Mean Vessel Diameter Research Articles

A Posteriori–Derived Dietary Patterns and Retinal Vessel Caliber in an Elderly Population

To examine the association between a posteriori-derived dietary patterns (DP) and retinal vessel caliber in an elderly population. This was a cross-sectional study of 288 elderly adults (>65 years) who participated in the European Eye study (EUREYE) Northern Irish cohort. DP were extracted using principal component analysis from completed food frequency questionnaires. Semi-automated computer grading was used to determine the mean retinal vessel diameters (central retinal arteriole equivalent [CRAE] and central retinal venule equivalent [CRVE]) from digitized visual field one images using a standard measurement protocol. THREE MAJOR DP WERE IDENTIFIED IN THIS POPULATION, WHICH ACCOUNTED FOR 21% OF THE TOTAL VARIANCE: a "healthy" pattern with high factor loadings for oily fish, fruits and vegetables, and olive oil; an "unhealthy" pattern with high factor loadings for red and processed meat, refined grains, eggs, butter, sugar and sweets; and a "snack and beverage" pattern with high factor loading for pizza, nuts, and coffee. Multivariable linear regression analysis indicated no significant association between major identified DP and mean CRAE or CRVE in all models. This is the first study to investigate associations between a posteriori-derived DP and retinal vessel caliber. There was no evidence of a relationship between extracted DP and retinal vessel measurements in this population. However, it is possible that potentially important relationships exist between single nutrients or foods and vessel diameters that cannot be identified using a DP approach. Further studies to examine the role of dietary factors in the microcirculation are required.

Changes in wood density, wood anatomy and hydraulic properties of the xylem along the root-to-shoot flow path in tropical rainforest trees

It is generally assumed that the largest vessels are occurring in the roots and that vessel diameters and the related hydraulic conductance in the xylem are decreasing acropetally from roots to leaves. With this study in five tree species of a perhumid tropical rainforest in Sulawesi (Indonesia), we searched for patterns in hydraulic architecture and axial conductivity along the flow path from small-diameter roots through strong roots and the trunk to distal sun-canopy twigs. Wood density differed by not more than 10% across the different flow path positions in a species, and branch and stem wood density were closely related in three of the five species. Other than wood density, the wood anatomical and xylem hydraulic traits varied in dependence on the position along the flow path, but were unrelated to wood density within a tree. In contrast to reports from conifers and certain dicotyledonous species, we found a hump-shaped variation in vessel diameter and sapwood area--specific conductivity along the flow path in all five species with a maximum in the trunk and strong roots and minima in both small roots and twigs; the vessel size depended on the diameter of the organ. This pattern might be an adaptation to the perhumid climate with a low risk of hydraulic failure. Despite a similar mean vessel diameter in small roots and twigs, the two distal organs, hydraulically weighted mean vessel diameters were on average 30% larger in small roots, resulting in ∼ 85% higher empirical and theoretical specific conductivities. Relative vessel lumen area in percent of sapwood area decreased linearly by 70% from roots to twigs, reflecting the increase in sclerenchymatic tissue and tracheids in acropetal direction in the xylem. Vessel size was more closely related to the organ diameter than to the distance along the root-to-shoot flow path. We conclude that (i) the five co-occurring tree species show convergent patterns in their hydraulic architecture despite different growth strategies, and (ii) the paradigm assuming continuous acropetal vessel tapering and decrease in specific conductance from fine roots towards distal twigs needs reconsideration.

A Statistical Cerebroarterial Atlas Derived from 700 MRA Datasets

The cerebroarterial system is a complex network of arteries that supply the brain cells with vitally important nutrients and oxygen. The inter-individual differences of the cerebral arteries, especially at a finer level, are still not understood sufficiently. The aim of this work is to present a statistical cerebroarterial atlas that can be used to overcome this problem. Overall, 700 Time-of-Flight (TOF) magnetic resonance angiography (MRA) datasets of healthy subjects were used for atlas generation. Therefore, the cerebral arteries were automatically segmented in each dataset and used for a quantification of the vessel diameters. After this, each TOF MRA dataset as well as the corresponding vessel segmentation and vessel diameter dataset were registered to the MNI brain atlas. Finally, the registered datasets were used to calculate a statistical cerebroarterial atlas that incorporates information about the average TOF intensity, probability for a vessel occurrence and mean vessel diameter for each voxel. Visual analysis revealed that arteries with a diameter as small as 0.5 mm are well represented in the atlas with quantitative values that are within range of anatomical reference values. Moreover, a highly significant strong positive correlation between the vessel diameter and occurrence probability was found. Furthermore, it was shown that an intensity-based automatic segmentation of cerebral vessels can be considerable improved by incorporating the atlas information leading to results within the range of the inter-observer agreement. The presented cerebroarterial atlas seems useful for improving the understanding about normal variations of cerebral arteries, initialization of cerebrovascular segmentation methods and may even lay the foundation for a reliable quantification of subtle morphological vascular changes.

