[Clinical Study of Peripherally Inserted Central Catheter-Related Thrombosis and Its Influence on the Blood Flow Status of the Inserted Veins in Cancer Patients].

Objective: To investigate the clinical features of peripherally inserted central catheter (PICC)-related thrombosis (PICCRT) within 2 weeks after PICC placement in cancer patients and its dynamic influence on the blood flow status of veins inserted with catheter, and to provide support for implementing thrombosis prevention and control measures. Methods: Between May 2019 and July 2020, patients who had solid tumors and who had PICC were prospectively enrolled at West China Hospital, Sichuan University. Scheduled color Doppler imaging was performed to examine the status of PICCRT formation at 8 points of time, with the first one conducted one day before the insertion of PICC and the other 7 completed within 2 weeks after the insertion of PICC. Then, based on whether patients had PICCRT, the patients were divided into two groups, a non-PICCRT group and a PICCRT group. The PICCRT group was further divided into two subgroups, an asymptomatic PICCRT group and a symptomatic PICCRT group, according to whether the patients had thrombosis-related symptoms and signs. Comparisons were made to study the incidence of PICCRT and the vascular diameter and the blood flow velocity in the veins inserted with catheters at different points of time in the patients of different groups. Results: Among 173 cancer patients in the cohort, 126 (72.8%) developed PICCRT, all of which occurred within 1 week after PICC insertion. There were 95 cases of asymptomatic PICCRT and 31 cases of symptomatic PICCRT. Before and after PICC insertion, the vascular diameter of both the asymptomatic and symptomatic PICCRT groups was significantly smaller than that of the non-PICCRT group and the blood flow velocity was significantly slower than that of the non-PICCRT group, with the difference continuing to increase with the prolongation of catheter indwelling time. Conclusion: Inserting catheters in veins with bigger vascular diameter and faster blood flow velocity may help reduce the incidence of PICCRT. The first week post catheter insertion is the key intervention period for the prevention of PICCRT.

Vascular Diameter as Clue for the Diagnosis of Clinically and/or Dermoscopically Equivocal Pigmented and Non-Pigmented Basal Cell Carcinomas and Nodular Melanomas.

Background and objectives: Dermoscopy is a useful tool for the early and non-invasive diagnosis of skin malignancies. Besides many progresses, heavily pigmented and amelanotic skin tumors remain still a challenge. We aimed to investigate by dermoscopy if distinctive morphologic characteristics of vessels may help the diagnosis of equivocal nodular lesions. Materials and Methods: A collage of 16 challenging clinical and dermoscopic images of 8 amelanotic and 8 heavily pigmented nodular melanomas and basal cell carcinomas was sent via e-mail to 8 expert dermoscopists. Results: Dermoscopy improved diagnostic accuracy in 40 cases. Vessels were considered the best clue in 71 cases. Focusing on the diameter of vessels improved diagnosis in 5 cases. Conclusions: vascular diameter in addition to morphology and arrangement may be a useful dermoscopic clue for the differential diagnosis of clinically equivocal nodular malignant tumors.

Vascular diameter and intima-media thickness to diameter ratio values of the carotid artery in 642 healthy children.

