Quantitative not qualitative histology differentiates aneurysmal from nondilated ascending aortas and reveals a net gain of medial components.

Medial degeneration is a common histopathological finding in aortopathy and is considered a mechanism for dilatation. We investigated if medial degeneration is specific for sporadic thoracic aortic aneurysms versus nondilated aortas. Specimens were graded by pathologists, blinded to the clinical diagnosis, according to consensus histopathological criteria. The extent of medial degeneration by qualitative (semi-quantitative) assessment was not specific for aneurysmal compared to nondilated aortas. In contrast, blinded quantitative assessment of elastin amount and medial cell number distinguished aortic aneurysms and referent specimens, albeit with marked overlap in results. Specifically, the medial fraction of elastin decreased from dilution rather than loss of protein as cross-sectional amount was maintained while the cross-sectional number, though not density, of smooth muscle cells increased in proportion to expansion of the media. Furthermore, elastic lamellae did not thin and interlamellar distance did not diminish as expected for lumen dilatation, implying a net gain of lamellar elastin and intralamellar cells or extracellular matrix during aneurysmal wall remodeling. These findings support the concepts that: (1) medial degeneration need not induce aortic aneurysms, (2) adaptive responses to altered mechanical stresses increase medial tissue, and (3) greater turnover, not loss, of mural cells and extracellular matrix associates with aortic dilatation.

Effect of collagen fibres and elastic lamellae content on the mechanical behaviour of abdominal aortic aneurysms.

PURPOSE: The main purpose of this study was a detailed analysis of the mechanical and structural characteristics of human abdominal aneurysms in comparison with normal abdominal aortae and determination of the correlations between their mechanical behaviour and the microstructural content. METHODS: Various mechanical properties, i.e., mechanical failure properties, elastic moduli, inflection point coordinates, index of anisotropy and incompressibility were determined under uniaxial loading conditions in the circumferential and axial directions. Constitutive parameters were derived from the commonly used constitutive model proposed by Holzapfel et al. [9]. The microstructural arrangement was examined by histological staining supported by scanning electron microscopy analysis. The content of collagen fibres and elastic lamellae was tested in relation to mechanical properties and constitutive parameters. RESULTS: Significant differences were found in the microstructural arrangement and layer composition of the aneurysmal specimens, compared to the normal aorta group. The mechanical properties and constitutive parameters of the aneurysmal specimens were significantly altered, indicating a weakening of the load-bearing properties of the walls of the aneurysms. A comparative analysis discovered significant correlations between structural composition and mechanical parameters, in particular with respect to the number of collagen fibres and failure stress, which can be important for clinical evaluation of abdominal aortic aneurysm (AAA) rupture. CONCLUSIONS: Changes in the content of collagen fibres and elastic lamellae correlate with mechanical and constitutive parameters, indicating AAA severity.

Some segmental morphological and morphometrical features of the intima and media of the aortic wall in Chinchilla lanigera.

BACKGROUND: The aim of this study is to describe the morphology, morphometry and ultrastructure of segments of the thoracic and abdominal aorta portions in Chinchilla lanigera. Thickness measurements of the tunica intima and media complex of the aorta were taken. MATERIALS AND METHODS: In all observed specimens, the thickness values for the tunica intima and media complex of the cranial thoracic aorta were significantly higher (mean: 702.19 µm) when compared to the values of other analysed aortic segments (means: 354.18 µm; 243.55 µm). Complex statistical methods were used to assess the differences between various aortic segments. RESULTS AND CONCLUSIONS: The components of the vessel walls show variations in structure and thickness, presumably due to an adaptation to functional demand.

Fine structure of human thoracic duct as revealed by light and scanning electron microscopy.