Ultrasonographic assessment of the spleen in 60 healthy sheep

AIM: To evaluate the sonographic appearance, size, location and shape of the spleen in 60 healthy sheep. METHODS: A 7.5 MHz linear scanner was used to examine the location, extent and appearance of the spleen from the left side of the sheep, in intercostal spaces (ICS) 8–12 and caudal of the last rib. RESULTS: The ultrasonographic appearance of the splenic parenchyma was homogeneous with a thin, smooth echogenic capsule. The spleen could be visualized in intercostal spaces 9–12 in all sheep, in intercostal space 8 in 25/60 sheep (42%) and caudal of the last rib in 24/60 sheep (40%). In intercostal spaces 8–12 and caudal of the last rib the spleen was visible in 16/60 sheep (27 %). The distance from the dorsal margin of the spleen to the spinous processes of the thoracic vertebrae was greatest in the 8th intercostal space: mean 19.32 (SD 2.76) cm and smallest in the 12th intercostal space: mean 6.61 (SD 1.94) cm. The dorsoventral splenic extent was greatest in the 11th intercostal space: mean 13.69 (SD 2.2) cm and smallest in the 8th intercostal space: mean 7.13 (SD 2.5) cm. The thickness of the spleen ranged from 21 (SD 9.0) mm in the 8th intercostal space to 49 (SD 7.0) mm in the 11th intercostal space. The mean vessel diameter was 1.9 (SD 0.7) mm. Spleen size did not correlate with age, body weight, or thoracic and abdominal circumference. CONCLUSIONS: Ultrasonography is a useful, straightforward and non-invasive method for evaluation of the spleen in sheep. CLINICAL RELEVANCE: These findings provide information which can be used as a reference for sonographic spleen examination and diagnosis of splenic lesions in sheep.

A global analysis of xylem vessel length in woody plants

Vessels are the chief conduit for long-distance water transport in the majority of flowering plants. Vessel length is a key trait that determines plant hydraulic efficiency and safety, yet relatively little is known about this xylem feature. • We used previously published studies to generate a new global data set of vessel length in woody plants. These data were used to examine how evolutionary history, plant habit, environment, and growth ring porosity influenced vessel length. We also examined the relationship between mean vessel length and mean vessel diameter and maximum vessel length. • Data on mean vessel length were available for stems of 130 species and on maximum vessel length for stems of 91 species. A phylogenetic analysis indicated that vessel length did not exhibit significant phylogenetic signal. Liana species had longer vessel lengths than in tree or shrub species. Vessel diameter was not predictive of mean vessel length, but maximum vessel length strongly predicted mean vessel length. Vessel length did not vary between species that differed in growth ring porosity. • Many traits often assumed to be linked to vessel length, including growth ring porosity and vessel diameter, are not associated with vessel length when compared interspecifically. Sampling for vessel length has been nonrandom, e.g., there are virtually no data available for roots, and sampling for environment has been confounded with sampling for habit. Increased knowledge of vessel length is key to understanding the structure and function of the plant hydraulic pathway.

148 Partial Lung Aeration Causes Ventilation/Perfusion Mismatch in the Lungs at Birth

BackgroundAlthough lung aeration increases pulmonary blood flow (PBF) at birth, the regional relationships between lung aeration and the increase PBF are unknown. We investigated the effect of partial ventilation on...

