Contractile effect of the aqueous extract of Psidium guajava leaves on aortic rings in rat.

PubMed

Olatunji-Bello, I I; Odusanya, A J; Raji, I; Ladipo, C O

2007-04-01

Aqueous leaves extract of Psidium guajava significantly and dose-dependently (0.25-2 mg/ml) contracted aorta rings. The effect was evaluated also in presence of nifedipine and phentolamine. The sensitivity of the aortic rings to cumulative doses of P. guajava was significantly enhanced in the presence of phentolamine suggesting that the effect of P. guajava was to a large extent mediated by activation of alpha-adrenoceptor and to a lesser extent by acting via calcium ion channel.

Deletion of AMPKα1 attenuates the anticontractile effect of perivascular adipose tissue (PVAT) and reduces adiponectin release.

PubMed

Almabrouk, Tarek A M; Ugusman, Azizah B; Katwan, Omar J; Salt, Ian P; Kennedy, Simon

2017-10-01

Perivascular adipose tissue (PVAT) surrounds most blood vessels and secretes numerous active substances, including adiponectin, which produce a net anticontractile effect in healthy individuals. AMPK is a key mediator of cellular energy balance and may mediate the vascular effects of adiponectin. In this study, we investigated the role of AMPK within PVAT in mediating the anticontractile effect of PVAT. Endothelium-denuded aortic rings from wild-type (WT; Sv129) and α 1 AMPK knockout (KO) mice were mounted on a wire myograph. Dose-response curves to the AMPK-independent vasodilator cromakalim were studied in vessels with and without PVAT, and effect of pre-incubation with conditioned media and adiponectin on relaxation was also studied. The effect of AMPKα1 KO on the secretory profile of PVAT was assessed by elisa. Thoracic aortic PVAT from KO mice was morphologically indistinct from that of WT and primarily composed of brown adipose tissue. PVAT augmented relaxation to cromakalim in WT but not KO aortic rings. Addition of WT PVAT augmented relaxation in KO aortic rings but KO PVAT had no effect in WT rings. PVAT from KO mice secreted significantly less adiponectin and addition of adiponectin to either KO or WT aortic rings without PVAT augmented relaxation to cromakalim. An adiponectin blocking peptide significantly attenuated relaxation in WT rings with PVAT but not in KO rings. AMPKα1 has a critical role in maintaining the anticontractile actions of PVAT; an effect independent of the endothelium but likely mediated through altered adiponectin secretion or sensitivity. This article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue - Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc. © 2016 The British Pharmacological Society.

Changes in vascular reactivity induced by acute hyperthyroidism in isolated rat aortae.

PubMed

Honda, H; Iwata, T; Mochizuki, T; Kogo, H

2000-06-01

Hyperthyroidism was induced by subcutaneous injections of L-thyroxine (T(4)) (500 mg/kg/day) for 3 days in order to study whether adrenergic and muscarinic receptor-mediated vascular responses alter at an early stage of the disease. T(4) treatment was sufficient to induce a significant degree of thyroid weight loss, tachycardia, cardiac hypertrophy, and an elevation in serum T(4) levels. The tension of aortic ring preparations isolated from rats was measured isometrically to investigate the influence of acute hyperthyroidism. The contractions induced by norepinephrine (NE) were significantly suppressed in aortic rings from rats treated with T(4) compared with control rats. N(G)-nitro-L-arginine (L-NOARG), an inhibitor of nitric oxide synthase (NOS), significantly enhanced NE-induced contraction in aortic rings from both control and T(4)-treated rats, and the enhancement was greater in rats treated with T(4) than control rats. The relaxations induced by either acetylcholine (ACh) or sodium nitroprusside (SNP) were also significantly enhanced by T(4) treatment. L-NOARG abolished the relaxation induced by ACh in aortic rings from both control and T(4)-treated rats. L-NOARG shifted SNP-induced relaxation curves of aortic rings from those of control rats to the left, but not with rats treated with T(4). T(4) treatment showed no influence on the amount of endothelial NOS (eNOS) protein. These results suggest that vascular responses alter at an early stage of hyperthyroidism and that it may be due to a modification in the NO system which is independent from the amount of eNOS protein.

Multidetector Computed Tomography for Congenital Anomalies of the Aortic Arch: Vascular Rings.

PubMed

García-Guereta, Luis; García-Cerro, Estefanía; Bret-Zurita, Montserrat

2016-07-01

The development of multidetector computed tomography has triggered a revolution in the study of the aorta and other large vessels and has replaced angiography in the diagnosis of congenital anomalies of the aortic arch, particularly vascular rings. The major advantage of multidetector computed tomography is that it permits clear 3-dimensional assessment of not only vascular structures, but also airway and esophageal compression. The current update aims to summarize the embryonic development of the aortic arch and the developmental anomalies leading to vascular ring formation and to discuss the current diagnostic and therapeutic role of multidetector computed tomography in this field. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Role of ATP-sensitive potassium channels in the piracetam induced blockade of opioid effects.

PubMed

Rehni, Ashish K; Singh, Nirmal; Jindal, Seema

2007-12-01

The present study has been designed to investigate the effect of piracetam on morphine/ buprenorphine-induced antinociception in rats and effect of piracetam on morphine or minoxidil induced relaxation in KCl-precontracted isolated rat aortic ring preparation. Nociceptive threshold was measured by the tail flick test in rats. The cumulative dose responses of morphine or minoxidil were recorded in KCl-precontracted isolated rat aortic ring preparation. Piracetam attenuated buprenorphine-induced antinociception in rats. Piracetam significantly reduced the morphine and minoxidil induced relaxation in KCl precontracted isolated rat aortic ring preparation suggesting that piracetam interferes with opioid receptor and ATP-sensitive potassium channel (KATP) opener mediated responses in vitro. Thus, it may be suggested that piracetam attenuates opioid effects by an opioid receptor-KATP channel linked mechanism.

Fracture mechanics of shear crack propagation and dissection in the healthy bovine descending aortic media.

PubMed

Haslach, Henry W; Siddiqui, Ahmed; Weerasooriya, Amanda; Nguyen, Ryan; Roshgadol, Jacob; Monforte, Noel; McMahon, Eileen

2018-03-01

This experimental study adopts a fracture mechanics strategy to investigate the mechanical cause of aortic dissection. Inflation of excised healthy bovine aortic rings with a cut longitudinal notch that extends into the media from the intima suggests that an intimal tear may propagate a nearly circumferential-longitudinal rupture surface that is similar to the delamination that occurs in aortic dissection. Radial and 45°-from-radial cut notch orientations, as seen in the thickness surface, produce similar circumferential crack propagation morphologies. Partial cut notches, whose longitudinal length is half the width of the ring, measure the influence of longitudinal material on crack propagation. Such specimens also produce circumferential cracks from the notch root that are visible in the thickness circumferential-radial plane, and often propagate a secondary crack from the base of the notch, visible in the intimal circumferential-longitudinal plane. Inflation of rings with pairs of cut notches demonstrates that a second notch modifies the propagation created in a specimen with a single notch. The circumferential crack propagation is likely a consequence of the laminar medial structure. These fracture surfaces are probably due to non-uniform circumferential shear deformation in the heterogeneous media as the aortic wall expands. The qualitative deformation morphology around the root of the cut notch during inflation is evidence for such shear deformation. The shear apparently results from relative slip in the circumferential direction of collagen fibers. The slip may produce shear in the longitudinal-circumferential plane between medial layers or in the radial-circumferential plane within a medial lamina in an idealized model. Circumferential crack propagation in the media is then a shear mechanical process that might be facilitated by disease of the tissue. An intimal tear of an apparently healthy aortic wall near the aortic arch is life-threatening because it may lead to full rupture or to wall dissection in which delamination of the medial layer extends around most of the aortic circumference. The mechanical events underlying dissection are not definitively established. This experimental fracture mechanics study provides evidence that shear rupture is the main mechanical process underlying aortic dissection. The commonly performed tensile strength tests of aortic tissue are not clinically useful to predict or describe aortic dissection. One implication of the study is that shear tests might produce more fruitful simple assessments of the aortic wall strength. A clinical implication is that when presented with an intimal tear, those who guide care might recommend steps to reduce the shear load on the aorta. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Biosynthesis of fibronectin by rabbit aorta.

PubMed

Takasaki, I; Chobanian, A V; Brecher, P

1991-09-15

The in vitro interactions between vascular cells and fibronectin have been shown to influence phenotypic expression of both cultured endothelial and smooth muscle cells. To more effectively assess the potential functional role of fibronectin in vivo in modulating vascular phenotypes, we have established methodology for studying fibronectin biosynthesis in the rabbit aorta using aortic rings that are morphologically and functionally intact and metabolically active. Aortic rings were incubated with 35S-labeled methionine in a supplemented physiological salt solution. The tissue was fractionated, and quantitative immunoprecipitation was performed using a polyclonal antibody directed against human plasma fibronectin. Newly synthesized fibronectin was most abundant in the fraction solubilized using 4% sodium dodecyl sulfate and in the incubation medium. In all fractions studied, fibronectin was present predominantly as a dimer with no detectable aggregates of fibronectin. Pulse-chase experiments showed that a substantial amount of newly synthesized fibronectin was found in the 4% sodium dodecyl sulfate extract after only 1 h, suggesting that fibronectin was rapidly incorporated into the extracellular matrix. The more soluble forms of newly synthesized fibronectin appeared to be the precursors for secreted fibronectin, and no precursor-product relationship between soluble and insoluble fibronectin was found. Dissection of aortic rings following incubation with labeled methionine showed that newly synthesized fibronectin was uniformally distributed in both intima-media and media-adventitia segments. Endothelial cell denudation caused only a 20% decrease of fibronectin biosynthesis concomitant with similar changes in total protein biosynthesis, consistent with the medial smooth muscle cell as the major source of newly synthesized fibronectin. Biosynthesis of fibronectin was increased following a 24-h preincubation of the aortic rings, and concomitant increases in steady state mRNA for fibronectin were found. These in vitro studies documented the utility of aortic rings for the general purpose of studying protein synthesis in vascular cells and provide new information on the characteristics of fibronectin biosynthesis by aortic tissue.

Dahl SS rats demonstrate enhanced aortic perivascular adipose tissue-mediated buffering of vasoconstriction through activation of NOS in the endothelium

PubMed Central

Spradley, Frank T.; Ho, Dao H.