In children, arterial alterations occur with increased intima-media thickness as well as vascular diameter enlargement. Both conditions correlate with higher cardiovascular risk in adults, and both the array and proportion of these alterations are important hemodynamic parameters. In terms of functional adaptation processes, they influence several arterial wall properties as for example the shear and tensile stress of the vessel. There are no reference values for the vascular diameter and intima-media thickness/diameter ratio of the carotid artery in children. Therefore, this study aimed to assess vascular diameter, intima-media thickness/diameter ratio and related tensile stress values in children and to further investigate the influence of sex, age, body mass index, and blood pressure. The parameters were measured with high-resolution semi-automated ultrasound. Sex- and age-dependent values were calculated with the LMS method for a cross-sectional sample of 642 healthy, non-obese children aged 8-17 years. The mean vascular diameter was 5.45 ± 0.46 mm; the median intima-media thickness/diameter ratio was 0.085 (0.079-0.092); the median tensile stress was 105.4 (95.2-116.4) kPa. The vascular diameter and the tensile stress were higher, and the intima-media thickness/diameter ratio was lower in boys than in girls. In comparison to the normal weight study population the excludedobese children had a significantly higher diameter, a lower intima-media thickness/diameter ratio, and a higher tensile stress. In multiple regression analyses of diameter, intima-media thickness/diameter ratio, and tensile stress, all parameters were influenced by sex and body mass index. Furthermore, systolic and diastolic blood pressure significantly influenced the vascular diameter, and systolic blood pressure significantly influenced the intima-media thickness/diameter ratio. Conclusion: This study is the first to report values for the diameter, the intima-media thickness/diameter ratio of the carotid artery, and the related tensile stress allowing a more differentiated view of cardiovascular adaptations as it combines structural and functional vascular parameters. What is known: • Intima-media thickness and vascular diameter are related to a higher cardiovascular risk in adults • The intima-media thickness/diameter ratio gives information about hemodynamic and functional vessel adaptation What is new: • Values for vascular diameter, intima-media thickness/diameter ratio, and tensile stress of the carotid artery in children are presented in this study • Intima-media thickness as a surrogate marker for arterial health in children should be complemented by intima-media thickness/diameter ratio measurement.

An Alternative Technique for Ascending and Arcus Aorta Repair in Case of Vascular Diameter Mismatch.

Complicated Type A intramural hematoma involving the arcus aorta requires emergency correction of the aortic arch. Surgical options include reimplantation of the brachiocephalic vessels as an island to a vascular graft, debranching aortic arch surgery, and Kazui technique. This report describes a modified technique for aortic arch repair in a patient with vascular diameter mismatch between the ascending and descending aorta, as well as an intimal tear between the brachiocephalic vessels.

Increased ipsilateral uterine artery vascular resistance in women with ovarian endometrioma.

AIM: The aim of this study was to elucidate whether the presence of an ovarian endometrioma is associated with impaired vascular flow. We investigated changes in vascular flow on the ipsilateral and contralateral side of the endometrioma, before and after surgery. METHODS: This prospective case-control study included 144 women (ovarian endometrioma [n = 40], endometriosis without ovarian endometrioma [n = 33], non-endometriotic ovarian cyst [n = 17], and normal pelvis [n = 54]). The uterine artery (UtA) vascular resistance indices (pulsatility index [PI] and resistance index [RI]) were measured using transvaginal Doppler sonography, and UtA diameters were measured using magnetic resonance imaging. RESULTS: The UtA PI and RI were significantly higher on the ipsilateral side of the endometrioma than on the contralateral unaffected side in the endometrioma group (P < 0.01), as well as in the non-endometriotic ovarian cyst group (P < 0.05), and normal pelvis group (P < 0.01). The UtA PI and RI on the ipsilateral side of the endometrioma were significantly lower after cystectomy than before cystectomy (P < 0.01). The UtA diameters were significantly larger (P < 0.01) on the ipsilateral side of the endometrioma than on the contralateral side. CONCLUSION: The UtA-vascular resistance might be higher on the ipsilateral side of the endometrioma than on the contralateral unaffected side, indicating a risk of subclinical atherosclerosis in women with endometriosis.

Ryanodine-induced vasoconstriction of the gerbil spiral modiolar artery depends on the Ca2+ sensitivity but not on Ca2+ sparks or BK channels.

BACKGROUND: In many vascular smooth muscle cells (SMCs), ryanodine receptor-mediated Ca2+ sparks activate large-conductance Ca2+-activated K+ (BK) channels leading to lowered SMC [Ca2+]i and vasodilation. Here we investigated whether Ca2+ sparks regulate SMC global [Ca2+]i and diameter in the spiral modiolar artery (SMA) by activating BK channels. METHODS: SMAs were isolated from adult female gerbils, loaded with the Ca2+-sensitive flourescent dye fluo-4 and pressurized using a concentric double-pipette system. Ca2+ signals and vascular diameter changes were recorded using a laser-scanning confocal imaging system. Effects of various pharmacological agents on Ca2+ signals and vascular diameter were analyzed. RESULTS: Ca2+ sparks and waves were observed in pressurized SMAs. Inhibition of Ca2+ sparks with ryanodine increased global Ca2+ and constricted SMA at 40 cmH2O but inhibition of Ca2+ sparks with tetracaine or inhibition of BK channels with iberiotoxin at 40 cmH2O did not produce a similar effect. The ryanodine-induced vasoconstriction observed at 40 cmH2O was abolished at 60 cmH2O, consistent with a greater Ca2+-sensitivity of constriction at 40 cmH2O than at 60 cmH2O. When the Ca2+-sensitivity of the SMA was increased by prior application of 1 nM endothelin-1, ryanodine induced a robust vasoconstriction at 60 cmH2O. CONCLUSIONS: The results suggest that Ca2+ sparks, while present, do not regulate vascular diameter in the SMA by activating BK channels and that the regulation of vascular diameter in the SMA is determined by the Ca2+-sensitivity of constriction.

