Cinthio, Magnus, Å sa Rydén Ahlgren, Jonas Bergkvist, Tomas Jansson, Hans W. Persson, and Kjell Lindström. Longitudinal movements and resulting shear strain of the arterial wall. Am J Physiol Heart Circ Physiol 291: H394 -H402, 2006. First published February 10, 2006 doi:10.1152/ajpheart.00988.2005.-There has been little interest in the longitudinal movement of the arterial wall. It has been assumed that this movement is negligible compared with the diameter change. Using a new high-resolution noninvasive ultrasonic method, we measured longitudinal movements and diameter change of the common carotid artery of 10 healthy humans. During the cardiac cycle, a distinct bidirectional longitudinal movement of the intimamedia complex could be observed in all the subjects. An antegrade longitudinal movement, i.e., in the direction of blood flow, in early systole [0.39 mm (SD 0.26)] was followed by a retrograde longitudinal movement, i.e., in the direction opposite blood flow [Ϫ0.52 mm (SD 0.27)], later in systole and a second antegrade longitudinal movement [0.41 mm (SD 0.33)] in diastole. The corresponding diameter change was 0.65 mm (SD 0.19). The adventitial region showed the same basic pattern of longitudinal movement; however, the magnitude of the movements was smaller than that of the intimamedia complex, thereby introducing shear strain and, thus, shear stress within the wall [maximum shear strain between the intima-media complex and the adventitial region was 0.36 rad (SD 0.26). These phenomena have not previously been described. Measurements were also performed on the abdominal aorta (n ϭ 3) and brachial (n ϭ 3) and popliteal (n ϭ 3) arteries. Our new information seems to be of fundamental importance for further study and evaluation of vascular biology and hemodynamics and, thus, for study of atherosclerosis and vascular diseases. carotid artery; vascular mechanics; arterial wall movements; shearing strain in arteries; vascular ultrasound IN CARDIOVASCULAR RESEARCH, radial movement of the arterial wall, i.e., diameter change, has been the subject of extensive research. Measurement of radial movements of arteries is an established tool in cardiovascular research (8,13,17,23), forming the basis for estimation of arterial wall stiffness. Increased stiffness of large central arteries has recently been shown to be an independent risk factor for cardiovascular mortality (4). In contrast to radial movements, there has been little interest in longitudinal movements of the arterial wall, i.e., along the vessel. It has been assumed that the longitudinal movement of the arterial wall during the cardiac cycle is negligible compared with the radial movement (21). Longitudinal movement of the arterial wall has not been studied, because, until the most recent improvements in ultrasound systems, it has not been possible to detect longitudinal movement in vivo. In the 1950s, using cinematographic observations of beads sutured to the surface of exposed vessels, Lawton and Greene (15) measured the longitudinal movement of the abd...
BackgroundCerebral intraventricular hemorrhage (IVH) is a major cause of severe neurodevelopmental impairment in preterm infants. To date, no therapy is available that prevents infants from developing serious neurological disability following IVH. Thus, to develop treatment strategies for IVH, it is essential to characterize the initial sequence of molecular events that leads to brain damage. In this study, we investigated extracellular hemoglobin (Hb) as a causal initiator of inflammation in preterm IVH.MethodsUsing a preterm rabbit pup model, we investigated the molecular mechanisms and events following IVH. We also characterized the concentrations of cell-free Hb metabolites and pro-inflammatory mediators in the cerebrospinal fluid (CSF) of preterm human infants and rabbit pups. Finally, Hb metabolites were evaluated as causal initiators of inflammation in primary rabbit astrocyte cell cultures.ResultsFollowing IVH in preterm rabbit pups, the intraventricular CSF concentration of cell-free methemoglobin (metHb) increased from 24 to 72 hours and was strongly correlated with the concentration of TNFα at 72 hours (r2 = 0.896, P <0.001). Also, the mRNA expression of TNFα, IL-1β, and Toll-like receptor-4 and TNFα protein levels were significantly increased in periventricular tissue at 72 hours, which was accompanied by extensive astrocyte activation (that is, glial fibrillary acidic protein (GFAP)staining). Furthermore, exposure of primary rabbit astrocyte cell cultures to metHb caused a dose-dependent increase in TNFα mRNA and protein levels, which was not observed following exposure to oxyhemoglobin (oxyHb) or hemin. Finally, a positive correlation (r2 = 0.237, P <0.03) between metHb and TNFα concentrations was observed in the CSF of preterm human infants following IVH.ConclusionsFollowing preterm IVH, increased metHb formation in the intraventricular space induces expression of pro-inflammatory cytokines. Thus, the formation of metHb might be a crucial initial event in the development of brain damage following preterm IVH. Accordingly, removal, scavenging, or neutralization of Hb could present a therapeutic opportunity and plausible approach to decreasing the damage in the immature brain following preterm IVH.
