Experimental study on the mechanism of injury and proliferation of intima in the process of cerebral aneurysm development

Under the hypothesis that cerebral aneurysms develop partly because of defective or decreased healing process at the site of intimal injury, namely at the site of cerebral arterial bifurcation, following experiments were performed. Experiment (1): Rats were treated with ligation of one common carotid artery and ligation of posterior branches of renal artery on both sides to induce cerebral aneurysms. Three months after the treatment, the contralateral carotid artery was ligated. Two months after the ligation, they were sacrificed and examined under light and electron microscopes. In 7 of 11 bifurcations which developed small cerebral aneurysms, prominent intimal thickening with proliferated smooth muscle cells and collagen was observed in the lumen of aneurysms. In 3 of 7 bifurcations which showed no aneurysmal development, apparent intimal thickening was also found at the site where aneurysms were expected to grow. In the group treated for inducing cerebral aneurysms but not ligated the contralateral carotid artery, none of 12 bifurcations with or without aneurysms showed such intimal thickening. Experiment (2): Rats were treated for inducing cerebral aneurysms. Three months after the treatment, reserpine was injected (0.75 mg/Kg B.W./day intraperitoneally) for 2 weeks. At the next day of the last injection, they were sacrificed and examined under the light microscope. In 6 of 12 bifurcations which developed small cerebral aneurysms, prominent intimal thickening was observed in the lumen of aneurysms. In 2 of 3 bifurcations which showed no aneurysmal development, apparent intimal thickening was also found at the site where aneurysms were expected to grow. In the group treated for cerebral aneurysms but not injected reserpine, none of 10 bifurcations with or without aneurysms showed such intimal thickening. Experiment (3): Rats were treated for inducing cerebral aneurysms. Two weeks after the treatment, FSF (fibrin stabilizing factor, known as blood coagulation factor XIII) was injected (10 U/100 g B.W./day, intravenously) for 5 days. Twelve days after the start of injection, they were sacrificed and examined under light and electron microscopes. In 11 of 20 bifurcations which developed small cerebral aneurysms, prominent intimal thickening was observed in the lumen of aneurysms. In the most advanced cases, the lumen of aneurysms were completely filled with proliferated smooth muscle cells and collagen. In 5 of 10 bifurcations which showed no aneurysmal development, apparent intimal thickening was found at the site where aneurysms were expected to grow. In the group treated for inducing cerebral aneurysms but not given FSF, none of 15 bifurcations with or without aneurysms showed such intimal thickening.     

Cerebral blood flow patterns at major vessel bifurcations and aneurysms in rats

Cerebral arterial bifurcations in rats were treated to induce cerebral aneurysms experimentally, and flow patterns of latex particles introduced under a constant flow rate were analyzed with a 16-mm cine-camera and videocassette recorder. Cerebral aneurysms were produced by ligating one common carotid artery, inducing experimental hypertension, and feeding the animals beta-aminopropionitrile. After perfusion and fixation, samples of cerebral arterial bifurcations with shallow invaginations and with small aneurysms were obtained and used for analysis. Bifurcations in rats without experimental treatment were used as control specimens. Flow studies in the control bifurcations showed that the apical intimal pad, not the apex itself, acted as the flow divider. Small particles tended to accumulate at the region just distal to the apical intimal pad, where the initial aneurysmal changes are known to occur. This indicates stagnation of flow at that site. In the bifurcations with shallow invaginations and small aneurysms, a marked pressure gradient was present at the proximal end of the aneurysm orifice. A tendency for stagnation of small particles near the aneurysm wall was also observed. The wall shear stress was highest at the distal end of the aneurysmal orifice, which may be responsible for the development of these lesions.     

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)     

A rabbit model of abdominal aortic aneurysm associated with intimal thickening.

A model of abdominal aortic aneurysm with intimal thickening was developed in the rabbit. A segment of the abdominal aorta just proximal to the bifurcation (1 or 2 cm in length) was dissected and isolated with clamps. This segment was perfused by injecting physiologic saline or 100 U/ml of hog pancreatic elastase from the lumen. Perfusion was performed manually for 5 min and the peak pressure in the segment was between 300 and 400 mm Hg in order to cause aortic wall injury. After 4 weeks, animals that had received perfusion with elastase had aneurysms in the perfused segment on arteriography. None of the other animals developed aortic aneurysms. Histologically, the segments of aorta perfused with saline exhibited intimal hyperplasia. In addition to the intimal hyperplasia, the segments of aorta perfused with elastase solution showed lysis of the elastic lamellae in the media that resulted in aneurysm formation.     

