The study of pulsatile flow through a stenosis is motivated by the need to obtain a better understanding of the impact of flow phenomena on atherosclerosis and stroke. MRI techniques have been employed to characterize flow emerging from a stenosis and non-stenotic tube. Detection and quantification of stenosis, serve as the basis for surgical intervention. In the future, the study of arterial blood flow will lead to the prediction of individual hemodynamic flows in any patient, the development of diagnostic tools to quantify disease, and the design of devices that mimic or alter blood flow. Blood flow and pressure are unsteady. The cyclic nature of the heart pump creates pulsatile conditions in all arteries. The heart ejects and fills with blood in alternating cycles called systole and diastole. Blood is pumped out of the heart during systole. The heart rests during diastole, and no blood is ejected. Pressure and flow have characteristic pulsatile shapes that vary in different parts of the arterial system. The experiments demonstrate that stenotic pulsatile flow exhibit flow disturbance phenomena which deviate the flow from the laminar behavior. In vitro measurements can simulate blood flow to a satisfactory degree, under various assumptions for flow. In this study, estimation of various hemodynamic parameters, are achieved by means of a flow phantom. The phantom can simulate pulsatile blood flow in arterial system, in our case blood flow in carotid artery. The phantom consists of an one-headed positive displacement diaphragm pump, driven by an electrocardiogram (ECG) generator, with the tube, creating a closed circuit. Within the circuit, water (as blood mimicking fluid) is driven, simulating blood flow. We studied the flow using velocity-encoded MR phase contrast sequences. Phase contrast angiography relies on dephasing the moving spins submitted to a bipolar gradient. For a bipolar gradient of a given intensity and time, the moving spins will dephase in proportion to their velocity. Similar to spatial encoding in the phase direction, the possible phase values range from – π to + π. Beyond this range of values, aliasing occurs, causing poor velocity encoding. The encoding gradient characteristics are thus defined in order to encode flows within a certain velocity range from -Venc to +Venc to be determined by the user. Any velocity outside this range will be poorly encoded (similar to what happens in pulsed and color Doppler with PRF). The present work refers to blood flow estimation by means of Magnetic Resonance Imaging. The MR imaging system used, is a 1.5 Tesla scanner (Intera 1.5T, Philips Medical Systems, Best, the Netherlands) of Attikon Hospital (Second Department of Radiology). CT imaging system is a Philips Brilliance 64, used to assess the percentage of the stenosis. The experimental set up consists of a flow phantom, simulating blood flow through blood vessels under chosen conditions. Gradient echo (phase contrast) sequences used, precisely: SQ flow and QFP sequences. MR phasecontrast technique quantifies and displays flow velocities in real times. The sequence uses a two-dimensional selective radiofrequency pulse followed by flow-sensitizing gradients with an echo planar readout. It provides the simultaneous display in real time of both an anatomic image for positioning and the through plane flow-velocity data. By controlling scan position and orientation interactively, one can optimize flow signal. The retrospective search of measurements is carried out with the database of a software used, called EVORAD. The software of the workstation automatically provided the following parameters: ROI area (cm2), vessel lumen diameter (cm), blood volume flow (ml/s), mean and maximum blood flow velocities (cm/s). The LOIs in respective, used for velocity profiles determination, were acquired by ImageJ software, by similar procedure at vertical and horizontal direction on the lumens’ plane perpendicular to the flow. Two different geometries were used: a PVC tube mimicking a healthy carotid artery of 6mm internal diameter and a stenotic glass tube to simulate arterial pathology, of 8mm internal diameter. Considering the non-stenotic PVC tube, VFR values are estimated volumetrically (for various bpm and pump output values) and via MRI (for straight and inclined position). VFR values are then compared. MR maximum velocity values are estimated too, and velocity profiles are plotted. The procedure is similar in the case of the stenotic glass tube, for various (bpm and PO; pump output) and at intervals of 1cm across the stenosis reaching 4cm upstream and downstream. In the sequence of estimation, percentage of stenosis follows; estimated from both MRI and CT scans. Finally, variation of pressure and SNR in order to assess the signal loss due to stenosis are estimated. Accounting for the non stenotic tube: The first significant issue to mention, is the greatest cv (correlation of variation) values at lower VFR values (measured at 10%pump output and pressure of 2,5b), among all VFR values for both 60 and 75 bpm, and the greatest std values noticed at the greatest VFRs (60%, 4.6b). VFR values are indeed greater at 75 bpm compared to those at 60 bpm, as expected. Values show no stable relevance between VFR and pump output. There are differences in VFR values from the inclined position, statistically significant, in cases of 5% for both 60,75bpm. Statistical differences (at 5% statistical significance), are noticed between volumetric measurements versus MRI extracted values as compared above, between SQflow and QFP sequences (60/20). VFR values comparison between volumetric and MRI measurements, show statistical differences. Concerning Vmax values from ROIs and LOIs V,H: there are statistical differences in 5, 10%PO, for both 60, 75bpm, indicating higher values in straight position. Concerning Vmax values extracted from MRI ROIs and LOIs V&H: there are statistically significant