The impact of vascular diameter ratio on hemodialysis maturation time: Evidence from data mining approaches and thermodynamics law.

BACKGROUND: Vascular Access (VA) is an important aspect for blood circulatory in Hemodialysis (HD). Arteriovenous Fistula (AVF) is a suitable procedure to gain VA. Maturation of the AVF is a status of AVF, which can be cannulated for HD. This study aimed to discover the parameters that effectively reduce the duration between VA and start of HD, which symbolizes the maturation time (MT). METHODS: Ninety-six patients who underwent AVF creation were selected for this study. The decision tree method was used based on CART/C4.5 algorithm, which is one of the data mining approaches for data classification. Vascular diameter ratio (VDR) coefficient was obtained (VDR=Artery/Vein diameters). RESULTS: We investigated the relationship between the VDR and MT in this study and found that MT is reversely related to VDR in elderly patients, while this relation was direct in younger patients. CONCLUSION: The analysis revealed a Spearman's correlation coefficient for Vein diameter with MT. MT decreases when diameters of vein and artery are close to one another. This study can help the surgeons to identify high- risk patients who elongate MT for HD.

Current opinions on the control and role of vascular smooth muscle cell adhesion, calcium sensitization, and the cytoskeleton in vascular structure and function.

Vascular smooth muscle contraction and relaxation play a preponderant role on the active (acute) and structural (long-term) control of vascular diameter. This editorial overview summarizes and highlights the opinions expressed in seven reviews contained in this special topic issue of Microcirculation. The reviews address diverse aspects of the mechanisms that influence cell adhesion, calcium homeostasis, and cytoskeletal remodeling, and how these mechanisms affect vascular structure and function at different levels of the circulation.

Aquaporins enriched in endothelial vacuole membrane regulate the diameters of microvasculature in hyperglycaemia.

AIMS: In patients with diabetic microvascular complications, decreased perfusion or vascular occlusion, caused by reduced vascular diameter, is a common characteristic that will lead to insufficient blood supply. Yet, the regulatory mechanism and effective treatment approach remain elusive. METHODS AND RESULTS: Our initial findings revealed a notable decrease in the expression of human AQP1 in both diabetic human retina samples (49 healthy vs. 54 diabetic samples) and high-glucose-treated human retinal microvascular endothelial cells. Subsequently, our investigations unveiled a reduction in vascular diameter and compromised perfusion within zebrafish embryos subjected to high glucose treatment. Further analysis indicated a significant down-regulation of two aquaporins, aqp1a.1 and aqp8a.1, which are highly enriched in ECs and are notably responsive to hyperglycaemic conditions. Intriguingly, the loss of function of aqp1a.1 and/or aqp8a.1 resulted in a reduction of intersegmental vessel diameters, effectively mirroring the phenotype observed in the hyperglycaemic zebrafish model. The overexpression of aqp1a.1/aqp8a.1 in zebrafish ECs led to notable enlargement of microvascular diameters. Moreover, the reduced vessel diameters resulting from high-glucose treatment were effectively rescued by the overexpression of these aquaporins. Additionally, both aqp1a.1 and apq8a.1 were localized in the intracellular vacuoles in cultured ECs as well as the ECs of sprouting ISVs, and the loss of Aqps caused the reduction of those vacuoles, which was required for lumenization. Notably, while the loss of AQP1 did not impact EC differentiation from human stem cells, it significantly inhibited vascular formation in differentiated ECs. CONCLUSION: EC-enriched aquaporins regulate the diameter of blood vessels through an intracellular vacuole-mediated process under hyperglycaemic conditions. These findings collectively suggest that aquaporins expressed in ECs hold significant promise as potential targets for gene therapy aimed at addressing vascular perfusion defects associated with diabetes.

