Introdução. As artérias perfurantes comumente são evidenciadas durante a dissecção microcirúrgica para clipagem de aneurismas intracranianos. A oclusão de artérias perfurantes pode ser responsável por infarto encefálico isquêmico e resultados clínicos indesejáveis. O presente estudo objetiva descrever a utilidade da vídeo-angiografia intra-operatória com indocianina verde (VAIICG) na avaliação do fluxo sanguíneo em artérias perfurantes visibilizadas no campo microcirúrgico, durante a clipagem de aneurismas intracranianos. Secundariamente, foi analisada a incidência de artérias perfurantes envolvidas durante a cirurgia de aneurismas intracranianos, e a ocorrência de infarto encefálico isquêmico causado pelo comprometimento das artérias perfurantes. Método. Sessenta pacientes, com 64 aneurismas intracranianos foram tratados cirurgicamente, e prospectivamente incluídos neste estudo. A VAIICG intra-operatória foi realizada com o uso de microscópio neurocirúrgico (Carl Zeiss Co. Oberkochen, Germany) com a tecnologia VAIICG integrada. A presença e o envolvimento de artérias perfurantes foram analisados no campo microcirúrgico durante a dissecção cirúrgica, e durante a clipagem do aneurisma. A patência vascular após a clipagem também foi investigada. Apenas artérias pequenas que não foram visibilizadas nas imagens pré-operatórias de angiografia digital com subtração (ADS) foram consideradas para análise. Resultados. A VAIICG permitiu a visibilização do fluxo sanguíneo em todos os casos que apresentaram artérias perfurantes no campo microcirúrgico. Dentre 36 casos cujas artérias perfurantes estavam visíveis à VAIICG, 11 casos (30,5%) apresentaram relação próxima entre o aneurisma e artérias perfurantes. Em um paciente (9,0%), dentre os 11 casos com relação próxima, a VAIICG evidenciou oclusão de uma artéria perfurante de P1 após a aplicação do clipe, cujo reposicionamento correto restabeleceu imediatamente o fluxo sanguíneo, o qual foi visibilizado com a VAIICG, sem conseqüências clínicas. Quatro pacientes (6,7%) apresentaram infarto pós-operatório em território de artérias perfurantes, sendo que em três deles, as artérias perfurantes estavam ausentes ou distantes do aneurisma clipado. Conclusão. O envolvimento de artérias perfurantes durante a clipagem microcirúrgica de aneurismas intracranianos é comum. A VAIICG intra-operatória fornece informação visual do fluxo sanguíneo em artérias de calibre milimétrico, e seu uso possibilita evitar a oclusão de artérias perfurantes e subseqüente infarto encefálico. / Background. Perforating arteries are commonly involved during the surgical dissection and clipping of intracranial aneurysms. Occlusion of perforating arteries may be responsible for ischemic infarction and poor outcome. The goal of this study was to describe the usefulness of near-infrared indocyanine green videoangiography (ICGA) for the intraoperative assessment of blood flow in perforating arteries that are visible in the surgical field during clipping of intracranial aneurysms. In addition we analyzed the incidence of perforating vessels involved during the aneurysms surgery and the incidence of ischemic infarct caused by compromising of these small arteries. Method. Sixty patients harboring 64 aneurysms were surgically treated and prospectively included in this study. Intraoperative ICGA was performed using a surgical microscope (Carl Zeiss Co. Oberkochen, Germany) with integrated ICGA technology. The presence and involvement of perforating arteries was analyzed in the microsurgical field, during surgical dissection, and during the clip application. Assessment of vascular patency after clipping was also investigated. Only those small arteries that were not visible on preoperative digital subtraction angiography (DSA) were considered for analysis. Results. In all cases in which perforating vessels were found in the microscope field, the ICGA was able to visualize flow. Among 36 cases whose perforating vessels were visible on ICGA, 11 cases (30,5%) presented a close relation between the aneurysm and perforating arteries. In one patient (9,0%), among these 11 cases with close relation, ICGA showed occlusion of a P1 perforating artery after clip application, which led to immediate correction of the clip confirmed by immediate re-establishment of flow visible with ICGA without clinical consequences. Four patients (6,7%) presented with postoperative perforating artery infarct of whom in 3 patients the perforating arteries were either not visible or distant from the aneurysm. Conclusion. The involvement of perforating arteries during clip application for aneurysm occlusion is a usual finding. Intraoperative ICGA provide visual information with regard to patency of these milimetric vessels, which may avoid their occlusion and further ischemic infarction.

