Arterial pulse pressure is critically important to a number of diseases such as isolated systolic hypertension, coronary artery disease and heart failure. Determining the cause of increased pulse pressure has been hampered for two reasons. First, pulse pressure results from contraction of the heart and the load formed by the complex arterial tree. Pressure pulses travel from the heart to the peripheral arteries. As they reach a bifurcation or change in arterial wall properties, some of the pulses get reflected and propagate retrograde towards the heart. Second, two different modeling approaches (0-D and 1-D) describe the arterial system. The Windkessel model ascribed changes in pulse pressure to changes in total arterial compliance (Ctot) and total arterial resistance, whereas the transmission model ascribed them to changes in the magnitude, timing and sites of reflection. Our investigation has addressed both these limitations by finding that a complex arterial system degenerates into a simple 2-element Windkessel model when wavelength of the propagated pulse increases. This theoretical development has yielded three practical results. First, isolated systolic hypertension can be viewed as a manifestation of a system that has degenerated into a Windkessel, and thus increased pulse pressure is due to decreased Ctot. Second, the well-discussed Augmentation Index does not truly describe augmentation of pulse pressure by pulse reflection. Third, the simple 2-element Windkessel can be used to characterize the interaction among heart, arterial system and axial-flow left ventricular assist device analytically. The fact that arterial systems degenerate into Windkessels explains why it becomes much easier to estimate total arterial compliance in hypertension?total arterial compliance is the dominant determinant of pulsatile pressure.

名古屋大学博士学位論文 学位の種類 : 博士(医学)(論文) 学位授与年月日:平成5年1月28日 平山正昭氏の博士論文として提出された

Magnetic resonance imaging is often used as a source for reconstructing vascular anatomy for the purpose of computational fluid dynamics (CFD) analysis. We recently observed large discrepancies in such “image-based” CFD models of the normal common carotid artery (CCA) derived from contrast enhanced MR angiography (CEMRA). A novel quantitative comparison of velocity profile shape of N=20 cases revealed an average 25% overestimation of velocities by CFD, attributed to a corresponding underestimation of lumen area in the CEMRA-derived geometries. We hypothesized that this was due to blurring of edges in the images caused by dilution of contrast agent during the relatively long elliptic centric CEMRA acquisitions, and confirmed this with MRI simulations. CFD simulations incorporating realistic inlet velocity profiles and non-Newtonian rheology had a negligible effect on velocity profile skewing, suggesting a role for other sources of error or modeling assumptions.

Magnetic resonance imaging is often used as a source for reconstructing vascular anatomy for the purpose of computational fluid dynamics (CFD) analysis. We recently observed large discrepancies in such “image-based” CFD models of the normal common carotid artery (CCA) derived from contrast enhanced MR angiography (CEMRA). A novel quantitative comparison of velocity profile shape of N=20 cases revealed an average 25% overestimation of velocities by CFD, attributed to a corresponding underestimation of lumen area in the CEMRA-derived geometries. We hypothesized that this was due to blurring of edges in the images caused by dilution of contrast agent during the relatively long elliptic centric CEMRA acquisitions, and confirmed this with MRI simulations. CFD simulations incorporating realistic inlet velocity profiles and non-Newtonian rheology had a negligible effect on velocity profile skewing, suggesting a role for other sources of error or modeling assumptions.

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No description available.