2015-01-01

Perivascular adipose tissue (PVAT) mediates buffering of vasoconstriction through activation of endothelium-derived factors. We hypothesized that the PVAT of Dahl salt-sensitive (Dahl SS) rats has reduced ability to buffer vasoconstriction. Vascular reactivity experiments were performed on aortic rings with PVAT intact (+PVAT) or removed (−PVAT), and endothelium intact (+ENDO) or removed (−ENDO) from Dahl SS rats and control SS.13BN rats (Dahl SS rats that have had chromosome 13 completely replaced with that of the Brown Norway rat, rendering this strain insensitive to high-salt or high-fat diet-induced hypertension). Endothelial dysfunction, assessed by ACh-mediated vasorelaxation, was confirmed in aortic rings of Dahl SS rats. The +PVAT+ENDO aortic rings had indistinguishable phenylephrine-induced vasoconstriction between genotypes. In both strains, removal of PVAT significantly enhanced vasoconstriction. Dahl SS rat −PVAT+ENDO aortic rings displayed exaggerated vasoconstriction to phenylephrine vs. SS.13BN rats, indicating that PVAT-mediated buffering of vasoconstriction was greater in Dahl SS rats. Removal of both the ENDO and PVAT restored vasoconstriction in both strains. The nitric oxide synthase (NOS) inhibitor, Nω-nitro-l-arginine methyl ester (l-NAME), produced a similar effect as that seen with −ENDO. These data indicate that the function of the PVAT to activate endothelium-derived NOS is enhanced in Dahl SS compared with SS.13BN rats and, most likely, occurs through a pathway that is distinct from ACh-mediated activation of NOS. PVAT weight and total PVAT leptin levels were greater in Dahl SS rats. Leptin induced a significantly decreased vasoconstriction in −PVAT+ENDO aortic rings from Dahl SS rats, but not SS.13BN rats. In contrast to our initial hypothesis, PVAT in Dahl SS rats buffers vasoconstriction by activating endothelial NOS via mechanisms that may include the involvement of leptin. Thus, the PVAT serves a vasoprotective role in Dahl SS rats on normal-salt diet. PMID:26608658

Right cervical aortic arch with aberrant left subclavian artery.

PubMed

Tjang, Yanto S; Aramendi, José I; Crespo, Alejandro; Hamzeh, Gadah; Voces, Roberto; Rodríguez, Miguel A

2008-08-01

The combination of right cervical aortic arch, aberrant retroesophageal left subclavian artery originating from a Kommerell's diverticulum, and a ligamentum arteriosum, constitutes a rare form of vascular ring. Two patients aged 21 days and 54 years, who were diagnosed by multislice 3-dimensional computed tomography and magnetic resonance imaging, underwent surgical division of a vascular ring. The adult required resection of a Kommerell's aneurysm and subclavian artery reimplantation.

Nucleotide-mediated relaxation in guinea-pig aorta: selective inhibition by MRS2179

PubMed Central

Kaiser, Robert A; Buxton, Iain L O

2002-01-01

The vasodilatory effects of nucleotides in the guinea-pig thoracic aorta were examined to determine the relationship between molecular expression and function of P2Y receptors. In aortic rings precontracted with norepinephrine, vasodilatory responses to purine nucleotides exhibited a rank-order of potency of 2-methylthio-ATP>ADP>ATP. Responses to UTP, but not UDP suggested a functional role for P2Y4 but not P2Y6 receptors. Aortic endothelial cells express at least four P2Y receptors; P2Y1, P2Y2, P2Y4 and P2Y6. In primary culture, these cells exhibit desensitizing transient calcium responses characteristic of P2Y1, P2Y2 and P2Y4, but not P2Y6 receptors. UDP had no effect on endothelial cell calcium. The pyrimidinergic receptor agonist UTP is capable of eliciting robust vasodilation in aortic rings and causing calcium responses in cultured guineapig aortic endothelial cells. These responses are equivalent to the maximum responses observed to ATP and ADP. Measurement of intracellular calcium release in response to ATP and 2-methylthio-ATP were similar, however only the 2-methylthio-ATP response was sensitive to the P2Y1 antagonist N6-methyl-2′-deoxyadenosine-3′,5′-bisphosphate (MRS2179). In aortic rings, vasodilatory responses to 2-methylthio-ATP, ATP and ADP were all blocked by pre-incubation of tissues with MRS2179. MRS2179 pretreatment had no effect of the ability of UTP to cause relaxation of norepinephrine responses in aortic rings or the ability of UTP to cause calcium release in aortic endothelial cells. We demonstrate robust effects of purine and pyrimidine nucleotides in guineapig aorta and provide functional and biochemical evidence that MRS2179 is a selective P2Y1 antagonist. PMID:11815389

Effect of the positioning of a balloon valve in the aorta on coronary flow during aortic regurgitation.

PubMed

Antonatos, P G; Anthopoulos, L P; Kandyla, D D; Karras, A D; Moulopoulos, S D

1984-07-01

The coronary artery flow changes relative to the function of a catheter-mounted balloon valve used for relief of aortic regurgitation were studied in 10 mongrel dogs. Acute aortic regurgitation was produced by severing the aortic cusps with a long needle. Coronary flow was recorded from the left anterior descending coronary artery through an electromagnetic flowmeter. When the balloon was functioning within the cavity of the left ventricle there were no significant changes in the coronary flow and aortic pressure, except for a slight decrease in the aortic end-diastolic pressure. When it was functioning in the aortic ring the coronary flow increased 6.52 +/- 1.65 ml/min/100 gm of myocardium (p less than 0.001) and became predominantly diastolic. When it was functioning in the ascending aorta the coronary flow decreased 6.22 +/- 1.16 ml/min/100 gm of myocardium (p less than 0.001) and remained predominantly systolic. Finally, when the balloon was functioning in the thoracic aorta the coronary flow did not change significantly. With the balloon functioning in the aortic ring, ascending aorta, or thoracic aorta, there was a significant increase in the aortic end-diastolic pressure and decrease in the pulse pressure distal to the location of the balloon. It is concluded that the location of the balloon valve inserted for relief of aortic regurgitation influences the effect on coronary arterial flow.

Effects of sub-chronic oral cyanide on endothelial function in rabbit aortic rings.

PubMed

Ozolu, R I; Okolie, N P; Ebeigbe, A B; Karikari, N

2007-02-01

We have investigated how the endothelium affects vascular responses following sub-chronic low dose cyanide administration. Cyanide exists in low levels in cassava foods, which are widely consumed in tropical Africa. Adult rabbits were administered 0.38 mg/kg per day KCN po for 25 days, and responses of the isolated aortic rings to noradrenaline (NA), calcium chloride (Ca2+) and acetylcholine (ACh) were measured in vitro in the presence and absence of the endothelium. In order to establish that the dose was not toxic, animal weight, some haematological indices, plasma alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were measured. Results show that endothelium denudation significantly (P <0.05) attenuates NA-induced contraction in rings from cyanide-treated rabbits. There was a similar reduction in response in Ca2+-depleted NA-precontracted endothelium-denuded aortic rings from cyanide-treated rabbits. Endothelium-denuded rings from cyanide-treated rabbits showed significantly (P <0.05) enhanced relaxation to ACh. In rings from control animals, the responses to NA and Ca2+ were not significantly altered, whether in the presence or absence of the endothelium. There were no significant changes in the studied toxicological indices. We conclude that endothelial compromise is necessary for low-dose sub-chronic cyanide-induced to alter vascular reactivity to NA and ACh.

Targeting the Nociceptin/Orphanin FQ Receptor for Scleroderma Therapy

DTIC Science & Technology

2016-08-01

quantified by flow cytometry. In the aortic ring assay, freshly isolated thoracic aorta rings will be harvested and mounted in a small- vessel...ring assay, freshly isolated thoracic aorta rings will be harvested and mounted in a small-vessel myograph. Vasodilation will be determined by

L-arginine and arginine analogues: effects on isolated blood vessels and cultured endothelial cells.

PubMed Central

Schmidt, H. H.; Baeblich, S. E.; Zernikow, B. C.; Klein, M. M.; Böhme, E.

1990-01-01

1. The present study examined effects of arginine (Arg) and various Arg analogues on the vascular tone of rabbit and rat aortic rings, the release of nitrite from cultured bovine aortic endothelial cells and the metabolism of L-Arg in bovine and porcine endothelial cell homogenates. The respective D-enantiomers or N-alpha-benzoyl-L-arginine ethyl ester did not substitute for L-Arg. 2. In bovine aortic endothelial cells, the release of nitrite was only observed in the presence of L-Arg or L-Arg methyl ester in the cell culture medium. 3. In dialyzed homogenates of porcine and bovine aortic endothelial cells, L-Arg was metabolized independently of NADPH and Ca2+ to yield L-ornithine (L-Orn) and L-citrulline (L-Cit). No concomitant nitrite formation was detected. 4. Pretreatment of rabbit and rat aortic rings with L-canavanine (L-Can) or NG-monomethyl-L-Arg (L-NMMA) inhibited ATP- and acetylcholine-induced relaxations (endothelium-dependent) but not glyceryltrinitrate-induced relaxations (endothelium-independent). 5. In rabbit aortic rings, Arg and monomeric Arg analogues induced endothelium-independent relaxations. L-Arg methyl ester induced an endothelium-independent contraction, and L-NMMA induced a relaxation in the absence of endothelium and a contraction in the presence of endothelium. Polymeric basic amino acids such as poly L-Arg induced endothelium-dependent relaxations (inhibited by L-Can), a subsequent refractoriness to endothelium-dependent vasodilators (not prevented by L-Can) and endothelial cell death.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2282457

Vascular tissue engineering by computer-aided laser micromachining.

PubMed

Doraiswamy, Anand; Narayan, Roger J

2010-04-28

Many conventional technologies for fabricating tissue engineering scaffolds are not suitable for fabricating scaffolds with patient-specific attributes. For example, many conventional technologies for fabricating tissue engineering scaffolds do not provide control over overall scaffold geometry or over cell position within the scaffold. In this study, the use of computer-aided laser micromachining to create scaffolds for vascular tissue networks was investigated. Computer-aided laser micromachining was used to construct patterned surfaces in agarose or in silicon, which were used for differential adherence and growth of cells into vascular tissue networks. Concentric three-ring structures were fabricated on agarose hydrogel substrates, in which the inner ring contained human aortic endothelial cells, the middle ring contained HA587 human elastin and the outer ring contained human aortic vascular smooth muscle cells. Basement membrane matrix containing vascular endothelial growth factor and heparin was to promote proliferation of human aortic endothelial cells within the vascular tissue networks. Computer-aided laser micromachining provides a unique approach to fabricate small-diameter blood vessels for bypass surgery as well as other artificial tissues with complex geometries.

[Right-side aortic arch with aberrant left subclavian artery and Kommerell's diverticulum. A cause of vascular ring].

PubMed

Tamayo-Espinosa, Tania; Erdmenger-Orellana, Julio; Becerra-Becerra, Rosario; Balderrabano-Saucedo, Norma; Segura-Standford, Begoña

The right-side aortic arch may be associated with aberrant left subclavian artery, in some cases this artery originates from an aneurismal dilation of the aorta called Kommerell's diverticulum. A report is presented on 2 cases of vascular ring formed by a right-side aortic arch, anomalous left subclavian artery, Kommerell's diverticulum and left patent ductus arteriosus. A review the literature was also performed as regards the embryological development and the imaging methods used to help in the diagnosis of this rare vascular anomaly. Copyright © 2017 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

Pharmacological study of the mechanisms involved in the vasodilator effect produced by the acute application of triiodothyronine to rat aortic rings

PubMed Central

Lozano-Cuenca, J.; López-Canales, O.A.; Aguilar-Carrasco, J.C.; Villagrana-Zesati, J.R.; López-Mayorga, R.M.; Castillo-Henkel, E.F.; López-Canales, J.S.