O objetivo é comparar o fluxo sanguíneo total (FS) e a reserva de fluxo coronariano (RFC) aos ramos revascularizados pelas artérias torácica interna esquerda (ATIE) e radial (AR) nos enxertos compostos com os enxertos isolados. Foi realizado um ensaio clínico randomizado de 42 pacientes que foram distribuídos em grupo A ou ATIE e AR composta em Y(n=14), grupo B ou ATIE e AR composta modificada(n=14) e grupo C ou ATIE pediculada para DA e AR aorto-coronariana(n=14). Os pacientes foram submetidos a fluxometria no pós-operatório imediato. A RFC foi de 2,1 ± 0,44, 1,96 ± 0,3 e 2,06±0,42 nos grupos A,B e C, (p=0.7208 A, B x C) e o FS, em ml/min, foi 110±30, 145±59 e 136±58, respectivamente (p=0.3232 A,B x C). Concluindo, não houve diferença significativa do FS total e nem da RFC nos grupos estudados / The objective is to compare the total blood flow (Bf) and coronary flow reserve (CFR) to the left coronary branches that were revascularized with left internal thoracic (LITA) and radial artery (RA) in composite and independent arterial grafts. A randomized trial was realized and 42 patients assigned in group A or composite LITA-RA in a Y configuration (n=14), group B or modified composite LITA-RA(n=14) and group C or pedicled LITA to LAD and aorto-coronary RA (n=14). Patients were submitted to postoperative Bf velocity analysis. CFR was 2,1 ± 0,44, 1,96 ± 0,3 e 2,06±0,42 in groups A,B and C (p=0.7208 A, B x C) and Bf, in ml/min, was 110±30, 145±59 and 136±58, respectively (p=0.3232 A, B x C). In conclusion there was no difference in Bf and CFR in the groups studied

Les antiangiogéniques (AAD) représentent une classe relativement récente d’anticancéreux indiqués dans un nombre croissant de cancers solides avancés. Ces traitements inhibent la voie du VEGF en amont avec le bevacizumab, un anticorps monoclonal dirigé contre le VEGF et en aval avec les inhibiteurs des tyrosines kinases des récepteurs impliqués dans cette voie de signalisation (sorafenib et sunitinib). Les AAD s’accompagnent d’effets secondaires dont le plus fréquent est l’hypertension artérielle. Ma thèse a pour objectif de mieux comprendre la physiopathologie de l’hypertension artérielle iatrogène induite par les AAD, notamment en mesurant l’effet des AAD sur les grosses artères. Le deuxième objectif est de déterminer des marqueurs précoces d’efficacité et d’optimisation de ces traitements, notamment avec un suivi thérapeutique pharmacologique (STP). Pour remplir ces objectifs nous avons mis en place une étude clinique prospective, observationnelle monocentrique dans laquelle nous avons suivi l’évolution de paramètres artériels au cours du traitement AAD avec des techniques non-invasives chez des patients atteints d’un cancer. Dans un premier travail nous avons montré qu’il y avait une augmentation précoce et cliniquement significative de la pression brachiale et centrale, de la rigidité artérielle et du diamètre carotidien sous AAD et que ces modifications étaient en partie indépendantes de la pression artérielle. Nous avons également montré que la présence d’ondes de réflexion amples et d’une rigidité aortique basse de base avant l’introduction des AAD prédisaient une augmentation de pression artérielle systolique (PAS) à un stade précoce d’exposition (coefficients de régression : 0.37[0.04-0.70] et -1.27[-2.43 ; -0.11], p<0.05 respectivement) alors qu’après une exposition chronique aux AAD, seule une rigidité artérielle basse de base prédisait une augmentation de la PAS (-2.46 [-4.02 ; -0.90], p<0.01). L’atteinte des grosses artères est positivement associée à l’évolution carcinologique. En effet une augmentation précoce de la rigidité aortique et carotidienne sous AAD étaient associées à un haut risque de progression (HR : 1.24 [1.01 ; 1.51], p=0.042 et 1.34 [1.03-1.73], p=0.027 respectivement). Dans la deuxième partie, nous avons montré à l’aide d’un modèle pharmacocinétique de population, que l’atteinte artérielle observée lors de la prise d’AAD était due à un effet pharmacologique des AAD sur les grosses