Little information has been available regarding microanatomy of human thoracic duct in spite of the importance for an understanding of pathophysiology in clinical medicine. The present study demonstrated a fine structure of human thoracic duct system by light and scanning electron microscopy. A number of longitudinal or spiral ridges and grooves were formed on luminal surfaces of the lymphangia and lymph sac, it likely facilitating fluent lymph flow. The endothelial cells displayed various cell shapes in compliance with their distributed regions. The lymph sac joining large vein composed a peculiar multiple valve structure presumably ensuring lymph storage and prevention of lymph backflow. The longitudinal muscle sheet in the tunica intima and circular muscle bundles in the tunica media constructed an integrated power unit probably eliciting spontaneous lymph propulsion. Furthermore, the thoracic duct was richly supplied with blood vessels not only in the tunica externa, but also just beneath the endothelium. The present findings provide a morphological basis for investigation of human thoracic duct in basic and clinical medicine.

Multiphoton microscopy observations of 3D elastin and collagen fiber microstructure changes during pressurization in aortic media.

Elastin and collagen fibers play important roles in the mechanical properties of aortic media. Because knowledge of local fiber structures is required for detailed analysis of blood vessel wall mechanics, we investigated 3D microstructures of elastin and collagen fibers in thoracic aortas and monitored changes during pressurization. Using multiphoton microscopy, autofluorescence images from elastin and second harmonic generation signals from collagen were acquired in media from rabbit thoracic aortas that were stretched biaxially to restore physiological dimensions. Both elastin and collagen fibers were observed in all longitudinal-circumferential plane images, whereas alternate bright and dark layers were observed along the radial direction and were recognized as elastic laminas (ELs) and smooth muscle-rich layers (SMLs), respectively. Elastin and collagen fibers are mainly oriented in the circumferential direction, and waviness of collagen fibers was significantly higher than that of elastin fibers. Collagen fibers were more undulated in longitudinal than in radial direction, whereas undulation of elastin fibers was equibiaxial. Changes in waviness of collagen fibers during pressurization were then evaluated using 2-dimensional fast Fourier transform in mouse aortas, and indices of waviness of collagen fibers decreased with increases in intraluminal pressure. These indices also showed that collagen fibers in SMLs became straight at lower intraluminal pressures than those in EL, indicating that SMLs stretched more than ELs. These results indicate that deformation of the aorta due to pressurization is complicated because of the heterogeneity of tissue layers and differences in elastic properties of ELs, SMLs, and surrounding collagen and elastin.

Rosuvastatin alleviates the development of monocrotaline-induced pulmonary hypertension in rats.

Statins can increase endothelial function through enhancement of the expression and activity of endothelial nitric oxide synthase (eNOS). The aim of this study is to evaluate the effect of rosuvastatin on the number of circulating endothelial progenitor cells (EPCs) and endothelial expression of eNOS in monocrotaline-induced pulmonary hypertensive rats. Sixty Sprague-Dawley (SD) rats were divided into three groups of 20: control (group A), pulmonary hypertension (PAH) + rosuvastatin group (group B), and PAH (group C). Monocrotaline (MCT; 60 mg/kg) was injected (intraperitoneally) to induce PAH. Rats in group B received rosuvastatin [10 mg/(kg. day)] for 2 weeks. Peripheral blood (5 mL) was aspirated from the femoral artery of each rat before and after 2 weeks of treatment. Mononuclear cells were isolated and subcultured to obtain EPCs. Small and moderately sized pulmonary arteries were collected 2 weeks later for histological analyses. eNOS gene expression in endothelial cells of pulmonary arteries were then determined at mRNA and protein levels. eNOS expression at mRNA and protein levels and the number of circulating EPCs were reduced significantly in groups B and C compared with group A (P less than 0.05), and a significant difference between group B and group C (P less than 0.05) was observed. Vascular remodeling in small and moderately sized pulmonary arteries was attenuated markedly in group B compared with group C. These results suggest that rosuvastatin can ameliorate the remodeling of pulmonary arteries in MCT-induced PAH rats by increasing the number of circulating EPCs and eNOS upregulation.