2016-01-01

A relationship between thyroid hormones and the cardiovascular system has been well established in the literature. The present in vitro study aimed to investigate the mechanisms involved in the vasodilator effect produced by the acute application of 10-8–10-4 M triiodothyronine (T3) to isolated rat aortic rings. Thoracic aortic rings from 80 adult male Wistar rats were isolated and mounted in tissue chambers filled with Krebs-Henseleit bicarbonate buffer in order to analyze the influence of endothelial tissue, inhibitors and blockers on the vascular effect produced by T3. T3 induced a vasorelaxant response in phenylephrine-precontracted rat aortic rings at higher concentrations (10-4.5–10-4.0 M). This outcome was unaffected by 3.1×10-7 M glibenclamide, 10-3 M 4-aminopyridine (4-AP), 10-5 M indomethacin, or 10-5 M cycloheximide. Contrarily, vasorelaxant responses to T3 were significantly (P<0.05) attenuated by endothelium removal or the application of 10-6 M atropine, 10-5 M L-NG-nitroarginine methyl ester (L-NAME), 10-7 M 1H-(1,2,4)oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), 10-6 M (9S,10R,12R)-2,3,9,10,11,12-Hexahydro-10-methoxy-2,9-dimethyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3′,2′,1′-kl]pyrrolo[3,4-i](1,6)benzodiazocine-10-carboxylic acid, methyl ester KT 5823, 10-2 M tetraethylammonium (TEA), or 10-7 M apamin plus 10-7 M charybdotoxin. The results suggest the involvement of endothelial mechanisms in the vasodilator effect produced by the acute in vitro application of T3 to rat aortic rings. Possible mechanisms include the stimulation of muscarinic receptors, activation of the NO-cGMP-PKG pathway, and opening of Ca2+-activated K+ channels. PMID:27464023

Endothelium-dependent and independent vasorelaxant effects of aqueous extract of Tridax procumbens Lin. leaf in rat aortic rings.

PubMed

Salahdeen, Hussein M; Idowu, Gbolahan O; Murtala, Babatunde A

2012-12-01

Tridax procumbens leaf extract induced aortic relaxation in a concentration-dependent manner, for both phenylephrine (PE) and KCl- induced contractions in isolated rat aortic rings. The relaxation effect of the extract on PE-induced contraction was 57% greater than that on KCl- induced contraction. The extract caused dose-dependent relaxations in precontracted isolated rat aorta with phenylephrine; the relaxation was attenuated by the removal of endothelium. However, the relaxation responses to sodium nitroprusside were not significantly abolished by the removal of endothelium. The vasorelaxatory effect of the extract was completely abolished in presence of L-NAME. The results indicate that the vasorelaxant effect of T. procumbens extract is probably mediated by both endothelium-dependent and-independent mechanisms.

Effects of phenylpropanoid and iridoid glycosides on free radical-induced impairment of endothelium-dependent relaxation in rat aortic rings.

PubMed

Ismailoglu, U B; Saracoglu, I; Harput, U S; Sahin-Erdemli, I

2002-02-01

The protective effect of phenylpropanoid glycosides, forsythoside B and alyssonoside, and the iridoid glycoside lamiide, isolated from the aerial parts of Phlomis pungens var. pungens, against free radical-induced impairment of endothelium-dependent relaxation in isolated rat aorta was investigated. Aortic rings were exposed to free radicals by the electrolysis of the physiological bathing solution. Free radical-induced inhibition of the endothelium-dependent relaxation in response to acetylcholine was countered by incubation of the aortic rings before electrolysis with the aqueous extract (200 microg/ml), phenylpropanoid fraction (100 microg/ml) and iridoid fraction (150 microg/ml) of P. pungens var. pungens. Major components of the phenylpropanoid fraction forsythoside B and alyssonoside also prevented the inhibition of the acetylcholine response, at 10(-4) M concentration. However, the major component of iridoid fraction lamiide was found ineffective at the same concentration. The protective activity of phenylpropanoid glycosides against the free radical-induced impairment of endothelium-dependent relaxation may be related to their free radical scavenging property.

A case of complete double aortic arch visualized by transthoracic echocardiography.

PubMed

Saito, Naka; Kato, Shingo; Saito, Noritaka; Nakachi, Tatsuya; Fukui, Kazuki; Iwasawa, Tae; Kosuge, Masami; Kimura, Kazuo

2017-08-01

A case of double aortic arch that was well visualized using transthoracic echocardiography is reported. A 38-year-old man underwent transthoracic echocardiography for the evaluation of dyspnea. A suprasternal view of transthoracic echocardiography showed the ascending aorta bifurcate to left and right aortic arches, with blood flow from the ascending aorta to bilateral aortic arches. The diagnosis of right side-dominant double aortic arch was made, and the patient's symptom was conceivably related to compression of the trachea due to a vascular ring. This report indicates the potential usefulness of transthoracic echocardiography for noninvasive detection of double aortic arch in adults. © 2017, Wiley Periodicals, Inc.

Endothelium-dependent desensitization to angiotensin II in rabbit aorta: the mechanisms involved.

PubMed

Jerez, S; de Bruno, M P; Coviello, A

2001-06-01

The aim of this study was to characterize the role of the endothelium in angiotensin II-desensitization and its mechanisms of action. Rabbit aortic rings were exposed to increasing doses of angiotensin II (Ang II, 10(-9) to 2.5 x 10(-6)) to generate two cumulative dose-response curves (CDRC I and II). A 50-min interval separated CDRC I and II. Desensitization was observed at all doses in unrubbed aortic tissue and at lower doses in rubbed aortic tissue. Tachyphylaxis was greater in arteries with endothelium. Treatment of intact rings with L-N(G)-nitroarginine methyl ester (L-NAME, 10(-4) M) did not prevent this phenomenon. However, indomethacin (10(-5) M) and miconazol (10(-6) M) attenuated Ang II-desensitization. Treatment of unrubbed rings with nifedipine (10(-6) M) and cromakalim (10(-6) M) inhibited the effect of indomethacin. To confirm the involvement of K+ channels, unrubbed and rubbed aortic rings were treated with the K(Ca2+) blockers apamin (10(-7) M), tetraethylammonium (TEA, 10(-3) M), and iberiotoxin (10(-8) M), and the K(ATP) blocker glibenclamide (10(-5) M). In both arteries apamin, TEA, and glibenclamide abolished the tachyphylaxis without changes in the maximal response. Iberiotoxin diminished Ang II-desensitization in rubbed but not unrubbed arteries. Results from this study suggest that Ang II-desensitization involves endothelium-dependent and -independent mechanisms. Endothelium-dependent desensitization could be mediated by a cyclooxygenase-cytochrome P450 product, which could act by increasing K(Ca2+) channel activity.

Reimplantation versus remodelling with ring annuloplasty: comparison of mid-term outcomes after valve-sparing aortic root replacement.

PubMed

Lenoir, Marien; Maesen, Bart; Stevens, Louis-Mathieu; Cartier, Raymond; Demers, Philippe; Poirier, Nancy; Tousch, Michaël; El-Hamamsy, Ismail

2018-02-08

Remodelling with extra-aortic ring annuloplasty has emerged as an alternative approach to root reimplantation. However, no studies have yet compared outcomes between procedures. The aim of this study was to compare mid-term outcomes in patients undergoing reimplantation versus remodelling with extra-aortic annuloplasty. From 2001 to 2017, 142 patients underwent root remodelling with extra-aortic annuloplasty (n = 83, 48 ± 13 years) or a reimplantation technique (n = 59, 48 ± 12 years) at the Montreal Heart Institute. No differences were observed in the incidence of connective tissue disease (24% vs 29%, P = 0.9) or preoperative aortic insufficiency ≥3 (37% vs 23%, P = 0.24). However, in the remodelling group, there were more bicuspid aortic valves (31% vs 9%; P < 0.01), and the mean preoperative aortic annulus diameter was larger (27.2 ± 3.6 mm vs 25.6 ± 2.4 mm; P = 0.01). The mean follow-up duration was 3.9 years (100% complete). There were no hospital deaths and 5 late deaths. At 5 years, overall survival was similar in both groups (100%, P = 0.98). Similarly, 5-year freedom from aortic valve reoperation was equivalent (97 ± 2% in both groups, P = 0.95). Furthermore, 5-year survival free from aortic insufficiency ≥2 or reoperation was 84 ± 5% in the remodelling with annuloplasty group vs 83 ± 6% in the reimplantation group (P = 0.62). The mean annular diameter was 24.3 ± 0.5 mm at 5 years vs 23.6 ± 0.3 mm at discharge in the remodelling group (P = 0.28) and 24.4 ± 0.6 mm vs 23.2 ± 0.3 mm, respectively, in the reimplantation group (P = 0.1). Despite a higher prevalence of bicuspid aortic valves and larger aortic annular diameters, mid-term outcomes after remodelling with extra-aortic annuloplasty and reimplantation are comparable. Extra-aortic ring annuloplasty is effective at stabilizing annular dimensions. © The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Hydrogen sulfide protects endothelial nitric oxide function under conditions of acute oxidative stress in vitro.

PubMed

Al-Magableh, Mohammad R; Kemp-Harper, Barbara K; Ng, Hooi H; Miller, Alyson A; Hart, Joanne L

2014-01-01

The aim of this study was to examine the ability of H2S, released from NaHS to protect vascular endothelial function under conditions of acute oxidative stress by scavenging superoxide anions (O2(-)) and suppressing vascular superoxide anion production. O2(-) was generated in Krebs' solution by reacting hypoxanthine with xanthine oxidase (Hx-XO) or with the O2(-) generator pyrogallol to model acute oxidative stress in vitro. O2(-) generation was measured by lucigenin-enhanced chemiluminescence. Functional responses in mouse aortic rings were assessed using a small vessel myograph. NaHS scavenged O2(-) in a concentration-dependent manner. Isolated aortic rings exposed to either Hx-XO or pyrogallol displayed significantly attenuated maximum vasorelaxation responses to the endothelium-dependent vasodilator acetylcholine, and significantly reduced NO bioavailability, which was completely reversed if vessels were pre-incubated with NaHS (100 μM). NADPH-stimulated aortic O2(-) production was significantly attenuated by the NADPH oxidase inhibitor diphenyl iodonium. Prior treatment of vessels with NaHS (100 nM-100 μM; 30 min) inhibited NADPH-stimulated aortic O2(-) production in a concentration-dependent manner. This effect persisted when NaHS was washed out prior to measuring NADPH-stimulated O2(-) production. These data show for the first time that NaHS directly scavenges O2(-) and suppresses vascular NADPH oxidase-derived O2(-) production in vitro. Furthermore, these properties protect endothelial function and NO bioavailability in an in vitro model of acute oxidative stress. These results suggest that H2S can elicit vasoprotection by both scavenging O2(-) and by reducing vascular NADPH oxidase-derived O2(-) production.

Relation of murine thoracic aortic structural and cellular changes with aging to passive and active mechanical properties.