differences in cases of 5,10% PO, at both 60,75bpm, leading to greater values at straight position. In the case of stenotic tube: Comparison, of VFR values at 75, 120 bpm, result in higher flow at the exit of the stenosis (49.16%, 80.14%). In the vicinity of stenosis (± 1cm), VFR is almost stable in the case of 120 bpm (0,74%), whereas the highest variation is noted at 75 bpm (133,9%). The highest VFR value intrastenotic is noted at 120 bpm (2,06ml/s). As flow increases, VFR variation is noted more distal to the stenosis. Percentage comparison indicate that greater variations for 60,75, 120bpm are noted in the vicinity of stenosis (±1cm), whereas for 100bpm at ±3cm. Considering Vmax extracted values at 4cm post stenosis in all cases of pulsatility are higher than the respective values 4cm pre stenosis. At the neck of the stenosis extracted values are indeed high as expected, since laminar flow persists across the stenosis. The highest Vmax value among all intra-stenotic values, appears at 60 bpm. As pump flow rate increases, maximum value occurs most post along stenosis. Post stenosis variations are expected to be higher at higher pulsatility. Vertical LOIs result in higher R squared values. In lower flow (corresponding to lower pulsatility 60,75bpm as mentioned above), parabolic profiles as noted pre and post stenosis (2cm,1cm pre and 4cm post). For higher flow, (100,120bpm), parabolic profiles are depicted post stenosis (2-4cm) and in the neck of stenosis for 100bpm. Severity of stenosis is calculated as the percentage rate of Vmax upstream or downstream the stenosis to the intrastenotic Vmax, minus the unity. The pump output is set up to 10%, flow rate ranges from 60 to 120 bpm. Calculations account for Vmax values from both ROIs and LOIs (V,H). Measurements from CT scan are also acquired (gold standard) for comparison. Due to turbulence, Xpre values are considered as more reliable. Better agreement for stenosis estimations to ROIs are acquired: in low flow from LOIsV, whereas at higher flow by LOIsH. Overall, values extracted by MR at 60 bpm imply a stenosis of 46% (LOIsH), 98% (LOIsV) and 93% (ROIs), whereas CT scans estimations lead to 90.2% using diameter stenosis and 99% using area stenosis. The LOIsH expectedly underestimate the percentage of stenosis. CT value of 99% is the exact value, that result by the relationship described in Ota et al.(2005) study: A=D*[2-(D/100)], where D=0,902 is the “diameter stenosis”. ΔP values at 60 and 100bpm, exceed the respective at 75, 120 bpm. In Vmax values, higher intrastenotic values were noted at those pulsatilities, indicating higher pressure energy loss converted to kinetic energy. Calculations of ΔP, a value of 4 is used for K factor and Vmax values are calculated in m/s in the neck of the stenosis. Calculations from linear and elliptical ROIs were made. By the same reasoning as before, we assume that the value of 15.92mmHg found at 60bpm from ROIs is the most reliable. A second calculation of ΔP by means of K=4.9 lead to higher values of 5.1%. Signal to noise ratio as indicative of the loss of signal as fluid flows along the stenosis. Rectangular ROIs are designed upstream and downstream the stenosis, thus SNR values: upstream the stenosis, are higher in contrast to all respective values downstream. Calculations lead to values of: 54.15% (60bpm), 71.08% (75bpm), 68.7% (100bpm) and 72.63% for 120 bpm. The highest loss is depicted at 120 bpm, and in descending order at 75, 100 and 60 bpm. There are certain factors that are limiting when it comes to comparing the executed study to clinical flow measurements, many of which are connected to properties of the pump and phantom used. At very low pump output as used, there was instability at several times. On the other hand at high PO the pressure reached maximum value (manometer) and was thus avoided. The PO values of 5, 10, 20% are quite lower than that usually found in patients. Thus, a direct comparison to in vivo values would be invalid. The tube in the phantom differs from that of a blood vessel as it is rigid, tube wall consists of PVC or glass, and BMF has different relaxation properties than those found in vivo. Furthermore, the size of the phantom used is much smaller than that of an actual patient, which can lead to a significant divergence in susceptibility variations in scanned material. Consequently, optimal future projects should include scanning faster flow, higher PO, higher magnitude of 3T, different sequences and modalities (various stenoses, oblique positions, blood mimicking fluids, different vessel walls; to more closely mimic in vivo conditions and to reduce the influence of partial volume effects) and a comparison among different techniques as ultrasound, computed tomography CT. Turbulence in flow is crucial for comprehension and interpretation of the flow across a stenosis. Hence, complete understanding of the interrelationship between pressure, flow, and symptoms for cardiovascular stenoses is a critical problem. New devices to repair stenotic arteries are continuously being developed. Thus fluid mechanics will continue to play an important role in the future diagnosis, understanding, and treatment of cardiovascular diseases. / Η μελέτη της παλμικής ροής μέσω στένωσης, υπαγορεύεται υπό την ανάγκη να υπάρξει βαθύτερη κατανόηση των επιπτώσεων των φαινομένων ροής σε περιπτώσεις αθηροσκλήρωσης και εγκεφαλικού επεισοδίου. Οι τεχνικές μαγνητικής τομογραφίας χρησιμοποιούνται για να χαρακτηρισθεί η ροή που εξέρχεται από μια στένωση και από μη στενωμένα αγγεία. Η ανίχνευση και η ποσοτικοποίηση της στένωσης χρησιμεύουν ως βάση στις επεμβατικές θεραπείες. Μελλοντικά, η μελέτη της αρτηριακής ροής του αίματος θα οδηγήσει στην πρόβλεψη των μεμονωμένων αιμοδυναμικών παραμετρων ροής για κάθε ασθενή, την ανάπτυξη διαγνωστικών εργαλείων για την ποσοτικοποίηση της νόσου, και τη σχεδίαση συσκευών που μιμούνται και δύναται να τροποποιήσουν τη ροή του αίματος. Η