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Evaluation of medial hypertrophy in resistance vessels of spontaneously hypertensive rats.

The role of smooth muscle cell hypertrophy, hyperploidy, and hyperplasia in medial hypertrophy of mesenteric resistance vessels of 107- to 111-day-old spontaneously hypertensive rats (SHR) was examined using a combination of morphometric, biochemical, and immunological techniques. Mesenteric arteries were classified on the basis of branching order for comparative purposes. Branch level I vessels were those that directly enter the jejunal wall, while Branches II to IV represented more proximal vessels; Branch IV vessels were those that branch from the superior mesenteric artery. Medial hypertrophy was assessed in perfusion-fixed vessels by morphometric evaluation of medial cross-sectional area and smooth muscle content. Medial cross-sectional area and smooth muscle content were significantly increased in larger (Branches III and IV) but not smaller (Branches I and II) mesenteric resistance vessels of SHR compared with control normotensive Wistar-Kyoto rats (WKY). Smooth muscle cell hypertrophy and hyperploidy were evaluated in isolated cells obtained by enzymatic dissociation of mesenteric resistance vessels. Approximately 80% of the cells in these preparations were identified as smooth muscle cells using a smooth muscle-specific isoactin antibody. Feulgen-DNA microdensitometric evaluation of isolated cells showed that polyploid cells were present in mesenteric resistance vessels but at very low frequencies, and no differences were apparent between SHR and WKY. Likewise, no differences in cellular protein content or relative smooth muscle cell size (i.e., area profile) were observed between cells obtained from SHR and WKY vessels. These results demonstrate that the increase in medial smooth muscle content observed in larger mesenteric resistance vessels of SHR cannot be accounted for by smooth muscle hypertrophy and hyperploidy, inferring that hyperplasia must be present. Results indicate that studies of the initiating mechanisms for medial smooth muscle hypertrophy in SHR resistance vessels, at least relatively early in hypertension, should focus on examination of factors that induce true cellular proliferation rather than hypertrophy and hyperploidy.

Animals↗

Dysplastic vessels after surgery for brain arteriovenous malformations.

BACKGROUND AND PURPOSE: The cause and clinical significance of residual dysplastic vessels after surgery for brain arteriovenous malformations (AVM) are unclear. We studied predictors and frequency of residual dysplastic vessels on cerebral angiography after AVM surgery. METHODS: The 240 prospectively enrolled surgical patients from the New York AVM Databank underwent 269 AVM-related surgical procedures. Reported postoperative brain angiographic findings were classified post hoc as showing (1) persistent dysplastic vessels, (2) a residual AVM, (3) focal hyperemia in the surgical bed, (4) other changes, or (5) a normal angiogram. Univariate and multivariate models were applied to test for an association between residual dysplastic vessels and patient age, sex, preoperative AVM size, anatomic AVM location, number of embolization procedures before surgery, and the time interval between AVM surgery and the postoperative angiogram. RESULTS: Of the 224 documented postoperative angiograms, 78 (35%) showed dysplastic vessels, 24 (11%) had evidence for a residual AVM, 16 (7%) showed focal hyperemia, 6 (2%) revealed other findings, and 100 (45%) were normal. The number of cases showing angiographic evidence for dysplastic vessels was significantly associated with increasing size of the AVM (in millimeter increments; P=0.0001); the mean diameter of AVMs in patients showing dysplastic vessels after surgery was significantly larger (41 mm, SD +/-14) than in those without residual dysplastic vessels (27 mm, SD +/-13; P<0.001). Symptomatic postoperative intracerebral hemorrhage occurred in 4 patients (1%), in 2 of whom dysplastic vessels were seen on the postoperative angiogram. CONCLUSIONS: The findings suggest that persistent dysplastic vessels may be found in approximately one third of angiograms after AVM surgery. Preoperative AVM size was found to be an independent predictor for the occurrence of dysplastic vessels on the postoperative angiogram.

Adult↗

Qualitative and quantitative analysis of embryonic pulmonary vessel formation.