Effect of normobaric hypoxia on the testis in a murine model

High-altitude hypoxia generates spermiogram impairment due to germinal epithelium, Leydig cells, sperm and seminal plasma alterations, but precise mechanisms involved are unknown. The objective of this work was to analyse the effect of normobaric hypoxia on the morphology of testicular interstitium and some associated molecular and hormonal factors. Twenty-four mice were exposed to normobaric hypoxia (8.1% inspired oxygen fraction) during 20 days. The effects on body weight, testicular weight, vascularisation, testosterone, HIF1-α and VEGF were analysed at different periods of exposure and compared to controls. Hypoxic mice had lower body weight than mice kept in normoxia. Testicular weight raised significantly the 1st day, but remained normal during the rest of experiment. Number of blood vessels per field and mean diameter of vessels were higher in hypoxic mice. Plasmatic and testicular testosterone raised during first 24 h of hypoxia, but decreased on the 5th day. Vascular/interstitial ratio (proportion of interstice occupied by blood vessels) duplicated at the end of the experiment. Most substantial early effects of hypoxia were testicular oedema, increase in number and diameter of blood vessels and elevation of plasmatic and testicular testosterone. Normobaric hypoxia generates similar effects to those induced by hypobaric hypoxia.

The Use of Multislice CT Angiography Preoperative Study for Supraclavicular Artery Island Flap Harvesting

The vascular anatomy of the supraclavicular artery island (SAI) flap has been investigated using both cadaveric anatomic dissections and angiographic studies. Accurate preoperative evaluation and localization of its vascular pedicle confirms its location, course, anatomic variation, and improves flap success. The objective of this report is to demonstrate the utility of multislice computed tomography (CT) angiography for confirming the presence of the vascular pedicle of the SAI flap when planning head and neck reconstruction. Patients were studied using 64-multislice CT angiography (CTA) to localize the supraclavicular artery, including its origin and destination. Axial images, multiplanar reconstructions, and 3D volume-rendered images were analyzed on a Philips workstation. Radiologic image findings and clinical experience will be described. SAI CT angiography was successfully performed in 15 patients (30 shoulders) ranging from ages 22 to 81 years. Accurate identification of the main vascular pedicle was achieved in 14/15 patients. Location, course, pedicle length, and anatomic variations were reported for 23 of 30 arteries. Mean vessel diameter was found to be 1.49 mm (range, 0.8-2.0 mm) on the right and 1.51 mm (range, 1.0-2.1 mm) on the left. The mean length of the artery was 38.3 mm on the right (range, 26.6-59.6 mm) and 38.4 mm on the left (range, 24.3-67.0 mm). In all patients, the supraclavicular artery originated off the transverse cervical artery-a branch of the thyrocervical trunk. Positioning of the patient's upper extremities at the side was helpful in the identification of the supraclavicular artery and its distribution. Contrast injection site should be contralateral to the side needed for the flap if sidedness is of importance, secondary to contrast bolus artifact. Preoperative evaluation of the SAI flap with multislice computed tomography angiography is feasible in patients. A radiologic study protocol has been developed which improves the ability to detect this vessel. This technique provides a noninvasive approach to the identification of the vascular anatomy and is easily standardized/reproducible. The identification of the vascular pedicle and its anatomy can be a benefit to the surgical team during preoperative design of the SAI flap; however, clinical experience confirming these radiologic findings will be needed to optimize surgical outcome.

Drought-induced embolism in current-year shoots of two Mediterranean evergreen oaks

Quercus suber and Quercus ilex trees are major elements of Mediterranean landscapes, which are threatened by the increasing water deficits related to climate change. To contribute to the understanding of the capacity of these oaks to withstand severe drought we assessed the vulnerability to xylem embolism and the anatomical traits in current-year shoots. Data were collected in mature trees at two sites, in central/coastal and southern/inland Portugal. In situ safety margins to hydraulic failure were evaluated from long-term predawn and midday leaf water potential records. Results showed that xylem vulnerability to embolism was similar in Q. ilex and Q. suber. The 50% loss in hydraulic conductivity (Ψxyl,50PLC) was observed at xylem water potentials of −2.9 and −3.2MPa in shoots of Q. suber and Q. ilex, respectively. Values of mean vessel diameter of Q. suber shoots at both sites suggest an intra-species adaptation to the local water availability, with larger vessels at the more mesic site. In situ hydraulic safety margins observed in shoots showed that, even during the driest periods, both oaks lived comfortably above the most critical embolism thresholds. However, the hydraulic safety margins were narrower in the driest site. Results are relevant to the understanding of survival, growth, and functional behaviour of evergreen oaks in Mediterranean climates, under recurrent/seasonal drought conditions.