ροή του αίματος και η πίεση του είναι ασταθείς. Η κυκλική φύση της άντλησης αίματος μέσω της καρδιάς μεταδίδει παλμικές συνθήκες ροής σε όλες τις αρτηρίες. Η καρδιά εξωθεί και γεμίζει με αίμα σε εναλλασσόμενους κύκλους που ονομάζονται συστολή και διαστολή αντίστοιχα. Αίμα αντλείται από την καρδιά κατά τη διάρκεια της συστολής. Η καρδιά αδρανεί κατά τη διαστολή, και δεν εξωθεί αίμα. Η πίεση και η ροή έχουν χαρακτηριστικές παλμικού σχήματος κυματομορφές που διαφέρουν στα διάφορα τμήματα του αρτηριακού συστήματος. Μελέτες υποδεικνύουν ότι η παλμική ροή μέσω στένωσης, παρουσιάζει φαινόμενα διαταραχής, ώστε η ροή τελικά να αποκλίνει από τη στρωτής συμπεριφοράς ροή. In vitro μετρησεις μπορούν να προσομοιάσουν τη ροή του αίματος σε ικανοποιητικό βαθμό, υπό την προυπόθεση διαφόρων προσεγγίσεων. Στην παρούσα εργασία η εκτίμηση των παραμέτρων ρόης γίνεται μέσω ομοιώματος. Το ομοίωμα μπορεί να προσομοιώσει την παλμική ροή αίματος στο αρτηριακό σύστημα, στην περίπτωσή μας στην καρωτιδική αρτηρία. Το ομοίωμα αποτελείται από μία βάση με αντλία διαφράγματος, “οδηγούμενη” από μία γεννήτρια συσκεύη ηλεκτροκαρδιογραφήματος (ΗΚΓ), δημιουργώντας ένα κλειστό κύκλωμα διαμέσω σωλήνα. Εντός του κυκλώματος, το νερό (όπως το αίμα), οδηγείται, προσομοιώνοντας την αιματική ροή. Μελετήσαμε τη ροή χρησιμοποιώντας ακολουθίες MR αντίθεσης φάσης. Η αγγειογραφία αντίθεσης βασίζεται σε αποσυμφασικοποίηση των κινούμενων spin, τα οποία υποβάλλονται σε διπολικό gradient (βαθμίδωση). Για μια διπολική βαθμίδωση δεδομένης έντασης και χρόνου, τα κινούμενα spin θα αποσυμφασικοποιούνται σε αναλογία με την ταχύτητά τους. Παρόμοιως με τη διαδικασία χωρικής κωδικοποίησης στην κατεύθυνση φάσεως, οι πιθανές τιμές φάσης κυμαίνονται μεταξύ - π και + π. Εκτός αυτού του εύρους τιμών, συμβαίνει aliasing, προκαλώντας κακή κωδικοποίηση ταχύτητας. Τα χαρακτηριστικά βαθμίδας κωδικοποίησης, καθορίζονται επομένως προκειμένου να κωδικοποιηθούν οι ροές εντός μίας ορισμένης περιοχής ταχύτητος από -Venc έως +Venc, όπως θα καθοριστούν από τον χειριστή. Κάθε ταχύτητα εκτός αυτού του εύρους θα κωδικοποιείται λανθασμένα (όπως συμβαίνει σε παλμικό και έγχρωμο Doppler με PRF). Η παρούσα εργασία, αναφέρεται στην εκτίμηση της ροής του αίματος με τη βοήθεια της μαγνητικής τομογραφίας. Το MR σύστημα απεικόνισης που χρησιμοποιείται, είναι το 1,5 Tesla (Intera 1.5T, Philips Medical Systems, Best) του Αττικού Νοσοκομείου (Β’ Τμήμα Ακτινολογίας). Το CT σύστημα απεικόνισης είναι το 64 Brilliance Philips, το οποίο χρησιμοποιείται για να εκτιμηθεί το ποσοστό της στένωσης. Η πειραματική διάταξη αποτελείται από ένα ομοίωμα ροής, που μιμείται τη ροή του αίματος μέσω των αγγείων κάτω από επιλεγείσες συνθήκες. Οι ακολουθίες (αντίθεσης φάσης) που χρησιμοποιούνται, είναι οι: SQ ροής και η ακολουθία QFP. Η MR τεχνική αντίθεσης φάσης ποσοτικοποιεί και παρουσιάζει ταχύτητες ροής σε πραγματικούς χρόνους. Η αλληλουχία χρησιμοποιεί ένα δισδιάστατο παλμό ραδιοσυχνότητας επιλογής, ακολουθούμενο από κλίσεις ευαισθητοποίησης ροής με μία ηχώ κατά το επίπεδο αναγνώσης. Παρέχει ταυτόχρονη απεικόνιση σε πραγματικό χρόνο μίας ανατομικής εικόνας αλλά και επίπεδο (εικόνα) δεδομένων ταχύτητας ροής. Με τη ρύθμιση της θέσης και του προσανατολισμού σάρωσης διαδραστικά, μπορεί κανείς να βελτιστοποιήσει το σήμα ροής. Η αναδρομική αναζήτηση των μετρήσεων πραγματοποιείται από τη βάση δεδομένων ενός λογισμικού, ονόματι EVORAD. Το λογισμικό του σταθμού εργασίας παρέχει αυτόματα τις ακόλουθες παραμέτρους: εμβαδόν περιοχής ενδιαφέροντος ROI (cm2), εμβαδόν διατομής αγγείου (cm), παροχή (ml / s), μέσες και μέγιστες ταχύτητες ροής του αίματος (cm / s). Οι γραμμές ενδιαφέροντος LOIs ,προς εκτίμηση των προφιλ ταχύτητας, αντίστοιχα σχεδιάστηκαν στο ImageJ λογισμικό, (κατά την κατακόρυφη και οριζόντια κατεύθυνση, στο επίπεδο του αυλού κάθετα προς τη ροή), και οι μετρήσεις εξάχθηκαν με παρόμοια διαδικασία. Δύο διαφορετικές γεωμετρίες χρησιμοποιήθηκαν: ένα αγγείο από PVC που μιμείται μία υγιή καρωτιδική αρτηρία και ένα στενωμένο γυάλινο αγγείο για την προσομοίωση αρτηριακής παθογένειας. ‘Oσον αφορά το μη στενωμένο PVC αγγείο, η παροχή εκτιμάται ογκομετρικά (για διάφορες τιμές παλμικότητας και τιμές κλάσματος εξόδου της αντλίας) αλλά και μέσω μαγνητικής τομογραφίας (σε ευθεία και κεκλιμένη θέση). Οι VFR τιμές έπειτα συγκρίνονται. Οι MR τιμές μέγιστης ταχύτητας εκτιμήθηκαν επίσης, και απεικονίζονται με προφίλ ταχύτητας. Η διαδικασία είναι παρόμοια για την στενωτικό γυάλινο αγγείο (για διάφορες τιμές παλμικότητας και τιμές κλάσματος εξόδου της αντλίας),σε διαστήματα του 1 εκατοστού, φθάνοντας 4 εκατοστά εκατέρωθεν της στένωσης. Στην σειρά εκτιμήσεων ακολουθεί το ποσοστό της στένωσης. Εκτιμάται τόσο από μαγνητική όσο και αξονική τομογραφία. Τέλος, η μεταβολή της πιέσεως και το κλάσμα σήματος προς θόρυβο, προκειμένου να αξιολογηθεί η απώλεια σήματος λόγω στένωσης. Αναφορικά με το μη στενωμένο αγγείο: Το πρώτο σημαντικό ζήτημα να αναφέρουμε, είναι οι μεγαλύτερες τιμές του συντελεστή συσχέτισης σε χαμηλά VFRs (Κ.Ε 10% και πίεση 2,5 b), σε 5% ΚΕ, τόσο για 60 όσο και 75 bpm,αλλά και οι μεγαλύτερες τιμές τυπικής απόκλισης στις μεγαλύτερες τιμές VFR (60%, 4.6b). Οι VFR τιμές είναι πράγματι μεγαλύτερες σε 75 bpm σε σύγκριση με εκείνες στις 60 bpm, όπως αναμενόταν. Οι τιμές, δεν δείχνουν σταθερή σχέση μεταξύ VFR και εξόδου της αντλίας (Κ.Ε). Υπάρχουν στατιστικά σημαντικές διαφορές στις τιμές VFR από την κεκλιμένη θέση, στις περιπτώσεις σύγκρισης με οριζόντια θέση. Σημαντικές στατιστικές διαφορές (στο 5% στατιστικής σημασίας), παρατηρούνται και μεταξύ ογκομετρικών και MRI μετρήσεων, αλλά και μεταξύ των SQflow και QFP ακολουθιών (60/20). Οι VFR τιμές δεν συσχετίζονται κατ 'ανάγκην με τις τιμές Vmax, αλλά με τις Vmean. Όσον αφορά τις τιμές Vmax που προέρχονται από τα MRI ROIs και LΟΙs V&Η: υπάρχουν στατιστικά σημαντικές διαφορές στις περιπτώσεις με 5,10% ΡΟ (Κ.