Endothelial injury and inflammatory response induced by hemodynamic changes preceding intracranial aneurysm formation: experimental study in rats

OBJECT: Intracranial aneurysms are the leading cause of subarachnoid hemorrhage, which is associated with high morbidity and mortality rates. Despite advances in the microsurgical and endovascular treatment of intracranial aneurysms, little is known about the mechanisms by which they originate, grow, and rupture. To clarify the series of early events leading to formation of intracranial aneurysms, the authors compared aneurysmal morphological changes on vascular corrosion casts with parallel pathological changes in the cerebral arteries of rats. METHODS: The authors induced cerebral aneurysms by renal hypertension and right common carotid artery ligation in 40 male Sprague-Dawley rats; 10 intact rats served as the controls. The anterior cerebral artery-olfactory artery bifurcation was assessed morphologically by using vascular corrosion casts of Batson plastic reagent and immunohistochemically by using antibodies against endothelial nitric oxide synthase, alpha-smooth muscle actin, macrophages, and matrix metalloproteinase-9. RESULTS: Surgically treated rats manifested different degrees of aneurysmal changes. Based on these staged changes, the authors propose that the formation of intracranial aneurysms starts with endothelial injury at the apical intimal pad (Stage I); this leads to the formation of an inflammatory zone (Stage II), followed by a partial tear or defect in the inflammatory zone. Expansion of this defect forms the nidus of the intracranial aneurysm (Stage III). CONCLUSIONS: This is the first study to demonstrate the in vivo mechanisms of intracranial aneurysm formation. The inflammatory response that follows endothelial injury is the basic step in the pathogenesis of these lesions. In this study the investigators have expanded the understanding of the origin of intracranial aneurysms and have contributed to the further development of measures to prevent and treat aneurysms.     

Vascular corrosion casts mirroring early morphological changes that lead to the formation of saccular cerebral aneurysm: an experimental study in rats

OBJECT: The formation of cerebral aneurysms involves complex processes and little is known about the mechanisms by which they originate, grow, and rupture. The purpose of this study was to identify early ultrastructural morphological changes that lead to the formation of experimental cerebral aneurysms. METHODS: Twenty male Sprague-Dawley rats were subjected to cerebral aneurysm induction (renal hypertension and right common carotid artery ligation); 10 intact rats served as the control group. The animals were killed after 2 months, and a vascular corrosion cast of their cerebral arteries was prepared and screened for aneurysm development by using a scanning electron microscope. Sequential morphological changes observed at the cerebral artery bifurcation in response to hemodynamic shear stress included endothelial changes, intimal pad elevation, and saccular dilation. Endothelial cell changes were the first observed morphological changes; they were followed by various degrees of artery wall dilation. No aneurysmal changes developed in any of the control rats. Of the 20 surgically treated rats, 11 displayed aneurysmal changes. In five of these animals only changes in the endothelial cell imprints could be identified. In the other six rats morphological changes in endothelial cells were associated with different stages of aneurysmal dilation. CONCLUSIONS: This is the first study to demonstrate in vivo early morphological changes that lead to the formation of cerebral aneurysms. The morphological findings indicate the principal role of endothelial cells in the pathogenesis of cerebral aneurysms and suggest that hemodynamic shear stress and blood flow patterns may precipitate these early changes.     