PubMed

Wheeler, Jason B; Mukherjee, Rupak; Stroud, Robert E; Jones, Jeffrey A; Ikonomidis, John S

2015-02-25

Maintenance of the structure and mechanical properties of the thoracic aorta contributes to aortic function and is dependent on the composition of the extracellular matrix and the cellular content within the aortic wall. Age-related alterations in the aorta include changes in cellular content and composition of the extracellular matrix; however, the precise roles of these age-related changes in altering aortic mechanical function are not well understood. Thoracic aortic rings from the descending segment were harvested from C57BL/6 mice aged 6 and 21 months. Thoracic aortic diameter and wall thickness were higher in the old mice. Cellular density was reduced in the medial layer of aortas from the old mice; concomitantly, collagen content was higher in old mice, but elastin content was similar between young and old mice. Stress relaxation, an index of compliance, was reduced in aortas from old mice and correlated with collagen fraction. Contractility of the aortic rings following potassium stimulation was reduced in old versus young mice. Furthermore, collagen gel contraction by aortic smooth muscle cells was reduced with age. These results demonstrate that numerous age-related structural changes occurred in the thoracic aorta and were related to alterations in mechanical properties. Aortic contractility decreased with age, likely because of a reduction in medial cell number in addition to a smooth muscle contractile deficit. Together, these unique findings provide evidence that the age-related changes in structure and mechanical function coalesce to provide an aortic substrate that may be predisposed to aortopathies. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Studies of vascular tolerance to nitroglycerin: effects of N-acetylcysteine, NG-monomethyl L-arginine, and endothelin-1.

PubMed

Lawson, D L; Haught, W H; Mehta, P; Mehta, J L

1996-09-01

Development of vascular tolerance to nitroglycerin (NTG) has been attributed to sulfhydryl (SH) depletion, guanylate cyclase desensitization, or both. Controversy regarding the precise contribution of these mechanisms may be due to variations in experimental design. To examine further the biochemical basis of NTG tolerance, norepinephrine (NE)-precontracted rat aortic rings were exposed to NTG (10(-5)M), which resulted in 84 +/- 6% relaxation. Other rings were first superfused with NTG (10(-6)M) and then contracted with NE. These rings showed a marked tolerance to the vasorelaxant effects of NTG (maximal relaxation 20 +/- 5%, n = 15, p < 0.001 vs. control rings). Similar tolerance to NTG was observed when the vascular rings were first superfused with acetylcholine (ACh 10(-6)M), indicating cross-tolerance between ACh and NTG. Treatment of NTG-tolerant rings with N-acetylcysteine (NAC) (10(-5)M) did not restore vascular smooth muscle (VSM) relaxation in response to NTG (maximal relaxation 23 +/- 5%, n = 8), suggesting that SH depletion may not be the basis of NTG tolerance in these experiments. Parallel sets of NTG-tolerant aortic rings were contracted with endothelin-1 (ET-1, n = 5) or the endothelium-derived relaxing factor (EDRF) synthase inhibitor NG-monomethyl L-arginine (L-NMMA, 10(-4)M, n = 8). In both ET-1- and L-NMMA-contracted rings, vascular relaxation in response to NTG was preserved (80 +/- 6 and 88 +/- 8% relaxation, respectively). Measurement of cyclic GMP in aortic rings showed marked accumulation on initial exposure of tissues to NTG (310 +/- 10 fmol/mg), whereas the NTG-tolerant rings showed much less cyclic GMP accumulation (48 +/- 29 fmol/mg). Rings contracted with L-NMMA or ET-1, but not NE, accumulated cyclic GMP when exposed to NTG (280 +/- 20 fmol/mg). These data indicate that NTG tolerance develops on exposure of vascular rings superfused with NTG or ACh and is probably not related to tissue SH depletion. Contraction of NTG-tolerant rings with ET-1 or L-NMMA restores NTG-mediated relaxation.

Small dense HDLs display potent vasorelaxing activity, reflecting their elevated content of sphingosine-1-phosphate.

PubMed

Perségol, Laurence; Darabi, Maryam; Dauteuille, Carolane; Lhomme, Marie; Chantepie, Sandrine; Rye, Kerry-Anne; Therond, Patrice; Chapman, M John; Salvayre, Robert; Nègre-Salvayre, Anne; Lesnik, Philippe; Monier, Serge; Kontush, Anatol

2018-01-01

The functional heterogeneity of HDL is attributed to its diverse bioactive components. We evaluated whether the vasodilatory effects of HDL differed across HDL subpopulations, reflecting their distinct molecular composition. The capacity of five major HDL subfractions to counteract the inhibitory effects of oxidized LDL on acetylcholine-induced vasodilation was tested in a rabbit aortic rings model. NO production, an essential pathway in endothelium-dependent vasorelaxation, was studied in simian vacuolating virus 40-transformed murine endothelial cells (SVECs). Small dense HDL3 subfractions displayed potent vasorelaxing activity (up to +31% vs. baseline, P < 0.05); in contrast, large light HDL2 did not induce aortic-ring relaxation when compared on a total protein basis. HDL3 particles were enriched with sphingosine-1-phosphate (S1P) (up to 3-fold vs. HDL2), with the highest content in HDL3b and -3c that concomitantly revealed the strongest vasorelaxing properties. NO generation was enhanced by HDL3c in SVECs (1.5-fold, P < 0.01), a phenomenon that was blocked by the S1P receptor antagonist, VPC 23019. S1P-enriched reconstituted HDL (rHDL) was a 1.8-fold ( P < 0.01) more potent vasorelaxant than control rHDL in aortic rings. Small dense HDL3 particles displayed potent protective effects against oxidative stress-associated endothelium dysfunction, potentially reflecting their elevated content of S1P that might facilitate interaction with S1P receptors and ensuing NO generation. Copyright © 2018 by the American Society for Biochemistry and Molecular Biology, Inc.

[Changes in endothelium-dependent dilation and α1-adrenoreactivity of rat aorta caused by inducible NO-synthase inhibition after motor activity restrictions].

PubMed

Solodkov, A P; Iatskovskaia, N M

2013-07-01

The aim of work was to study the influence of the highly selective blocker of the inducible NO-synthase (iNOS) of S-methylthiourea on the alteration of the endothelium-dependent vasodilation and α1-adrenoreactivity of the isolated rat aortic rings which underwent a short-term restriction of physical activity. The experiments were carried out on rat aortic rings preparations from female-rats bathed in Krebs-Henseleit solution, bubbled with 95% O2 and 5% CO2 and contracting in isometric mode. Endothelium-dependent dilation was caused by cumulative addition of acetylcholine (10-(10)-10(-4) M) after phenylephrine precontraction(10(-6) M). Adrenoreactivity was assessed through the response to increasing concentrations of α1-adrenergic receptor agonist. The 60-minute immobilization stress, characterized by the increase of the relative weight of the adrenal glands by 19.5%, the concentration of glucocorticoids (twice as much), of NO2/NO3 (stable NO degradation products) by 35%, the reduction in the level of thyroxine (by 16%), triiodothyronine (by 10%) and the increase in thyrotropic hormone by 45%, interleukin-1b (twice as much) and the appearance of tumour necrosis factor alpha in the blood serum, was accompanied by the two types of reaction of isolated aortic rings to acetylcholine and phenylephrine. The first one was expressed in the enhancing of acetylcholine-induced dilation of isolated aortic rings and the reduction of its response to α1-adrenergic stimulant phenylephrine. The second one showed a decrease in the response of isolated aortic rings to acetylcholine and enhancing the response to phenylephrine. But both of these reaction types were eliminated by using highly selective inducible NO-synthase inhibitor with S-methylisothiourea. However, it was differently directed with a different type of reaction. Taken together, these results suggest that the iNOS is formed in the cells of rat aorta under short-term stress. In some cases it can be a source of a large number of NO (coupling state of iNOS), and in another contribute reduce its bioavailability (uncoupling state of iNOS).

Impairment of endothelium-dependent relaxation of rat aortas by homocysteine thiolactone and attenuation by captopril.

PubMed

Liu, Yu-Hui; You, Yu; Song, Tao; Wu, Shu-Jing; Liu, Li-Ying

2007-08-01

To explore the effects of angiotensin-converting enzyme (ACE) inhibitors on endothelial dysfunction induced by homocysteine thiolactone (HTL). Both endothelium-dependent relaxation and nondependent relaxation of thoracic aortic rings in rats induced by acetylcholine (Ach) or sodium nitroprusside (SNP) and biochemical parameters including malondialdehyde (MDA) and nitric oxide (NO) were measured in rat isolated aorta. Exposure of aortic rings to HTL (3 to 30 mM) for 90 minutes made a significant inhibition of endothelium-dependent relaxation induced by Ach, decreased contents of NO, and increased MDA concentration in aortic tissue. After incubation of aortic rings with captopril (0.003 to 0.03 mM) attenuated the inhibition of endothelium-dependent relaxation (EDR) and significantly resisted the decrease of NO content and elevation of MDA concentration caused by HTL (30 mmol/L) in aortic tissues, a similarly protective effect was observed when the aortic rings were incubated with both N-acetylcysteine (0.05 mM). Treatment with enalaprilat (0.003 to 0.01 mM) made no significant difference with the HTL (30 mM) group regarding EDR, but enalaprilat (0.03 mM) and losartan (0.03 mM) could partly restore the EDR in response to HTL (30 mM). Captopril was more effective than enalaprilat and losartan in attenuation of the inhibition of on acetylcholine-stimulated aortic relaxation by HTL in the same concentration. Moreover, superoxide dismutase (SOD, 200 U/mL), which is a scavenger of superoxide anions, apocynin (0.03 mM), which is an inhibitor of NADPH oxidase, and l-Arginine (3 mmol/L), a precursor of nitric oxide (NO), could reduce HTL (30 mM)-induced inhibition of EDR. After pretreatment with not only the NO synthase inhibitor Nomega-nitro-l-arginine methyl ester (L-NAME, 0.01 mM) but also the free sulfhydryl group blocking agent p-hydroxymercurybenzoate (PHMB, 0.05 mM) could abolish the protection of captopril and N-acetylcysteine, respectively. These results suggest that mechanisms of endothelial dysfunction induced by HTL may include the decrease of NO and the generation of oxygen free radicals and that captopril can restore the inhibition of EDR induced by HTL in isolated rat aorta, which may be related to scavenging oxygen free radicals and may be sulfhydryl-dependent.

Erythropoietin has an antiapoptotic effect after myocardial infarction and stimulates in vitro aortic ring sprouting

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mansson Broberg, Agneta; Grinnemo, Karl-Henrik; Genead, Rami

Aims were to explore if darbepoietin-{alpha} in mouse can induce angiogenesis and if moderate doses after myocardial infarction stimulates periinfarct capillary and arteriolar densities, cell proliferation, and apoptosis. Myocardial infarction was induced by ligation of LAD. Mouse aortic rings (0.8 mm) were cultured in matrigel and the angiogenic sprouting was studied after addition of darbepoietin-{alpha} with and without VEGF-165. After 12 days the hemoglobin concentration was 25% higher in the darbepoietin-{alpha} treated mice than in the control group. No difference in capillary densities in the periinfarct or noninfarcted areas was seen with darbepoietin-{alpha}. Cell proliferation was about 10 times highermore » in the periinfarct area than in the noninfarcted wall. Darbepoietin-{alpha} treatment led to a decrease of cell proliferation (BrdU, (p < 0.02)) and apoptosis (TUNEL, p < 0.005) with about 30% in the periinfarct area. Darbepoietin-{alpha} and VEGF-165 both independently induced sprouting from aortic rings. The results suggest that darbepoietin-{alpha} can induce angiogenesis but that moderate doses after myocardial infarction are not angiogenic but antiapoptotic.« less

Magnesium prevents phosphate-induced vascular calcification via TRPM7 and Pit-1 in an aortic tissue culture model.

