent relaxations in lambs with high pulmonary blood flow and pulmonary hypertension

Congenital heart disease associated with increased pulmonary blood flow produces pulmonary hypertension. To characterize vascular alterations in the nitric oxide (NO)-cGMP cascade induced by increased pulmonary blood flow and pulmonary hypertension, 10 fetal lambs underwent in utero placement of an aortopulmonary vascular graft (shunt). When the lambs were 4-6 wk of age, we assessed responses of pulmonary arteries (PAs) and pulmonary veins (PVs) isolated from lungs of control and shunted lambs. PVs from control and shunted lambs relaxed similarly to exogenous NO (S-nitrosyl-acetyl-penicillamine), to NO produced endogenously (zaprinast and A-23187), and to cGMP (atrial natriuretic peptide). In contrast, relaxations to A-23187 and zaprinast were blunted in PAs isolated from shunted lambs relative to controls. Inhibitors of NO synthase (NOS) and soluble guanylate cyclase constricted control but not shunt PAs, indicating reduced basal NOS activity in shunt PAs. Pretreatment of shunt PAs with the substrates L-arginine and sepiapterin, a precursor for tetrahydrobiopterin synthesis, did not augment A-23187 relaxations. However, pretreatment with superoxide dismutase and catalase significantly enhanced A-23187 relaxations in shunt PAs. We conclude that increased pulmonary blood flow induces an impairment of endothelium-dependent relaxation that is selective to PAs. The impaired relaxation may be mediated in part by excess superoxide production.     

Estimation of regional circulation in rats: results obtained by using 15 and 50 micron diameter microspheres and rubidium]

Radioactive microspheres, 15 or 50 micron in diameter, were used to estimate the distrubtion of cardiac output and the degree of shunting of microspheres through the systemic and pulmonary circulations in anaesthetized rats. Extraction of 15 micron spheres by the pulmonary capillaries was nearly 100% and the amounts of microspheres per gram of lung tissue were not significantly different in the various lobes of lung. After injection into the left ventricle, the proportion of microspheres shunted to the lungs was almost identical using 15 or 50 micron spheres. Similar results were observed after injection into the internal of external carotid artery. The distribution of cardiac output showed a significant difference between 15 and 50 micron spheres, the proportion of 50 micron spheres found in the stomach being higher, which suggests the existence in this organ of arteriovenous shunts larger than 15 micron. The rubidium method yielded higher fractions of cardiac output in the liver (hepatic artery), lung and skin whereas the microspheres distribution to the heart, spleen and digestive tract exceeded that of rubidium. The origins of these differences are discussed.     

Platelets induce endothelial tissue factor expression in a mouse model of acid-induced lung injury

Although the lung expresses procoagulant proteins under inflammatory conditions, underlying mechanisms remain unclear. Here, we addressed lung endothelial expression of tissue factor (TF), which initiates the coagulation cascade and expression of which signifies development of a procoagulant phenotype in the vasculature. To establish the model of acid-induced acute lung injury (ALI), we intranasally instilled anesthetized mice with saline or acid. Then 2 h later, we isolated pulmonary vascular cells for flow cytometry and confocal microscopy to detect the leukocyte antigen, CD45 and the endothelial markers VE-cadherin and von Willebrand factor (vWf). Acid increased both the number of vWf-expressing cells as well as TF and P-selectin expressions on these cells. All of these effects were markedly inhibited by treating mice with antiplatelet serum, suggesting the involvement of platelets. The increased expressions of TF, vWf, and P-selectin in response to acid also occurred in platelets. Moreover, the effects were replicated in endothelial cells derived from isolated, blood-perfused lungs. However, the effect was inhibited completely in lungs perfused with platelet-depleted and, to a lesser extent, with leukocyte-depleted blood. Acid injury increased endothelial expressions of the platelet proteins, CD41 and CD42b, providing evidence that platelet proteins were transferred to the vascular surface. Reactive oxygen species (ROS) were implicated in these responses, in that the endothelial and platelet protein expressions were inhibited. We conclude that acid-induced ALI causes NOX2-mediated ROS generation that activates platelets, which then generate a procoagulant endothelial surface.     

Transcatheter embolization of brain arteriovenous malformations and meningiomas. Evoked responses correlations

Transcatheter embolization of selective arteries of the carotid and vertebral systems were performed in several patients with brain arteriovenous malformations, angiomas and chemodectomas. All patients were submitted to angiography and electrophysiological examination consisting of a conventional EEG and of visual, auditory and somatosensory evoked responses before and after embolization. Patients with tumors showed a marked decrease of blood flow and tumoral necrosis after embolization, facilitating subsequent surgical procedures. Most patients showed an electrophysiological improvement after embolization, in those regions in which angiography revealed brain decompression resulting from the size reduction of the abnormal tissue. Transcatheter embolization can be very useful in the treatment of brain arteriovenous malformations and intracranial tumors, often facilitating surgical procedures.     