Exploring Morphometry of Endometrial Glands and Blood Vessels in Reproductive Age Women With Abnormal Uterine Bleeding.

Background Abnormal uterine bleeding (AUB) is one of the most common problems encountered in gynaecological practice. Defective endometrial angiogenesis has been implicated in various benign and malignant disorders of the endometrium. Aim This study aims to assess morphometry of endometrial glands and blood vessels in patients with AUB. Material and methods This is a one year retrospective cross sectional analysis of endometrial samples received with the diagnosis of AUB in reproductive age group. All samples were routinely processed and stained. Sections were analysed for morphometry of blood vessels and endometrial glands. Results A total of 374 cases were included. Most common histological group was proliferative followed by secretory phase. A significant difference was noted in mean vascular density, diameter, mitotic scores and height of glandular epithelium in different benign and malignant groups. Conclusion This study highlights the fact that glandular and vascular morphometry can be used to differentiate between various proliferative disorders of the endometrium. In the current era of new anti-angiogenic therapies, endometrial angiogenesis and changes in vascular morphology can be targeted, thus improving treatment modalities and patient care.

Comparison of Two Spectral-domain Optical Coherence Tomography Scan Modes for Measuring Retinal Vessel Diameter.

Purpose: To assess the agreement between Line 3-5 raster scan mode and circular scan mode for measuring retinal vessel diameter, and to analyze the influence of scanning distance on retinal vessel diameter and agreement.Methods: 79 healthy participants (79 eyes) were scanned with two modes. The scanning distance was defined as the distance from the center of the optic disc to the intersection of the blood vessel and the scan line on the raster image. The large superior temporal vessel was measured, with the distance between vascular wall hyperreflectivities measured to obtain vessel diameters. The degree of agreement between the line 3-5 raster scan and circular scan modes, and the effect of scanning distance on agreement and vascular diameter were assessed.Results: There was good agreement between line 3 subgroup and the circular scan for measuring venous and arterial diameter (venous: intraclass correlation coefficients (ICCs) = 0.87, p < .001; arterial: ICCs = 0.84, p < .001). Unexpectedly, diameters from the fourth raster scan were only comparable to the circular scan in measuring venous diameter (ICCs = 0.86, p < .001), despite the same scanning distance between the fourth raster line and circular scan. Vessels with a scanning distance between 1400 µm - 1799 µm showed good agreement with the circular scan (venous and arterial: all ICCs ≥ 0.84, p < .001). In addition, venous diameter and arterial diameter decreased with increasing distance from the optic disc center, with venous and arterial diameter decreasing by 0.02 µm/µm (p < .001) and 0.007 µm/µm (p = .02), respectively.Conclusion: Arterial and venous diameter measured by the circular mode was comparable to only one scan line and two scan lines of the raster scan mode, respectively. Our study identified a difference between the two scan modes, with the difference not fully attributable to differences in scanning distance. Prospective studies reporting vascular diameter as a primary outcome should report the scan mode used.

Retinal Microvascular Signs as Screening and Prognostic Factors for Cardiac Disease: A Systematic Review of Current Evidence.

The substantial burden of heart disease promotes an interest in new ways of screening for early disease diagnosis, especially by means of noninvasive imaging. Increasing evidence for association between retinal microvascular signs and heart disease prompted us to systematically investigate the relevant current literature on the subject. We scrutinized the current literature by searching PubMed and Embase databases from 2000 to 2020 for clinical studies of the association between retinal microvascular signs and prevalent or incident heart disease in humans. Following exclusions, we extracted the relevant data from 42 publications (comprising 14 prospective, 26 cross-sectional, and 2 retrospective studies). Our search yielded significant associations between retinal vascular changes, including diameter, tortuosity, and branching, and various cardiac diseases, including acute coronary syndrome, coronary artery disease, heart failure, and conduction abnormalities. The findings of our research suggest that the retinal microvasculature can provide essential data about concurrent cardiac disease status and predict future risk of cardiac-related events.