Ε), για 60 και 75 bpm, με τιμές υψηλότερες για οριζόντια θέση του αγγείου. Στην περίπτωση στενωμένου αγγείου: Σύγκριση, των τιμών VFR στα 75, 120 bpm, δίνει υψηλότερη ροή στην έξοδο της στένωσης (49.3%, 80%). Στην περιοχή της στένωσης (± 1cm), VFR τιμές είναι σχεδόν σταθερές στην περίπτωση των 120 bpm (0,74%), ενώ η υψηλότερη μεταβολή σημειώνεται στα 75 bpm (133,9%). Η υψηλότερη τιμή εντός της στένωσης VFR σημειώνεται στα 120 bpm (2,06 ml / s). Καθώς αυξάνει η ροή, οι VFR μεταβολές σημειώνονται πιο μακριά (μετά) από τη στένωση. Τα ποσοστά συγκρίσης δείχνουν ότι οι μεγαλύτερες μεταβολές για 60,75, 120 bpm σημειώνονται στην περιοχή της στένωσης (± 1 cm), ενώ για τα 100bpm σε ± 3cm. Όσον αφορά τις τιμές Vmax όπως εξάγονται 4 εκατοστά μετά την στένωση, σε όλες τις περιπτώσεις παλμικότητας είναι υψηλότερες από τις αντίστοιχες 4 εκατοστά πριν από την στένωση. Αυτό μπορεί να υποδηλώνει την εμμονή του jet ροής στα 4 εκατοστά. Στο λαιμό της στένωσης οι τιμές όπως αναμένεται είναι μέγιστες, εφόσον παραμένει στρωτή ροή εντός της στένωσης. Η υψηλότερη τιμή Vmax μεταξύ όλων των εντός της στένωσης τιμών, εμφανίζεται σε 60 bpm. Καθώς αυξάνεται η ταχύτητα ροής της αντλίας, η μέγιστη τιμή εμφανίζεται αργότερα κατά μήκος της στένωσης. Μετά τη στένωση, οι μεταβολές αναμένεται να είναι υψηλότερες σε υψηλότερη παλμικότητα. Τα κάθετα Lois δίνουν υψηλότερες τιμές R2 συντελεστή διαφοροποίησης. Στην κατώτερη ροή (που αντιστοιχεί σε μικρή παλμικότητα 60,75 bpm όπως αναφέρθηκε παραπάνω), παραβολικά προφίλ παρουσιάζονται πριν και μετά την στένωση (2 εκατοστά, 1 εκατοστό πριν και 4 εκατοστά μετά). Σε υψηλότερη ροή, (100,120 bpm), τα παραβολικά προφίλ απεικονίζονται μετά τη στένωση (2-4cm) και στο λαιμό της στένωσης για 100bpm. Η σοβαρότητα της στένωσης υπολογίζεται ως ο ποσοστιαίος λόγος τών τιμών Vmax πριν ή μετά τη στένωση, προς την τιμή της Vmax εντός της στένωσης, αφαιρούμενο από τη μονάδα. Η έξοδος της αντλίας είναι ρυθμισμένη στο 10%, ενώ οι τιμές του ρυθμού ροής κυμαίνοται από 60 έως 120 bpm. Υπολογισμοί των Vmax τιμών γίνονται μέσω ελλειπτικών και γραμμικών περιοχών ενδιαφέροντος. Μετρήσεις παρουσιάζονται επίσης από την αξονική τομογραφία (gold standard) προς σύγκριση. Δεδομένου ότι οι τιμές ταχύτητας μετά τη στένωση είναι λιγότερο αξιόπιστες (λόγω στροβιλισμών), οι Xpre υπολογισμένες τιμές μπορεί να θεωρηθούν αντίστοιχα περισσότερο αξιόπιστες. Καλύτερη συμφωνία (για τις εκτιμήσεις στένωσης) συγκριτικά με τα ROIs αποκτώνται: σε χαμηλή ροή από LOIsV, ενώ σε υψηλότερες ροή από LOIsH. Συνολικά, οι τιμές που προέρχονται από 60 bpm συνεπάγονται μια στένωση του 46% (LOIsH), 98% (LOIsV) και 93% (ROIs), ενώ οι αξονικής τομογραφίας εκτιμήσεις δίνουν 90,2% μέσω στένωσης διαμέτρου και 99% μέσω στένωσης εμβαδού. Η τελευταία, είναι ακριβώς η τιμή που προκύπτει από τη σχέση που περιγράφεται στην μελέτη των Ota et al (2005): Α = D * [2 -(D/100)], όπου D = 0.902 ως εκτιμώμενη μέσω διαμέτρου στένωση. Οι ΔΡ τιμές στα 60 και 100bpm, υπερβαίνουν τις αντίστοιχες σε 75, 120 bpm. Vmax τιμές, υψηλότερες τιμές εντός της στένωσης, παρατηρήθηκαν σε αυτές τις παλμικότητες, δείχνοντας μεγαλύτερη απώλεια ενέργειας πίεσης και μετατροπή αυτής σε κινητική. Οι διακυμάνσεις της πίεσης, σε χαμηλότερες παλμικότητες, ΔΡ είναι πράγματι υψηλότερες. Για τον υπολογισμό των τιμών ΔΡ, η τιμή 4 χρησιμοποιείται για Κ παράγοντα και σαν Vmax τιμές θεωρούνται σε m / s οι τιμές στο λαιμό της στένωσης. Με την ίδια λογική όπως και πριν, υποθέτουμε ότι η τιμή του 15.92mmHg βρέθηκαν σε 60bpm από ROIs είναι η πιο αξιόπιστη. Ένας δεύτερος υπολογισμός του ΔΡ μέσω του Κ = 4,9 οδηγούν σε υψηλότερες τιμές του 5,1%. Ο λόγος σήματος προς θόρυβο υπολογίστηκε ως δείκτης της απώλειας σήματος όταν ρευστό ρέει κατά μήκος της στένωσης,. Ορθογώνια ROIs έχουν σχεδιαστεί πριν και μετά τη στένωση, έτσι SNR τιμές: πριν της στένωσης είναι υψηλότερα σε αντίθεση με όλες τις αντίστοιχες τιμές μετά. Οι υπολογισμοί οδηγούν σε τιμές: 54,15% (60bpm), 71,08% (75bpm), 68,7% (100bpm) και 72,63% για 120 bpm. Η μεγαλύτερη απώλεια εμφανίζεται στα 120 bpm,όπως αναμένεται και σε φθίνουσα σειρά σε 75, 100 και 60 bpm. Υπάρχουν ορισμένοι παράγοντες που περιορίζουν όταν πρόκειται να συγκριθεί η μελέτη με κλινικές μετρήσεις ροής, πολλοί από τους οποίους είναι συνδεδεμένοι με τις ιδιότητες της χρησιμοποιούμενης διάταξης (αντλία και ομοίωμα). Σε πολύ χαμηλά κλάσματα εξώθησης της αντλίας, υπήρχε μεταβλητοτητα των αποτελεσμάτων (κακή επαναληψιμότητα) σε μετρήσεις όταν επαναλήφθηκαν αρκετές φορές. Από την άλλη πλευρά σε υψηλό Κ.Ε η πίεση έφθανε στη μέγιστη κλίμακα (μανόμετρου) και, επομένως, αποφεύχθηκε. Οι τιμές Κ.Ε των 5, 10, 20% είναι αρκετά μικρότερες από εκείνες που συνήθως βρίσκονται σε κλινικό περιβάλλον. Έτσι, μια άμεση σύγκριση με in vivo τιμές θα είναι άτοπη. Το αγγείο ομοίωμα διαφέρει από ένα αιμοφόρο αγγείο, αφού το τοίχωμά του είναι άκαμπτο, με υλικό από PVC ή γυαλί, και το ρευστό που μιμείται το αίμα BMF έχει διαφορετικούς χρόνους χαλάρωσης. Επιπλέον, το μέγεθος του χρησιμοποιούμενου ομοιώματος είναι πολύ μικρότερο από εκείνο ενός πραγματικού ασθενή, και μπορεί να οδηγήσει σε μια σημαντική απόκλιση από τις παραλλαγές επιδεκτικότητας σε σαρωμένα υλικά. Συμπερασματικά, μελλοντικά πιο ολοκληρωμένες μελέτες, πρέπει να περιλαμβάνουν μέτρηση ταχύτερης ροής, υψηλότερων Κ.Ε, υψηλότερης έντασης μαγνητικό πεδίο 3Τ, διαφορετικές ακολουθίες και διαδικασίες (στενώσεις, επικλινείς θέσεις, BMFs, αγγεία από διαφορετικά υλικά, ώστε να μιμούνται καλύτερα τις in νίνο συνθήκες και να μειώνουν την επιρροή του φαινομένου μερικού όγκου), ίσως επίσης σύγκριση μεταξύ των διαφόρων τεχνικών, όπως υπερηχογράφημα, αξονική τομογραφία CT. Η διαταραχή στη ροή είναι ζωτικής σημασίας για την κατανόηση και την ερμηνεία της ροής σε μια στένωση. Ως εκ τούτου, η πληρέστερη κατανόηση της αλληλεξάρτησης μεταξύ πίεσης, ροής, και των συμπτώματων των καρδιαγγειακών στενώσεων, παραμένει ένα κρίσιμο κλινικό θέμα. Οι νέες εφαρμογές για την αποκατάσταση στένωσης των αρτηριών είναι σε στάδιο συνεχούς ανάπτυξης. Η ρευστομηχανική θα εξακολουθήσει λοιπόν να παίζει σημαντικό ρόλο στη μελλοντική διάγνωση, την κατανόηση, και τη θεραπεία των καρδιαγγειακών παθήσεων.

