scholarly journals Blood Flow Within Bioengineered 3D Printed Vascular Constructs Using the Porcine Model

2021 ◽  
Vol 8 ◽  
Author(s):  
Nhu Thao N. Galván ◽  
Samantha J. Paulsen ◽  
Ian S. Kinstlinger ◽  
Juan C. Marini ◽  
Inka C. Didelija ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cell Function ◽  
Arteriovenous Shunt ◽  
Vascular Connection ◽  
Glycol Diacrylate ◽  
Surgical Model ◽  
Arterial Blood ◽  
Engineered Tissues ◽  
3D Printed

Recently developed biofabrication technologies are enabling the production of three-dimensional engineered tissues containing vascular networks which can deliver oxygen and nutrients across large tissue volumes. Tissues at this scale show promise for eventual regenerative medicine applications; however, the implantation and integration of these constructs in vivo remains poorly studied. Here, we introduce a surgical model for implantation and direct in-line vascular connection of 3D printed hydrogels in a porcine arteriovenous shunt configuration. Utilizing perfusable poly(ethylene glycol) diacrylate (PEGDA) hydrogels fabricated through projection stereolithography, we first optimized the implantation procedure in deceased piglets. Subsequently, we utilized the arteriovenous shunt model to evaluate blood flow through implanted PEGDA hydrogels in non-survivable studies. Connections between the host femoral artery and vein were robust and the patterned vascular channels withstood arterial pressure, permitting blood flow for 6 h. Our study demonstrates rapid prototyping of a biocompatible and perfusable hydrogel that can be implanted in vivo as a porcine arteriovenous shunt, suggesting a viable surgical approach for in-line implantation of bioprinted tissues, along with design considerations for future in vivo studies. We further envision that this surgical model may be broadly applicable for assessing whether biomaterials optimized for 3D printing and cell function can also withstand vascular cannulation and arterial blood pressure. This provides a crucial step toward generated transplantable engineered organs, demonstrating successful implantation of engineered tissues within host vasculature.

Red cell function at extreme altitude on Mount Everest

1984 ◽  
Vol 56 (1) ◽  
pp. 109-116 ◽  
Author(s):  
R. M. Winslow ◽  
M. Samaja ◽  
J. B. West
Keyword(s):  
Cell Function ◽  
Blood Gases ◽  
Hemoglobin Concentration ◽  
Respiratory Alkalosis ◽  
Blood Collection ◽  
Red Cell ◽  
Arterial Blood ◽  
Extreme Altitude ◽  
2,3 Dpg

As part of the American Medical Research Expedition to Everest in 1981, we measured hemoglobin concentration, red cell 2,3-diphosphoglycerate (2,3-DPG), Po2 at which hemoglobin is 50% saturated (P50), and acid-base status in expedition members at various altitudes. All measurements were made in expedition laboratories and, with the exception of samples from the South Col of Mt. Everest (8,050 m), within 2 h of blood collection. In vivo conditions were estimated from direct measurements of arterial blood gases and pH or inferred from base excess and alveolar PCO2. As expected, increased 2,3-DPG was associated with slightly increased P50, when expressed at pH 7.4. Because of respiratory alkalosis, however, the subjects' in vivo P50 at 6,300 m (27.6 Torr) was slightly less than at sea level (28.1 Torr). The estimated in vivo P50 was progressively lower at 8,050 m (24.9 Torr) and on the summit at 8,848 m (19.4 Torr in one subject). Our data suggest that, at extreme altitude, the blood O2 equilibrium curve shifts progressively leftward because of respiratory alkalosis. This left shift protects arterial O2 saturation at extreme altitude.

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.

Metabolic Effect and Uptake of [3H]Digoxin in the Forearm of Man

1972 ◽  
Vol 42 (5) ◽  
pp. 567-577
Author(s):  
R. I. Ogilvie ◽  
G. A. Klassen
Keyword(s):  
Blood Flow ◽  
Oleic Acid ◽  
Forearm Blood Flow ◽  
Digoxin Concentration ◽  
Normal Male ◽  
Ethanol Group ◽  
Arterial Blood ◽  
Electrolyte Flux ◽  
Arterial Plasma

1. The forearm perfusion technique was used to study the effect of intra-arterial injections of ethanol with or without digoxin on the metabolism and electrolyte flux of forearm tissues in normal male volunteers. 2. In six subjects infusion of ethanol alone (2·9 mg/min over 30 min) resulted in no alterations of forearm blood flow, O2 consumption, carbohydrate metabolism, or flux of potassium and calcium. Although there was no change in extraction of [14C]oleic acid, a significant net output of oleic and total free fatty acids was observed from both deep venous and superficial venous systems. 3. In six subjects the intra-arterial infusion of [3H]digoxin (0·09 μg/min with ethanol, 2·9 mg/min over 30 min) resulted in no alteration of forearm blood flow. During the steady state achieved after 5–8 min of perfusion, 50·3% of the calculated local arterial plasma digoxin concentration of 2·73 μg/l was extracted by the deep venous system with a significant increase in glucose extraction. The respiratory quotient and fractional utilization of O2 by glucose increased. No change in extraction of [14C]oleic acid from arterial blood was observed. However, the net output of oleic and total free acids from both deep and superficial venous systems was insignificant in comparison with that observed in the ethanol control subjects. The changes in K+ flux were similar to those noted in the ethanol group. In the post-digoxin period there was a significantly increased uptake of Ca2+ by forearm tissues. 4. This is the first demonstration of the stimulatory effects of digoxin on glucose metabolism, the antilipolytic effects of this drug and its effect on Ca2+ fluxes in vivo in man.

scholarly journals Hippocampus has lower oxygenation and weaker control of brain blood flow than cortex, due to microvascular differences

