scholarly journals PKCα Activates eNOS and Increases Arterial Blood Flow In Vivo

2005 ◽  
Vol 97 (5) ◽  
pp. 482-487 ◽  
Author(s):  
Chohreh Partovian ◽  
Zhenwu Zhuang ◽  
Karen Moodie ◽  
Michelle Lin ◽  
Noriyuki Ouchi ◽  
...  
Keyword(s):  
Blood Flow ◽  
Arterial Blood Flow ◽  
Arterial Blood

Abstract 249: Delayed Gene Transfer Increases Transgene Expression in Vein Grafts

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Liang Du ◽  
Jingwan Zhang ◽  
Alexander Clowes ◽  
David Dichek
Keyword(s):  
Gene Expression ◽  
Blood Flow ◽  
Gene Transfer ◽  
Transgene Expression ◽  
Ex Vivo ◽  
Arterial Blood Flow ◽  
Vein Grafts ◽  
Arterial Blood ◽  
En Face

Background Autogenous vein grafts are effective therapies for obstructive arterial disease. However, their long-term utility is limited by stenosis and occlusion. Genetic engineering of veins that prevents intimal hyperplasia and atherosclerosis could significantly improve the clinical utility of vein grafts. We recently reported that a helper-dependent adenoviral vector (HDAd) reduces atherosclerosis 4 wks after gene transfer in fat-fed rabbits and can express a therapeutic transgene (apo AI) in normal rabbit carotids for at least 48 wks. Use of HDAd for vein graft gene therapy will depend on achievement of similarly high and persistent transgene expression in grafted veins. Hypothesis We tested the hypothesis that Ad-mediated transgene expression in grafted veins (at an early time point) can be increased by varying the timing of gene transfer. Methods Rabbit external jugular veins were transduced by exposure to a beta galactosidase (b-gal)-expressing Ad: in situ either without (a) or with (b) immediate arterial grafting; c) ex vivo with grafting after overnight incubation with Ad; d) in vivo immediately after grafting and e) in vivo 4 wks after grafting (n = 6 - 19 veins/group). Transgene expression was measured in veins removed 3 d after Ad exposure by PCR quantitation of b-gal mRNA and by en-face planimetry of blue-stained area. Results B-gal transgene expression was higher in ungrafted veins than in veins grafted immediately after gene transfer (84 ± 17 vs 9.4 ± 2.0 arbitrary units (AU); P < 0.0001). Overnight incubation of veins with Ad increased gene expression ex vivo by 10-fold but neither this nor performing vector infusion immediately after grafting improved gene expression (11 ± 4.7 and 9.1 ± 1.8 AU; P > 0.9 for both vs immediately grafted veins). Delaying gene transfer until 4 wks after grafting significantly increased gene expression, to a level equivalent to transgene expression in ungrafted veins (61 ± 11 AU; P = 0.3 vs ungrafted veins). En face planimetry yielded similar results. Conclusions Exposure of a transduced vein to arterial blood flow is associated with significant loss of transgene expression. Transgene expression in grafted veins is significantly higher when gene transfer is performed 4 wks after exposure of the vein to arterial blood flow.

Spiral Laminar Flow in Vivo

1996 ◽  
Vol 91 (1) ◽  
pp. 17-21 ◽  
Author(s):  
P. A. Stonebridge ◽  
P. R. Hoskins ◽  
P.L. Allan ◽  
J. F. F. Belch
Keyword(s):  
Blood Flow ◽  
Reverse Flow ◽  
Arterial Disease ◽  
Flow Patterns ◽  
Endothelial Damage ◽  
Arterial Blood Flow ◽  
Arterial Tree ◽  
Arterial Blood ◽  
Blood Flow Patterns

1. Blood flow patterns are poorly understood despite their impact on arterial disease. There have been few measurements in vivo of the three-dimensional blood flow patterns; we present the results of such studies using a new non-invasive in-vivo method of examining biplanar arterial blood flow patterns. 2. Multiple colour Doppler ultrasound directional velocity images were obtained at two different beam target angles from the artery in the plane perpendicular to its axis. Ensemble average images were constructed; the absolute velocity and direction were calculated by compounding the left and right averaged images. Simple directional, non-directional velocity and vector maps were constructed. 3. Flow patterns were sampled in 11 healthy male volunteers at four points of the pulse cycle; peak systole, systolic downswing, diastolic reverse flow and diastolic forward flow and at three sites; the right common and distal superficial femoral and the left common femoral arteries. 4. Stable rotational flow was observed in all subjects, the direction of rotation varying between sides and individuals. 5. There are theoretical advantages to spiral laminar blood flow; the forward-directed, rotationally induced stability and reduction of laterally directed forces may reduce turbulence in the tapering branching arterial tree and at stenoses and have a beneficial effect on mechanisms of endothelial damage and repair.

scholarly journals Endothelial miR-17∼92 cluster negatively regulates arteriogenesis via miRNA-19 repression of WNT signaling