Quantifying Changes in Corneal Neovascularization Using Fluorescein and Indocyanine Green Angiography

To quantify changes in corneal neovascularization in patients with active keratitis after treatment using color imaging, fluorescein angiography (FA), and indocyanine green angiography (ICGA). Prospective, interventional case series. Twelve consecutive patients were studied. A comparison of corneal neovascularization parameters was undertaken before and after resolution of the keratitis. A slit-lamp digital camera acquired images of the neovascularization using color imaging, FA, and ICGA. The best-quality images were selected using a grading system, and the neovascular regions of interest were analyzed using automated in-house software. The parameters of analysis were vessel area, diameter, tortuosity, and FA dye leakage. There was a significant reduction in the area of neovascularization after treatment on color imaging (0.78 mm(2); P < .05), FA (2.33 mm(2); P < .01), and ICGA (2.07 mm(2); P < .01). There was also a significant reduction in mean vessel diameter across the region of interest for each patient, more marked on FA (42.74 to 32.52 μm; P < .01) and ICGA (44.77 to 33.29 μm; P < .01) than on color imaging (29.10 to 25.17 μm; P < .01). A significant change in vessel tortuosity was not observed. There was a significant increase in FA dye leakage time (12.41 seconds; P < .05) after treatment. We demonstrate application of an objective method for analyzing changes in corneal neovascularization. The excellent vessel delineation with ICGA even in the presence of stromal scars makes it an ideal agent for measurement of vessel parameters. FA is useful at detecting vessel leakage, and the time to leakage provides a possible measure of vessel staging.

Perivascular-Like Cells Contribute to the Stability of the Vascular Network of Osteogenic Tissue Formed from Cell Sheet-Based Constructs

In recent years several studies have been supporting the existence of a close relationship in terms of function and progeny between Mesenchymal Stem Cells (MSCs) and Pericytes. This concept has opened new perspectives for the application of MSCs in Tissue Engineering (TE), with special interest for the pre-vascularization of cell dense constructs. In this work, cell sheet technology was used to create a scaffold-free construct composed of osteogenic, endothelial and perivascular-like (CD146+) cells for improved in vivo vessel formation, maturation and stability. The CD146 pericyte-associated phenotype was induced from human bone marrow mesenchymal stem cells (hBMSCs) by the supplementation of standard culture medium with TGF-β1. Co-cultured cell sheets were obtained by culturing perivascular-like (CD146+) cells and human umbilical vein endothelial cells (HUVECs) on an hBMSCs monolayer maintained in osteogenic medium for 7 days. The perivascular-like (CD146+) cells and the HUVECs migrated and organized over the collagen-rich osteogenic cell sheet, suggesting the existence of cross-talk involving the co-cultured cell types. Furthermore the presence of that particular ECM produced by the osteoblastic cells was shown to be the key regulator for the singular observed organization. The osteogenic and angiogenic character of the proposed constructs was assessed in vivo. Immunohistochemistry analysis of the explants revealed the integration of HUVECs with the host vasculature as well as the osteogenic potential of the created construct, by the expression of osteocalcin. Additionally, the analysis of the diameter of human CD146 positive blood vessels showed a higher mean vessel diameter for the co-cultured cell sheet condition, reinforcing the advantage of the proposed model regarding blood vessels maturation and stability and for the in vitro pre-vascularization of TE constructs.

24 Confocal Laser Endomicroscopy to Assess Mucosal Microcirculation: A Quantitative Analysis in a Porcine Model of Septic Shock and in Patients With Severe Sepsis