颅内动脉瘤破裂出血后假性动脉瘤的血管内治疗时机与并发症防治

目的探讨颅内动脉瘤破裂出血后在其破口周围所形成的假性动脉瘤与真性动脉瘤（TAN-FAN）复合体的血管内栓塞时机及并发症防治方法。方法采用电解可脱性弹簧圈对58例TAN—FAN复合体进行血管内栓塞。结果58例TAN—FAN复合体中24例（41．4％）为出血后7天内进行栓塞，20例（34．5％）为出血后7天～2周内进行栓塞，14例（24．1％）为出血后2周～1个月内进行栓塞。58个动脉瘤均被成功栓塞，其中真性动脉瘤腔100％闭塞者46个，95％闭塞者9个，90％闭塞者3个；13例A型与31例B型假性动脉瘤腔均未行弹簧圈填塞，14例C型中11例仅用弹簧圈疏松填塞假性动脉瘤腔，另3例用3D-GDC仅栓塞真性动脉瘤腔部分。术中并发动脉瘤破裂1例；并发脑血管痉挛2例；并发脑梗死3例。1例复发者经二次补充GDC栓塞而治愈。其治疗结果根据Glasgow预后评分：Ⅰ级43例，Ⅱ级11例，Ⅲ级3例，全组死亡1例，死亡率1．7％。术后随访3～60个月均无再出血。结论对动脉瘤破裂后形成的TAN—FAN复合体应早期进行血管内栓塞；只有根据TAN—FAN复合体不同的类型采用不同的栓塞方法进行个体化治疗，并具有丰富的动脉瘤栓塞经验，才能最大限度的降低并发症。     

Traumatic dissections of the extracranial internal carotid artery

Traumatic dissections of the extracranial internal carotid artery (ICA) in 18 patients aged 19 to 55 years were studied. All had suffered blunt head or neck injury of marked or moderate severity; motor-vehicle accidents were the leading cause of the injury. Delayed focal cerebral ischemic symptoms were the most common presenting symptoms. Less commonly noted was focal unilateral headache associated with oculosympathetic paresis or bruit. Following a head injury, the abrupt onset of focal cerebral symptoms after a lucid interval should raise the suspicion of arterial injury, particularly when computerized tomography fails to show abnormalities that would explain the evolving neurological deficits on the basis of direct trauma to the brain. Unilateral headaches, oculosympathetic palsy, and bruits also help in establishing the diagnosis. Focal cerebral ischemic symptoms may develop months or years after the initial trauma. These delayed symptoms are caused by embolization from a thrombus within a residual dissecting aneurysm. Common angiographic findings, in decreasing order of frequency, are: aneurysm, stenosis of the lumen, occlusion, intimal flap, distal branch occlusion (embolization), and slow ICA-to-middle cerebral artery flow. Although two patients died as the result of massive cerebral infarction and edema and some were left with severe neurological deficits, most made a good recovery. Residual dissecting aneurysms and occlusion seem to occur more frequently with traumatic dissections than with spontaneous dissections of the extracranial ICA.     

Marked and prolonged depression of Factor XIII after esophageal resection

Anastomotic leakage is one of the most common complications of esophagectomy and, since Factor XIII is required for normal wound healing, we investigated the temporal changes in plasma Factor XIII following esophagectomy and hepatectomy. A control group of patients undergoing other abdominal operations was also studied. Factor XIII activity was determined before surgery and on postoperative days (POD) 1, 3, 7 and 14. The plasma levels of acute phase protein were also measured. The plasma Factor XIII activity decreased significantly in both the hepatectomy and control groups until POD 7, reaching the lowest level on POD 3. In contrast, the esophagectomy group showed significant decreases in Factor XIII levels throughout the postoperative study period, with a nadir with an average activity of 56 per cent on POD 7. Preoperative transferrin levels had a positive correlation with Factor XIII levels measured on POD 3 and there was also a positive significant correlation between Factor XIII activity and alpha 2-macroglobulin levels on POD 3. These results suggest that there is a marked and prolonged depression of plasma Factor XIII activity following esophagectomy which may be attributed to accelerated tissue demands, inadequate synthesis or increased degradation. Moreover, the severe and sustained decrease in Factor XIII activity may be related to poor wound healing after esophagectomy.     

Pathological mechanism and three-dimensional structure of cerebral dissecting aneurysms

OBJECT: The goal of this study was to investigate the pathological mechanism and precise three-dimensional (3D) structure of cerebral dissecting aneurysms in association with their clinical course. METHODS: Nine aneurysm specimens were excised from eight patients. Of the nine aneurysms, seven arose from the vertebral artery, one from the anterior cerebral artery, and one from the superior cerebellar artery. Eight aneurysms were accompanied with subarachnoid hemorrhage (SAH) and one with infarction. Seven aneurysms were obtained at autopsy and two were obtained during surgery (trapping and bypass). All nine aneurysms were sectioned into serial axial slices measuring 5 to 10 microm in thickness. Taking each slice as an element, we reconstructed the 3D structure of the aneurysm. The true lumen communicated with a pseudolumen through the disrupted portion of the internal elastic lamina (IEL) in all nine aneurysms. The ruptured portion was located just above the disrupted IEL. Two aneurysms had an exit back into the true lumen. but the other seven had no such exit. CONCLUSIONS: The primary mechanism by which a cerebral dissecting aneurysm is created is by the sudden disruption of the IEL. The plane of dissection extends through the media. The majority of aneurysms have one entrance into the pseudolumen (entry-only type). This type is associated with an unstable clinical course. Some cerebral dissecting aneurysms have both an entrance and exit (entry-exit type). This type of aneurysm occasionally contains a constant flow of blood through the pseudolumen and is clinically more stable than entry-only aneurysms.     