Regulation of lung neutrophil recruitment by VE-cadherin

Lung inflammatory disease is characterized by increased polymorphonuclear leukocyte (PMN) infiltration and vascular permeability. PMN infiltration into tissue involves signaling between endothelial cells and migrating PMNs, which leads to alterations in the organization of adherens junctions (AJs). We addressed the possible role of the protein constituents of AJs, endothelium-specific vascular-endothelial (VE)-cadherin, in the migration of PMNs. Studies were made using VE-cadherin mutant constructs lacking the extracellular domain (DeltaEXD) or, additionally, lacking the COOH-terminus beta-catenin-binding domain (DeltaEXDDeltabeta). Either construct was transduced in pulmonary microvessel endothelia of mice using cationic liposome-encapuslated cDNA constructs injected intravenously. Optimal expression of constructs was seen by Western blot analysis within 24 h. Vessel wall liquid permeability measured as the lung microvessel capillary filtration coefficient increased threefold in DeltaEXD-transduced lungs, indicating patency of interendothelial junctions, whereas the control DeltaEXDDeltabeta construct was ineffective. To study lung tissue PMN recruitment, we challenged mice intraperitoneally with LPS (3 mg/kg) for 6 h and measured PMN numbers by bronchoalveolar lavage and their accumulation morphometrically in lung tissue. DeltaEXD expression markedly reduced the PMN sequestration and migration seen in nontransfected (control wild type) or DeltaEXDDeltabeta-transfected (negative control) mice challenged with LPS. In addition, DeltaEXD transfection suppressed LPS-induced activation of NF-kappaB and consequent ICAM-1 expression. These results suggest that disassembly of VE-cadherin junctions serves as a negative signal for limiting transendothelial PMN migration secondary to decreased ICAM-1 expression in the mouse model of LPS-induced sepsis.     

口服他莫昔芬法建立ICR小鼠子宫腺肌病模型

目的使用口服他莫昔芬法建立ICR小鼠子宫腺肌病模型,并检测其病灶特征、动情周期、血管生成、子宫炎症等变化,以介绍和评价这一动物模型。方法新生ICR小鼠（15只）连续4 d滴喂他莫昔芬,并与同龄对照小鼠（15只）分别于42、85-95、135-145日龄处死,使用苏木素-伊红染色检测子宫病理改变;阴道脱落细胞法检测动情周期变化;免疫组化补体31（CD31）染色计算子宫微血管的密度、直径及所占面积比;逆转录-聚合酶链反应（RT-PCR）检测子宫缓激肽受体、神经激肽受体的基因表达。结果使用口服他莫昔芬法建立ICR小鼠子宫腺肌病模型的造模率为100%,且疾病严重程度随病程进展。部分给药小鼠可出现动情周期紊乱。85-95及135-145日龄给药小鼠子宫肌层微血管密度和面积比均高于对照小鼠（P〈0.05）。135-145日龄给药小鼠子宫缓激肽受体、神经激肽受体的基因表达较对照组明显升高（P〈0.05）。结论口服他莫昔芬法可方便、高效的建立腺肌病小鼠模型,出现腺肌病相关的血管生成、炎症状态、疼痛相关受体表达增高等特征,是研究腺肌病发生、发展的良好模型。     

Stroke in hereditary hemorrhagic telangiectasia patients. New evidence for repeated screening and early treatment of pulmonary vascular malformations: two case reports

Background  

Paradoxical embolism due to pulmonary arteriovenous malformations is the main mechanism of brain infarction in patients with hereditary hemorrhagic telangiectasia. International Guidelines have recently been published to clarify the performance of screening tests and the effectiveness of treatment for pulmonary arteriovenous malformations.     

Th1- and Th2-dependent endothelial progenitor cell recruitment and angiogenic switch in asthma

Increased numbers of submucosal vessels are a consistent pathologic component of asthmatic airway remodeling. However, the relationship between new vessel formation and asthmatic inflammatory response is unknown. We hypothesized that angiogenesis is a primary event during the initiation of airway inflammation and is linked to the recruitment of bone marrow-derived endothelial progenitor cells (EPC). To test this hypothesis, circulating EPC and EPC-derived endothelial cell colony formation of individuals with asthma or allergic rhinitis and health controls was evaluated. Circulating EPC were increased in asthma, highly proliferative, and exhibited enhanced incorporation into endothelial cell tubes as compared with controls. In an acute allergen challenge murine asthma model, EPC mobilization occurred within hours of challenge and mobilized EPC were selectively recruited into the challenged lungs of sensitized animals, but not into other organs. EPC recruitment was Th1 and Th2 dependent and was temporally associated with an increased microvessel density that was noted within 48 h of allergen challenge, indicating an early switch to an angiogenic lung environment. A chronic allergen challenge model provided evidence that EPC recruitment to the lung persisted and was associated with increasing microvessel density over time. Thus, a Th1- and Th2-dependent angiogenic switch with EPC mobilization, recruitment, and increased lung vessel formation occurs early but becomes a sustained and cumulative component of the allergen-induced asthmatic response.     

Coexistence of intradural spinal arteriovenous malformation and associated developmental anomalies - report of two cases

Spinal arteriovenous malformations (AVM) have been devided into dural (Type I), intramedullary glomus (Type II), juvenile (Type III), and perimedullary direct arteriovenous fistulae (Type IV). AVMs are usually associated with subacute myelopathy in what has been known as Foix-Alajouanine syndrome. We presented two patients with two intradural spinal arteriovenous malformations associated in what we call Foix-Alajouanine syndrome. The both patient developed acute back pain and paresthesias, followed by paraplegia and incontinence. The clinical status of one patient has been improved after particle embolization for a 17 years when he deteriorated up to paraplegia after spinal angiography for follow up. Clinical status in another patient deteriorated, because particle emoblisation cannot be performed due to very descrete presentation of the feeding artery. Extensive neuroradiological examination in both patients revealed coexistence of numerous associated developmental anomalies in both patients. We conclude that arteriovenous malformations occasionally are associated with other vascular and nonvascular developmental anomalies elsewhere in the body. These findings rise attention about keep in mind the suspicion of mutual etiopathogenesis and congenital origin of these anomalies. Early timing of the diagnostic and therapeutic interventiosn are stressed to prevent or delay irreversible ishaemic myellopathy or haemorrhage. For the definitive diagnosis of spinal arteriovenous malformations and evaluation of its occlusion grade after the therapy spinal angiography is needed