Cerebral small vessel disease (SVD) is associated with increased risks of stroke and dementia, however the mechanisms remain unclear. Low cerebral blood flow (CBF) has long been suggested and accepted, but clinical evidence is conflicting. On the other hand, growing evidence suggests that increased intracranial pulsatility due to vascular stiffening might be an alternative mechanism. Pulse-gated phase-contrast MRI is an imaging technique that allows measuring of CBF contemporaneously with pulsatility in multiple vessels and cerebrospinal fluid (CSF) spaces. The overall aim of this thesis was to provide an overview of existing clinical evidence on both hypotheses, to test the reproducibility of CBF and pulsatility measures in phase-contrast MRI, and to explore the relationship between CBF and intracranial pulsatility and SVD features in a group of patients with minor stroke and SVD changes on brain imaging. I first systematically reviewed and meta-analysed clinical studies that have assessed CBF or intracranial pulsatility in SVD patients. There were 38 studies (n=4006) on CBF and 27 (n=3356) on intracranial pulsatility. Most were cross-sectional, and longitudinal studies were scarce. There were large heterogeneities in patient characteristics and indices used particularly for measuring and calculating pulsatility. Methods to reduce bias such as blinding and the expertise of structural image readers were generally poorly reported, and many studies did not account for the impact of confounding factors (e.g. age, vascular risk factors and disease severity) on CBF or pulsatility. Evidence for falling CBF predating SVD was not supported by longitudinal studies; high pulsatility in one large artery such as internal carotid arteries (ICA) or middle cerebral arteries might be related to SVD, but studies that measured arteries, veins and CSF in the same patients were very limited and the reliability of some pulsatility measures, especially in CSF, needs to be tested. In order to test the reproducibility of the CBF and intracranial pulsatility measures, I repeated 2D phase-contrast MRI scans of vessels and CSF on healthy volunteers during two visits. I also compared the ICA pulsatility index derived from the MRI flow waveform to that from the Doppler ultrasound velocity waveform in patients with minor stroke and SVD features. In 10 heathy volunteers (age 35.2±9.78 years), the reproducibility of CBF and vascular pulsatility indices was good, with within-subject coefficients of variability (CV) less than 10%; whereas CSF flow and pulsatility measures were generally less reproducible (CV > 20%). In 56 patients (age 67.8±8.27 years), the ICA pulsatility indices in Doppler ultrasound and MRI were acceptably well-correlated (r=0.5, p < 0.001) considering the differences in the two techniques. We carried out a cross-sectional study aiming to recruit 60 patients with minor stroke and SVD features. We measured CBF and intracranial pulsatility using phase-contrast MRI, as well as aortic augmentation index (AIx) using a SphygmoCor device. I first investigated the relationship between intracranial measures, and systemic blood pressure or aortic AIx, and then focused on how the intracranial haemodynamic measures related to two main SVD features (white matter hyperintensities (WMH) and perivascular spaces (PVS)). We obtained usable data from 56/60 patients (age 67.8±8.27 years), reflecting a range of SVD burdens. After the adjustment for age, gender, and history of hypertension, higher pulsatility in the venous sinuses was associated with lower diastolic blood pressure and lower mean arterial pressure (e.g. diastolic blood pressure on straight sinus pulsatility index (PI): β=-0.005, P=0.029), but not with aortic AIx. Higher aortic AIx was associated with low ICA PI (β=-0.011, P=0.040). Increased pulsatility in the venous sinuses, not low CBF, was associated with greater WMH volume (e.g. superior sagittal sinus PI: β=1.29, P=0.005) and more basal ganglia PVS (e.g. odds ratio=1.379 per 0.1 increase in superior sagittal sinus PI) after the adjustment for age, gender and blood pressure. The thesis is the first to summarise the literature on CBF and intracranial pulsatility in SVD patients, addressed the major limitations of current clinical studies of SVD, and also assessed CBF and intracranial pulsatility contemporaneously in well-characterised patients with SVD features. The overall results of the thesis challenge the traditional hypothesis of the cause and effect between low CBF and SVD, and suggest that increased cerebrovascular pulsatility, which might be due to intrinsic cerebral small vessel pathologies rather than just aortic stiffness, is important for SVD. More importantly, this pilot study also provides a reliable methodology for measuring intracranial pulsatility using phase-contrast MRI for future longitudinal or larger multicentre studies, and shows that intracranial pulsatility could be used as a secondary outcome in clinical trials of SVD. However, future research is required to elucidate the implication of venous pulsatility and to fully explore the passage of pulse wave transmission in the brain. Overall, this thesis advances knowledge and suggest potential targets for future SVD studies in terms of mechanisms, prevention and treatment.

Intracranial monitoring after severe traumatic brain injury offers the possibility for early detection and amelioration of physiological insults. In this thesis, I explore cerebral insults due raised intracranial pressure, decreased cerebral perfusion pressure and impaired cerebral pressure reactivity after traumatic brain injury. In chapter 2, the importance of intracranial pressure, cerebral perfusion pressure and pressure reactivity in regulating the cerebral circulation is elucidated along with a summary of the existing evidence supporting intracranial monitoring in traumatic brain injury. In chapter 4, intracranial pressure, cerebral perfusion pressure, and pressure reactivity insults are demonstrated to be common, prognostically important, and responsive to long-term changes in management policies. Further, while these insults often occur independently, coexisting insults portend worse prognosis. In chapter 5, I examine possible imaging antecedents of raised intracranial pressure and demonstrate that initial subarachnoid haemorrhage is associated with the subsequent development of elevated intracranial pressure. In addition, elevated glucose during the intensive care stay is associated with worse pressure reactivity. Cortical blood flow and brain tissue oxygenation are demonstrated to be sensitive to increases in intracranial pressure in chapter 6. In chapter 7, a method is proposed to estimate the cerebral perfusion pressure limits of reactivity in real-time, which may allow for more nuanced intensive care treatment. Finally, I explore a recently developed visualisation technique for intracranial physiological insults and apply it to the cerebral perfusion pressure limits of reactivity. Taken together, this thesis outlines the scope, risk factors and consequences of intracranial insults after severe traumatic brain injury. Novel signal processing applications are presented that may serve to facilitate a physiological, personalised and precision approach to patient therapy.

A capacidade de alterar a função vascular dependente do endotélio pode ser importante na intervenção ou até mesmo na prevenção de doenças cardiovasculares. O exercício representa uma importante estratégia anti-aterogênica que pode restaurar a dilatação dependente do fluxo. O objetivo deste estudo foi avaliar a composição corporal (CC), a força muscular (FM), o fluxo sangüíneo do antebraço (FSA) e a produção de Óxido Nítrico (NO) antes e depois de 16 semanas de treinamento de força (TF). Foram avaliadas 17 mulheres pós-menopáusicas (idade média 57,2 ± 4,74 anos): 11 no grupo treinadas (GT) e 6 no grupo controle (GC). As voluntárias compareceram ao Hospital de Clínicas de Porto Alegre (HCPA) e realizaram o seguinte protocolo de teste: 20 minutos de repouso, coleta de sangue (níveis plasmáticos de nitritos e nitratos (NOx)) e aferição do FSA através da técnica de pletismografia de oclusão venosa em repouso e após o protocolo de exercício. O exercício consistiu de 5 segundos de contração e 5 segundos de relaxamento de preensão manual a 30 % da carga voluntária máxima (CVM) num total de 2 minutos. O TF consistiu de 8 exercícios envolvendo grandes grupos musculares, progredindo de 30 a 75% de 1RM. Para análise dos dados, foram realizados testes de normalidade de Shapiro-Wilk e a distribuição dos dados de composição corporal e de força (1RM) foi considerada normal enquanto os dados do FSA e da produção de NO não. Assim, para o efeito do TF na composição corporal e na força foi utilizado o teste t de Student pareado e para comparar os grupos teste t de Student independente. Para a comparação das alterações no FSA e na produção de NO (através dos níveis plasmáticos NOx) intragrupos foi utilizado o teste não paramétrico de Wilcoxon. Para avaliar as diferenças entre os grupos utilizou-se o teste não paramétrico Kruskall-Wallis seguido do procedimento de Dunn. Adotou-se como significância p<0,05. Os resultados estão expressos em média ± desvio padrão. O GC apresentou redução na massa muscular enquanto o GT apresentou aumento (21,24 ± 1,68 vs 20,60 ± 1,83 e 20,48 ± 2,52 vs 21 ± 2,66 kg, respectivamente). Não houve, porém, diferenças significativas entre os grupos. O GT aumentou a força máxima em todos os exercícios testados. O GT apresentou aumento no FSA pós-exercício, pré- e pós-treinamento (2,74 + 0,61 vs 3,98 + 1,81ml . 