An autopsy case of persistent primitive hypoglossal artery with multiple cerebral aneurysms

An autopsy case of persistent primitive hypoglossal artery (PPHA) with multiple cerebral aneurysms is reported. A 54-year-old man with subarachnoid hemorrhage was admitted to Kuwana Hospital three days after the onset. The patient was stuporous and had stiffness of the neck. A computed tomogram showed hematoma in the interhemispheric fissure, subarachnoid hemorrhage in the basal cisterns and bilateral Sylvian fissures, and maxked dilatation of ventricles. Cerebral angiogram revealed the left PPHA and multiple aneurysms at the right anterior cerebral artery (A 2) (ruptured), anterior communicating artery, left anterior cerebral artery (A 1), left internal carotid-anterior choroidal artery junction, right internal carotid artery (C 1), and right middle cerebral artery. Neck clipping of the ruptured aneurysm and ventricular drainage were performed on the day of admission. Eight days after admission he died of rupture of the residual aneurysm. In pathological study, the PPHA was originated from the extracranial portion of the left internal carotid artery, 2 cm distal from the cervical carotid bifurcation, entered the intracranial space through the hypoglossal foramen, and turned into the basilar artery. There were six aneurysms which were shown on cerebral angiogram and another aneurysm on the left anterior inferior cerebellar artery. Microscopic examination revealed atherosclerotic change of the PPHA, true aneurysmal changes of the seven aneurysms and defect of tunica media (Forbus' medial gap) at all of the arterial bifurcations without early aneurysmal changes.     

Role of estrogen deficiency in the formation and progression of cerebral aneurysms. Part II: experimental study of the effects of hormone replacement therapy in rats

OBJECT: The increased incidence of cerebral aneurysms in postmenopausal women appears to be related to low levels of circulating estrogen. Using a rat model of aneurysm induction, the authors found that oophorectomy increased the incidence of experimental cerebral aneurysms (Part I in this issue). In the current study they examined the effects of hormone replacement therapy (HRT) on the formation of cerebral aneurysms in rats. METHODS: Forty-five female Sprague-Dawley rats were divided into three equal groups. The animals in Groups A and B were subjected to a cerebral aneurysm induction procedure (renal hypertension and right common carotid artery ligation) followed 1 month later by bilateral oophorectomy. After an additional week the rats in Group A received 17beta estradiol continuous-release pellets. The rats in Group C served as controls. Three months after the aneurysm induction procedure, all the rats were killed and vascular corrosion casts of their cerebral arteries were prepared and checked for aneurysmal changes. Using a scanning electron microscope, the authors recorded aneurysmal changes as endothelial changes alone (Stage I), endothelial changes with intimal pad elevation (Stage II), and saccular aneurysm formation (Stage III). Aneurysmal changes (Stages I, II, and III) occurred in one third of rats that had undergone oophorectomy and were receiving HRT (Group A), compared with 87% of the rats that had undergone oophorectomy but did not receive HRT (Group B). Although most of the aneurysmal changes identified in Group A rats were limited to Stage I or II, most changes in Group B animals were identified as saccular dilation (Stage III). CONCLUSIONS: The findings demonstrated the significant protective role of estrogen against the formation and progression of cerebral aneurysms. It appears to be related to the beneficial effects of estrogen on the function and growth of endothelial cells, which play a major role in preserving the integrity of the vascular wall.     