PubMed

Sonou, Tomohiro; Ohya, Masaki; Yashiro, Mitsuru; Masumoto, Asuka; Nakashima, Yuri; Ito, Teppei; Mima, Toru; Negi, Shigeo; Kimura-Suda, Hiromi; Shigematsu, Takashi

2017-06-01

Previous clinical and experimental studies have indicated that magnesium may prevent vascular calcification (VC), but mechanistic characterization has not been reported. This study investigated the influence of increasing magnesium concentrations on VC in a rat aortic tissue culture model. Aortic segments from male Sprague-Dawley rats were incubated in serum-supplemented high-phosphate medium for 10 days. The magnesium concentration in this medium was increased to demonstrate its role in preventing VC, which was assessed by imaging and spectroscopy. The mineral composition of the calcification was analyzed using Fourier transform infrared (FTIR) spectroscopic imaging, scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) mapping. Magnesium supplementation of high-phosphate medium dose-dependently suppressed VC (quantified as aortic calcium content), and almost ablated it at 2.4 mm magnesium. The FTIR images and SEM-EDX maps indicated that the distribution of phosphate (as hydroxyapatite), phosphorus and Mg corresponded with calcium content in the aortic ring and VC. The inhibitory effect of magnesium supplementation on VC was partially reduced by 2-aminoethoxy-diphenylborate, an inhibitor of TRPM7. Furthermore, phosphate transporter-1 (Pit-1) protein expression was increased in tissues cultured in HP medium and was gradually-and dose dependently-decreased by magnesium. We conclude that a mechanism involving TRPM7 and Pit-1 underpins the magnesium-mediated reversal of high-phosphate-associated VC.

Early alterations in vascular contractility associated to changes in fatty acid composition and oxidative stress markers in perivascular adipose tissue.

PubMed

Rebolledo, Alejandro; Rebolledo, Oscar R; Marra, Carlos A; García, María E; Roldán Palomo, Ana R; Rimorini, Laura; Gagliardino, Juan J

2010-10-21

To test the early effect of fructose-induced changes in fatty acid composition and oxidative stress markers in perivascular adipose tissue (PVAT) upon vascular contractility. Adult male Wistar rats were fed a commercial diet without (CD) or with 10% fructose (FRD) in the drinking water for 3 weeks. We measured plasma metabolic parameters, lipid composition and oxidative stress markers in aortic PVAT. Vascular contractility was measured in aortic rings sequentially, stimulated with serotonin (5-HT) and high K+-induced depolarization using intact and thereafter PVAT-deprived rings. Comparable body weights were recorded in both groups. FRD rats had increased plasma triglyceride and fructosamine levels. Their PVAT had an increased saturated to mono- or poly-unsaturated fatty acid ratio, a significant decrease in total superoxide dismutase and glutathione peroxidase activities and in the total content of glutathione. Conversely, lipid peroxidation (TBARS), nitric oxide content, and gluthathione reductase activity were significantly higher, indicating an increase in oxidative stress. In aortic rings, removal of PVAT increased serotonin-induced contractions, but the effect was significantly lower in rings from FRD rats. This effect was no longer observed when the two contractions were performed in PVAT-deprived rings. PVAT did not affect the contractions triggered by high K+-induced depolarization either in CD or FRD rats. FRD induces multiple metabolic and endocrine systemic alterations which also alter PVAT and the vascular relaxant properties of this tissue. The changes in PVAT would affect its paracrine modulation of vascular function.

Hydroxy-oleic acid, but not oleic acid, inhibits pharmacologic ...

EPA Pesticide Factsheets

Oleic acid (OA) and other fatty acids can become abundant in the systemic circulation after air pollution exposure as endogenously released lipolysis byproducts or by entering the body as a component of air pollution. Vascular damage has been observed with OA infusion, but it is not yet established whether increased circulating OA is able to produce the type of adverse cardiovascular effects associated with exposure to air pollution, or the mechanisms involved with such damage. Based on responses observed upon exposure of cultured endothelial cells, we hypothesized that OA and a hydroxylated metabolite (12-OH OA) would increase vascular tissue injury and impair vascular reactivity. Thoracic descending aorta tissue was collected from male Wistar Kyoto rats, aged 13-16 weeks. Prior to reactivity testing, independent LDH assays were performed with aortic rings to establish a subcytotoxic OA dose. To determine changes in vascular reactivity, aortic ring segments (n=3-4) were exposed for 1 hr to 100 µM OA, 12-OH OA, or an equivalent EtOH vehicle, followed by testing using myography and pharmacologic agents. Only 12-OH OA exposure significantly inhibited acetylcholine-induced endothelium-dependent vasorelaxation in aortic ring segments (25-30% reduction relative to EtOH control), based on maximum relaxation and dose-response. No change was seen in smooth muscle sensitivity to an exogenous nitric oxide source, sodium nitroprusside. Maximum aortic contractile force ge

Prosthetic valve sparing aortic root replacement: an improved technique.

PubMed

Leacche, Marzia; Balaguer, Jorge M; Umakanthan, Ramanan; Byrne, John G

2008-10-01

We describe a modified surgical technique to treat patients with a previous history of isolated aortic valve replacement who now require aortic root replacement for an aneurysmal or dissected aorta. This technique consists of replacing the aortic root with a Dacron conduit, leaving intact the previously implanted prosthesis, and re-implanting the coronary arteries in the Dacron graft. Our technique differs from other techniques in that we do not leave behind any aortic tissue remnant and also in that we use a felt strip to obliterate any gap between the old sewing ring and the newly implanted graft. In our opinion, this promotes better hemostasis. We demonstrate that this technique is safe, feasible, and results in acceptable outcomes.

Nitric oxide production contributes to Bacillus anthracis edema toxin-associated arterial hypotension and lethality: ex vivo and in vivo studies in the rat

PubMed Central

Li, Yan; Cui, Xizhong; Xu, Wanying; Ohanjanian, Lernik; Sampath-Kumar, Hanish; Suffredini, Dante; Moayeri, Mahtab; Leppla, Stephen; Fitz, Yvonne

2016-01-01

We showed previously that Bacillus anthracis edema toxin (ET), comprised of protective antigen (PA) and edema factor (EF), inhibits phenylephrine (PE)-induced contraction in rat aortic rings and these effects are diminished in endothelial-denuded rings. Therefore, employing rat aortic ring and in vivo models, we tested the hypothesis that nitric oxide (NO) contributes to ET's arterial effects. Compared with rings challenged with PA alone, ET (PA + EF) reduced PE-stimulated maximal contractile force (MCF) and increased the PE concentration producing 50% MCF (EC50) (P < 0.0001). Compared with placebo, l-nitro-arginine methyl-ester (l-NAME), an NO synthase (NOS) inhibitor, reduced ET's effects on MCF and EC50 in patterns that approached or were significant (P = 0.06 and 0.03, respectively). In animals challenged with 24-h ET infusions, l-NAME (0.5 or 1.0 mg·kg−1·h−1) coadministration increased survival to 17 of 28 animals (60.7%) compared with 4 of 27 (14.8%) given placebo (P = 0.01). Animals receiving l-NAME but no ET all survived. Compared with PBS challenge, ET increased NO levels at 24 h and l-NAME decreased these increases (P < 0.0001). ET infusion decreased mean arterial blood pressure (MAP) in placebo and l-NAME-treated animals (P < 0.0001) but l-NAME reduced decreases in MAP with ET from 9 to 24 h (P = 0.03 for the time interaction). S-methyl-l-thiocitrulline, a selective neuronal NOS inhibitor, had effects in rings and, at a high dose in vivo models, comparable to l-NAME, whereas N′-[3-(aminomethyl)benzyl]-acetimidamide, a selective inducible NOS inhibitor, did not. NO production contributes to ET's arterial relaxant, hypotensive, and lethal effects in the rat. PMID:27448553

Early alterations in vascular contractility associated to changes in fatty acid composition and oxidative stress markers in perivascular adipose tissue

PubMed Central

2010-01-01

Aim To test the early effect of fructose-induced changes in fatty acid composition and oxidative stress markers in perivascular adipose tissue (PVAT) upon vascular contractility. Methods Adult male Wistar rats were fed a commercial diet without (CD) or with 10% fructose (FRD) in the drinking water for 3 weeks. We measured plasma metabolic parameters, lipid composition and oxidative stress markers in aortic PVAT. Vascular contractility was measured in aortic rings sequentially, stimulated with serotonin (5-HT) and high K+-induced depolarization using intact and thereafter PVAT-deprived rings. Results Comparable body weights were recorded in both groups. FRD rats had increased plasma triglyceride and fructosamine levels. Their PVAT had an increased saturated to mono- or poly-unsaturated fatty acid ratio, a significant decrease in total superoxide dismutase and glutathione peroxidase activities and in the total content of glutathione. Conversely, lipid peroxidation (TBARS), nitric oxide content, and gluthathione reductase activity were significantly higher, indicating an increase in oxidative stress. In aortic rings, removal of PVAT increased serotonin-induced contractions, but the effect was significantly lower in rings from FRD rats. This effect was no longer observed when the two contractions were performed in PVAT-deprived rings. PVAT did not affect the contractions triggered by high K+-induced depolarization either in CD or FRD rats. Conclusions FRD induces multiple metabolic and endocrine systemic alterations which also alter PVAT and the vascular relaxant properties of this tissue. The changes in PVAT would affect its paracrine modulation of vascular function. PMID:20964827

Long-term treatment with nebivolol improves arterial reactivity and reduces ventricular hypertrophy in spontaneously hypertensive rats.

PubMed

Guerrero, Estela; Voces, Felipe; Ardanaz, Noelia; Montero, María José; Arévalo, Miguel; Sevilla, María Angeles

2003-09-01

The aim of this study was to assess the effects of long-term nebivolol therapy on high blood pressure, impaired endothelial function in aorta, and damage observed in heart and conductance arteries in spontaneously hypertensive rats (SHR). For this purpose, SHR were treated for 9 weeks with nebivolol (8 mg/kg per day). Untreated SHR and Wistar Kyoto rats were used as hypertensive and normotensive controls, respectively. The left ventricle/body weight ratio was used as an index of cardiac hypertrophy, and to evaluate vascular function, responses induced by potassium chloride, noradrenaline, acetylcholine, and sodium nitroprusside were tested on aortic rings. Aortic morphometry and fibrosis were determined in parallel by a quantitative technique. Systolic blood pressure, measured by the tail-cuff method, was lower in treated SHR than in the untreated group (194 +/- 3 versus 150 +/- 4 mm Hg). The cardiac hypertrophy index was significantly reduced by the treatment. In aortic rings, treatment with nebivolol significantly reduced the maximal response to both KCl and NA in SHR. In vessels precontracted with phenylephrine relaxant, activity due to acetylcholine was higher in normotensive rats than in SHR and the treatment significantly improved this response. The effect of sodium nitroprusside on aortic rings was similar in all groups. Medial thickness and collagen content were significantly reduced in comparison with SHR. In conclusion, the chronic antihypertensive effect of nebivolol in SHR was accompanied by an improvement in vascular structure and function and in the cardiac hypertrophy index.