100ml-1 . min-1) e pós-treinamento, antes e após o exercício (2,37 + 1,03 vs 3,98 + 1,81 ml . 100ml-1 . min-1). O GC apresentou aumento no FSA após 16 semanas em repouso pré- e pós-treinamento (1,90 + 0,44 vs. 2,68 + 1,10 ml . 100ml-1 . min-1). O efeito do exercício após o treinamento e o efeito do treinamento após o exercício foram significativamente maiores somente no GT (0,23 ± 0,81 vs 1,62 ± 1,57 e -0,14 ± 1,30 vs 1,25 ± 1,88 ml . 100ml-1 . min-1, respectivamente). No período pré-treinamento houve um acréscimo significativo no NOx após o exercício nos dois grupos (GT: 1,65 ± 0,21 vs 2,02 ± 0,21 e GC: 1,61 + 0,13 vs 1,46 + 0,1 mmol . l-1), mas somente no GT houve redução significativa de NOx em repouso e após o exercício depois do treinamento (1,65 ± 0,21 vs 1,29 ± 0,1 e 2,02 ± 0,21 vs 1,55 ± 0,14 mmol . l-1, respectivamente). Concluímos que o treinamento de força sistêmico foi capaz de aumentar a massa, a força muscular e o FSA em resposta ao exercício apesar de a força no antebraço não ter sido alterada. Porém, o treinamento levou a uma redução na produção de NO. Palavras-chave: treinamento de força, mulheres pós-menopáusicas, massa muscular, força muscular, fluxo sangüíneo no antebraço, produção de NO. / The capacity to alter endothelium-dependent vascular function can be important for cardiovascular disease intervention or prevention. Physical exercise represents an important anti-atherogenic strategy because it can restore flow-dependent dilation. The aim of this study was to evaluate body composition (BC), muscular strength (MS), forearm blood flow (FBF), and nitric oxide production (NO), before and after 16 weeks strength training (ST). Seventeen post-menopausal women were evaluated (mean age = 57.2 ± 4.74 years) and divided as following: trained group (TG), n = 11; and control group (CG), n = 6. The volunteers were conducted to Hospital de Clínicas de Porto Alegre (HCPA) and they were performed the following test protocol: 20 min rest, blood samples for nitrates e nitrites plasma levels (NOx), venous occlusion pletismography to FBF evaluation, and exercise protocol. The exercise consisted of 5 s contraction and 5 s rest handgrip at 30% of maximal voluntary workload (MVW) during 2 minutes. The ST consisted of 8 exercises for the main muscle groups, and it progressed from 30 to 75% of one maximal-repetition (1RM). Data analysis was made through Shapiro-Wilk for normality test. Body composition and muscular strength data were considered normal, but not the FBF and NO production. Thus, paired student t test was used to evaluate ST effect on body composition, and independent t test to compare groups. The intra-groups differences on the FBF and NO production were tested by Wilcoxon test, and intergroups by Kruskall-Wallis followed by Dunn’s procedure. The level of significance was considered p < 0.05. There were no differences for maximal strength between groups. The CG group presented muscle mass reduction while the GT group presented an increase (21.24 ± 1.68 vs 20.60 ± 1.83 e 20.48 ± 2.52 vs 21 ± 2.66, respectively). Maximal strength was increased at all exercises for TG group. The GT group increased the post-exercise FBF when the pre- and post-training levels were compared (2.74 + 0.61 vs 3.98 + 1.81ml . 100ml-1 . min-1), and the post-training FBF when before and after levels were compared (2.37 + 1.03 vs 3.98 + 1.81 ml . 100ml-1 . min-1). The CG increased rest FBF after 16 weeks training (1.90 + 0.44 vs. 2.68 + 1.10 ml . 100ml-1 . min-1). The post-training exercise effect and post-exercise training effect were increased for TG (0.23 ± 0.81 vs 1.62 ± 1.57 e -0.14 ± 1.30 vs 1.25 ± 1.88 ml . 100ml-1 . min-1, respectively). Both groups increased the after-exercise NOx at pre-training period (GT: 1.65 ± 0.21 vs 2.02 ± 0.21 e GC: 1.61 + 0.13 vs 1.46 + 0.1 mmol . l-1). After training, only TG had significant reduction of rest and after exercise NOx (1.65 ± 0.21 vs 1.29 ± 0.1 e 2.02 ± 0.21 vs 1.55 ± 0.14 mmol . l-1, respectively). We concluded that systemic strength training increased muscle mass, strength, and FBF exercise response despite forearm strength didn’t change. The strength training reduced NO production.

A aterosclerose é uma doença cardiovascular (DCV) que afeta 4 em cada 1.000 pessoas, e é caracterizada por lesões arteriais inflamatórias que evoluem com o desenvolvimento da doença. Está envolvida neste processo uma alta produção de citocinas pró-inflamatórias cuja expressão é mediada pela ativação do fator de transcrição nuclear kappa B (NF-B), responsável por desencadear processos de proliferação celular e migração de células musculares lisas nas regiões de lesões arteriais, contribuindo para o agravamento da doença. Estudos de nosso laboratório mostraram que prostaglandinas ciclopentenônicas (CP-PGs), que são anti-inflamatórias, revertem as lesões ateromatosas em modelos animais, num processo que depende da indução de proteínas de choque térmico - HSP (do inglês Heat Shock Protein) por estas CP-PGs. HSPs impedem a desnaturação de proteínas intracelulares e “desligam” o fator nuclear NF-B, que é um dos principais envolvidos na doença inflamatória vascular da aterosclerose. Por isso, decidimos investigar o efeito direto da expressão de HSPs via choque térmico, no processo inflamatório da aterosclerose, pelo método de “hot tub” realizado semanalmente em camundongos machos nocaute para o receptor de LDL (KO-LDLr), em dieta hiperlipídica e hipercolesterolêmica. Para avaliar estes efeitos os animais foram semanalmente (num período de oito semanas) submetidos a um banho térmico elevando a temperatura corporal para 41,5°C por 15 min. Os resultados demonstraram que, na aorta torácica, o choque térmico aumentou a expressão da HSP70 em cerca de 50% o que foi acompanhado de aumento de 100% na expressão do fator de choque térmico – HSF e dramática queda na ativação do fator NF-kB (75%). Em paralelo, o choque térmico reduziu em mais de 50% a deposição de lípides na parede da aorta e na gordura epididimal e a lipoperoxidação em cerca de 40%. As análises com ultrassonografia Doppler demonstraram que o choque térmico melhorou o fluxo sanguíneo, reduziu a espessura da parede aórtica e melhorou a performance cardíaca. O tratamento também melhorou o status glicêmico (redução de glicemia de jejum e aumento de sensibilidade à insulina) além de reduzir significativamente os valores de colesterol total e LDL, aumentando a proporção de HDL. Os mecanismos envolvidos nestes efeitos benéficos do tratamento com choque térmico encontram-se em estudo em nosso laboratório. / Atherosclerosis is a cardiovascular disease (CVD) that affects four in every 1,000 people, and is characterized by inflammatory arterial lesions which evolve with the development of the disease. It is involved in this process a high production of proinflammatory cytokines whose expression is mediated by the activation of nuclear transcription factor kappa B (NF-B), responsible for triggering the processes of cell proliferation and migration of smooth muscle cells into the arterial lesions, thus contributing to the worsening of the disease. Studies of our laboratory have shown that cyclopentenone prostaglandins (CP-PGs), which are anti-inflammatory, revert atherosclerotic lesions in animal models in a process that depends on the induction of heat shock proteins - HSPs by these CP-PGs. HSPs prevent denaturation of intracellular proteins and "turn off" nuclear factor NF-B, which is a major player involved in the inflammatory vascular disease that accompanies atherosclerosis. Therefore, we decided to investigate the effect of the direct expression of HSPs via heat shock, on the inflammatory process of atherosclerosis, by the "hot tub" method performed weekly in male mice knockout for the LDL receptor (LDLr-KO) under a high fat and hypercholesterolemic diet. To assess these effects, the animals were weekly subjected to a thermal bath (for a period of eight weeks) by raising the body temperature to 41.5 ° C for 15 min. The results demonstrated that in the thoracic aorta, the heat shock increased HSP70 expression approximately 50%, which was accompanied by an increase of 100% in the expression of heat shock factor - HSF and a dramatic decrease in the activation of nuclear factor NF-kB (75%). In parallel, heat shock decreased by more than 50% lipid deposition in the aortic wall and in the epididymal fat, and lipid peroxidation by about 40%. Ultrasound with Doppler analysis showed that heat shock improved blood flow, reduced thickness of the aortic wall and improved cardiac performance. The treatment also improved the glycemic status (reduction of fasting blood glucose and increased insulin sensitivity) and significantly lower levels of total and LDL cholesterol and by increasing the rates of HDL. The mechanisms involved in these beneficial effects of treatment with heat shock are under investigation in our laboratory.