artères indépendamment de l’augmentation de pression induite par les AAD. L’augmentation de rigidité artérielle était proportionnelle à la concentration plasmatique d’AAD et à l’augmentation de la pression artérielle (coefficient de corrélation standardisé : 0.37 et 0.35, p<0.01, respectivement), expliquant respectivement 13% et 11% de la variance. Nous avons également montré que la progression et la mortalité liées au cancer étaient moindre chez les patients les plus exposés aux AAD (HR : 0.60 [0.38 ; 0.97], p=0.035 et HR=0.38 [0.19-0.79], P=0.01 respectivement) et enfin, nous avons pu déterminer une concentration sérique cible qui permettra aux cliniciens d’avoir un objectif à atteindre pour optimiser l’efficacité des AAD. En conclusion, nous avons pu démontrer l’existence d’une atteinte précoce des grosses artères se traduisant par une augmentation de la rigidité artérielle et un remodelage carotidien sous traitement AAD. Cette atteinte artérielle est directement liée à un effet pharmacologique des AAD de manière indépendante de l’augmentation de pression induite par ces traitements. Nous avons montré que les altérations de la paroi artérielle ainsi que le suivi thérapeutique pharmacologique prédisaient le pronostic carcinologique. Le suivi des propriétés artérielles combinée au STP des AAD pourraient optimiser les chances d’efficacité de ces traitements. / Antiangiogenic drugs (AAD) are a relatively new class of anti-cancer therapy indicated in an increasing number of advanced solid tumors. By inhibiting the VEGF pathway, upstream with an anti-VEGF monoclonal antibody, bévacizumab, and downstream with tyrosine kinase inhibitors of receptors involved in this signaling pathway (sorafenib and sunitinib), AAD induce arterial hypertension which is the most common side effect. The principal objective of my thesis is to improve the understanding of the pathophysiology of hypertension induced by AAD, by determining the effect of AAD on large arteries. The second objective is to determine early marker of efficacy and optimization of AAD, by the use of therapeutic drug monitoring. To fulfill those objectives, we set up a clinical prospective, observational, single center study in which we followed the time-course of several arterial parameters after AAD by the use of non-invasive techniques in patients with metastatic solid tumors. In a first work we showed that brachial and central blood pressure, arterial stiffness and carotid diameter significantly increased after AAD, partly independently of blood pressure changes. We also showed that high reflection waves and low aortic stiffness at baseline (i.e. before AAD initiation) predicted early systolic blood pressure (SBP) increase (regression coefficients: 0.37[0.04; 0.70] and -1.27[-2.43; -0.11], P<0.05 respectively) while only low aortic stiffness predicted SBP increase after chronic AAD exposure (-2.46 [-4.02 ; -0.90], P<0.01). Large arteries damage under AAD is positively associated with cancer progression. Indeed, early increase of aortic and carotid stiffness after AAD were associated with a higher risk of cancer progression (HR: 1.24 [1.01; 1.51], P=0.042 and 1.34 [1.03; 1.73], P=0.027 respectively). In a second part, using a pharmacokinetic model of population, we showed that large arteries damage observed after AAD was partly due to a pharmacological effect of AAD on large arteries independently of blood pressure increase. Arterial stiffness increase was proportional to AAD blood concentration and blood pressure increase (standardized correlation coefficients: 0.37 and 0.35, P<0.01, respectively), explaining 13% and 11% of the variance respectively. We also showed that progression and mortality related to cancer were lower in patients high AAD blood concentrations (HR: 0.60 [0.38; 0.97], P=0.035 and HR=0.38 [0.19; 0.79], P=0.01 respectively). And finally, we determined a target AAD blood concentration which will allow the clinicians to have an objective to reach in order to optimize the efficacy of AAD. In conclusion, we were able to demonstrate the existence of large arteries damage translated by large arteries stiffening and a remodeling of carotid artery after AAD. This arterial damage is directly related to a pharmacological effect of AAD independently of blood pressure changes induced by these treatments. We showed that infringement of the arterial wall and the therapeutic drug monitoring predicted tumor prognosis. Thus, the monitoring of arterial properties monitoring and the therapeutic drug monitoring might optimize the chances of efficiency of AAD.