Chronic administration of the probiotic kefir improves the endothelial function in spontaneously hypertensive rats.

PubMed

Friques, Andreia G F; Arpini, Clarisse M; Kalil, Ieda C; Gava, Agata L; Leal, Marcos A; Porto, Marcella L; Nogueira, Breno V; Dias, Ananda T; Andrade, Tadeu U; Pereira, Thiago Melo C; Meyrelles, Silvana S; Campagnaro, Bianca P; Vasquez, Elisardo C

2015-12-30

The beverage obtained by fermentation of milk with kefir grains, a complex matrix containing acid bacteria and yeasts, has been shown to have beneficial effects in various diseases. However, its effects on hypertension and endothelial dysfunction are not yet clear. In this study, we evaluated the effects of kefir on endothelial cells and vascular responsiveness in spontaneously hypertensive rats (SHR). SHR were treated with kefir (0.3 mL/100 g body weight) for 7, 15, 30 and 60 days and compared with non-treated SHR and with normotensive Wistar-Kyoto rats. Vascular endothelial function was evaluated in aortic rings through the relaxation response to acetylcholine (ACh). The balance between reactive oxygen species (ROS) and nitric oxide (NO) synthase was evaluated through specific blockers in the ACh-induced responses and through flow cytometry in vascular tissue. Significant effects of kefir were observed only after treatment for 60 days. The high blood pressure and tachycardia exhibited by the SHR were attenuated by approximately 15 % in the SHR-kefir group. The impaired ACh-induced relaxation of the aortic rings observed in the SHR (37 ± 4 %, compared to the Wistar rats: 74 ± 5 %), was significantly attenuated in the SHR group chronically treated with kefir (52 ± 4 %). The difference in the area under the curve between before and after the NADPH oxidase blockade or NO synthase blockade of aortic rings from SHR were of approximately +90 and -60 %, respectively, when compared with Wistar rats. In the aortic rings from the SHR-kefir group, these values were reduced to +50 and -40 %, respectively. Flow cytometric analysis of aortic endothelial cells revealed increased ROS production and decreased NO bioavailability in the SHR, which were significantly attenuated by the treatment with kefir. Scanning electronic microscopy showed vascular endothelial surface injury in SHR, which was partially protected following administration of kefir for 60 days. In addition, the recruitment of endothelial progenitor cells was decreased in the non-treated SHR and partially restored by kefir treatment. Kefir treatment for 60 days was able to improve the endothelial function in SHR by partially restoring the ROS/NO imbalance and the endothelial architecture due to endothelial progenitor cells recruitment.

"Ring pledget": a new concept for secure apex closure during transapical aortic valve implantation.

PubMed

Astarci, Parla; Glineur, David; Kefer, Joelle; Renkin, Jean; Vanoverschelde, Jean-Louis; El Khoury, Gebrine

2010-03-01

Transapical aortic valve implantation requires puncture of the left ventricle apex and insertion of a 32-French delivery sheath. A critical step in the procedure consists of secure closure of the ventricular apex. We describe 2 cases of apical rupture of 42 transapical aortic valve implantations. Furthermore, we describe the use of a newly designed single circular Teflon pledget that can help to avoid this complication. This pledget provides a more secure and uniform shrinkage of the entire apex to close the defect left by the delivery sheath.

Prosthetic Valve Endocarditis Caused by Bartonella henselae: A Case Report of Molecular Diagnostics Informing Nonsurgical Management

PubMed Central

Bartley, Patricia; Angelakis, Emmanouil; Raoult, Didier; Sampath, Rangarajan; Bonomo, Robert A.

2016-01-01

Identifying the pathogen responsible for culture-negative valve endocarditis often depends on molecular studies performed on surgical specimens. A patient with Ehlers-Danlos syndrome who had an aortic graft, a mechanical aortic valve, and a mitral anulloplasty ring presented with culture-negative prosthetic valve endocarditis and aortic graft infection. Research-based polymerase chain reaction (PCR)/electrospray ionization mass spectrometry on peripheral blood samples identified Bartonella henselae. Quantitative PCR targeting the16S-23S ribonucleic acid intergenic region and Western immunoblotting confirmed this result. This, in turn, permitted early initiation of pathogen-directed therapy and subsequent successful medical management of B henselae prosthetic valve endocarditis and aortic graft infection. PMID:27844027

Effect of Mucuna pruriens Seed Extract Pretreatment on the Responses of Spontaneously Beating Rat Atria and Aortic Ring to Naja sputatrix (Javan Spitting Cobra) Venom

PubMed Central

Fung, Shin Yee; Tan, Nget Hong; Sim, Si Mui; Aguiyi, John C.

2012-01-01

Mucuna pruriens Linn. (velvet bean) has been used by native Nigerians as a prophylactic for snakebite. Rats pretreated with M. pruriens seed extract (MPE) have been shown to protect against the lethal and cardiovascular depressant effects of Naja sputatrix (Javan spitting cobra) venoms, and the protective effect involved immunological neutralization of the venom toxins. To investigate further the mechanism of the protective effect of MPE pretreatment against cobra venom toxicity, the actions of Naja sputatrix venom on spontaneously beating rat atria and aortic rings isolated from both MPE pretreated and untreated rats were studied. Our results showed that the MPE pretreatment conferred protection against cobra venom-induced depression of atrial contractility and atrial rate in the isolated atrial preparations, but it had no effect on the venom-induced contractile response of aortic ring preparation. These observations suggested that the protective effect of MPE pretreatment against cobra venom toxicity involves a direct protective action of MPE on the heart function, in addition to the known immunological neutralization mechanism, and that the protective effect does not involve action on blood vessel contraction. The results also suggest that M. pruriens seed may contain novel cardioprotective agent with potential therapeutic value. PMID:21785646

[Protective effects of polysacchride of Spirulina platensis and Sargassum thunbeergii on vascular of alloxan induced diabetic rats].

PubMed

Huang, Zhi-xuan; Mei, Xue-ting; Xu, Dong-hui; Xu, Shi-bo; Lv, Jun-yi

2005-02-01

To study the protective effects of polysaccharide of Spirulina platensis and Sargassum thunbeergii on vascular of alloxan (ALX) induced diabetic rats. With the doses of polysaccharide of Spirulina platensis (PSP) and Sargassum thunbeergii (PST) compound (1:1) 12.261, 36.783, 110.349 mg x kg(-1) by i.g. administration to alloxan induced diabetic rats respectively for 6 weeks. Then the blood glucose and the TC, HDL-C, TG, NO, ET in serum were detected. The contraction and relaxation response to NE and ACh in aortic rings of the alloxan induced diabetic rats has been studied. The results showed the compound of PSP and PST could decrease the blood glucose and the TC, TG, NO, ET in serum and increase HDL-C than in the alloxan induced diabetic rats. The contraction responses to NE in aortic rings of the alloxan induced diabetic rats were significantly elevated in the normal rats, and the responses to ACh were significantly lower. PSP and PST compound could significantly lower the responses to NE and significantly elevate the responses to ACh in aortic rings of the alloxan induced diabetic rats. PSP and PST compound could decrease blood glucose and could protect the vascular of alloxan induced diabetic rats.

[Feasibility and possibility of Inoue stent graft for thoracic aortic aneurysms].

PubMed

Marui, Akira; Kimura, Takeshi; Tazaki, Junichi; Sakata, Ryuzo; Inoue, Kanji

2011-01-01

Open surgical repair is a traditional treatment for patients with thoracic aortic aneurysms. Despite recent advances in surgical techniques and anesthetic management, the surgical repair of thoracic aortic aneurysms is still associated with significant mortality and morbidity. Endovascular aneurysm repair of thoracic aortic aneurysms is emerging as an alternative method for repair in selected patients. Although endovascular stent grafting is less invasive than open surgical repair, involvement of branch vessels and precipitous curvature of the aortic arch limits the application of stent grafting. Inoue stent graft system consists of soft nitinol ring-type stent which enables very flexible stent graft, and it can well comply with the precipitous curvature of the aortic arch. The system also provides a stent graft with a side branch to manage the left subclavian artery. This system does not require the surgical revascularization of the left subclavian artery. In this report, we show the feasibility and possibility of Inoue stent graft system to manage the aortic arch aneurysm.

Multidetector-row computed tomography of thoracic aortic anomalies in dogs and cats: Patent ductus arteriosus and vascular rings

PubMed Central

2011-01-01

Background Diagnosis of extracardiac intrathoracic vascular anomalies is of clinical importance, but remains challenging. Traditional imaging modalities, such as radiography, echocardiography, and angiography, are inherently limited by the difficulties of a 2-dimensional approach to a 3-dimensional object. We postulated that accurate characterization of malformations of the aorta would benefit from 3-dimensional assessment. Therefore, multidetector-row computed tomography (MDCT) was chosen as a 3-dimensional, new, and noninvasive imaging technique. The purpose of this study was to evaluate patients with 2 common diseases of the intrathoracic aorta, either patent ductus arteriosus or vascular ring anomaly, by contrast-enhanced 64-row computed tomography. Results Electrocardiography (ECG)-gated and thoracic nongated MDCT images were reviewed in identified cases of either a patent ductus arteriosus or vascular ring anomaly. Ductal size and morphology were determined in 6 dogs that underwent ECG-gated MDCT. Vascular ring anomalies were characterized in 7 dogs and 3 cats by ECG-gated MDCT or by a nongated thoracic standard protocol. Cardiac ECG-gated MDCT clearly displayed the morphology, length, and caliber of the patent ductus arteriosus in 6 affected dogs. Persistent right aortic arch was identified in 10 animals, 8 of which showed a coexisting aberrant left subclavian artery. A mild dilation of the proximal portion of the aberrant subclavian artery near its origin of the aorta was present in 4 dogs, and a diverticulum analogous to the human Kommerell's diverticulum was present in 2 cats. Conclusions Contrast-enhanced MDCT imaging of thoracic anomalies gives valuable information about the exact aortic arch configuration. Furthermore, MDCT was able to characterize the vascular branching patterns in dogs and cats with a persistent right aortic arch and the morphology and size of the patent ductus arteriosus in affected dogs. This additional information can be of help with regard to improved diagnoses of thoracic anomalies and the planning of surgical interventions. PMID:21943366

Vascular response of ruthenium tetraamines in aortic ring from normotensive rats.