xvii, 245 p. : ill. A print copy of this thesis is available through the UO Libraries. Search the library catalog for the location and call number. / There has been a lot of research investigating the effects of heat stress and exercise on the physiological adaptations to heat acclimation. It is well documented that heat acclimation improves heat tolerance and performance in a hot environment; however, some of the mechanisms of adaptation are not clear. Furthermore, the role of heat acclimation on exercise performance in cool environments is currently unknown. Therefore, in Chapter IV we aimed to determine the effects of heat acclimation on lactate threshold and maximal oxygen uptake (VO 2max ) in cool and hot conditions. We also sought to investigate the effects of heat acclimation on leg blood flow and oxygen delivery during a single-leg knee extensor exercise. We found that heat acclimation improved lactate threshold and VO 2max in cool and hot environments but did not alter the leg blood flow and oxygen delivery during the leg kicking exercise. In Chapter V we investigated the heat acclimation effects on performance during a 1-hour time trial in hot and cool environmental conditions and the potential mechanisms by which this occurs. A secondary objective was to study whether the pacing strategy was modified during the time trial post-heat acclimation. The results demonstrated that heat acclimation improved time trial performance in both thermal environments by approximately 7% but pacing strategy was not altered. The purpose of the studies in Chapter VI were twofold. First, we sought to investigate how heat acclimation affects the skin blood flow and sweating responses to pharmacological treatment with specific dosages of the muscarinic receptor agonist acetylcholine. Second, we examined the maximal skin blood flow responses to a period of heat acclimation by locally heating the forearm with a water spray device for 45 minutes and measured brachial artery blood flow via ultrasound. We found that heat acclimation increased sweat rate and skin blood flow responses to given concentrations of acetylcholine, suggesting a role for peripheral mechanisms. On the other hand, maximal skin blood flow remained unchanged after heat acclimation. / Committee in charge: Christopher Minson, Chairperson, Human Physiology; John Halliwill, Member, Human Physiology; Andrew Lovering, Member, Human Physiology; Michael Sawka, Member, Not from U of 0; Scott Frey, Outside Member, Psychology

Master of Science / Department of Kinesiology / Timothy I. Musch / Chronic heart failure (CHF) reduces nitric oxide (NO) bioavailability and impairs skeletal muscle vascular control during exercise. Reduction of nitrite (NO[subscript]2-) to NO may impact exercise-induced hyperemia particularly in muscles with pathologically-reduced O[subscript]2 delivery. We tested the hypothesis that NO[subscript]2- infusion would increase exercising skeletal muscle blood flow (BF) and vascular conductance (VC) in CHF rats with a preferential effect in muscles composed primarily of type IIb+IId/x fibers. CHF (coronary artery ligation) was induced in adult male, Sprague-Dawley rats. Following a >21 day recovery, mean arterial pressure (MAP, carotid artery catheter) and skeletal muscle BF (radiolabelled microspheres) were measured during treadmill exercise (20 m•min[superscript]-1, 5% incline) with and without NO[subscript]2- infusion. The myocardial infarct size (35 ± 3%) indicated moderate CHF. NO[subscript]2- infusion increased total hindlimb skeletal muscle VC (CHF: 0.85 ± 0.09, CHF+NO[subscript]2-: 0.93 ± 0.09 ml•min[superscript]-1•100g[superscript]-1•mmHg[superscript]-1, p<0.05) without changing MAP (CHF: 123 ± 4 mmHg, CHF+NO[subscript]2-: 120 ± 4 mmHg, p=0.17). Total hindlimb skeletal muscle BF was not significantly different (CHF: 102 ± 7, CHF+NO[subscript]2-: 109 ± 7 ml•min[superscript]-1•100g[superscript]-1, p>0.05). BF increased in 6 (~21%) and VC in 8 (~29%) of the 28 individual muscles and muscle parts. Muscles and muscle portions exhibiting greater BF and VC following NO[subscript]2- infusion were comprised of ≥63% type IIb+IId/x muscle fibers. These data demonstrate that NO[subscript]2- infusion can augment skeletal muscle vascular control during exercise in CHF rats. Given the targeted effects shown herein, a NO[subscript]2[superscript]--based therapy may provide an attractive “needs-based” approach for treatment of the vascular dysfunction in CHF.