Abstract Atherosclerosis is a multifactorial disease with numerous genes and environmental factors affecting its intiation and progression. During the past years many candidate genes for atherosclerosis have been suggested, and it has also become evident that the immune system plays a part in atherogenesis. Early atherosclerotic changes can be effectively detected by measuring carotid artery intima-media thickness (IMT). In the present study the associations between IMT and polymorphisms of three candidate genes for atherosclerosis were studied: endothelial nitric oxide synthase (eNOS), apolipoprotein E (apoE) and paraoxonase-1 (PON1). To assess the role of immunological factors determining carotid atherosclerosis, CRP and circulating autoantibodies to oxidised LDL were studied in relation to IMT. The study population consisted of 519 hypertensive and 526 control subjects from a middle-aged population in Oulu, Finland. The results showed that the investigated polymorphisms of eNOS and PON1 genes were not associated with IMT, suggesting that these polymorphisms are not major risk factors for atherosclerosis in the general Caucasian population. A significant interaction between the apoE polymorphism and smoking in relation to IMT was observed among men, indicating that carriers of the ε4 allele may be particularly prone to the atherogenic effects of smoking. This interaction was especially clear in hypertensive subjects. CRP was strongly associated with IMT before adjusting for confounding factors. After the adjustment, this association diasppeared. The finding suggests that instead of early atherosclerosis CRP may be related to the later phases of the disease. This may partly explain the strong correlation between CRP and future cardiovascular events. IgM type of autoantibodies binding to oxidised LDL were inversely associated with IMT, and this finding remained after adjusting for previously known risk factors for atherosclerosis, implying a possible protective role for these antibodies in atherogenesis.

Arterial stiffness is an important biometric in predicting cardiovascular diseases, since mechanical properties serve as indicators of several pathologies such as e.g. atherosclerosis. Shear Wave Elastography (SWE) could serve as a valuable non-invasive diagnostic tool for assessing arterial stiffness, with the technique proven efficient in large homogeneous tissue. However the accuracy within arterial applications is still uncertain, following the lack of proper validation. Therefore, the aim of this study was to assess the accuracy of SWE in arterial phantoms of poly(vinyl alcohol) cryogel by developing an experimental setup with an additional mechanical testing setup as a reference method. The two setups were developed to generate identical stress states on the mounted phantoms, with a combination of axial loads and static intraluminal pressures. The acquired radiofrequency-data was analysed in the frequency domain with retrieved dispersion curves fitted to a Lamb-wave based wave propagation model. The results indicated a significant correlation between SWE and mechanical measurements for the arterial phantoms, with an average relative error of 10 % for elastic shear moduli in the range of 23 to 108 kPa. The performed accuracy quantification implies a satisfactory performance level and as well as a general feasibility of SWE in arterial vessels, indicating the potential of SWE as a future cardiovascular diagnostic tool.