Vessel formation in the lung has been described as occurring by two mechanisms: proximal, or branch, pulmonary arteries develop via angiogenesis; and distal, smaller vessels form by vasculogenesis. Connections between the proximal and distal vessels establish the final vascular network. The preponderance of vessel formation has been suspected to occur during the canalicular stage of lung development. To test these hypotheses, reporter gene expression under control of the regulatory domain of fetal liver kinase-1 (flk), an early endothelial cell-specific marker, was used to evaluate mouse lungs from embryonic day 10.5 (E10.5) through 2 wk postnatal age. Morphologic assessment was performed after histochemical staining, and quantification of vessel development by a chemiluminescent assay was compared with overall embryonic lung growth. LacZ expression under flk promoter control allowed: (1) early identification of differentiating endothelial cells of the branch pulmonary arteries; (2) visualization of distal vessels forming in the lung mesenchyme (primary capillary network) with subsequent remodeling; (3) recognition of early continuity between proximal and distal vessels, occurring by E10.5; and (4) assessment of developing pulmonary veins and venous confluence. Quantitative analysis revealed increased flk regulated beta-galactosidase (beta-gal) activity of 12 ng beta-gal/lung at E12.5 to 3,215 ng beta-gal/lung at 2 wk, which corresponded to overall lung growth during this period as shown by an increase in total protein content per lung from 35 microg at E12.5 to 6,456 microg at 2 wk after birth. We identified endothelial cell precursors of the developing pulmonary vasculature before vessel lumen formation. Continuity between the proximal pulmonary artery and vessels forming in the distal mesenchyme was present even at the earliest stage evaluated, suggesting endothelial cell differentiation at the site of vessel formation (i.e., vasculogenesis) as occurs with development of the aorta. Finally, we demonstrated that lung vessel development was not accentuated during the canalicular stage, but occurred at all stages and directly corresponded to overall lung growth.

Animals↗

Glioblastoma cells do not intravasate into blood vessels.

Glioblastoma is very rarely found outside the central nervous system. The ability of rat C6 glioblastoma cells to intravasate into central nervous system and pial blood vessels is tested using a rat homografting model and two in vitro models. In vivo, scanning electron microscopy demonstrates that upon grafting C6 cells into implantation pockets in rat cortex, blood vessels can be spared in large digestion cysts formed in host brain parenchyma. Immunocytochemistry of the grafted rat cortex reveals that the glioblastoma cells are upon the blood vessel basement membrane, surrounded by the extracellular matrix material, fibronectin. The endothelial cells of the blood vessel are inside the laminin and fibronectin, and there were areas of endothelial cell hyperplasia. C6 cells are not observed inside blood vessels. In vitro, C6 cell cultures seeded with blood vessels from fresh rat pia exhibit the same relationship of the C6 glioblastoma cells to the blood vessel as those in the other models. The C6 cells migrate upon the pial blood vessel basement membrane but do not intravasate into the blood vessel. To ascertain whether structure and components of the blood vessel basement membrane are important factors in glioblastoma cell exclusion from blood vessels, C6 cells are seeded upon artificial basement membrane hydrated gel wafers. C6 cells migrate into the artificial basement membrane gel wafer by 1 day after seeding. These data indicate that glioblastoma cells are confined to the central nervous system by an inability to pass through vital basement membrane.

Animals↗

ICGA-guided laser photocoagulation of feeder vessels of choroidal neovascular membranes in age-related macular degeneration. Indocyanine green angiography.

PURPOSE: To report the ability of indocyanine green angiography (ICGA) with a confocal scanning laser ophthalmoscope (SLO) to identify feeder vessels of choroidal neovascular membranes (CNVM) secondary to age-related macular degeneration (ARMD) and to show the feasibility of inducing complete closure of the CNVM by photocoagulation targeted exclusively to the feeder vessels. METHODS: Five consecutive patients with exudative ARMD in whom ICGA with the confocal SLO showed extrafoveal feeder vessels supplying choroidal neovascular nets had laser photocoagulation done only to the feeder vessels. In two patients, two separate membranes were seen. RESULTS: Laser photocoagulation resulted in closure of the feeder vessels and the CNVM in four patients. Complete closure was achieved with one treatment in one patient and with two treatments in three patients. In one patient, two treatments failed to close the feeder vessel and the CNVM, but a third, more intense laser treatment resulted in temporary closure of the feeder vessel and CNVM, which recanalized 2 to 4 weeks later with development of a large rip in the retinal pigment epithelium. In one patient, two separate CNVMs grew from the edge of the laser scars, but they were not directly related to the original CNVM and its feeder vessel, and were treated successfully. The same eye later developed subfoveal occult CNVM with gradual deterioration of visual acuity. In the other four patients, visual acuity improved in two and was unchanged in two. CONCLUSIONS: Indocyanine green angiography with the confocal SLO can identify choroidal feeder vessels supplying CNVM secondary to ARMD. Laser treatment to such extrafoveal feeder vessels, particularly in membranes that are large or subfoveal, may be effective in closing the feeder vessel and CNVM with preservation of the fovea and central vision. More than one treatment may be required, however, and failures and complications may be expected with this treatment modality.