Segmental and age differences in the elastin network, collagen, and smooth muscle phenotype in the tunica media of the porcine aorta.

The porcine aorta is often used in studies on morphology, pathology, transplantation surgery, vascular and endovascular surgery, and biomechanics of the large arteries. Using quantitative histology and stereology, we estimated the area fraction of elastin, collagen, alpha-smooth muscle actin, vimentin, and desmin within the tunica media in 123 tissue samples collected from five segments (thoracic ascending aorta; aortic arch; thoracic descending aorta; suprarenal abdominal aorta; and infrarenal abdominal aorta) of porcine aortae from growing domestic pigs (n=25), ranging in age from 0 to 230 days. The descending thoracic aorta had the greatest elastin fraction, which decreased proximally toward the aortic arch as well as distally toward the abdominal aorta. Abdominal aortic segments had the highest fraction of actin, desmin, and vimentin positivity and all of these vascular smooth muscle markers were lower in the thoracic aortic segments. No quantitative differences were found when comparing the suprarenal abdominal segments with the infrarenal abdominal segments. The area fraction of actin within the media was comparable in all age groups and it was proportional to the postnatal growth. Thicker aortic segments had more elastin and collagen with fewer contractile cells. The collagen fraction decreased from ascending aorta and aortic arch toward the descending aorta. By revealing the variability of the quantitative composition of the porcine aorta, the results are suitable for planning experiments with the porcine aorta as a model, i.e. power test analyses and estimating the number of samples necessary to achieving a desirable level of precision. The complete primary morphometric data, in the form of continuous variables, are made publicly available for biomechanical modeling of site-dependent distensibility and compliance of the porcine aorta.

Histologic comparison between the internal mammary artery and the deep inferior epigastric artery and clinical implications for microsurgical breast reconstruction.

BACKGROUND: The internal mammary artery (IMA) is one of the most popular recipients for microsurgical breast reconstruction. However, it is often separated into sleeve-like layers when it is handled. This study tried to explain this unique behaviour of the IMA through histologic observation. METHODS: Nine pairs of IMAs and DIEAs were harvested and subject for haematoxylin-eosin and Verhoeff's elastic staining. Thickness of the tunica media and the number of elastic lamellae were compared. Samples of the IMA, the DIEA, and the thoracodorsal artery from another patient were observed through the transmission electron microscope to further show the structural differences. RESULTS: The most notable difference was presence of multiple elastic lamellae in tunica media in the IMAs, which was barely present in the DIEAs. The mean number of elastic lamellae was 9.2 in the IMA group and 1.0 in the DIEA group (p < 10(-9)). A transmission electron microscope showed that the tunica media of the DIEA and the TDA was densely packed with smooth muscle cells, while the muscle cells distributed sparsely in the IMA. CONCLUSIONS: The IMA is an elastic artery which is characterised by multiple layers of elastic lamellae while relatively lacking in smooth muscle cells. The wall of the IMA is easily dissected between the tunica media and the adventitia, or at the outer 1/3 of the tunica media. The inner structure is easily torn if microsutures do not engage the tunica adventitia.

Morphological characteristics of the walls of thrombophlebitic saphenous vein.

INTRODUCTION: To investigate the morphological changes in the walls of thrombophlebitic saphenous veins. METHODS: Fifty-four specimens were made into slices for haematoxylin and eosin and Masson trichrome staining; ultrathin slices were also created. Slices were observed under light microscopy and electron microscopy. RESULTS: Under light microscopy, the tunica intima of venous wall in the thrombophlebitic saphenous veins group was obviously thickened and incomplete; intravascular papillary endothelial hyperplasia was observed. Hyperplasia of collagenous fibres in the tunica media was observed. Elastic fibres in the tunica externa became fewer, whereas nourishing vessels were significantly increased in number. Infiltration of many inflammatory cells was observed. Under electron microscopy, Auer bodies with high electron density and round granules could be seen in endothelial cells in the thrombophlebitic saphenous veins group. Smooth muscle cells had an irregular karyotype, with blurred cristae in some mitochondria. Myofilaments basically disappeared. CONCLUSION: Thrombus formation might aggravate re-modelling of the walls of varicose veins.