BackgroundIntraventricular hemorrhage (IVH) with post-hemorrhagic ventricular dilatation (PHVD) is a major cause of neurodevelopmental impairment and mortality in preterm infants. The mechanisms leading to PHVD and brain damage remain largely unknown. The choroid plexus and the ependyma, which constitute an essential part of the blood-brain barrier (BBB), are the first structures to encounter the damaging effects of extravasated blood. The breakdown of the BBB is a critical upstream event leading to brain damage following IVH. In this study we investigated the impact of hemorrhage and hemoglobin (Hb) metabolites on the choroid plexus epithelium.MethodsUsing a preterm rabbit pup model of IVH, the structural and functional integrity, cellular, inflammatory and oxidative response of the choroid plexus, at 24 and 72 hours following IVH + PHVD, were investigated. In order to further characterize cellular and molecular mechanisms, primary human choroid plexus epithelial cells were exposed to cerebrospinal fluid (CSF) from preterm infants with IVH as well as to Hb-metabolites. Finally, the blocking effects of the Hb-scavenger haptoglobin (Hp) were investigated both in vivo and in vitro.ResultsFollowing IVH + PHVD, an up-regulation of mRNA for the receptor-related genes TLR-4, IL1R1, FAS, the transcription factor NF-Κβ and for the pro-inflammatory and chemotactic effector molecules, IL-1β, TNFα, MCP-1, IL-8, and IL-6 was observed in the choroid plexus at 24 and 72 hours. This was associated with structural disintegration, caspase activation and cell death in the choroid plexus epithelium. In vitro characterization of choroid plexus epithelial cells, following exposure to hemorrhagic CSF and to the Hb-metabolites metHb and heme, displayed apoptotic and necrotic cell death and an up-regulation of receptor-related and inflammatory effector molecules similar to that observed in vivo following IVH + PHVD. Intraventricular injection of the Hb-scavenger Hp in vivo and co-incubation with Hp in vitro reversed or reduced the cellular activation, inflammatory response, structural damage and cell death.ConclusionHb-metabolites are important causal initiators of cell death following IVH and removal or scavenging of Hb-metabolites may present an efficient means to reduce the damage to the immature brain following IVH.
It has recently been demonstrated that superparamagnetic iron oxide nanoparticles can be used as magnetomotive ultrasound contrast agents. A time-varying external magnetic field acts to move the particles and, thus, the nanoparticle-laden tissue. However, the difficulty of distinguishing this magnetomotive motion from undesired movement induced in regions without nanoparticles or other motion artifacts has not been well reported. Using a high-frequency linear-array system, we found that displacements outside nanoparticle-laden regions can be similar in magnitude to those in regions containing nanoparticles. We also found that the displacement outside the nanoparticle regions had a phase shift of approximately π radians relative to that in the nanoparticle regions. To suppress signals arising from undesirable movements, we developed an algorithm based on quadrature detection and phase gating at the precise frequency of nanoparticle displacement. Thus, clutter at other frequencies can be filtered out, and the processed signal can be color-coded and superimposed on the B-mode image. The median signal-to-clutter ratio improvement using the proposed algorithm was 36 dB compared with simply summing the movement energy at all frequencies. This clutter rejection is a crucial step to move magnetomotive ultrasound imaging of nanoparticles toward in vivo investigations.