Aged↗

Effectiveness of the ultrasonic coagulating shears, LigaSure vessel sealer, and surgical clip application in biliary surgery: a comparative analysis.

Advancements in laparoscopic surgery are often dictated by the limitations of technical instrumentation. Energy sources other than electrosurgery have become popular with the promise of quick and effective vascular control. With their success surgeons have begun using these on structures other than blood vessels with little or no data establishing their efficacy or safety. This study evaluates alternative energy sources in sealing ductal structures for possible use in liver or gallbladder surgery. After elective cholecystectomy cystic ducts (n = 45) were resealed ex vivo with surgical clips (n = 14), ultrasonic coagulating shears (n = 16), or electrothermal bipolar vessel sealer (n = 15), and bursting pressures were measured. Nineteen additional human cystic ducts were randomized to seal by ultrasonic coagulating shears (n = 9) or electrothermal bipolar vessel sealer (n = 10) and fixed in 10 per cent buffered formalin for histologic evaluation of thermal spread (mm). After this nine adult pigs were randomized to laparoscopic ligation and transection of the common bile duct using surgical clips (n = 3), ultrasonic coagulating shears (n = 3), or electrothermal bipolar vessel sealer (n = 3). The animals underwent necropsy for assessment of seal integrity on the sixth postoperative day. In the ex vivo study the mean cystic duct bursting pressure was 621 mm Hg with surgical clips and 482 mm Hg with the electrothermal bipolar vessel sealer (P = 0.39). The mean cystic duct bursting pressure after ultrasonic coagulating shears was 278 mm Hg, which was statistically less than surgical clips (P = 0.007) and electrothermal bipolar vessel sealer (P = 0.02). The mean thermal spread was 3.5 mm for ultrasonic coagulating shears and 13.4 mm for electrothermal bipolar vessel sealer (P = 0.0002). All animals undergoing ligation and transection of the common bile duct with ultrasonic coagulating shears and electrothermal bipolar vessel sealer developed bile peritonitis by postoperative day 6 as a result of seal leak. All animals undergoing surgical clip ligation and transection of the common bile duct maintained seal integrity. The mean common bile duct pressure above the surgical clip was 12 mm Hg (range 10-14). In conclusion the acute ex vivo study demonstrated a significant difference in the cystic duct bursting pressure between surgical clips and ultrasonic coagulating shears and between electrothermal bipolar vessel sealer and ultrasonic coagulating shears. The ultrasonic coagulating shears and electrothermal bipolar vessel sealer failed to maintain seal integrity in the in vivo animal study. Given the failure of the ultrasonic coagulating shears and electrothermal bipolar vessel sealer in the animal model these energy sources should not be used for transection of the cystic duct or major hepatic ducts during hepatobiliary surgery.

Animals↗

[Histomorphological structural changes of head and neck blood vessels after pre- or postoperative radiotherapy].