PubMed

Conceição-Vertamatti, Ana Gabriela; Ramos, Luiz Alberto Ferreira; Calandreli, Ivy; Chiba, Aline Nunes; Franco, Douglas Wagner; Tfouni, Elia; Grassi-Kassisse, Dora Maria

2015-03-01

Ruthenium (Ru) tetraamines are being increasingly used as nitric oxide (NO) carriers. In this context, pharmacological studies have become highly relevant to better understand the mechanism of action involved. To evaluate the vascular response of the tetraamines trans-[Ru(II)(NH3)4(Py)(NO)](3+), trans-[Ru(II)(Cl)(NO) (cyclan)](PF6)2, and trans-[Ru(II)(NH3)4(4-acPy)(NO)](3+). Aortic rings were contracted with noradrenaline (10(-6) M). After voltage stabilization, a single concentration (10(-6) M) of the compounds was added to the assay medium. The responses were recorded during 120 min. Vascular integrity was assessed functionally using acetylcholine at 10(-6) M and sodium nitroprusside at 10(-6) M as well as by histological examination. Histological analysis confirmed the presence or absence of endothelial cells in those tissues. All tetraamine complexes altered the contractile response induced by norepinephrine, resulting in increased tone followed by relaxation. In rings with endothelium, the inhibition of endothelial NO caused a reduction of the contractile effect caused by pyridine NO. No significant responses were observed in rings with endothelium after treatment with cyclan NO. In contrast, in rings without endothelium, the inhibition of guanylate cyclase significantly reduced the contractile response caused by the pyridine NO and cyclan NO complexes, and both complexes caused a relaxing effect. The results indicate that the vascular effect of the evaluated complexes involved a decrease in the vascular tone induced by norepinephrine (10(-6) M) at the end of the incubation period in aortic rings with and without endothelium, indicating the slow release of NO from these complexes and suggesting that the ligands promoted chemical stability to the molecule. Moreover, we demonstrated that the association of Ru with NO is more stable when the ligands pyridine and cyclan are used in the formulation of the compound.

Syndecan-4 shedding impairs macrovascular angiogenesis in diabetes mellitus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Ran; Xie, Jun; Wu, Han

Purpose: Syndecan-4 (synd4) is a ubiquitous heparan sulfate proteoglycan cell surface receptor that modulates cell proliferation, migration, mechanotransduction, and endocytosis. The extracellular domain of synd4 sheds heavily in acute inflammation, but the shedding of synd4 in chronic inflammation, such as diabetes mellitus (DM), is still undefined. We investigated the alterations of synd4 endothelial expression in DM and the influence of impaired synd4 signaling on angiogenesis in human umbilical vein endothelial cells (HUVECs), diabetic rats, synd4 null mice, and db/db mice. Material and methods: HUVECs were incubated with advanced glycation end products (AGEs). Western blot analysis was used to determine synd4more » protein expression and ELISA was used to detect soluble synd4 fragments. The concentration of synd4 in the aortic endothelia of diabetic rats was detected by immunohistochemical staining. Aortic ring assays were performed to study the process of angiogenesis in the diabetic rats and in synd4 null and db/db mice. Recombinant adenoviruses containing the synd4 gene or null were constructed to enhance synd4 aortic expression in db/db mice. Results: Western blot analysis showed decreased expression of the synd4 extracellular domain in HUVECs, and ELISA detected increased soluble fragments of synd4 in the media. Synd4 endothelial expression in the aortas of diabetic rats was decreased. Aortic ring assay indicated impaired angiogenesis in synd4 null and db/db mice, which was partially reversed by synd4 overexpression in db/db mice. Conclusion: Synd4 shedding from vascular endothelial cells played an important role in the diabetes-related impairment of angiogenesis. -- Highlights: •Synd4 shedding from endothelial cells is accelerated under the stimulation of AGEs. •Extracellular domain of synd4 is diminished in the endothelium of DM rats. •Aortic rings of synd4 null mice showed impaired angiogenesis. •Overexpression of synd4 partly rescues macrovascular angiogenesis in db/db mice.« less

Vascular activation of K+ channels and Na+-K+ ATPase activity of estrogen-deficient female rats.

PubMed

Ribeiro Junior, Rogério Faustino; Fiorim, Jonaina; Marques, Vinicius Bermond; de Sousa Ronconi, Karoline; Botelho, Tatiani; Grando, Marcella D; Bendhack, Lusiane M; Vassallo, Dalton Valentim; Stefanon, Ivanita

2017-12-01

The goal of the present study was to evaluate vascular potassium channels and Na + -K + -ATPase activity in estrogen deficient female rats. Female rats that underwent ovariectomy were assigned to receive daily treatment with placebo (OVX) or estrogen replacement (OVX+E2, 1mg/kg, once a week, i.m.). Aortic rings were used to examine the involvement of K + channels and Na + -K + -ATPase in vascular reactivity. Acetylcholine (ACh)-induced relaxation was analyzed in the presence of L-NAME (100μM) and K + channels blockers: tetraethylammonium (TEA, 5mM), 4-aminopyridine (4-AP, 5mM), iberiotoxin (IbTX, 30nM), apamin (0.5mM), charybdotoxin (ChTX, 0.1mM) and iberiotoxin plus apamin. When aortic rings were pre-contracted with KCl (60mM) or pre-incubated with TEA (5mM), 4-aminopyridine (4-AP, 5mM) and iberiotoxin (IbTX, 30nM) plus apamin (0.5μM), the ACh-induced relaxation was less effective in the ovariectomized group. Additionally, 4-AP and IbTX decreased the relaxation by sodium nitroprusside in all groups but this reduction was greater in the ovariectomized group. Estrogen deficiency also increased aortic functional Na + -K + ATPase activity evaluated by K + -induced relaxation. L-NAME or endothelium removal were not able to block the increase in aortic functional Na + -K + ATPase activity, however, TEA (5mM) restored this increase to the control level. We also found that estrogen deficiency increased superoxide anion production and reduced nitric oxide release in aortic ring from ovariectomized animals. In summary, our results emphasize that the process underlying ACh-induced relaxation is preserved in ovariectomized animals due to the activation of K + channels and increased Na + -K + ATPase activity. Copyright © 2017 Elsevier Inc. All rights reserved.

Insights from diversified anti-angiogenic models: Role of β-interferon inducer DEAE-Dextran.

PubMed

Bakrania, Anita K; Variya, Bhavesh C; Patel, Snehal S

2018-04-17

Angiogenesis, the physiological process involving growth of new blood vessels from preexisting vessels, is essential for organ growth and repair. However, the imbalance in angiogenesis contributes to copious pathologies including cancer. Preceding the development of anti-angiogenic or proangiogenic agents, its evaluation is equally imperative; hence, precise and adequate models required. Valid mammalian models are expensive, time-consuming and not easy to set up, instigating legal and ethical aspects making it necessary to establish models with satisfactory activity and limited drawbacks. We investigated the activity of DEAE-Dextran on diversified models viz. in vitro cell migration assay, ex vivo aortic ring assay, in vitro chick yolk sac membrane assay and in vivo matrigel plug xenograft model corroborating its anti-angiogenic potential and establishing the best means of evaluation. Assorted models were reproducible and correlative to one another. DEAE-Dextran exhibited excellent anti-angiogenic effect in cell migration assay over a duration of 24 h compared to the vehicle control fibroblast cell line and aortic ring possessed an alleviated rate of sprouting when treated with DEAE-Dextran with contrast to vehicle control aorta. Similarly, decreased vascular density was observed in DEAE-Dextran treated chick embryos implicating potency of the β-interferon inducer. Augmenting to these results, the matrigel plugs also mitigated vascular net as well as reduced levels of angiogenic marker CD31. Substantially, DEAE-Dextran leads to anti-tumor activity through anti-angiogenic action and a combination of in vitro and in vivo model is vital for the judgement of anti-angiogenic potential since an in vitro model exempts mammalian-culture considerations. Copyright © 2018 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

Double Aortic Arch With Previously Undescribed Head and Neck Vessel Branching.

PubMed

Hashemi, Sassan; Parks, W James; Sallee, Denver; Slesnick, Timothy

2017-04-01

Vascular ring in the form of a double aortic arch is a rare anomaly that can cause airway compression. It occasionally occurs with unusual head and neck vessel branching. A 5-year-old boy with chronic respiratory symptoms was referred because of a tracheal indentation on his chest x-ray. Magnetic resonance imaging showed a double aortic arch with arch origins of a common carotid, vertebral, and subclavian on the right and internal and external carotids, vertebral, and subclavian arteries on the left. Our case represents, to our knowledge, the first report of a double aortic arch with 7 separate vessels arising from the transverse arches. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Flaxseed oil increases aortic reactivity to phenylephrine through reactive oxygen species and the cyclooxygenase-2 pathway in rats

PubMed Central

2014-01-01

Background Flaxseed oil has the highest concentration of omega-3 α-linolenic acid, which has been associated with cardiovascular benefit. However, the mechanism underlying the vascular effects induced through flaxseed oil is not well known. Thus, in the present study, we investigated the effects of flaxseed oil on vascular function in isolated rat aortic rings. Methods Wistar rats were treated daily with flaxseed oil or a control (mineral oil) intramuscular (i.m.) for fifteen days. Isolated aortic segments were used to evaluate cyclooxygenase-2 (COX-2) protein expression, superoxide anion levels and vascular reactivity experiments. Results Flaxseed oil treatment increased the vasoconstrictor response of aortic rings to phenylephrine. Endothelium removal increased the response to phenylephrine in aortic segments isolated from both groups, but the effect was smaller in the treated group. L-NAME incubation similarly increased the phenylephrine response in segments from both groups. The TXA2 synthase inhibitor furegrelate, the selective COX-2 inhibitor NS 398, the TP receptor antagonist SQ 29.548, the reactive oxygen species (ROS) scavenger apocynin, the superoxide anion scavengers tiron and the phospholipase A2 inhibitor dexamethasone partially reversed the flaxseed oil-induced increase in reactivity to phenylephrine. Conclusions These findings suggest that flaxseed oil treatment increased vascular reactivity to phenylephrine through an increase in ROS production and COX-2-derived TXA2 production. The results obtained in the present study provide new insight into the effects of flaxseed oil treatment (i.m.) on vascular function. PMID:24993607

Vasorelaxant effects of aqueous leaf extract of Tridax procumbens on aortic smooth muscle isolated from the rat.

PubMed

Salahdeen, Hussein M; Murtala, Babatunde A

2012-01-01

Tridax procumbens is commonly used in traditional medicine in southern part of Nigeria for the treatment of hypertension. However, the mechanism of its antihypertensive properties remains unclear. Attempts were made to investigate the properties of direct actions of aqueous extract of the leaves of T. procumbens on mechanical responses of smooth muscles in aortic ring preparations isolated from the rat. Endothelium-intact aortic rings, isolated from the normotensive rats, had been pre-contracted with noradrenaline, and cumulative addition of the aqueous extract (0.15-1.05 mg/mL) to the bathing fluid induced a concentration-dependent relaxation. Aqueous extract of T. procumbens also attenuated the contractile responses to KCl and shifted the concentration-response curve to the right. The contractile responses to serotonin were also attenuated and the concentration-response curve was shifted to the right in the presence of the extract. The results of this study indicated that aqueous leaf extract of T. procumbens possesses vasodilatory effects on the aortic smooth muscles isolated from the rat. Based on these results, a possible mechanism involved in the relaxing actions of the extract on vascular smooth muscle was discussed. The results of this study may provide a scientific basis for the use of this extract to the treatment of hypertension in Nigerian traditional medicine.

Exercise training improves relaxation response and SOD-1 expression in aortic and mesenteric rings from high caloric diet-fed rats.