Aim Microcirculatory alterations play a central role in the pathophysiology of sepsis. Even if systemic hemodynamic parameters appear to be adequate, septic patients may suffer from significant intestinal microcirculatory alterations. It has been suggested that these changes play a central role in regard to morbidity and mortality. The present study first assessed the feasibility of In Vivo detection of mucosal microcirculation in different segments of the gastrointestinal tract in an animal model of septic shock using probe-based confocal laser endomicroscopy (pCLE) (Mauna Kea Technologies, Paris, France). Subsequently, we assessed duodenal microcirculation in patients suffering from severe sepsis in the early phase of the disease. Materials and Methods First, anesthetized and mechanically ventilated pigs were observed over 8 hrs. Septic shock was triggered by inducing fecal peritonitis (0.75 g autologous feces per kg body weight). Mucosal microcirculation was assessed simultaneously using pCLE in stomach, duodenum, terminal ileum and rectum at baseline, 4 hours after induction of septic shock as well as 2 hours after treatment of the condition. Second, six patients who presented with a severe sepsis on the intensive care unit were examined regarding their duodenal microcirculation after obtaining informed consent from their nearest relatives. These patients were compared to ten healthy controls. Four to six areas were examined for each site and images were analysed in a blinded fashion offline thereafter in both parts of the study. Mean capillary diameter, capillary length and functional capillary density (FCD) were measured quantitatively. Results Two hours after induction of sepsis in the animal model, FCD was markedly decreased in the duodenal (-20.8, p < 0.001), the ileal (-13.4, p < 0.001), the gastric (-11.9%, p < 0.001), and in the rectal mucosal beds (-5.5, p<0,01). After administration of 30 mg x kg-1 of gelatine (30 kDa) FCD increased in all mucosal compartments to 90.0% (duodenum), 94.4% (ileum), 95.4% (gastric) and 97% (rectum) of baseline values. Interestingly, mean vessel diameter was unchanged in all compartments investigated. In patients suffering from severe sepsis we found a significant decrease in mean vessel diameter (-5.0%, p<0.001) as well as in FCD (-9,4%, p<0.001) of the duodenal mucosa, as well. Conclusions During the early phase of septic shock, pCLE may be able to quantify microcirculatory alterations in the gastrointestinal mucosa. Fluid resuscitation improves but does not completely restore intestinal microcirculation in the septic shock model. pCLE may represent a useful tool in order to assess the efficacy of therapeutic interventions on mucosal microcirculation, possibly even in clinical practice.

In vivo imaging of vessel diameter, size, and density: A comparative study between MRI and histology

The aim of this study was to compare magnetic resonance imaging (MRI) and histological estimates of the mean vessel diameter (mVD), the vessel density (Density), and the vessel size index (VSI) obtained in the same tumor-bearing animals. Twenty-seven rats bearing intracranial glioma (C6 or RG2) were imaged by MRI. Changes in transverse relaxations (ΔR 2* and R(2)) were induced by the injection of an iron-based contrast agent and were mapped using a multi gradient-echo spin-echo sequence. Then, brain vascular network was studied ex vivo by histology. Three regions of interest were drawn in apparently normal tissue (neocortex and striatum) and in the tumor. In vivo mVD(MRI), Density(MRI), and VSI(MRI) were measured; ex vivo, mVD(histo), Density(histo), and VSI(histo) were quantified on the same animals. MRI and histology measurements differed by -15 to 26%. A positive correlation was found between MRI and histology for mVD, Density, and VSI counterparts (R(2) = 0.62, 0.50, 0.73, respectively; P < 0.001 in all cases). This study indicates that MRI and histology yields well correlated the estimates of mVD, Density, and VSI. VSI is the closest MRI estimate to histology. As Density and mVD or VSI provide complementary information, it is worth computing them to characterize angiogenesis beyond blood volume fraction.

Hydraulic properties and embolism in small-diameter roots of five temperate broad-leaved tree species with contrasting drought tolerance

Abstract • Context It has been estimated that about half of a plant’s total hydraulic resistance is located belowground, but it is not well known how temperate tree species differ in root hydraulic properties and how these traits vary with the species’ drought tolerance. • Aims We examined root anatomical and hydraulic traits in five broad-leaved tree species with different drought tolerance, analyzed the relation between root anatomy and hydraulic conductivity and root embolism, and investigated the relation of these traits to the species’ drought tolerance. • Methods In small-diameter roots (2–6 mm), we measured vessel diameters and vessel density, specific hydraulic conductivity, and the percental loss of conductivity (“native” embolism) during summer in a mixed forest. • Results Specific conductivity was positively related to vessel diameter but not to vessel density. Drought-tolerant Fraxinus showed the smallest mean vessel diameters and drought-sensitive Fagus the largest. Specific conductivity was highly variable among different similar-sized roots of the same species with a few roots apparently functioning as “high-conductivity roots”. • Conclusion The results show that coexisting tree species can differ largely in root hydraulic traits with more drought-sensitive trees apparently having larger mean vessel diameters in their roots than tolerant species. However, this difference was not related to the observed root conductivity losses due to embolism.