<p>The vascular contribution to tumor radiation response is controversial, but may have profound clinical implications. This is especially true of a new class of radiation therapies which employ spatial fractionation techniques--high radiation doses delivered in a spatially modulated pattern across the tumor. Window chamber tumor models may prove useful in investigating vascular parameters due to their facilitation of non-invasive, serial measurements of living tumors. However, presently there do not exist automated and accurate algorithms capable of quantitatively analyzing window chamber data.</p><p>Here we attempt to address these two problems through (1) the generation of novel optical data processing techniques for the quantification of vascular structural and functional parameters, and (2) the application of these methods to the study of vascular radiation effects in window chamber models.</p><p>Results presented here demonstrate the versatility and functionality of the data processing methods that we have developed. In the first part of Aim 1, we have developed a vessel segmentation algorithm specifically designed for processing tumor vessels, which present a challenge to existing algorithms due to their highly branching, tortuous structure. This provides us with useful information on vascular structural parameters. In the second part of Aim 1, we demonstrate a complementary vascular functional analysis algorithm, which generates quantitative maps of speed and direction. We prove the versatility of this method by applying it to a number of different studies, including hemodynamic analysis in the dorsal window chamber, the pulmonary window, and after neural electro-stimulation. Both the structural and functional techniques are shown capable of generating accurate and unbiased vascular structural and functional information. Furthermore, that automated nature of these algorithms allow for the rapid and efficient processing of large data sets. These techniques are validated against existing techniques.</p><p>The application of these methods to the study of vascular radiation effects produced invaluable quantitative data which suggest startling tumor adaptations to radiation injury. Window chamber grown tumors were treated with either widefield, microbeam, or mock irradiation. After microbeam treatment, we observed a profound angiogenic effect within the radiation field, and no signs of vascular disruption. Upregulation of HIF-1, primarily in the tumor rim, suggested that this response may have been due to bystander mechanisms initiated by oxidative stress. This HIF-1 response may have also initiated an epithelial-mesenchymal transition in the cells of the tumor rim, as post-treatment observation revealed evidence of tumor cell mobilization and migration away from the primary tumor to form secondary satellite clusters. These data indicate the possibility of significant detrimental effects after microbeam treatment facilitated through a HIF-1 response.</p> / Dissertation

Altered cerebral hemodynamics contributes to mechanisms of unexplained syncope. Wecompared dynamic interaction between respiration and cerebral autoregulation in two groups ofsubjects from 28 healthy adults. Based on development of tilt-induced presyncope, subjects wereclassified as Non-Presyncopals (n=23) and Presyncopals (n=5). Airflow, CO2, Doppler cerebralblood flow velocity (CBF), ECG and blood pressure (BP) were recorded. To determine whetherinfluences of mean BP (MBP) and systolic BP (SBP) on CBF were altered in Presyncopals, thecoherencies and transfer functions between these variables and mean and peak CBF (CBFm andCBFp) were estimated. To determine influence of end-tidal CO2 (ETCO2) on CBF, relative CO2reactivity was calculated. The two primary findings were, during tilt in Presyncopals: (1) Inrespiratory frequency region, coherence between SBP and CBFp (p=0.02) and transfer functiongain between BP and CBFm was higher (MBP, p=0.01, and SBP, p=0.01) than in Non-Presyncopals. (2) In the last 3 minutes prior to presyncope, Presyncopals had a reduced relativeCO2 reactivity (p=0.005). Thus the relationship of CBF with systemic BP was more pronouncedor cerebral autoregulation was less effective preceding presyncope. This decreasedautoregulation, secondary to decreased ETCO2, may contribute in the cascade of events leadingto unexplained syncope.