Spiral artery (SA) remodeling is a fundamental process during early pregnancy that involves the action of vascular smooth muscle cells (VSMCs), maternal immune cells, but also fetal extravillous trophoblast cells (EVTs) and the extracellular matrix (ECM). Mast cells (MCs) and their mediator chymase, have been identified as prominent players for a sufficient SA remodeling process at the fetal-maternal interface in vivo. In contrast, endocrine disrupting chemicals (EDC), especially Bisphenol A (BPA) and 17-α-ethinylestradiol (EE2), have been shown to have a negative impact on SA remodeling in animal models in vivo. However, neither the mechanisms underlying the positive effects of MCs and chymases for the remodeling process, nor the interference of EDCs on SA remodeling, have been elucidated. The purpose of the present work was to evaluate the effect of MCs and recombinant human chymase CMA1 (rhuCMA1) on the phenotype and/or behavior of VSMCs, EVTs and ECM in vitro. Moreover, the influence of BPA and EE2 on the functionality of EVTs in vitro was observed. Using an immortalized human trophoblast cell line (HTR8/SV-neo), a mouse trophoblast cell line (SM9-2), human primary uterine vascular smooth muscle cells (HUtSMCs) and mouse primary uterine smooth muscle cells (SMCs), we assessed the effects of the human MC cell line HMC-1, the mouse mast cell line MC/9 and rhuCMA1 on VSMCs, EVTs and ECM. Additionally, the HTR- 8/SV-neo cells functionality was evaluated after treatment with BPA or EE2. We found that mouse MC/9 cells induce fibronectin expression and migration in SMCs. Furthermore MC/9 cells increase the proliferation and migration of SM9-2 cells. Both human HMC-1 cells and rhuCMA1 stimulate the migration, proliferation, and change of synthetic/contractile marker expression in HUtSMCs. In addition, HMC-1 cells increase the proliferation and migration of HTR8/SVneo trophoblast cells while having an impact on the expression of tissue remodeling genes. HTR8/SVneo cells presented increased migration rates along with decreased expression of the matrix-metalloproteinase regulator genes (TIMPs) upon treatment with rhuCMA1. Moreover, BPA interfered with HTR-8/SV-neo cell proliferation and reduced MMP2 expression in HTR-8/SV-neo. Interestingly, EE2 had no impact on proliferation or migration but suppressed the MMP2 expression in HTR-8/SV-neo cells. The obtained results indicate that MCs, and partly their mediator chymase CMA1, shape the phenotype and modulate the functionality of VSMCs and EVTs. Collectively, possible mechanisms by which MCs and specifically rhuCMA1 promote SA remodeling were identified. The findings are relevant for the understanding of this crucial step in pregnancy and thus, for the comprehension of dysregulated pathways that can lead to pregnancy complications like fetal growth restriction and preeclampsia. Moreover, this work contributes to the knowledge about how EDCs impact on early pregnancy and highlights the high risk of EDCs exposure disturbing the fundamental reproductive process of SA remodeling.