2015 ◽  
Vol 112 (41) ◽  
pp. 12812-12817 ◽  
Author(s):  
Shira Landskroner-Eiger ◽  
Cong Qiu ◽  
Paola Perrotta ◽  
Mauro Siragusa ◽  
Monica Y. Lee ◽  
...  
Keyword(s):  
Blood Flow ◽  
Wnt Signaling ◽  
Critical Role ◽  
Arterial Blood Flow ◽  
In Vivo Model ◽  
Mirna Regulation ◽  
Arterial Blood ◽  
Specific Deletion

The contribution of endothelial-derived miR-17∼92 to ischemia-induced arteriogenesis has not been investigated in an in vivo model. In the present study, we demonstrate a critical role for the endothelial-derived miR-17∼92 cluster in shaping physiological and ischemia-triggered arteriogenesis. Endothelial-specific deletion of miR-17∼92 results in an increase in collateral density limbs and hearts and in ischemic limbs compared with control mice, and consequently improves blood flow recovery. Individual cluster components positively or negatively regulate endothelial cell (EC) functions in vitro, and, remarkably, ECs lacking the cluster spontaneously form cords in a manner rescued by miR-17a, -18a, and -19a. Using both in vitro and in vivo analyses, we identified FZD4 and LRP6 as targets of miR-19a/b. Both of these targets were up-regulated in 17∼92 KO ECs compared with control ECs, and both were shown to be targeted by miR-19 using luciferase assays. We demonstrate that miR-19a negatively regulates FZD4, its coreceptor LRP6, and WNT signaling, and that antagonism of miR-19a/b in aged mice improves blood flow recovery after ischemia and reduces repression of these targets. Collectively, these data provide insights into miRNA regulation of arterialization and highlight the importance of vascular WNT signaling in maintaining arterial blood flow.

scholarly journals Oxygen-limited thermal tolerance in Antarctic fish investigated by MRI and 31P-MRS

2002 ◽  
Vol 283 (5) ◽  
pp. R1254-R1262 ◽  
Author(s):  
F. C. Mark ◽  
C. Bock ◽  
H. O. Pörtner
Keyword(s):  
Blood Flow ◽  
Thermal Tolerance ◽  
Ph Regulation ◽  
Antarctic Fish ◽  
Blood Oxygenation ◽  
Arterial Blood Flow ◽  
Aerobic Scope ◽  
Arterial Blood ◽  
Cardiovascular Capacity

The hypothesis of an oxygen-limited thermal tolerance was tested in the Antarctic teleost Pachycara brachycephalum. With the use of flow-through respirometry, in vivo31P-NMR spectroscopy, and MRI, we studied energy metabolism, intracellular pH (pHi), blood flow, and oxygenation between 0 and 13°C under normoxia (Po 2: 20.3 to 21.3 kPa) and hyperoxia (Po 2: 45 kPa). Hyperoxia reduced the metabolic increment and the rise in arterial blood flow observed under normoxia. The normoxic increase of blood flow leveled off beyond 7°C, indicating a cardiovascular capacity limitation. Ventilatory effort displayed an exponential rise in both groups. In the liver, blood oxygenation increased, whereas in white muscle it remained unaltered (normoxia) or declined (hyperoxia). In both groups, the slope of pHi changes followed the alpha-stat pattern below 6°C, whereas it decreased above. In conclusion, aerobic scope declines around 6°C under normoxia, marking the pejus temperature. By reducing circulatory costs, hyperoxia improves aerobic scope but is unable to shift the breakpoint in pH regulation or lethal limits. Hyperoxia appears beneficial at sublethal temperatures, but no longer beyond when cellular or molecular functions become disturbed.

Doxorubicin-induced vascular toxicity: Targeting potential pathways to reduce procoagulant activity.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13080-e13080
Author(s):  
Hadas Bar-Joseph ◽  
Irit Ben-Aharon ◽  
Moran Tzabari ◽  
Naftaly Savion ◽  
Ruth Shalgi ◽  
...  
Keyword(s):  
Blood Flow ◽  
Real Time ◽  
Platelet Adhesion ◽  
Platelet Rich Plasma ◽  
Fold Increase ◽  
Acute Effect ◽  
Arterial Blood Flow ◽  
Vascular Toxicity ◽  
Arterial Blood