BACKGROUND: Patients with squamous cell carcinomas of the oral cavity are being increasingly treated by multimodal interdisciplinary regimes using a combination of surgery, chemo- and radiotherapy. Inflammatory alterations of the vascular endothelium following preoperative radiotherapy frequently cause healing delays of free flaps in the irradiated graft bed. The aim of the study was to investigate quantitative and qualitative changes of irradiated neck recipient vessels and transplant vessels used for microsurgical anastomoses in free flaps in patients undergoing preoperative radiotherapy or radiochemotherapy. PATIENTS AND METHODS: In 348 patients (October 1995-March 2002) receiving primarly or secondary 356 microvascular hard- and soft tissue reconstruction, a total of 209 vessels were obtained from neck recipient vessels and transplant vessels during anastomosis. Three groups were analysed: group 1 (27 patients) treated with no radiotherapy or chemotherapy; group 2 (29 patients) treated with preoperative irradiation (40-50 Gy) and chemotherapy (800 mg/m2/day 5-FU and 20 mg/m2/day cisplatin) 1.5 months prior to surgery; group 3 (20 patients) treated with radiotherapy (60-70 Gy) (median interval 78.7 months; IQR: 31.3 months) prior to surgery. From each of the 209 vessel specimens, 3 sections were investigated histomorphometrically, qualitatively and quantitatively (ratio media area/total vessel area) by NIH-Image-digitized measurements. To evaluate these changes as a function of age, radiation dose and chemotherapy, a statistical analysis was performed using an analysis of covariance and chi 2 tests (p > 0.05, SPSS V10). RESULTS: In group 3, qualitative changes (intima dehiscence, hyalinosis) were found in recipient arteries significantly more frequently than in groups 1 and 2. For group 3 recipient arteries, histomorphometry revealed a significant decrease in the ratio media area/total vessel area (median 0.51, IQR 0.10) in comparison with groups 1 (p = 0.02) (median 0.61, IQR 0.29) and 2 (p = 0.046) (median 0.58, IQR 0.19). No significant difference was found between the vessels of groups 1 and 2 (p = 0.48). There were no significant differences in transplant arteries and recipient or transplant veins between the groups. Age and chemotherapy did not appear to have a significant influence on vessel changes in this study (p > 0.05). CONCLUSIONS: Following irradiation with 60-70 Gy, significant qualitative and quantitative histological changes to the recipient arteries, but not to the recipient veins, could be observed. In contrast, irradiation at a dose of 40-50 Gy and chemotherapy given at a median interval of 1.5 months prior to operation did not lead to significant histological changes to the recipient vessels.

Adult↗

Hemodynamic parameters in blood vessels in choroidal melanoma xenografts and rat choroid.

PURPOSE: Choroidal melanoma is the most common primary ocular cancer among the adult population. To avoid enucleation, there has been a concerted effort to develop therapies that spare the affected eye and the patient's vision. Blood flow helps shape the tumor's microenvironment, plays a key role in the tumor's response to many different types of therapy, and is necessary for delivery of chemotherapeutic agents. To rationally design new therapies and optimize existing treatments, it is essential to learn as much as possible about blood flow and the microcirculation in this tumor. In recent years, much has been discovered about the anatomy of the microvasculature and the dynamics of overall blood flow in choroidal melanoma, but little is known about the factors that determine microvascular blood flow. In this study hemodynamic parameters in individual microvessels of a human choroidal melanoma xenograft were compared with those same parameters in a normal rat choroid. METHODS: Nude, athymic WAG/RijHs-rnu rats were used in this study. The human choroidal melanoma cell line OCM-1 was used to grow solid tumors subcutaneously in the flanks of donor rats. Small pieces of these tumors were then implanted into the choroidal space of recipient rats. After 6 to 8 weeks, the rats were anesthetized with a subcutaneous injection of urethane, and the sclera was exposed. Rhodamine-labeled liposomes and red blood cells (RBCs) labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) were injected intravenously. Epifluorescent, intravital microscopy was used to visualize the flow of fluorescent RBCs through individual vessels in the choroid or tumor. Flow through multiple vessels was recorded on videotape for later analysis. From the recordings, RBC flux, RBC velocity (V(c)), and microvascular hematocrit (HCT(m)) were determined. Similar experiments were performed in rats with no tumor growth, and these same parameters were calculated in normal choroidal vessels. RBC flow was characterized in 55 vessels in six OCM-1 tumors and in 153 choroidal vessels in five non-tumor-bearing rats. RESULTS: RBC flux was higher in larger tumor vessels (>30 micro m in diameter) compared with similarly sized choroidal vessels. There were no differences in the velocities of RBCs through the two types of vessels. HCT(m) was significantly higher in medium-sized (>20 micro m in diameter) and larger tumor vessels compared with normal choroidal vessels. CONCLUSIONS: These experiments demonstrate differences between hemodynamic parameters in normal choroidal microvessels and microvessels in choroidal melanoma in this animal model. Because HCT(m) is a key determinant of apparent viscosity, abnormally high HCT(m) in the tumor vessels would increase vascular resistance and decrease flow. This could have a negative impact on the tumor oxygen levels and on the ability to deliver drugs effectively. On the contrary, higher local HCT(m) has also been shown to increase oxygen delivery. The impact and interplay of these two effects on tumor oxygenation remain to be determined.