POLAR Registry (Promus eluting stent registry in Latin America): 1 year Follow-up Results

Background: Drug-eluting stents have been used in patients to achieve success with low clinical and angiographic restenosis since 2002. Since late thrombosis adverse events were associated with first generation everolimus- and paclitaxel-eluting stents, second-generation everolimus and zotarolimus-eluting stents were developed. Methods: The POLAR registry was a prospective, non-randomised, multicentre study, which included 988 patients and 1,362 lesions that were treated with the Promus® everolimus-eluting stent. To represent clinical practice, almost all patient and lesion subtypes were included in this registry. Clinical follow-ups were performed at one, six, 12, and 24 months after the procedure. Results: Most of the patients were male (69.8%), with a mean age of 64.9 ± 9.4 years, 35.2% were diabetics, and 55% had been treated for acute coronary syndrome. The mean vessel diameter of the patients was 2.95 ± 0.43 mm, and their lesions extended 20.5 ± 5.6 mm. A total of 1.14 ± 0.38 stents were implanted per patient, with a procedural success rate of 96.6%. Major adverse cardiac events occurred in 4.5% of patients, and stent thrombosis was observed in five patients (0.5%) after 12 months of clinical follow-up. Conclusions: The present registry suggests that everolimuseluting stents are safe and effective in daily clinical practice, with a low rate of major adverse cardiac events after 12 months of follow-up.

Microsurgery in liver research: End-to-side portocaval microanastomoses in dogfish

The use of an operating microscope in animal liver surgery has made it possible to obtain new experimental models. The goal of this prospective animal study is to present our experience with dogfish portocaval microanastomoses. Nineteen portocaval microanastomoses were performed in dogfish. The end-to-side anastomoses were accomplished using continuous 11-0 sutures. The diameter of the vessels and time required for the anastomoses were measured. A patency test and its outcome were also prospectively evaluated at the time of anastomoses and then 3 and 6 months after. The mean vessel diameter was 2.5 ± 0.2mm. The mean anastomosis time was 14 ± 1.5 min. The anastomoses patency rate was 100% at the time of surgery. A postoperative control performed after 3 and 6 months showed a partial stenosis in three animals. The dogfish appears to be a reliable experimental model in liver research. Moreover, this technique could be used for microsurgical training.

Changes of xylem hydraulic efficiency and native embolism of Tamarix ramosissima Ledeb. seedlings under different drought stress conditions and after rewatering

To understand the factors controlling the survival of native Tamarix ramosissima Ledeb. in an extreme drought zone, the Tarim River Basin in northwestern China, we studied the impact of drought stress and water recovery treatments on hydraulic traits. These traits included initial hydraulic specific conductivity (K s (init)), maximum hydraulic specific conductivity (K s (max)) and native embolism (PLC, %) of lateral root, main stem and twigs, as well as the xylem anatomical structures of lateral roots and twigs of two-year old T. ramosissima seedlings. Results showed that drought stress and water recovery treatments had significant impacts on K s (max) value of lateral root, (K s init) value and native embolism rate of all different organs (p < 0.01). Severely drought stress treatment induced a significant decrease in K s (init) values of all organs (p < 0.05), however, the values of K s (max) in lateral root increased significantly (p < 0.01). The native embolism rate increased with the intensity of soil drought stress in all different organ and short-term re-watering had only significant impacts on embolism recovery for lateral roots (p < 0.01), embolism recovered 20% as compared to severely water stressed seedlings. Lateral roots had a larger mean vessel diameter ( d mean, d h) and lower vessel density (VD) compared to the twigs, and their K s (max) values were strongly correlated with xylem vessel diameter.