Morphometric study of aortic wall parameters evolution in newborn and child.

The largest artery in the human body, intimately connected to the heart, aorta is usually regarded as the major source of oxygenated blood for the circulatory system. The three concentric layers, which surround the aortic lumen-the tunics intima, media and adventitia, transform the aorta in a large elastic duct, which is irregular calibrated according to its segments. The special aortic distensibility is facilitated by its elastic circumferential lamellar complex. Any disturbance of its structural components is able to interfere with its normal and vital activity. Our study intends to reveal that the development of elastic lamellae should be regarded not only as an indispensable step for the aortic wall configuration, but also like a process in a firm connection with the rest of aortic wall components. The transition from intrauterine life to a new stage of life, childhood, has to determine an adequate adaptation of almost all the components of aortic wall, in order to sustain a consistent pulsatile blood flow. Stereological quantitative analysis of thoracic aortic fragments prelevated from newborns and children was performed in order to estimate the dynamic of vascular wall increase. We first estimated the general configuration of the thoracic aortic wall, quantifying the principal constituents; the connective tissue profile, investigated through its main elements, collagen and elastic fibers, supports the idea that each type of fiber has a distinct evolution in different groups of ages and has to be correlated with their involvement in maintaining of the aortic wall mechanical properties. Elastic fibers percentage volume was increased in both examined groups, with a small difference reported in children aorta, while collagen fibers exhibit a slow increase in children aorta. Our morphometric quantitative assessment suggests that further studies have to draw of in a precisely manner the outline of the secretory well defined function of vascular smooth muscle cells; the elucidation of the manner in which the secretory pathway for each type of fiber becomes fully adapted to every stage of aortic development will allow a new perspective in aortic pathology.

Continuous exposure to low amplitude extremely low frequency electrical fields characterizing the vascular streaming potential alters elastin accumulation in vascular smooth muscle cells.

In normal development and pathology, the vascular system depends on complex interactions between cellular elements, biochemical molecules, and physical forces. The electrokinetic vascular streaming potential (EVSP) is an endogenous extremely low frequency (ELF) electrical field resulting from blood flowing past the vessel wall. While generally unrecognized, it is a ubiquitous electrical biophysical force to which the vascular tree is exposed. Extracellular matrix elastin plays a central role in normal blood vessel function and in the development of atherosclerosis. It was hypothesized that ELF fields of low amplitude would alter elastin accumulation, supporting a link between the EVSP and the biology of vascular smooth muscle cells. Neonatal rat aortic smooth muscle cell cultures were exposed chronically to electrical fields characteristic of the EVSP. Extracellular protein accumulation, DNA content, and electron microscopic (EM) evaluation were performed after 2 weeks of exposure. Stimulated cultures showed no significant change in cellular proliferation as measured by the DNA concentration. The per-DNA normalized protein in the extracellular matrix was unchanged while extracellular elastin accumulation decreased 38% on average. EM analysis showed that the stimulated cells had a 2.85-fold increase in mitochondrial number. These results support the formulation that ELF fields are a potential factor in both normal vessel biology and in the pathogenesis of atherosclerotic diseases including heart disease, stroke, and peripheral vascular disease.

A comparative ultrastructural study of a new type of autoschizis versus a survival cellular mechanism that involves cell membranes of cerebral arteries in humans.

The authors analyzed by transmission electron microscopy the modifications of plasmalemma and nuclear envelope in the cerebral arterial wall in humans. Their ultrastructural observations are performed on the tunica media and endothelium. During autoschizis, some smooth muscle cells showed deep invaginations of the nuclear envelope with multiple craters that disintegrate the nucleus, whereas in the endothelium repetitive invaginations of plasmalemma lead to cell demise by cytoplasmic self-excisions. During survival mechanism, a perinuclear constriction of plasmalemma occurs, which conserves nucleus and cytoskeleton, and only a segregated cytoplasmic area, without organelles, is removed in lumen.