Animals↗

Polyurethane elastomer: a new material for the visualization of cadaveric blood vessels.

A multitude of various materials are available for the visualization of cadaveric vessels, ranging from natural materials like gelatin and latex to synthetic materials like silicone rubber or acrylates. To achieve a detailed overview of the vascular architecture in microvascular studies in experimental flap surgery, the injected material should have low viscosity to assure perfusion of even the smallest vessels. In addition, the material ideally should have either no or only minimal shrinkage, and should harden within a reasonable time, but retain sufficient elasticity and resistance to withstand tearing off the delicate vessels during subsequent dissection or casting. Because none of the available injection materials adequately combines these attributes, we evaluated the polyurethane elastomer "PU4ii" in latissimus dorsi muscles as a new material for the visualization of cadaveric vessels in comparison with the frequently used silicone rubber. The dissection of vessels injected with PU4ii proved easy largely because of its exceptional hardness. Even if not visible before dissection, the completely perfused vessels were easily palpated in the surrounding fat or muscle tissue of the microsurgical latissimus dorsi model. Despite the significantly higher hardness of PU4ii over silicone rubber (98 Sh-A vs. 12 Sh-A), PU4ii proved enough elasticity (20-25 N/mm(2) E modulus) and a high tear resistance (64-68 N/mm vs. 15 N/mm) preventing breakage during dissection even within the smallest vessels. In contrast to silicone rubber (and latex or gelatin), the high corrosion resistance and form stability of PU4ii also allowed building of casts for qualitative examination by scanning electron microscopy and quantitative analysis of the vessel density using micro-computed tomography with accurate 3D representation. In this study we show that PU4ii has physical characteristics that make it a multi-purpose material that allows at the same breath an excellent gross visualization of the architecture of cadaveric blood vessels as well as a detailed evaluation of casts by modern microscopic and or radiologic tools. Thus, the new polyurethane elastomer PU4ii is in many respects superior to the widely used silicone rubber and can be strongly recommended as a visualization material for a comprehensive evaluation of cadaveric blood vessels in microsurgery.

Aged↗

The effects of intense pulsed light (IPL) on blood vessels investigated by mathematical modeling.

BACKGROUND AND OBJECTIVES: Intense pulsed light (IPL) sources have been successfully used for coagulation of blood vessels in clinical practice. However, the broadband emission of IPL hampers the clinical evaluation of optimal light parameters. We describe a mathematical model in order to visualize the thermal effects of IPL on skin vessels, which was not available, so far. STUDY DESIGN/MATERIALS AND METHODS: One IPL spectrum was shifted towards the near infrared range (near IR shifted spectrum: NIRSS) and the other was heavily shifted toward the visible range (visible shifted spectrum: VSS). The broadband emission was separated in distinct wavelengths with the respective relative light intensity. For each wavelength, the light and heat diffusion equations were simultaneously solved with the finite element method. The thermal effects of all wavelengths at the given radiant exposure (15 or 30 J/cm2) were added and the temperature in the vessels of varying diameters (60, 150, 300, 500 microm) was calculated for the entire pulse duration of 30 milliseconds. RESULTS: VSS and NIRSS both provided homogeneous heating in the entire vessel. With the exception of the small vessels (60 microm), which showed only a moderate temperature increase, all vessels exhibited a temperature raise within the vessel sufficient for coagulation with each IPL parameter. The time interval for effective temperature raise in larger vessels (diameter >60 microm) was clearly shorter than the pulse duration. In most instances, the vessel temperature was higher for VSS when compared to NIRSS. CONCLUSIONS: We presented a mathematical model capable of calculating the photon distribution and the thermal effects of the broadband IPL emission within cutaneous blood vessels.

Blood Vessels↗

Lymphatic vessel density at the site of deepest penetration as a predictor of lymph node metastasis in submucosal colorectal cancer.