The distribution of blood flow in the carotid and vertebral arteries during dynamic exercise in humans

The mechanism underlying the plateau or relative decrease in cerebral blood flow (CBF) during maximal incremental dynamic exercise remains unclear. We hypothesized that cerebral perfusion is limited during high-intensity dynamic exercise due to a redistribution of carotid artery blood flow. To identify the distribution of blood flow among the arteries supplying the head and brain, we evaluated common carotid artery (CCA), internal carotid artery (ICA), external carotid artery (ECA) and vertebral artery (VA) blood flow during dynamic exercise using Doppler ultrasound. Ten subjects performed graded cycling exercise in a semi-supine position at 40, 60 and 80% of peak oxygen uptake (VO2 peak) for 5 min at each workload. The ICA blood flow increased by 23.0 ± 4.6% (mean ± SE) from rest to exercise at 60% (VO2 peak). However, at 80% (VO2 peak), ICA blood flow returned towards near resting levels (9.6 ± 4.7% vs. rest). In contrast, ECA, CCA and VA blood flow increased proportionally with workload. The change in ICA blood flow during graded exercise was correlated with end-tidal partial pressure of CO2 (r = 0.72). The change in ICA blood flow from 60% (VO2 peak) to 80% (VO2 peak) was negatively correlated with the change in ECA blood flow (r = −0.77). Moreover, there was a significant correlation between forehead cutaneous vascular conductance and ECA blood flow during exercise (r = 0.79). These results suggest that during high-intensity dynamic exercise the plateau or decrease in ICA blood flow is partly due to a large increase in ECA blood flow, which is selectively increased to prioritize thermoregulation.

Quantitative coronary angiography findings of patients who received previous breast radiotherapy

PurposeTo compare the coronary angiographic findings between patients who had previous left sided versus right sided breast cancer radiotherapy (RT). Materials and methodsBetween 1995 and 2009, 12,696 patients who underwent curative RT for breast cancer at Princess Margaret Hospital were screened to assess if they had been investigated with a post-RT coronary angiogram. Two cardiologists, blinded to the laterality of radiation treatment, assessed all angiograms and measured the percentage of stenotic lesions, the mean diameters of each segment of the left anterior descending artery (LAD) and the right coronary artery (RCA) using quantitative coronary angiography (QCA). ResultsNinety-one patients were included, 49 patients with left sided RT and 42 with right sided RT. The median time from RT to coronary angiogram was 4.2years (range: 22days–16.9years). Seventeen patients (35%) in the left sided RT group and 17 (40%) in the right sided RT group needed coronary revascularization (percutaneous coronary intervention or by-pass surgery). The LAD territory was revascularized in 12 (24%) and 11 (26%) patients, respectively. The proportion of clinically significant stenoses, degree of stenoses and mean vessel diameter were not significantly different between the two groups. In 33 patients who had coronary angiograms >5years after breast RT (17 left-sided and 16 right-sided), the only statistically significant finding was marginally narrower mid RCA segments among those who had right sided RT: 2.52mm versus 2.92mm (P=0.039). ConclusionsIn our patients, left sided breast cancer RT did not increase the risk of coronary artery disease within the first few years, when compared to right sided RT. However, with the limitation of short duration between radiotherapy and coronary angiogram, late development of coronary artery stenoses 10–15years after left sided RT could not be excluded.

Combinational Therapy of Interferon-α and Chemotherapy Normalizes Tumor Vasculature by Regulating Pericytes Including the Novel Marker RGS5 in Melanoma

Several large randomized clinical trials show that chemotherapy in combination with interferon-α (IFN-α) seems superior to single-agent chemotherapy, such as dacarbazine (DTIC) in melanoma, but the molecular mechanism of this better efficacy is unclear. IFN-α has antiangiogenic activity and could downregulate expression of regulator of G-protein signalling-5 (RGS5) recognized as a novel pericyte marker and a master gene loss of which results in pericyte maturation, vascular normalization, and consequent marked reductions in tumor hypoxia and vessel leakiness in pancreatic carcinoma. Here, we investigated the molecular mechanism of the effects of this combination therapy on melanoma tumor growth. In B16 tumor-bearing mice, the addition of IFN-α to DTIC treatment significantly reduced tumor volume, compared with control or DTIC alone. Consistently, Digital Radiography data showed less chaotic vessel morphology and a decrease in microvessel density and mean vessel diameter in the combinational treatment. Furthermore, the combination therapy showed a remarkable reduction in tumor hypoxia, downregulated RGS5 expression, and increased mature pericyte coverage. Our data suggest that the combination of IFN-α and DTIC therapy more efficiently inhibits tumor growth by normalizing tumor vasculature. This study shows a previously unrecognized role of IFN-α in melanoma vascular normalization and suggests that pericyte including its novel marker RGS5 is an important target of IFN-α.