Retinal Vascular Signs as Screening and Prognostic Factors for Chronic Kidney Disease: A Systematic Review and Meta-Analysis of Current Evidence.

BACKGROUND: The substantial burden of kidney disease fosters interest in new ways of screening for early disease diagnosis, especially by non-invasive imaging. Increasing evidence for an association between retinal microvascular signs and kidney disease prompted us to investigate the relevant current literature on such an association systematically by performing a meta-analysis of our findings. METHODS: We scrutinized the current literature by searching PubMed and Embase databases from for clinical studies of the association between retinal microvascular signs and prevalent or incident kidney disease. After excluding cases that did not meet our criteria, we extracted relevant data from 42 published studies (9 prospective, 32 cross-sectional, and 1 retrospective). RESULTS: Our investigation yielded significant associations between retinal vascular changes (including retinopathy and retinal vascular diameter) and kidney dysfunction (including chronic kidney disease (CKD), end-stage renal disease (ESRD), albuminuria, and estimated glomerular filtration rate (eGFR) decline). According to our meta-analysis, retinopathy was associated with ESRD (hazard ratio (HR) 2.12 (95% confidence interval CI; 1.39-3.22)) and with CKD prevalence in the general population (odds ratio (OR) 1.31 (95% CI; 1.14-1.50)), and specifically in type 2 diabetic patients (OR 1.68 (95% CI; 1.68-2.16)). CRAE was associated with prevalent CKD (OR 1.41 (95% CI; 1.09-1.82)). CONCLUSIONS: Our findings suggest that the retinal microvasculature can provide essential data about concurrent kidney disease status and predict future risk for kidney disease development and progression.

Retinal vascular diameter changes assessed with a computer-assisted software after strabismus surgery.

AIM: To quantitatively investigate the retinal vascular diameter changes, analyzing the early and long-term effects on the retinal circulation, with 6-month follow-up. METHODS: Patients underwent horizontal strabismus surgery were enrolled prospectively. Retinal vessel diameters on color fundus photographs were assessed before and 1, 7d, 6mo after surgery, using a computer-assisted quantitative assessment software. To evaluate the retinal vascular caliber changes, retinal vascular diameters were calculated by means of the Parr-Hubbard formula as the central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE). The arteriovenous ratio (AVR) was calculated as CRAE divided by CRVE. RESULTS: A total of 154 eyes of 104 consecutive patients were included. Compared with the data before surgery (121.55±24.67), the mean CRAE (131.18±28.29) significantly increased 1d after surgery (P=0.003), but went back to baseline level at 7d (118.89±30.35, P=0.15), and 6mo (123.22±15.32, P=0.60), so did the AVR (P<0.001, P=0.08, P=0.07). As for the mean CRVE, there was no significant difference between those four time points (172.43±33.25, 175.57±36.98, 174.03±40.18, 174.86±20.46, P=1.00). CONCLUSION: Strabismus surgery on both lateral and media rectus muscles, or single media rectus muscle may increase retinal blood flow during the early postoperative period, but would return to normal later. The number of transected anterior ciliary arteries rather might be the main cause of retinal hemodynamic changes early after strabismus surgery.

A novel computer-aided diagnosis system for the early detection of hypertension based on cerebrovascular alterations.

Hypertension is a leading cause of mortality in the USA. While simple tools such as the sphygmomanometer are widely used to diagnose hypertension, they could not predict the disease before its onset. Clinical studies suggest that alterations in the structure of human brains' cerebrovasculature start to develop years before the onset of hypertension. In this research, we present a novel computer-aided diagnosis (CAD) system for the early detection of hypertension. The proposed CAD system analyzes magnetic resonance angiography (MRA) data of human brains to detect and track the cerebral vascular alterations and this is achieved using the following steps: i) MRA data are preprocessed to eliminate noise effects, correct the bias field effect, reduce the contrast inhomogeneity using the generalized Gauss-Markov random field (GGMRF) model, and normalize the MRA data, ii) the cerebral vascular tree of each MRA volume is segmented using a 3-D convolutional neural network (3D-CNN), iii) cerebral features in terms of diameters and tortuosity of blood vessels are estimated and used to construct feature vectors, iv) feature vectors are then used to train and test various artificial neural networks to classify data into two classes; normal and hypertensive. A balanced data set of 66 subjects were used to test the CAD system. Experimental results reported a classification accuracy of 90.9% which supports the efficacy of the CAD system components to accurately model and discriminate between normal and hypertensive subjects. Clinicians would benefit from the proposed CAD system to detect and track cerebral vascular alterations over time for people with high potential of developing hypertension and to prepare appropriate treatment plans to mitigate adverse events.