PURPOSE: Lymph node metastasis is an important factor that influences curability after endoscopic treatment of submucosal colorectal cancer. This study was designed to determine the usefulness of identification of lymphatic vessels by immunohistochemistry in predicting lymph node metastasis of submucosal colorectal cancer. METHODS: Lymphatic involvement was assessed by hematoxylin and eosin staining and podoplanin immunostaining on samples resected from 268 patients with submucosal colorectal cancer. Lymphatic vessel density was estimated by two investigators by average count of three fields (x200) in the area of greatest number of podoplanin-positive capillaries at the site of deepest submucosal penetration. Relations with other clinicopathologic parameters also were investigated. RESULTS: Lesions with high lymphatic vessel density (> or =9 vessels per field) showed a significantly greater incidence of lymph node metastasis than did those with low lymphatic vessel density (<9 vessels per field; 23.3 vs. 8.4 percent). By multivariate analysis, lymphatic vessel density was determined to be an independent risk factor for lymph node metastasis of submucosal colorectal cancer (P = 0.0044). Lymphatic vessel density also correlated with tumor budding and the degree of inflammation at the invasive front. CONCLUSIONS: Identification of lymphatic vessels by podoplanin immunostaining provides objective and accurate evaluation of lymphatic involvement. Lymphatic vessel density at the site of deepest penetration is a useful predictor of lymph node metastasis of submucosal colorectal cancer.

Colorectal Neoplasms↗

Effect of Coronary Collateral Vessels on Regional Myocardial Blood Flow in Patients With Coronary Artery Disease.

The effect of radiographically graded coronary collateral vessels on regional myocardial blood flow was evaluated with intracoronary injection of xenon-1233 at rest and during contrast agent-induced coronary hyperemia in 24 patients with coronary artery disease. Eleven patients had no coronary collateral vessels demonstrated radiologically, whereas 13 had such vessels. In 7 of the 13 these were high grade and noncompromised, whereas in 6 they were of lesser grade. Regional myocardial blood flow at rest in patients with and without collateral channels was similar and increased during hyperemia. However, the increase in flow was significantly greater in the patients with high grade noncompromised collateral vessels than in those with lesser grade collateral vessels (80 +/- 16 versus 31 +/- 9 plercent, p < 0.05). To evaluate the functional significance of the high grade noncompromised collateral vessels against that of vessels of lesser grade, various indexes of global and regional ventricular function were compared in the 13 patients in the present study, as well as in 24 patients whose collateral vessels had been subjected to similar grading systems in previous studies of regional myocardial blood flow. There were no significant differences in degree of regional asynergy, ejection fraction or left ventricular end-diastolic pressure between the patients with high and lower grades of collateral vessels. Thus, high grade noncompromised collateral vessels do not appear to have a beneficial effect on resting left ventricular function despite their enhanced vasoldilatory reserve.

Collateral Circulation↗

A comparison of the relative risk of vessel injury with conical versus pyramidal laparoscopic trocars in a rabbit model.

OBJECTIVE: Our purpose was to compare the relative risk of vessel injury after use of a 5 mm conical-tipped trocar, a 5 mm pyramidal-tipped trocar, and a 10 mm pyramidal-tipped trocar in a rabbit vessel model. STUDY DESIGN: Plastic templates were placed in front of and behind 108 mesenteric vessels in 11 anesthetized New Zealand White rabbits. Laparoscopic trocars were inserted through the templates and mesentery. The incidence of vessel injury was determined at distances from the vessels ranging from 0 to 5 mm. RESULTS: The 5 mm conical trocar resulted in a vessel injury rate of 88% at 0 mm from the vessel but 0% at 1 or 2 mm. The 5 mm pyramidal trocar resulted in 100%, 88%, and 62% injury rates of 0, 1, and 2 mm from the vessels, respectively. The 10 mm pyramidal trocar resulted in a 100% injury rate at 0, 1, 2, or 3 mm from the vessels and 80% and 40% at 4 mm and 5mm, respectively. CONCLUSION: The relative risk of vessel injury is significantly increased by the use of pyramidal-tipped trocars when compared with conical-tipped trocars, especially if larger diameter trocars are used.

Animals↗

Differential patterns of relaxation by atrial natriuretic peptide in major blood vessels of two distantly related teleosts.