Age-dependent ultrastructural changes of coronary artery in spontaneously hypertensive rats.

The age-dependent differences in basic cardiovascular parameters, geometry and structure of coronary arteries between Wistar and spontaneously hypertensive rats (SHR) were evaluated. SHR of the age 3-, 9-, 17-, and 52-week and age-matched Wistar rats were used. Blood pressure (BP) was measured by the plethysmographic method. Animals were perfused with a glutaraldehyde fixative under pressure of 90 mmHg (3-week-old) and 120 mmHg (9-, 17-, 52-week-old). Coronary arteries were processed for electron microscopy. The proportions and cross sectional areas (CSA) of extracellular matrix in intima and media, endothelial and muscle cells were determined by point counting method. Cardiac hypertrophy and except of 3-week-old rats also BP increase and coronary wall hypertrophy was found in all ontogenic periods in SHR compared to Wistar rats. Arterial wall hypertrophy was evoked by increase of CSA of medial extracellular matrix and smooth muscle cells. In 52-week-old SHR, CSA of muscle cells did not differ from that in 17-week-old SHR but the CSA of intimal and medial extracellular matrix significantly increased. The CSA of endothelial cells and CSA of intimal extracellular matrix were increased only in 52-week-old SHR. The independency between BP and trophicity of individual components of the coronary wall during ontogeny of SHR was documented.

[Intima-media thickness and its relation with the SCORE function in Spain]. / Grosor íntimo-medial carotídeo y su relación con la función SCORE en España.

BACKGROUND AND OBJECTIVE: Measurement of carotid intima-media thickness (IMT) has been proposed for the evaluation of subclinical atherosclerosis as part of the cardiovascular prevention strategy. The objectives are to describe the association between IMT and the presence of other cardiovascular risk (CVR) factors and with CVR estimated by the SCORE function. SUBJECTS AND METHODS: Descriptive study in general population through non-probability sampling. There were 1,118 participants to whom we estimated their cardiovascular risk according to the SCORE function. We selected 467 participants who underwent carotid echo-doppler in which IMT was determined and carotid plaque was evaluated. RESULTS: Of the 467 individuals, 24, 49 and 27% belonged to the CVR, medium and high respectively. The population mean IMT was 0.63745 mm. The mean IMT for the cardiovascular risk groups low, medium and high was 0.5629, 0.66269 and 0.66016 mm respectively. IMT increased with age and was associated with other cardiovascular risk factors. In 13% of carotid ultrasound performed, atherosclerotic plaques were found. The highest percentage of individuals with atherosclerotic plaques were seen in the intermediate and high CVR groups. CONCLUSIONS: The results of this study show similar values of carotid IMT and presence of carotid plaque in subjects of intermediate and high CVR. We also found an association between increased carotid IMT and age, weight and diabetes.

Role of echocardiographic left ventricular mass and carotid intima-media thickness in the cardiovascular risk assessment of asymptomatic patients with type 2 diabetes mellitus.