The microvascular extracellular matrix in brains with Alzheimer's disease neuropathologic change (ADNC) and cerebral amyloid angiopathy (CAA).

BACKGROUND: The microvasculature (MV) of brains with Alzheimer's disease neuropathologic change (ADNC) and cerebral amyloid angiopathy (CAA), in the absence of concurrent pathologies (e.g., infarctions, Lewy bodies), is incompletely understood. OBJECTIVE: To analyze microvascular density, diameter and extracellular matrix (ECM) content in association with ADNC and CAA. METHODS: We examined samples of cerebral cortex and isolated brain microvasculature (MV) from subjects with the National Institute on Aging-Alzheimer's Association (NIA-AA) designations of not-, intermediate-, or high ADNC and from subjects with no CAA and moderate-severe CAA. Cases for all groups were selected with no major (territorial) strokes, ≤ 1 microinfarct in screening sections, and no Lewy body pathology. MV density and diameter were measured from cortical brain sections. Levels of basement membrane (BM) ECM components, the protein product of TNF-stimulated gene-6 (TSG-6), and the ubiquitous glycosaminoglycan hyaluronan (HA) were assayed by western blots or HA ELISA of MV lysates. RESULTS: We found no significant changes in MV density or diameter among any of the groups. Levels of BM laminin and collagen IV (col IV) were lower in MV isolated from the high ADNC vs. not-ADNC groups. In contrast, BM laminin was significantly higher in MV from the moderate-severe CAA vs. the no CAA groups. TSG-6 and HA content were higher in the presence of both high ADNC and CAA, whereas levels of BM fibronectin and perlecan were similar among all groups. CONCLUSIONS: Cortical MV density and diameter are not appreciably altered by ADNC or CAA. TSG-6 and HA are increased in both ADNC and CAA, with laminin and col IV decreased in the BM of high ADNC, but laminin increased in moderate-severe CAA. These results show that changes in the ECM occur in AD and CAA, but independently of one another, and likely reflect on the regional functioning of the brain microvasculature.

Vascular ultrasound in pediatrics: estimation of depth and diameter of jugular and femoral vessels.

OBJECTIVES: To estimate, on the basis of anthropometric and demographic variables, the depth (Dp) and diameter (Dm) of femoral and jugular vessels, which have been located and measured by ultrasound, in pediatric patients. METHOD: 750 measurements of Dp and Dm of the femoral vein (FV), femoral artery (FA) and internal jugular vein (IJV) were made in 125 pediatric patients. The values were correlated with patients' sex, weight, age, size and body surface area (BSA). RESULTS: Mean Dp values were 0.72 (0.34) cm for FA, 0.79 (0.35) cm for FV and 0.77 (0.24) cm for IJV. Mean antero-posterior Dm values were 0.37 (0.17) cm for FA, 0.42 (0.22) cm for FV and 0.59 (0.23) cm for IJV. In the studied pediatric patients, femoral and jugular vessels depth correlated with age, size, weight and BSA (R = 0.46-0.60); vascular depth could be estimated from patients' weight and size (FA-Dp: R = 0.71; FV-Dp: R = 0.72; IJV-Dp: R = 0.53). Correlation with diameter was better for FA and FV (R = 0.81-0.89) than for IJV (R = 0.42-0.51); vascular diameter could be estimated from patient's size (FA-Dm: R = 0.89; FV-Dm: R = 0.86; IJV-Dm: R = 0.52). CONCLUSIONS: FV, FA and IJV depth and diameter correlated with weight, size, age and body surface area in the studied pediatric patients. Correlation was better for femoral than for jugular vessels. Depth could be estimated from patients' weight and size, while diameter could be estimated from the size. Such estimations may facilitate the choice of vessels to be cannulated, length and diameter of cannulation needles and the diameter of catheters to be used in pediatric patients.