In order to elucidate the role of the atrial hormone in the teleost circulation, the vascular effects of atrial natriuretic peptide (ANP) have been compared in major blood vessels of the cod (Gadus morhua) and of Atlantic salmon (Salmo salar). The relaxing effects of ANP from eel (eANP) have been examined in ventral aorta (VA) versus dorsal aorta (DA) in the cod and in VA versus the coeliaco mesenteric artery (CMA), a major branch of DA, in the salmon. The vessels were precontracted by acetylcholine (ACh) and adrenaline (A) and by the mammalian endothelium-derived vasoconstrictor peptide endothelin-1 (ET-1). The role of endothelial integrity for these responses has been assessed in vessels either mechanically probed or chemically impaired by indomethacin or the L-arginine analogue, NG-monomethyl-L-arginine (L-NMMA). Adrenaline and noradrenaline (NA) failed to contract the salmon VA. In the salmon vessels, eANP was without relaxing effects in ACh-contracted VA, while completely relaxing CMA when precontracted with ACh. The eANP was also a relaxant of A-contracted CMA and of ET-1-contracted VA. The cod vessels, which were insensitive to ACh were markedly relaxed by eANP when precontracted with either A (VA) or ET-1 (DA). In DA also the resting tension was reversed, an effect of eANP that was highly potentiated in mechanical probed vessels. Otherwise the relaxing effects of eANP in these vessels were seemingly independent of endothelial factors. In conclusion ANP is not a general relaxant of the precontracted VA which in teleosts is the first possible target vessel for the myocardial release of this hormone. On the arterial side ANP serves as a relaxant both in the salmon and the cod vessels, indicating that myocardial release of ANP in teleosts may have an important role in regulation of blood flow via diverse, species-specific effects on major blood vessels on both sides of the gills.

Acetylcholine↗

Impact of deep vessel wall injury on acute response and remodeling of coronary artery segments after cutting balloon angioplasty.

Deep vessel wall injury is believed to affect vessel dimension following coronary intervention. The cutting balloon is designed to treat coronary artery stenoses with dilatation and surgical incisions, thereby reducing excess vessel injury. This study examines the effect of deep vessel wall injury on acute and late coronary arterial response after cutting balloon angioplasty. Serial volumetric intravascular ultrasound (IVUS) analyses were performed in 63 lesions treated with cutting balloon angioplasty alone. Before intervention, the longitudinal range of the lesion segment that included the smallest lumen area (LA) was determined as LA <4 mm(2) and/or LA stenosis >60%. The exact corresponding site at postintervention and follow-up was aligned using peri- and intravascular landmarks. Average vessel area (VA), plaque area (PA), and LA were measured. Lesion segments were categorized as with or without deep vessel wall injury, which was defined as the presence of plaque/vessel wall fracture extending to the sonolucent (medial) layer. Before intervention, the lesion vessel size of deep injury group was smaller than that of the nondeep injury group (p <0.05 for average VA and PA), whereas average lesion LA, lesion length, and reference vessel size did not differ. Immediately after cutting balloon angioplasty, the deep injury group showed a significant increase in VA (p <0.0001) and a lesser decrease in PA (p <0.01) compared with the nondeep injury group. During follow-up, the increase of VA tended to be greater in the deep injury group than in the nondeep injury group (p = 0.06), whereas the change of PA did not differ. Consequently, LA decrease was less in the deep injury group than in the nondeep injury group (p <0.05). From these results, it is suggested that deep vessel wall injury tends to occur in lesions with relatively small size and such lesions show favorable vessel response after cutting balloon angioplasty.

Aged↗

Dynamics of bubble oscillation in constrained media and mechanisms of vessel rupture in SWL.