BACKGROUND: Standard cardiovascular (CV) risk assessment may underestimate risk in people with type 2 diabetes mellitus (T2DM). Cardiac and vascular imaging to detect subclinical disease may augment risk prediction. This study investigated the association between CV risk, left ventricular hypertrophy (LVH) and carotid intima-media thickness (CIMT) in patients with T2DM free of CV symptoms. METHODS: People with T2DM without known CV disease were recruited from general practice. The 5-year risk of CV events was calculated using an adjusted Framingham equation and the prevalence of LVH and abnormal CIMT across bands of CV risk assessed. In those at intermediate risk, the number needed to scan (NNS) to reclassify one person to high risk was calculated across the group and compared in those above and below 55 years. The association between LV mass and CIMT was also assessed. RESULTS: Mean age 57 years (SD11), 51% female. Median 5-year CV risk 14.3% (interquartile range 10.3, 19.5), 51% had LVH (American Society of Echocardiography criteria) and 31% an abnormal CIMT (age and sex criteria). In the 52% at intermediate risk, 37% had LVH and 36% an abnormal CIMT. The NNS was 1.7 using both imaging techniques, 2.7 using cardiac imaging alone or 2.8 using vascular imaging alone. Almost twice as many people >55 years had an abnormal CIMT than those <55 years. CONCLUSIONS: Cardiac and vascular imaging to detect subclinical disease can be used to augment prediction of CV risk in people with T2DM at intermediate risk. The value of reclassifying risk is as yet unproven and requires outcome data from intervention studies.

Medial artery calcification of uremic patients: a histological, histochemical and ultrastructural study.

Recent findings suggest that vascular calcification (VC) is an active process similar to bone mineralization, the vascular smooth muscle cells (VSMCs) undergoing phenotypic differentiation into osteoblastic cells and synthesizing calcification-regulating proteins found in bone. This study has investigated the VC process of uremic patients, with a morphologic approach. Epigastric artery samples from 49 uremic, non-diabetic patients were taken during kidney transplantation. Sections from paraffin-embedded samples were stained with hematoxylin/eosin and von Kossa. CD68 was immunohistochemically detected, and sections from frozen samples were stained with Oil Red O. Deeply calcified samples were stained with Picrosirius Red, PAS, and Alcian blue. Specimens from one patient with moderate and one with severe VC were examined under the electron microscope. None of the samples had atherosclerosis. Calcifications were found in the media of 38 patients. In 23, dot-like calcifications were irregularly scattered near the adventitia (light VC); in 11, granular calcifications formed concentric rings near the adventitia (moderate-advanced VC); in 4, zones of consolidated calcifications were found (severe VC). These zones were poor in collagen, glycoproteins and proteoglycans. In cases with moderate or severe VC, VSCMs showed necrotic changes. Matrix vesicles could be recognized in the extracellular spaces. In cases with severe VC, uncalcified or partially calcified membranous bodies were found, together with Liesegang rings. Patches of fibrin were also found. These findings point to a mainly degenerative mechanism of VC, which proceeds from the outer portion of the media. An active mechanism, however, cannot be excluded. A unifying hypothesis is suggested.

Hair follicle-derived smooth muscle cells and small intestinal submucosa for engineering mechanically robust and vasoreactive vascular media.

Our laboratory recently reported a new source of smooth muscle cells (SMCs) derived from hair follicle (HF) mesenchymal stem cells. HF-SMCs demonstrated high proliferation and clonogenic potential as well as contractile function. In this study, we aimed at engineering the vascular media using HF-SMCs and a natural biomaterial, namely small intestinal submucosa (SIS). Engineering functional vascular constructs required application of mechanical force, resulting in actin reorganization and cellular alignment. In turn, cell alignment was necessary for development of receptor- and nonreceptor-mediated contractility as soon as 24 h after cell seeding. Within 2 weeks in culture, the cells migrated into SIS and secreted collagen and elastin, the two major extracellular matrix components of the vessel wall. At 2 weeks, vascular reactivity increased significantly up to three- to fivefold and mechanical properties were similar to those of native ovine arteries. Taken together, our data demonstrate that the combination of HF-SMCs with SIS resulted in mechanically strong, biologically functional vascular media with potential for arterial implantation.

Morphological changes in varicocele veins: ultrastructural study.