Morphometric and histological changes in the vascular wall after external radiation for the prevention of intimal hyperplasia

BACKGROUND: Recent reports describe spontaneous dissections and aneurysms after coronary and peripheral artery irradiation for the prevention of intimal hyperplasia. We investigated histological changes and the vasomotor reaction in the vascular wall after external radiation for the prevention of intimal hyperplasia in rabbits. MATERIALS AND METHODS: The aorta was experimentally injured in 34 rabbits who were then assigned to one of three groups: irradiation with 20 Gy; with 25 Gy; and a control group with no irradiation. Before the arterial injury and 45 days later, vasomotor function was assessed with an intravascular ultrasound catheter. The aorta was resected for morphometric and histological studies. RESULTS: After injury and irradiation, vasomotor responses were significantly lower in the two irradiated groups (P < 0.05). Intimal thickness and the intima/media ratio were significantly lower in irradiated groups. In the irradiated group histological examination showed reduced intimal proliferation with an intact endothelium. In the 20-Gy irradiated group the vascular media contained necrotic areas, and in the 25-Gy irradiated group, severe fibrosis. CONCLUSION: After arterial injury, external irradiation at 20 and 25 Gy effectively reduces aortic intimal and medial thickening. Histological changes include recasting with necrosis and fibrosis causing a decreased vasomotor response. Further investigations are needed to confirm medial necrosis and replacement with fibrosis. Because the irradiation doses in this study match those currently used and also recommended for experimental and clinical use, if confirmed in humans parietal recasting might possibly explain the reported spontaneous dissections and aneurysm formation after irradiation.     

Morphological and histopathological aspects of aneurysms after patch aortoplasty for coarctation

Repair of coarctation of the aorta by synthetic patch grafting has been complicated by late aneurysm formation. These aneurysms differ macroscopically from atherosclerotic thoracic aortic dilatations. Specimens for microscopic examination were taken from 14 of 20 patients undergoing aneurysm resection. Histological analysis of the specimens showed medionecrosis in 13 patients of the specimens showed medionecrosis in 13 patients (93%), foreign body reaction in 11 patients (78%), and intimal thickening in 3 patients (21%). The three layers of the aortic wall could be identified in the aneurysms. On the basis of these results, we discuss the etiologic factors and pathogenetic mechanisms involved in the development of these aneurysms.     

Healing process for cerebral dissecting aneurysms presenting with subarachnoid hemorrhage

OBJECTIVE: This was a pathological study to investigate the healing process for cerebral dissecting aneurysms presenting with subarachnoid hemorrhage (SAH). METHODS: Thirteen dissecting aneurysms that presented with SAH were obtained from 13 patients. Nine aneurysms arose from the vertebral artery, two arose from the anterior cerebral artery, one arose from the internal carotid artery, and one arose from the superior cerebellar artery. Eight aneurysm specimens were collected during autopsy and five were resected during surgery (trapping with or without bypass). The period between the onset of SAH and the time of specimen collection ranged from 6 hours to 35 days. All 13 aneurysms were pathologically examined with immunohistochemical staining, with a focus on the chronological healing process after SAH. RESULTS: All dissecting aneurysms were generated with sudden widespread disruption of the internal elastic lamina and media. The healing process occurred with neointimal proliferation. The neointima, consisting mainly of newly synthesized smooth muscle cells and collagen fibers, extended from the disrupted ends of the media proper forward to the ruptured portion. CONCLUSION: It is assumed that the healing process, with neointimal proliferation, begins after 1 week and may not be complete even after 1 month, depending on the extent of the wall injury.     

Study of the elastic skeleton of intracranial arteries in animal and human vessels and experimentally induced cerebral aneurysms]

In an attempt to clarify the elastic skeleton of cerebral arteries in animals and human, and experimentally induced cerebral aneurysms, following experiments were performed. Experiment (1): The elastic skeleton of major cerebral arteries in rats, monkeys, and one human were studied by scanning electron microscopy after hot-formic acid extraction followed by freeze-drying. For a comparative study, the thoracic aorta and femoral arteries of rats were also examined. The cerebral arteries of rats had one distinct internal elastic lamina connected with medial elastic tissue. This internal elastic lamina had fenestrations, which were less frequent in cerebral arteries than in extracranial arteries, and fold-like protrusions into the lumen. This finding has not been recognized before. Such protrusions were more prominent in cerebral arteries than in extracranial arteries. At the apical intimal pad, the internal elastic lamina appeared to be continuous, making a honeycomb-like structure there. These folds and fenestrations were numerous in the apical region. There were no essential differences between species. Experiment (2): Cerebral aneurysms were produced by ligating unilateral carotid artery and bilateral posterior branches of renal arteries, and feeding beta-aminoproprionitrile fumarate. The first noted change was the loss of fold-like structures protruding from the internal elastic lamina. Morphological changes of the internal elastic lamina, considered to be primarily responsible for aneurysmal formation, occurred after the loss or disintegration of the media. The internal elastic lamina disappeared after these consequences. In a large aneurysm with a thick dome, the wall contained fine proliferated elastic lamellae. The present study shows that the internal elastic lamina is not a simple sheet but part of the complicated architecture of the elastic tissue of the vessel wall. It seems probable that the complex elastic skeleton of the arterial wall may account for the mechanical properties of the artery and that growth of the aneurysm occurs due to disintegration of the elastic skeleton and not simply with rupture of the internal elastic lamina. We believe that such changes in the elastic skeleton are a property of the functional state of cells that produce elastin.     