2019 ◽  
Author(s):  
K. Shaw ◽  
L. Bell ◽  
K. Boyd ◽  
D.M. Grijseels ◽  
D. Clarke ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Flow ◽  
Cell Function ◽  
Regional Blood Flow ◽  
Blood Oxygenation ◽  
Endothelial Cell Function ◽  
Function Modelling ◽  
Visual Cortical

AbstractThe hippocampus is essential for spatial and episodic memory but is damaged early in Alzheimer’s disease and is very sensitive to hypoxia. Understanding how it regulates its oxygen supply is therefore key for designing interventions to preserve its function. However, studies of neurovascular function in the hippocampus in vivo have been limited by its relative inaccessibility. Here we compared hippocampal and visual cortical neurovascular function in awake mice, using two photon imaging of individual neurons and vessels and measures of regional blood flow and haemoglobin oxygenation. We show that blood flow, blood oxygenation and neurovascular coupling were decreased in the hippocampus compared to neocortex, because of differences in both the vascular network and pericyte and endothelial cell function. Modelling oxygen diffusion indicates that these features of the hippocampal vasculature could explain its sensitivity to damage during neurological conditions, including Alzheimer’s disease, where the brain’s energy supply is decreased.

C5a-induced myocardial ischemia: role for CD18-dependent PMN localization and PMN-platelet interactions

1993 ◽  
Vol 265 (5) ◽  
pp. H1750-H1761 ◽  
Author(s):  
M. P. Fletcher ◽  
G. L. Stahl ◽  
J. C. Longhurst
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Myocardial Ischemia ◽  
Myocardial Segment ◽  
Artery Blood Flow ◽  
Arterial Blood ◽  
Pmn Functions ◽  
Dependent Mechanism

Intracoronary C5a in swine decreases coronary blood flow and regional myocardial segment shortening, responses mediated by thromboxane (Tx) A2-induced coronary vasoconstriction and intramyocardial trapping of granulocytes (PMNs). We sought to determine the origin of TxA2 and to investigate the role of CD18-dependent PMN function by utilizing an anti-CD18 monoclonal antibody, IB4. Isolated C5a-stimulated PMNs or platelets did not produce TxB2. However, together, C5a-stimulated PMNs and platelets produced TxB2. IB4 bound porcine PMN surface CD18 and blocked C5a-induced PMN functions. In vivo, IB4 loading (2 mg/kg) transiently decreased arterial blood pressure and circulating platelet counts in six of nine animals (390 +/- 31 vs. 176 +/- 41 X 10(6)/ml, control vs. IB4; P < 0.002) and significantly ameliorated C5a-induced decreases in coronary venous PMN count (-4.1 +/- 0.6 vs. -1.4 +/- 0.8 X 10(6) cells/ml), coronary artery blood flow (-10 +/- 1 vs. -4 +/- 1 ml/min), and segment shortening (-15 +/- 2 vs. -8 +/- 2%, C5a vs. C5a + IB4). We conclude that 1) production of TxB2 in response to C5a is mediated by a PMN-platelet interaction, 2) IB4 functionally blocks CD18 on porcine PMNs, and 3) C5a-induced myocardial PMN extraction is mediated, in part, by a CD18-dependent mechanism. These results suggest that PMN-platelet interactions and CD18-dependent PMN extraction are important in C5a-induced myocardial ischemia.

Intracoronary intermedin 1–47 augments cardiac perfusion and function in anesthetized pigs: role of calcitonin receptors and β-adrenoreceptor-mediated nitric oxide release

2009 ◽  
Vol 107 (4) ◽  
pp. 1037-1050 ◽  
Author(s):  
Elena Grossini ◽  
Claudio Molinari ◽  
David A. S. G. Mary ◽  
Francesca Uberti ◽  
Philippe Primo Caimmi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cardiac Function ◽  
Coronary Blood Flow ◽  
No Synthase ◽  
Cardiac Response ◽  
No Production ◽  
Receptor Complexes ◽  
Arterial Blood

Systemic intermedin (IMD)1–47 administration has been reported to result in vasodilation and marked hypotension through calcitonin-related receptor complexes. However, its effects on the coronary circulation and the heart have not been examined in vivo. The present study was therefore planned to determine the primary in vivo effect of IMD1–47 on coronary blood flow and cardiac function and the involvement of the autonomic nervous system and nitric oxide (NO). In 35 anesthetized pigs, IMD1–47, infused into the left anterior descending coronary artery at doses of 87.2 pmol/min, at constant heart rate and arterial blood pressure, augmented coronary blood flow and cardiac function. These responses were graded in a further five pigs by increasing the infused dose of IMD1–47 between 0.81 and 204.1 pmol/min. In the 35 pigs, the blockade of cholinergic receptors (intravenous atropine, 5 pigs), α-adrenoceptors (intravenous phentolamine, 5 pigs), and β1-adrenoceptors (intravenous atenolol, 5 pigs) did not abolish the cardiac response to IMD1–47, the effects of which were prevented by blockade of β2-adrenoceptors (intravenous butoxamine, 5 pigs), NO synthase (intracoronary Nω-nitro-l-arginine methyl ester, 5 pigs), and calcitonin-related receptors (intracoronary CGRP8–37/AM22–52, 10 pigs). In porcine coronary endothelial cells, IMD1–47 induced the phosphorylation of endothelial NO synthase and NO production through cAMP signaling leading to ERK, Akt, and p38 activation, which was prevented by the inhibition of β2-adrenoceptors, calcitonin-related receptor complexes, and K+ channels. In conclusion, IMD1–47 primarily augmented coronary blood flow and cardiac function through the involvement of calcitonin-related receptor complexes and β2-adrenoreceptor-mediated NO release. The intracellular signaling involved cAMP-dependent activation of kinases and the opening of K+ channels.

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