Indiana University-Purdue University Indianapolis (IUPUI) / There is no consensus on which vascular segment or what size of vessels is most important in the process of collateral growth, the degree to which these vessels can enlarge, or the mechanisms that mediate collateral vessel expansion and its impairment. Chapter I identifies the major collateral vessels that develop in response to femoral arterial occlusion in the pig, rat, and mouse hindlimbs for comparison to humans. Pre-existent small named arteries enlarged ~2-3-fold to become the major collateral vessels in each species, these major collaterals displayed characteristics similar to large arteries experiencing flow-mediated outward remodeling, and important differences in vascular wall thickness were observed between rodents and pigs. Chapter II utilized Rac2-/- and Nox2-/- mice to investigate the hypothesis that Nox2-NAD(P)H oxidase is required for major collateral growth subsequent to femoral arterial occlusion. Previous studies suggest bone marrow cell (BMC)-derived reactive oxygen species (ROS) produced by the Nox2 subunit of NAD(P)H oxidase plays an important role in neovascularization and recovery of hindlimb perfusion subsequent to femoral arterial occlusion; but did not investigate collateral growth. The hematopoietic cell restricted protein Rac2 has been shown to bind to and activate Nox2-NAD(P)H oxidase and Rac2-/- and Nox2-/- leukocytes display impaired ROS related functions. The data demonstrated that Rac2 and Nox2 are not essential for major collateral growth, but both are important for the recovery of hindlimb perfusion and preservation of distal tissue morphology. Chapter III investigated BMC and antioxidant therapy in the age-related impairment of collateral growth. Aging, like all cardiovascular disease risk factors is associated with elevated ROS and impaired collateral growth. Studies also suggest BMCs promote collateral growth by secreting paracrine factors but elevated ROS may affect the efficacy of BMCs. The data revealed that neither BMC injection nor antioxidant therapy via apocynin enhanced the process of major collateral artery growth in aged mice.

The study applies in vivo technique for profiling hemodynamics and wall shear stress (WSS) distribution in human coronary arteries. The methodology involves fusion of 2D Intra Vascular Ultra Sound and Bi-plane angiograms to reproduce the 3D arterial geometry. This geometry is then used in a Computational Fluid Dynamics (CFD) module for flow modeling. The Walburn and Schneck constitutive relation was used to represent the non-Newtonian blood rheology. The methodology is applied to study the relationship between WSS and Neointimal Hyperplasia (NIH) in two groups of diabetic patients after being treated separately with bare metal stents (BMS) and Sirolimus Eluting Stents (SES). The stent assignments were blinded until the end of the study. The study was repeated for the patients after 9 months. The predicted WSS ranged from (0.1- 8 N/m2) and was categorized into five classes: low ( < 1 N/m2); low-normal (1-2 N/m2); normal (2-3 N/m2); high-normal (3-4 N/m2); high ( > 4 N/m2). The results indicate NIH in 5 of the patients treated with BMS and none in SES cases. These results correlate with our predicted WSS distribution.

Plasmalemmale Kalzium- und Kaliumkanäle sind wichtige Regulatoren der kontraktilen Kraft glatter Gefäßmuskelzellen. Bei Untersuchungen an einer Vielzahl nicht humaner glatter Muskelzellen wurden verschiedene Kalzium- und Kaliumkanaltypen identifiziert. Allerdings ist über das Vorkommen, die biophysikalisch-pharmakologischen Eigenschaften, Regulation, Bedeutung und differentielle Expression von spannungsabhängigen Kalzium- und Kaliumkanälen in humanen arteriellen Gefäßmuskelzellen noch wenig bekannt. In dieser Arbeit wurden spannungsabhängige Kalzium- und Kaliumkanalströme in frisch-isolierten Gefäßmuskelzellen humaner Koronararterien analysiert. Die wichtigsten Ergebnisse waren: (1) Gefäßmuskelzellen humaner Koronararterien exprimieren funktionell aktive spannungsabhängige L-Typ-Kalziumkanäle. (2) Die hohe Permeationsrate von L-Typ-Kanälen in Lösungen mit physiologischer Ca2+-Konzentration wird durch die (1- Kanaluntereinheit bestimmt. (3) L-Typ-Kanäle der C-Klasse werden durch G-Proteine und Proteinkinase C moduliert. (4) Die Expression von L-Typ-Kanälen in Gefäßmuskelzellen wird differentiell reguliert. (4) Vier diverse Kaliumkanalströme kommen in Gefäßmuskelzellen humaner Koronararterien vor: IK(dr), IBK(Ca), IK(ATP) und STOCs. (5) Spontane