Current methods for intra-surgical guidance to localize metastases at cancer surgery are based on radioactive tracers that cause logistical challenges. We propose the use of a novel ultrasound-based method, magnetomotive ultrasound (MMUS) imaging that employ a nanoparticle-based contrast agent that also may be used for pre-operative PET/MRI imaging. Since MMUS is radiation free, this eliminates the dependence between pre- and intra-operative imaging and the radiation exposure for the surgical staff. This study investigates a hypothetical clinical scenario of pre-operative PET imaging, combined with intra-operative MMUS imaging, implemented in a sentinel lymph node (SLN) rat model. At one-hour post injection of 68Ga-labelled magnetic nanoparticles, six animals were imaged with combined PET/CT. After two or four days, the same animals were imaged with MMUS. In addition, ex-vivo MRI was used to evaluate the amount of nanoparticles in each single SLN. All SLNs were detectable by PET. Four out of six SLNs could be detected with MMUS, and for these MMUS and MRI measurements were in close agreement. The MRI measurements revealed that the two SLNs undetectable with MMUS contained the lowest nanoparticle concentrations. This study shows that MMUS can complement standard pre-operative imaging by providing bedside real-time images with high spatial resolution.
Ahlgren ÅR, Cinthio M, Steen S, Nilsson T, Sjöberg T, Persson HW, Lindström K. Longitudinal displacement and intramural shear strain of the porcine carotid artery undergo profound changes in response to catecholamines. Am J Physiol Heart Circ Physiol 302: H1102-H1115, 2012. First published December 23, 2011 doi:10.1152/ajpheart.00470.2011The effects of catecholamines on longitudinal displacements and intramural shear strain of the arterial wall are unexplored. Therefore, the common carotid artery of five anaesthetized pigs was investigated using an in-house developed noninvasive ultrasonic technique. The study protocol included intravenous infusion of low-dose epinephrine (-adrenoceptor activation), as well as intravenous boluses of norepinephrine (␣-adrenoceptor activation). Further, the effects of -blockade (metoprolol) were studied. There were significant positive correlations between pulse pressure and longitudinal displacement of the intima-media complex (r ϭ 0.72; P Ͻ 0.001), as well as between pulse pressure and intramural shear strain (r ϭ 0.48; P Ͻ 0.001). Following administration of norepinephrine, the longitudinal displacement of the intimamedia complex and intramural shear strain profoundly increased (median 190%, range 102-296%, and median 141%, range 101-182%, respectively, compared with baseline), also when given during -blockade (median 228%, range 133-266%, and median 158%, range 152-235%, respectively). During infusion of low-dose epinephrine, the longitudinal displacement of the intima-media complex and intramural shear strain decreased (median 88%, range 69 -122%, and median 69%, range 47-117%, respectively, compared with baseline). In conclusion, the present study shows, for the first time, that the longitudinal displacement and intramural shear strain of the porcine carotid artery undergo profound changes in response to catecholamines. Increase in longitudinal displacements seems to be strongly related to ␣-adrenoceptor activation. Thus metoprolol is insufficient to counteract a profound increase in longitudinal displacement and intramural shear strain following a surge of norepinephrine. longitudinal movements; epinephrine; norepinephrine; metoprolol; vascular mechanics; ultrasound CARDIOVASCULAR DISEASE IS a leading cause of morbidity and mortality in the industrialized countries. Mental stress is considered a risk factor for cardiovascular disease both acutely, following strong emotional stress, and chronically. The mechanisms behind this association still remain unclear.In cardiovascular research, the radial movement of the arterial wall, the diameter change, has been the subject of extensive research; measurement of the diameter change of arteries is now an established tool in cardiovascular research (2,21,26), forming the basis for estimation of arterial wall stiffness. Increased stiffness of large central arteries has been shown to be an independent risk factor for cardiovascular mortality (5, 19). In contrast, there are few studies on the longitudinal movement of the arterial wa...
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