Objetivo: Avaliar o efeito da compressão elástica e enfaixamento compressivo funcional associados à cinesioterapia sobre o fluxo sanguíneo do membro superior com linfedema secundário ao tratamento do câncer de mama. Métodos: Trata-se de ensaio clínico randomizado cego crossover, com período washout de sete dias entre os tratamentos. Foram avaliadas 20 mulheres com idade média de 66.85 anos (DP = 11.76), submetidas a três tipos de procedimentos terapêuticos aplicados aleatoriamente mediante sorteio: cinesioterapia (C), cinesioterapia + enfaixamento compressivo funcional (ECF), cinesioterapia + compressão elástica (CE). O fluxo sanguíneo, incluindo velocidade média e máxima, foi avaliado por meio de ultrassom Doppler antes e após procedimento terapêutico, nos tempos 0, 15, 30 minutos. Foi utilizado análise de variância (ANOVA) de medidas repetidas seguido do teste de Bonferroni, considerado um nível de significância de 5%. Resultados: Os grupos CE e ECF apresentaram incremento significativo da velocidade média do fluxo sanguíneo das artérias e veias axilar e braquial, quando comparados ao grupo que recebeu apenas cinesioterapia (C). Quando realizadas as comparações entre os grupos CE e ECF, não foi observada diferença significativa (p>0.05). Foi observada interação grupo-versus-tempo para a artéria (F=7.033, p<0.001) e veia axilar (F=5.524, p<0.001), e para artéria (F= 11.195, p<0.001) e veia braquial (F=10.521, p<0.001), sendo os grupos CE e ECF com incremento circulatório mais significativo (p<0.05). Com relação à velocidade máxima, foi observada significativa interação grupo-versus-tempo para a artéria braquial (F=2.492, p=0.029). Conclusão: A CE e o ECF associados à C produzem incremento do fluxo sanguíneo do membro superior com linfedema. / Objective: To evaluate the effect of elastic compression, functional compressive bandaging and kinesiotherapy on blood flow of the upper limb with lymphedema secondary to the treatment of breast cancer. Methods: This was a randomized blind crossover clinical trial with washout period of seven days between treatments. We evaluated 20 women with a mean age of 66.85 years (standard deviation = 11.76), submitted to three types of therapeutic procedures randomly applied by lot: kinesiotherapy, kinesiotherapy + functional compressive bandaging (FCB), kinesiotherapy + elastic compression (EC). Blood flow, including mean and maximum velocity, was assessed by Doppler ultrasound before and after therapeutic procedure (immediately after, 15 and 30 minutes). We used 2-way analysis of variance for repeated measures followed by Bonferroni\'s test, considering a significance level of 5%. Results: The EC and FCB groups showed significant increase in the mean velocity of blood flow of the axillary and brachial arteries and veins when compared to the group that received only kinesiotherapy (p<0.05). When made comparisons between the EC and FCB groups, there was no significant difference (p>0.05). Regarding to the maximum velocity the EC and FCB groups showed greater increase of the maximum velocity of blood flow in the brachial artery (p<0.05) when compared to the group that received only kinesiotherapy, but no difference between them (p>0.05). Conclusion: The elastic compression and functional compressive bandaging associated to kinesiotherapy produce increased blood flow of upper limb lymphedema

O sinal de fluxo cutâneo obtido via fluxometria Laser Doppler (SFLD) tem flutuações de baixas frequências que estão relacionadas a mecanismos de controle do fluxo microvascular. Análises espectrais, via transformada de Fourier e transformada de wavelet, têm sido usadas para correlacionar as flutuações de SFLD com os seguintes mecanismos de controle de fluxo: metabólico, metabólico NO-dependente, neurogênico e miogênico, nos respectivos intervalos de frequência 0,005-0,0095 Hz, 0,0095-0,02 Hz, 0,02-0,05 Hz e 0,05-0,15 Hz. A potência do sinal, em cada intervalo de frequência, geralmente é usada como uma medida da atividade do mecanismo de controle microvascular relacionado. Uma vez que os métodos usados de análise são espectrais, as características das flutuações do SFLD, em cada intervalo de frequência, no domínio do tempo são desconhecidas. Como consequência, há ausência de critérios objetivos para medir adequadamente, em cada intervalo de frequência, os parâmetros hemodinâmicos relacionados. O objetivo deste trabalho foi caracterizar e quantificar flutuações temporais, espaciais e espaço-temporais do SFLD em cada faixa de frequência, usando um método no domínio do tempo. Os fluxos basais (320C) e termicamente estimulados à (420C) das regiões volares de antebraços de 20 voluntários saudáveis foram coletados em duas regiões próximas e analisados. As análises dos dados obtidos indicam que janelas temporais pequenas (1 minuto) são aceitáveis para a quantificação do fluxo médio, e que janelas temporais maiores são necessários para quantificar as flutuações de fluxo. A análise espaço-temporal revelou uma forte correlação entre sinais (em todas as bandas, exceto na banda B5) das duas regiões investigadas, durante longos intervalos de tempo, quando as duas regiões estudadas foram termicamente estimuladas, e menor variabilidade intragrupo quando comparada à obtida para os valores médios das flutuações, sugerindo que o intervalo de tempo de correlação é um parâmetro promissor para estudar mecanismos de controle do fluxo microvascular. / The laser Doppler flow signal from the skin (LDFS) has low-frequency fluctuations which are related to microvascular mechanisms of flow control. The Fourier and the wavelet spectral analysis has been used to correlate fluctuations in the LDFS with the metabolic, metabolic NO-dependent, neurogenic and myogenic mechanisms of control in the frequency intervals 0.005-0.0095 Hz, 0.0095-0.02 Hz, 0.02-0.05 Hz and 0.05-0.15 Hz, respectively. The signal power, in each frequency interval, is generally used as a measure of the activity of the related mechanism of microvascular control. Since spectral analysis methods have been used, the time-domain characteristics of the fluctuations in the LDFS in each frequency interval are unknown. As a consequence, there is a lack of objective criteria to properly measure, in each frequency interval, the related hemodynamic parameters. The aim of this work was characterizing and quantifying temporal, spatial and spatial-temporal fluctuations in the LDFS in each frequency band, using a time-domain method. Baseline (320C) and thermally stimulated (420C) LDFS of volar forearms from 20 healthy volunteers were collected from two close regions and analyzed. The data obtained indicate that short-time windows (1 minute) are acceptable for quantifying the mean flow, and that larger time-windows are needed for quantifying the flow fluctuations. The spatialtemporal analysis revealed strong correlations between signals (all bands, except B5) from the two investigated regions, during large time intervals when thermally stimulated, and lower intragroup variability than the ones obtained for the mean values of fluctuations, suggesting that the time interval of correlation is a promising parameter for studying mechanisms of microvascular flow control.

Made available in DSpace on 2014-06-11T19:24:48Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-02-29Bitstream added on 2014-06-13T19:06:39Z : No. of bitstreams: 1 lima_sg_me_bauru.pdf: 696120 bytes, checksum: fd461774d6acd3a1375e66216adb687f (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Muitas das vezes, o Ensino de Ciências e Biologia não apresenta os determinantes e contextos que estão envolvidos na construção de um conceito, mostrando-o de modo dogmático e memorístico. A perpetuação deste modelo deve-se, principalmente, ao processo de formação dos atuais professores, e a forma como o conteúdo presente no material didático utilizado por estes é apresentado. Visto que os conceitos são construídos de forma lenta, gradual, com avanços e recuos, pois expressam as tentativas de argumentação elaboradas ao longo da história; os fatores no Ensino de Ciências e Biologia acima citados tornam-se obstáculos para a inserção da História da Ciência no Ensino de Ciências e Biologia. O processo de construção dos conceitos sobre circulação sanguínea não expressa tentativa de entendimento do movimento do sangue no corpo humano. Além disso, o levantamento e pesquisa bibliográfica que realizamos caracteriza de forma exemplar, a construção de uma explicação científica e a influência do contexto social e religioso na produção de um conhecimento científico e, também, a resistência às mudanças por parte principalmente de indivíduos respeitados da época, evidenciam os percalços pelos quais a ciência passa. Enfrentamos diversas dificuldades ao realizar esse levantamento e pesquisa bibliográfica. Entre algumas, podemos citar a dificuldade de acesso às fontes primárias, barreiras lingüísticas e problemas na interpretação dos determinantes históricos. Essas barreiras são também enfrentadas por autores de livros didáticos e professores que desejam inserir a História da Ciência, respectivamente, no material didático e na prática docente. Assim, esse trabalho tem por objetivo produzir um texto didático para o ensino, apontando o dinamismo e a não neutralidade da ciência e, com isso... / Frequently, Science and Biology teaching does not present the determinants and contexts involved in the building of a concept, showing it so dogmatic and rote. The perpetuation of such a model is due, mainly, to the process of training of current teachers, and how the content in the teaching material used by them is presented. Since the concepts are built on a slow, gradual, with advances and setbacks, because attempts to express the arguments made throughout history, factors in the Teaching of Science and Biology mentioned above become obstacles to the insertion of the History of Science in the Teaching of Science and Biology. The process of concepts construction expressed on blood circulation does not attempt to understanding the movement of blood in the human body. Moreover, the lifting and literature search conducted in this study features in an exemplary fashion, the construction of a scientific explanation and the influence of social and religious context in the production of scientific knowledge and also the resistance to change, mainly from respected individuals of the time , highlighting the mishaps faced by science. Various difficulties were faced to achieve this survey and literature search. Among some, we can cite the difficulty of access to primary sources, language barriers and problems in the interpretation of historical determinants. These barriers are also faced by authors of textbooks and teachers who wish to enter the History of Science, respectively, in the educational materials and teaching practice. Thus, this work aims to produce a teaching text for teaching, indicating the dynamism and non-neutrality of science and thereby, helping to minimize some of the difficulties found in integrating the History of Science in Science and Biology teaching.