Histopathological study of venous aneurysms in patients with dural arteriovenous fistulas

OBJECT: Of all intracranial dural arteriovenous fistulas (DAVFs), those with cortical venous drainage associated with cortical venous ectasia or varices are predisposed to an aggressive course and produce progressive neurological symptoms or hemorrhages. The authors undertook a histological examination of venous aneurysms and arterialized veins in the proximity of these aneurysms that had been surgically removed in patients with DAVFs. METHODS: Surgical specimens were obtained in eight patients. The excised venous aneurysms and the arterialized veins in their proximity were stained using hematoxylin and eosin, van Gieson's elastic, and Masson's trichrome stain. Immunostaining was also performed for alpha smooth-muscle actin, desmin, and factor VIII antigen. Five of the patients had presented with venous hypertension, and three had intracranial hemorrhages. The arterialized vein obtained in the proximity of the venous aneurysm exhibited local irregular intimal thickening; the internal elastic lamina (IEL) was grossly preserved. All venous aneurysms in patients with venous hypertension manifested medial thickening and local intimal thickening with loss of IEL; the thickness of the wall was relatively uniform. In contrast, the wall thickness of venous aneurysms in patients with hemorrhage was extremely irregular and there was no clear delineation between the media and the intima. In media with complete disappearance of IEL, there was scant muscle tissue. CONCLUSIONS: Degenerative changes in venous aneurysms in patients with hemorrhage were much greater than in patients with venous hypertension, possibly because hemorrhages result from a more complicated interplay of anatomical, hemodynamic, and degenerative factors.     

Connective tissue changes in syngeneic aortal vein grafts in rats

The supradiaphragmatic inferior vena cava was syngeneically transplanted into the infrarenal part of the abdominal aorta in rats of inbred strains. The initial histologic changes coincided with the changes usually seen in wound healing during the inflammatory phase and the phase of fibroplasia. Later the reparative process occurred predominantly in the luminal part of the vein wall, and was usually seen as intimal hyperplasia. In some grafts this process caused a narrowing of the lumen. In this particular experimental model the thickening of the intimal layer was mainly due to organization of fibrin layering thrombus. This was shown by detection of lamellar fibrin deposits and a high concentration of fibronectin in this layer. A large amount of fibronectin was detected in and around the proliferating fibroblasts and in thrombi. This explains the high concentration of fibronectin in the proliferating intimal layer of the graft.     

Fusiform vertebral artery aneurysms as a cause of dissecting aneurysms. Report of two autopsy cases and a review of the literature.

Two autopsy cases of angiographically determined fusiform aneurysms of the vertebral arteries (VAs) are reported and the appropriate literature is reviewed to investigate the pathological characteristics of both fusiform and dissecting VA aneurysms and the pathogenesis of dissecting aneurysms. One patient had suffered a subarachnoid hemorrhage (SAH) due to dissection of a previously documented incidental fusiform aneurysm. The other patient had harbored incidental fusiform aneurysms coexistent with a ruptured aneurysm of the posterior inferior cerebellar artery. The location and pathological features of the aneurysms were similar in the two cases. The aneurysms in both cases displayed intimal thickening, disruption of the internal elastic lamina, and degeneration of the media. A mural hemorrhage and patchy calcification were also found in the case that included SAH. Based on their pathological investigation of these two cases and a review of reported cases, the authors propose that incidental fusiform aneurysms in the VAs are characterized by weakness in the internal elastic lamina and, therefore, have the potential to become dissecting aneurysms, resulting in a fatal prognosis. This suggests that long-term control of blood pressure is mandatory in patients with incidental fusiform aneurysms in the VAs.