Assessing Direct Vascular Actions of Estrogens.

Estrogens are known to affect vascular function. In order to decipher the underlying mechanisms, it is essential to study the direct actions of estrogenic substances on blood vessels. There are two widely used approaches to assess the effects of estrogenic substances directly on blood vessels, the isolated perfused intact mesenteric vascular bed (McGregor preparation) and the isolated perfused/pressurized vessel approach. The McGregor preparation relies on constant flow with vascular reactivity assessed as changes in perfusion pressure. The isolated perfused/pressurized vessel approach uses a single vessel mounted on glass micropipettes. The main readout in this approach is vascular diameter. This chapter describes these approaches which remain cornerstones in the investigation of direct vascular actions of estrogenic substances.

BK Channels in the Vascular System.

Autoregulation of blood flow is essential for the preservation of organ function to ensure continuous supply of oxygen and essential nutrients and removal of metabolic waste. This is achieved by controlling the diameter of muscular arteries and arterioles that exhibit a myogenic response to changes in arterial blood pressure, nerve activity and tissue metabolism. Large-conductance voltage and Ca(2+)-dependent K(+) channels (BK channels), expressed exclusively in smooth muscle cells (SMCs) in the vascular wall of healthy arteries, play a critical role in regulating the myogenic response. Activation of BK channels by intracellular, local, and transient ryanodine receptor-mediated "Ca(2+) sparks," provides a hyperpolarizing influence on the SMC membrane potential thereby decreasing the activity of voltage-dependent Ca(2+) channels and limiting Ca(2+) influx to promote SMC relaxation and vasodilation. The BK channel α subunit, a large tetrameric protein with each monomer consisting of seven-transmembrane domains, a long intracellular C-terminal tail and an extracellular N-terminus, associates with the ß1 and γ subunits in vascular SMCs. The BK channel is regulated by factors originating within the SMC or from the endothelium, perivascular nerves and circulating blood, that significantly alter channel gating properties, Ca(2+) sensitivity and expression of the α and/or ß1 subunit. The BK channel thus serves as a central receiving dock that relays the effects of the changes in several such concomitant autocrine and paracrine factors and influences cardiovascular health. This chapter describes the primary mechanism of regulation of myogenic response by BK channels and the alterations to this mechanism wrought by different vasoactive mediators.

Constriction of porcine retinal arterioles induced by endothelin-1 and the thromboxane analogue U46619 in vitro decreases with increasing vascular branching level.

PURPOSE: The retinal blood flow depends on the diameter of retinal arterioles, but diameter changes in these vessels have hitherto only been assessed in vessels larger than approximately 100 µm. Therefore, a new method was developed for studying diameter changes along the vascular tree of arterioles in whole perfused segments of porcine retinas, and the effect of known vasoconstrictors on the diameter of retinal arterioles at different branching levels were studied. METHODS: Thirty-four whole-mounted porcine retinas were placed in a specially designed tissue chamber. On the basis of video recordings through an inverted microscope, the diameter of retinal arterioles was measured at five different branching levels before and after addition of a high potassium concentration, or increasing concentrations of endothelin-1, the prostaglandin analogue U46619, noradrenaline or none (time controls). RESULTS: The baseline diameter ranged from 136 µm (95% CI 132-140 µm) for 1st order arterioles to 33 µm (95% CI 21-44 µm) for 5th order arterioles. In 1st order arterioles, endothelin produced 56.6% (95% CI 47.6-64.0) and U46619 14.6% (95% CI 5.7-22.6) relative constriction compared with baseline, which for both compounds decreased significantly with increasing branching level (p<0.0001 and p<0.0001, respectively). The change in diameter during addition of noradrenaline did not differ significantly from the time controls (p=0.07). CONCLUSIONS: The effect of retinal vasoconstrictors differs among larger and smaller arterioles. The study highlights the need for investigating diameter regulation in smaller retinal arterioles as a basis for understanding normal and pathological changes in retinal blood flow.