e13080 Background: In a former study in mice using the gonads as an end-organ prototype, we have characterized by real-time intravital imaging an acute deleterious effect of doxorubicin (DXR) on the gonadal vasculature, manifested by a reduction in blood flow and disintegration of the vessel wall. We hypothesized this pattern may represent the formation of microthrombi. We aimed to further characterize the effect of DXR on platelets’ function and to use potentially protectants to reduce DXR acute effect on the blood flow. Methods: 100 µg/mouse 24 hours and 1 hour prior to DXR treatment (8 mg/kg), or with eptifibatide (integrilin,75µg/mouse) 90min prior to DXR treatment. Testicular arterial blood flow was examined in real-time by pulse wave Doppler ultrasound. Platelet adhesion to confluent endothelial cells (EC) was evaluated following exposure of EC to DXR (100 µM) for 4h followed by exposure to whole blood under defined shear rates. Fixed platelets were immunostained by anti- CD41a antibody. DXR effect on platelet adhesion was determined by pre-incubation of platelet rich plasma for 15min with increasing concentrations of DXR and induction of aggregation by ADP. For in vivo study, mice were injected with either LMWH (Enoxaparin; Clexane). Results: There was a significant 3.6-fold increase in platelet adhesion to DXR-exposed EC (p<0.002) reflecting the toxic effect of DXR on EC. Yet, significant DXR- dose dependent decrease in platelet aggregation was observed reaching up to 40% inhibition at 100 µM (p<0.001). Testicular arterial blood flow was preserved as a result of pre-treatment with LMWH or eptifibatide prior to DXR (P<0.01). Conclusions: DXR-induced acute vascular toxicity may trigger the coagulation pathway while enhancing platelet adhesion yet inhibiting massive aggregation, which result in compromised blood flow due to microthrombi formation. Anti-platelet/anti-coagulant agents appear to be effective in reducing the detrimental effect of DXR on the vasculature.

BOLD indirect vs. ASL direct measurement of muscle perfusion

2005 ◽  
Vol 99 (1) ◽  
pp. 376-377 ◽  
Author(s):  
A. Leroy-Willig
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Maximal Voluntary Contraction ◽  
Venous Occlusion ◽  
Voluntary Contraction ◽  
Arterial Blood Flow ◽  
Muscle Perfusion ◽  
Arterial Blood ◽  
Planar Images

The following is the abstract of the article discussed in the subsequent letter: Although skeletal muscle perfusion is fundamental to proper muscle function, in vivo measurements are typically limited to those of limb or arterial blood flow, rather than flow within the muscle bed itself. We present a noninvasive functional MRI (fMRI) technique for measuring perfusion-related signal intensity (SI) changes in human skeletal muscle during and after contractions and demonstrate its application to the question of occlusion during a range of contraction intensities. Eight healthy men (aged 20–31 yr) performed a series of isometric ankle dorsiflexor contractions from 10 to 100% maximal voluntary contraction. Axial gradient-echo echo-planar images (repetition time = 500 ms, echo time = 18.6 ms) were acquired continuously before, during, and following each 10-s contraction, with 4.5-min rest between contractions. Average SI in the dorsiflexor muscles was calculated for all 240 images in each contraction series. Postcontraction hyperemia for each force level was determined as peak change in SI after contraction, which was then scaled to that obtained following a 5-min cuff occlusion of the thigh (i.e., maximal hyperemia). A subset of subjects ( n = 4) performed parallel studies using venous occlusion plethysmography to measure limb blood flow. Hyperemia measured by fMRI and plethysmography demonstrated good agreement. Postcontraction hyperemia measured by fMRI scaled with contraction intensity up to 60% maximal voluntary contraction. fMRI provides a noninvasive means of quantifying perfusion-related changes during and following skeletal muscle contractions in humans. Temporal changes in perfusion can be observed, as can the heterogeneity of perfusion across the muscle bed.

MRI measures of perfusion-related changes in human skeletal muscle during progressive contractions

2004 ◽  
Vol 97 (6) ◽  
pp. 2385-2394 ◽  
Author(s):  
D. M. Wigmore ◽  
B. M. Damon ◽  
D. M. Pober ◽  
J. A. Kent-Braun
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Maximal Voluntary Contraction ◽  
Human Skeletal Muscle ◽  
Venous Occlusion ◽  
Voluntary Contraction ◽  
Arterial Blood Flow ◽  
Arterial Blood ◽  
Planar Images

Although skeletal muscle perfusion is fundamental to proper muscle function, in vivo measurements are typically limited to those of limb or arterial blood flow, rather than flow within the muscle bed itself. We present a noninvasive functional MRI (fMRI) technique for measuring perfusion-related signal intensity (SI) changes in human skeletal muscle during and after contractions and demonstrate its application to the question of occlusion during a range of contraction intensities. Eight healthy men (aged 20–31 yr) performed a series of isometric ankle dorsiflexor contractions from 10 to 100% maximal voluntary contraction. Axial gradient-echo echo-planar images (repetition time = 500 ms, echo time = 18.6 ms) were acquired continuously before, during, and following each 10-s contraction, with 4.5-min rest between contractions. Average SI in the dorsiflexor muscles was calculated for all 240 images in each contraction series. Postcontraction hyperemia for each force level was determined as peak change in SI after contraction, which was then scaled to that obtained following a 5-min cuff occlusion of the thigh (i.e., maximal hyperemia). A subset of subjects ( n = 4) performed parallel studies using venous occlusion plethysmography to measure limb blood flow. Hyperemia measured by fMRI and plethysmography demonstrated good agreement. Postcontraction hyperemia measured by fMRI scaled with contraction intensity up to ∼60% maximal voluntary contraction. fMRI provides a noninvasive means of quantifying perfusion-related changes during and following skeletal muscle contractions in humans. Temporal changes in perfusion can be observed, as can the heterogeneity of perfusion across the muscle bed.

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