Hemodinamikos pokyčiai kepenų operacijų metu yra svarbūs perioperacinėms išeitims. Tyrimo tikslas: išsiaiškinus hemodinaminių pokyčių pobūdį bei priežastis parinkti optimalią pacientų monitoravimo metodiką darant kepenų rezekci¬nes operacijas. Tikslui pasiekti iškelti šie uždaviniai: palyginti širdies minutinio tūrio monitoravimo neinvaziniu impe¬dan¬so kardiografijos būdu vertę su invaziniu intermituojančios termodiliucijos būdu pacientams, kuriems daromos kepenų rezek¬cijos, nustatyti dažniausiai kintančius hemodinaminius parametrus kepe¬nų operacijų metu, nustatyti hemodinaminių rodiklių pokyčių priežastis, rasti hemodinaminius veiksnius, įtakojančius didesnį kraujo nete¬kimą operacijos metu. Remiantis tyrimo rezultatais, daromos šios išvados: siekiant sumažinti perioperacinį sergamumą ir mirštamumą darant kepenų rezekcijas būtina monitoruoti centrinės hemodinamikos ro¬dik¬lius. Širdies minutinio tūrio monitoravimui tinka saugus, nebrangus ir tikslus neinvazinis impedanso kardiografijos metodas. Kepenų rezekcinių operacijų metu stebimi hemodinaminiai pokyčiai yra vidurinio arterinio kraujo spaudimo sumažėjimas (hipotenzija), susijęs su širdies indekso su¬ma¬žėjimu, ir slėgio apatinėje tuščiojoje venoje padidėjimas. Hipotenzijos bei širdies indekso sumažėjimo priežastis dažniau yra apatinės tuščiosios venos perspaudimas, pasireiškiantis didėjančiu slėgiu šlaunies venoje, kurį sąlygoja chirurginės manipuliacijos. Hipotenzijos priežastį kepenų rezekcinių operacijų metu galima... [toliau žr. visą tekstą] / Aim of the study: select optimal methods for patient’s monitoring du¬ring hepatic resection after evaluation the character, causes and rate of hemodynamic changes. Main goals: to compare the value of non-invasive impedance cardiography for moni¬toring of cardiac output to invasive intermittent thermodilution method in patients undergoing hepatic resection, to determine mostly changing hemodynamic parameters during the hepatic surgery, to determine the causes of hemodynamic changes, to determine hemodynamic factors, influencing increase in blood loss during the surgery. Conclusions: non-invasive ICG method may be used to monitor cardiac output during the hepatic resection surgery, most common hemodynamic changes during hepatic resection surgery include the reduction in mean arterial blood pressure (hypotension), decreased cardiac index, and elevated pressure in the inferior vena cava, more common cause of hypotension is clamping of the inferior vena cava, which is caused by surgical manipulations; less common – blood loss. Cause of hypotension during hepatic resection surgery may be determined by pressure monitoring in the superior and inferior vena cava, blood loss is related to the number of clamping of the inferior vena cava and increasing pressure in the superior vena cava. Practical recommendations: in order to reduce the number of hemodynamic changes during the surgery, it is essential to monitor arterial blood pressure, cardiac output and pressures in the superior and... [to full text]

Atherosclerosis is a chronic inflammatory disease of arterial blood vessels, characterized by deposition of lipoproteins in the arterial wall. Atherosclerotic plaques form preferentially in distinct regions of the vasculature such as branch points, curvatures and bifurcations, suggesting that local hemodynamic forces may contribute to disease susceptibility. Shear stress imparted on endothelial cells (ECs) by the flowing blood has been shown to modulate gene expression and remodelling of the artery. In this thesis, an in vitro model was established to recreate the contrasting environments found in atherosclerosis-prone and atherosclerosis-resistant regions of the vasculature to demonstrate a direct causal-relationship between shear stress and expression of endothelial nitric oxide synthase (eNOS) and p65 in ECs. In vitro assessment of cell shape and expression patterns of these anti- and atherogenic genes demonstrated that shear stress can induce cell morphology and gene expression patterns that are similar to ECs in atherosclerosis-prone and atherosclerosis-resistant regions of the mouse vasculature. Regulation of eNOS transcription by shear stress was demonstrated using a transgenic mouse model and in vitro heterogeneous nuclear RNA (hnRNA) quantification. Similar to ECs in atherosclerosis-prone regions, epithelial cells lining the small intestine lumen express high levels of p65. To investigate the effects of p65 expression levels on constitutive and tumour necrosis factor α (TNFα)-induced nuclear factor-κB (NF-κB) signalling, p65 expression was suppressed in HeLa cells by RNA interference. Lower p65 expression resulted in reduced TNFα-induced expression of NF-κB target genes, including many subunits of inhibitor of nuclear factor κB (IκB), demonstrating modulation of NF-κB priming by p65 expression levels. Suppression of p65 also affected constitutive expression levels of IκB, and resulted in re-setting of the NF-κB/IκB equilibrium. Experiments using inhibitors of canonical NF-κB signalling found that basal expression of NF-κB components is independent of nuclear factor κB kinase β (IKKβ) activity and proteasome-mediated degradation of IκBα. Together, these studies elucidate the mechanism of flow-mediated gene regulation and the effect of resulting changes in p65 expression on NF-κB signalling.