BACKGROUND: Varicocele consists of dilatation of the pampiniform venous plexus and the internal spermatic veins. It is present in 15% of male population and is a common cause of male infertility. OBJECTIVE: To describe the normal structure of the internal spermatic vein and the morphological changes in grade 3 varicocele. METHODS: The authors dissected and analyzed a 2- to 3-cm tract of the pampiniform venous plexus of 20 patients undergoing varicocelectomy for left varicocele and of 10 consecutive patients undergoing surgery for left inguinal hernia. The histological examination was performed with hematoxylin­eosin and Masson trichrome stains. The ultrastructural evaluation was done using both scanning and transmission electron microscopy. RESULTS: Compared with normal internal spermatic veins, varicocele veins showed narrowing and/or obliteration of the lumens, destruction of the endothelial cells, invagination of the intima, and deposition of collagen bundles in the media (light microscopy). The ultrastructural changes in varicocele veins included elongation of the endothelial cells with features of cellular damage, loss of the internal elastic lamina, and the appearance of ghost bodies and degenerative vacuoles in the subendothelial layer. CONCLUSIONS: The authors believe this is the first report analyzing ultrastructual changes in normal human internal spermatic vein samples and in varicocele. The underlying molecular mechanisms of these changes await further studies.

Structural organization of hepatic portal vein in rat with special reference to musculature, intimal folds, and endothelial cell alignment.

Structural organization of hepatic portal vein (HPV) was examined in adult rats by means of light and electron microscopy. Three characteristic features were found in the wall structure of rat HPV. (1) Tunica media consisted of two kinds of smooth muscle. The inner circular smooth muscle (CSM) was composed with one or two layer of smooth muscle cells, and was found in the entire length of the HPV and its tributaries. The outer longitudinal smooth muscle (LSM) was limited to a specific region of HPV; in particular it was well-developed at distal half of HPV. CSM counteracts luminal hydrostatic pressure to prevent circumferential hyperextension of venous wall, whereas LSM is likely to counteract a tractive force produced by gravity and movement of small intestine. (2) Intima of HPV showed a unique feature, intimal folds, which protruded into the lumen and were aligned almost circumferentially. Intimal folds were found only at the same region where the LSM was well-developed. Thus, LSM is presumably involved in the formation of intimal folds. (3) The endothelial cells between intimal folds were circumferentially aligned along the folds, although those in the other regions of HPV were arrayed along the longitudinal axis of HPV or the direction of blood flow as reported in other kinds of blood vessel. This finding implied that the circumferential blood flow locally occurs on the surface of intima between the intimal folds.

Dose-dependent ultrastructural and morphometric alterations after erythropoietin treatment in rat femoral artery vasospasm model.

PURPOSE: Cerebral vasospasm is the common cause of poor outcome after aneurysmal subarachnoid hemorrhage (aSAH). Although many agents are experimentally and clinicaly used to protect or recover from vasospasm, an effective neurotherapeutic drug is still missing. Erythropoietin (EPO) is recently a promising candidate. The aim of this study is to investigate the dose-dependent effects of recombinant human EPO (rhEPO) on arterial wall in a rat femoral artery vasospasm model. METHODS: Thirty two animals were divided into four groups: vasospasm without any treatment (group A), vasospasm +250 IU/kg rhEPO group (group B), vasospasm +500 IU/kg rhEPO group (group C), and control group (group D). Rat femoral artery vasospasm model was used. For groups B and C, 7 days of 250 IU/kg and 500 IU/kg intraperitoneal rhEPO in 0.3 ml saline were administered respectively; and for groups A and D, 0.3 ml saline were administered intraperitoneally without any treatment. After 7 days, histological and morphometric analyses were carried out. RESULTS: Vasospasm alone group demonstrated the highest vessel wall thicknesses, comparing to other groups (p < 0.001). While for groups B and C, vessel wall thickness values were significantly higher than the control group (p < 0.001), between these two groups, there was no significant difference achieved (p > 0.05). CONCLUSION: In our study, there was no significant difference between the two rhEPO treatment groups, but rhEPO treatment was shown to be histologically and morphometrically effective in vasospasm. However, if dosage of EPO treatment is augmented, successful results may be achieved.