Rupture of small blood vessels is a primary feature of the vascular injury associated with shock-wave lithotripsy (SWL) and cavitation has been implicated as a potential mechanism. To understand more precisely the underlying mechanical cause of the injury, the dynamics of SWL-induced bubble dynamics in constrained media were investigated. Silicone tubing and regenerated cellulose hollow fibers of various inner diameters (0.2 to 1.5 mm) were used to fabricate vessel phantoms, which were placed in a test chamber filled with castor oil so that cavitation outside the phantom could be suppressed. Degassed water seeded with 0.2% Albunex contrast agent was circulated inside the vessel phantom, and intraluminal bubble dynamics during SWL were examined by high-speed shadowgraph imaging and passive cavitation detection via a 20-MHz focused transducer. It was observed that, in contrast to the typical large and prolonged expansion and violent inertial collapse of SWL-induced bubbles in a free field, the expansion of the bubbles inside the vessel phantom was significantly constrained, leading to asymmetric elongation of the bubbles along the vessel axis and, presumably, much weakened collapse. The severity of the constraint is vessel-size dependent, and increases dramatically when the inner diameter of the vessel becomes smaller than 300 microm. Conversely, the rapid, large intraluminal expansion of the bubbles causes a significant dilation of the vessel wall, leading to consistent rupture of the hollow fibers (i.d. = 200 microm) after less than 20 pulses of shock wave exposure in a XL-1 lithotripter. The rupture is dose-dependent, and varies with the spatial location of the vessel phantom in the lithotripter field. Further, when the large intraluminal bubble expansion was suppressed by inversion of the lithotripter pressure waveform, rupture of the hollow fiber could be avoided even after 100 shocks. Theoretical calculation of SWL-induced bubble dynamics in blood confirms that the propensity of vascular injury due to intraluminal bubble expansion increases with the tensile pressure of the lithotripter shock wave, and with the reduction of the inner diameter of the vessel. It is suggested that selective truncation of the tensile pressure of the shock wave may reduce tissue injury without compromising the fragmentation capability of the lithotripter pulse.

Acoustics↗

Hemostasis of punctured blood vessels using high-intensity focused ultrasound.

The hemorrhagic complications of vascular injury can be significant. We report on the use of high-intensity focused ultrasound (HIFU) to stop the hemorrhage of punctured blood vessels in pigs. Two HIFU transducers with frequencies of 3.5 and 2.0 MHz, each equipped with a water-filled conical housing, were used. Major blood vessels (femoral artery and vein, axillary artery, carotid artery and jugular vein), 2-10 mm in diameter, of anesthetized pigs were exposed surgically and punctured with 14- and 18-gauge needles to produce moderate to profuse bleeding. Complete hemostasis was achieved in less than 3 min of HIFU treatment in most blood vessels, and all vessels were patent after the treatment. Both HIFU frequencies were effective in producing hemostasis. Gross examination of the HIFU-treated vessels showed a consistent hardening of the soft tissue surrounding the blood vessels, providing a seal for the puncture hole. Microscopic examination of the vessels showed a remarkably localized HIFU treatment, resulting in coagulation of the adventitia, and an extensive fibrin network around the vessels and in the puncture hole. The vessel walls exhibited focal swelling, without evidence of irreversible injury. HIFU may provide a useful method for achieving hemostasis of punctured and traumatized blood vessels in a variety of clinical settings.

Animals↗

Permeability properties of tumor surrogate blood vessels induced by VEGF-A.

Malignant tumors generate new blood vessels by secreting growth factors, particularly members of the vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) family. Overall, the new blood vessels that form are hyperpermeable to plasma proteins, a property that is thought to be important for generating new stroma. However, tumor blood vessels are structurally heterogeneous and include microvessels of at least the following distinct types: mother vessels (MV), glomeruloid microvascular proliferations (GMP), arterio-venous-like vascular malformations and capillaries. Our goal was to determine whether macromolecular tracers leaked from all or from only a subset of these vessel types and to elucidate the extravasation pathways. As blood vessels are only a minor component of tumors, and therefore, difficult to study in situ, we used an adenoviral vector to express VEGF-A164, the most important member of the VPF/VEGF family, in mouse tissues. So expressed, VEGF-A164 induces large numbers of surrogate vessels of each type found in tumors in a highly reproducible manner. Overall permeability to plasma proteins was assessed qualitatively with Evan's blue dye and quantitatively with a dual tracer method employing radioactive albumin. Leaky vessels were identified by confocal microscopy (FITC-dextran) and by electron microscopy (ferritin). MV, and to a lesser extent GMP, were found to be hyperpermeable but capillaries and vascular malformations were not. Ferritin extravasated primarily by two trans-cellular routes, vesiculo-vacuolar organelles (VVOs) and fenestrae. This occurred despite a considerable reduction in VVO frequency as VVO membranes translocated to the plasma membrane during MV formation. However, reduction in the number and complexity of VVOs was offset by extensive endothelial cell thinning and a greatly shortened extravasation pathway. Extrapolating these findings to tumors predicts that only a subset of tumor vessels, MV and GMP, is hyperpermeable, and that measures of overall vessel permeability greatly underestimate the permeability of individual MV and GMP.

Animals↗