transiente Auswärtsströme (STOCs) werden durch Ca2+-Sparks ausgelöst. (6) Ca2+-Sparks entstehen durch Öffnung von Ca2+-Freisetzungskanälen (Ryanodinrezeptoren) des sarkoplasmatischen Retikulums. (7) KATP-Kanäle fungieren als Zielstruktur für diverse endogene und synthetische Vasodilatatoren. (8) Ca2+-Sparks und STOCs bewerkstelligen die Feineinstellung des myogenen Gefäßtonus. (9) Der Ca2+-Spark/STOC-Signalweg stellt potenziell ein neuartiger Angriffsort für Hormone und Pharmaka dar, über den der Gefäßtonus von geringlumigen Arterien beeinflusst werden kann. Diese Ergebnisse tragen zum Verständnis der Bedeutung von plasmalemmalen Ionenkanälen bei chronischen Gefäßerkrankungen wie Atherosklerose und Hypertonie bei und eröffnen möglicherweise neue therapeutische Möglichkeiten. / Plasmalemmal calcium- and potassium channels represent important regulators of the contractile force of smooth muscle. Studies on various human smooth muscle cells have identified different calcium and potassium channels. However, relatively little is known on the presence, biophysical and pharmacological properties, regulation, function, and differential expression of voltage-dependent calcium and potassium channels in human coronary arteries. In this study, voltage-depedent calcium and potassium channels in human coronary arteries were studied. The main findings are: (1) Smooth muscle cells of human coronary arteries exhibit functional voltage-dependent, L-type calcium channels. (2) The high permeation rate of L-type channels in solutions with physiological calcium concentrations is determined by the (1 channel subunit. (3) C-class L-type channels are modulated by G proteins and protein kinase C. (4) The expression of L-type channels in vascular smooth muscle cells is differentially regulated. (4) Four diverse potassium channel currents are present in smooth muscle cells from human coronary arteries: IK(dr), IBK(Ca), IK(ATP) and STOCs. (5) Spontaneous transient outward currents (STOCs) are induced by Ca2+ sparks. (6) Ca2+ sparks are generated by the opening of calcium release channels (ryanodine receptors) in the sarcoplasmic reticulum. (7) KATP channels function as target for diverse endogeneous and synthetic vasodilators. (8) Ca2+ sparks and STOCs control the myogenic tone of arterial vessels. (9) The Ca2+ spark/STOC signaling pathway represents a novel target for hormones and drugs to regulate the diameter of small, resistance-sized arteries. These results contribute to a better understanding of the role of plasmalemmal ion channels in chronic vascular disease, such as atherosclerosis and hypertension. They may open novel therapeutic possibilites in the treatment of chronic vascular disease.

This study was aimed at determining whether the digital volume pulse waveform using the Pulse Sensor can be used to extract features related to arterial compliance. The Pulse Sensor, a low-cost photoplethysmograph, measures green light reflection in the finger and generates output, which is indicative of blood flow and can be read by the low-cost Arduino UNO™. The Pulse Sensor code was modified to increase the sampling frequency and to capture the data in a file, which is subsequently used for waveform analysis using programs written in the R system. Waveforms were obtained using the Pulse Sensor during two 30-s periods of seated rest, in each of 44 participants, who were between the ages of 20 and 80 years. For each cardiac cycle, the first four derivatives of the waveform were calculated and low-pass filtered by convolution before every differentiation step. The program was written to extract 19 features from the pulse waveform and its derivatives. These features were selected from those that have been reported to relate to the physiopathology of hemodynamics. Results indicate that subtle features of the pulse waveform can be calculated from the fourth derivative. Feature misidentification occurred in cases of saturation or low voltage and resulted in outliers; therefore, trimmed means of the features were calculated by automatically discarding the outliers. There was a high efficiency of extraction for most features. Significant relationships were found between several of the features and age, and systolic, diastolic, and mean arterial blood pressure, suggesting that these features might be employed to predict arterial compliance. Further improvements in experimental design could lead to a more detailed evaluation of the Pulse Sensor with respect to its capability to predict factors related to arterial compliance.