PubMed

de Moraes, Camila; Davel, Ana Paula Couto; Rossoni, Luciana Venturini; Antunes, Edson; Zanesco, Angelina

2008-05-29

Obesity has been associated with a variety of disease such as type II diabetes mellitus, arterial hypertension and atherosclerosis. Evidences have shown that exercise training promotes beneficial effects on these disorders, but the underlying mechanisms are not fully understood. The aim of this study was to investigate whether physical preconditioning prevents the deleterious effect of high caloric diet in vascular reactivity of rat aortic and mesenteric rings. Male Wistar rats were divided into sedentary (SD); trained (TR); sedentary diet (SDD) and trained diet (TRD) groups. Run training (RT) was performed in sessions of 60 min, 5 days/week for 12 weeks (70-80% VO2max). Triglycerides, glucose, insulin and nitrite/nitrate concentrations (NOx-) were measured. Concentration-response curves to acetylcholine (ACh) and sodium nitroprusside (SNP) were obtained. Expression of Cu/Zn superoxide dismutase (SOD-1) was assessed by Western blotting. High caloric diet increased triglycerides concentration (SDD: 216 +/- 25 mg/dl) and exercise training restored to the baseline value (TRD: 89 +/- 9 mg/dl). Physical preconditioning significantly reduced insulin levels in both groups (TR: 0.54 +/- 0.1 and TRD: 1.24 +/- 0.3 ng/ml) as compared to sedentary animals (SD: 0.87 +/- 0.1 and SDD: 2.57 +/- 0.3 ng/ml). On the other hand, glucose concentration was slightly increased by high caloric diet, and RT did not modify this parameter (SD: 126 +/- 6; TR: 140 +/- 8; SDD: 156 +/- 8 and TRD 153 +/- 9 mg/dl). Neither high caloric diet nor RT modified NOx- levels (SD: 27 +/- 4; TR: 28 +/- 6; SDD: 27 +/- 3 and TRD: 30 +/- 2 microM). Functional assays showed that high caloric diet impaired the relaxing response to ACh in mesenteric (about 13%), but not in aortic rings. RT improved the relaxing responses to ACh either in aortic (28%, for TR and 16%, to TRD groups) or mesenteric rings (10%, for TR and 17%, to TRD groups) that was accompanied by up-regulation of SOD-1 expression and reduction in triglycerides levels. The improvement in endothelial function by physical preconditioning in mesenteric and aortic arteries from high caloric fed-rats was directly related to an increase in NO bioavailability to the smooth muscle mostly due to SOD-1 up regulation.

Role of inducible nitric oxide synthase in endothelium‐independent relaxation to raloxifene in rat aorta

PubMed Central

Au, Chak Leung; Tsang, Suk Ying; Lau, Chi Wai; Yao, Xiaoqiang; Cai, Zongwei

2017-01-01

Background and Purpose Raloxifene can induce both endothelium‐dependent and ‐independent relaxation in different arteries. However, the underlying mechanisms by which raloxifene triggers endothelium‐independent relaxation are still incompletely understood. The purpose of present study was to examine the roles of NOSs and Ca2+ channels in the relaxant response to raloxifene in the rat isolated, endothelium‐denuded aorta. Experimental Approach Changes in isometric tension, cGMP, nitrite, inducible NOS protein expression and distribution in response to raloxifene in endothelium‐denuded aortic rings were studied by organ baths, radioimmunoassay, Griess reaction, western blot and immunohistochemistry respectively. Key Results Raloxifene reduced the contraction to CaCl2 in a Ca2+‐free, high K+‐containing solution in intact aortic rings. Raloxifene also acutely relaxed the aorta primarily through an endothelium‐independent mechanism involving NO, mostly from inducible NOS (iNOS) in vascular smooth muscle layers. This effect of raloxifene involved the generation of cGMP and nitrite. Also, it was genomic in nature, as it was inhibited by a classical oestrogen receptor antagonist and inhibitors of RNA and protein synthesis. Raloxifene‐induced stimulation of iNOS gene expression was partly mediated through activation of the NF‐κB pathway. Raloxifene was more potent than 17β‐estradiol or tamoxifen at relaxing endothelium‐denuded aortic rings by stimulation of iNOS. Conclusions and Implications Raloxifene‐mediated vasorelaxation in rat aorta is independent of a functional endothelium and is mediated by oestrogen receptors and NF‐κB. This effect is mainly mediated through an enhanced production of NO, cGMP and nitrite, via the induction of iNOS and inhibition of calcium influx through Ca2+ channels in rat aortic smooth muscle. PMID:28138957

Green synthesis of silver nanoparticles using Achillea biebersteinii flower extract and its anti-angiogenic properties in the rat aortic ring model.

PubMed

Baharara, Javad; Namvar, Farideh; Ramezani, Tayebe; Hosseini, Nasrin; Mohamad, Rosfarizan

2014-04-15

Silver nanoparticles display unique physical and biological properties which have attracted intensive research interest because of their important medical applications. In this study silver nanoparticles (Ab.Ag-NPs) were synthesized for biomedical applications using a completely green biosynthetic method using Achillea biebersteinii flowers extract. The structure and properties of Ab.Ag-NPs were investigated using UV-visible spectroscopic techniques, transmission electron microscopy (TEM), zeta potential and energy dispersive X-ray spectrometers (EDS). The UV-visible spectroscopic analysis showed the absorbance peak at 460 nm, which indicates the synthesis of silver nanoparticles. The average particle diameter as determined by TEM was found to be 12±2 nm. The zeta potential analysis indicated that Ab.Ag-NPs have good stability EDX analysis also exhibits presentation of silver element. As angiogenesis is an important phenomenon and as growth factors imbalance in this process causes the acceleration of several diseases including cancer, the anti-angiogenic properties of Ab.Ag-NPs were evaluated using the rat aortic ring model. The results showed that Ab.Ag-NPs (200 μg/mL) lead to a 50% reduction in the length and number of vessel-like structures. The synthesized silver nanoparticles from the Achillea biebersteinii flowers extract, which do not involve any harmful chemicals were well-dispersed and stabilized through this green method and showed potential therapeutic benefits against angiogenesis.

Antioxidant effects of methylprednisolone and hydrocortisone on the impairment of endothelium dependent relaxation induced by reactive oxygen species in rabbit abdominal aorta

PubMed Central

Lee, Hee Jong; Song, Hyun Hoo; Jeong, Mi Ae; Yeom, Jong Hoon; Kim, Dong Won

2013-01-01

Background The reperfusion following ischemia produces reactive oxygen species (ROS). We studied the influences of methylprednisolone (MPD) and hydrocortisone (CRT) on ROS effects using the endothelium of rabbit abdominal aorta. Methods Isolated rabbit aortic rings were suspended in an organ bath filled with Krebs-Henseleit (K-H) solution. After precontraction with norepinephrine, changes in arterial tension were recorded following the cumulative administration of acetylcholine (ACh). The percentages of ACh-induced relaxation of aortic rings before and after exposure to ROS, generated by electrolysis of K-H solution, were used as the control and experimental values, respectively. The aortic rings were pretreated with MPD or CRT at the same concentrations, and the effects of these agents were compared with the effects of ROS scavenger inhibitors: superoxide dismutase inhibitor, diethylthiocarbamate (DETCA), and the catalase inhibitor, 3-amino-1,2,4-triazole (3AT). Results Both MPD and CRT maintained endothelium-dependent relaxation induced by ACh in a dose-related manner in spite of ROS attack. The restored ACh-induced relaxation of MPD and CRT group was not attenuated by pretreatment of 3AT and DETCA. Conclusions MPD and CRT preserve the endothelium-dependent vasorelaxation against the attack of ROS, in a dose-related manner. Endothelial protection mechanisms of MPD and CRT may be not associated with hydrogen peroxide and superoxide scavenging. PMID:23372887

Oesophageal foreign body and a double aortic arch: rare dual pathology.

PubMed

O'Connor, T E; Cooney, T

2009-12-01

We report the rare case of an oesophageal foreign body which lodged above the site of oesophageal compression by a double aortic arch. Case report and a review of the literature surrounding the classification, embryology, diagnosis and management of vascular rings and slings. An eight-month-old male infant presented with symptoms of tracheal compression following ingestion of an oesophageal foreign body. Following removal of the oesophageal foreign body, the infant's symptoms improved initially. However, subsequent recurrence of respiratory symptoms lead to a repeat bronchoscopy and the diagnosis of a coexisting double aortic arch, causing tracheal and oesophageal compression. To our knowledge, this is only the second reported case of a double aortic arch being diagnosed in a patient following removal of an oesophageal foreign body.

[Effects of intermediate conductance calcium-activated potassium channel blocker TARAM-34 on β-glycerophosphate induced vascular smooth muscle cells calcification].

PubMed

Zhang, S L; Xu, J S; Yang, S; Bai, Y L; Zhang, J X; Cui, L W; Yu, Q Y

2016-06-24

To observe the role of TRAM-34 (1-((2-chlorophenyl)diphenylmethyl)-1H-pyrazole), the blocker of intermediate conductance calcium-activated potassium channel (KCa3.1), on β-glycerophosphate induced vascular calcification in vitro. Vascular smooth muscle cells(VSMCs) were obtained from rat thoracic aorta, and VSMCs after the fourth passage and aortic rings were divided into control group (cultured in DMEM with 10% fetal bovine serum), high phosphorus group (cultured in DMEM with 10% fetal bovine serum and 10% β-glycerophosphate) and TRAM-34 group(20 nmol/L TRAM-34 was added into high phosphorus DMEM). Calcium deposition of VSMCs and aortic rings were measured by o-cresolphthalein complexone method.Calcium influx of VSMCs was measured by immunofluorescence probe Fluo-3 AM.The expression of runt-related transcription factor 2(Runx2)was detected by RT-PCR and Western blot for cells and immunohistochemistry for aortic rings.ALP activity was measured by alkaline phosphatase activity detection kit. (1) Compared with control group, calcification was significantly increased in high phosphorus group ((121.67±6.17) mg/g vs. (84.38±8.17) mg/g, P<0.05) and this effect could be attenuated by TRAM-34 ((93.31±11.36) mg/g, P<0.05 vs. high phosphorus group) after 12 days culture. Similar results were found in aortic rings cultured for 12 days-high phosphorus group: (7.17±0.57) mg/g vs. (1.18±0.13) mg/g (P<0.05) and TRAM-34: (4.71±0.42) mg/g, P<0.05 vs. high phosphorus group.(2) Compared with control group, the calcium influx was higher in high phosphorus group (349.22±40.47 vs. 151.67±16.94, P<0.05) and reduced in TRAM-34 group (194.67±22.21, P<0.05 vs. high phosphorus group) in VSMCs simulated for 4 days. (3) Both mRNA and protein expressions of Runx2 in high phosphorus groups were higher than in control group (0.630±0.033 vs.0.340±0.058 and 0.865±0.031 vs.0.414±0.011, both P<0.05) and lower in TRAM-34 group (0.399±0.023 and 0.575±0.014, both P<0.05 vs. high phosphorus group) in VSMCs simulated for 4 days.Besides, compared with high phosphorus group, the expression of Runx2 was decreased in control group(0.113±0.010 vs.0.067±0.008, P<0.05) and TRAM-34 group (0.069±0.006, P<0.05) after aortic rings were cultured for 4 days. (4) Compared with control group, the activity of ALP was significantly increased in high phosphorus group (96.56±9.84 vs.46.92±4.60, P<0.05) and decreased in TRAM-34 group(70.20±8.41, P<0.05 vs. high phosphorus group) in VSMCs simulated for 12 days. KCa3.1 blocker TRAM-34 can inhibit β-glycerophosphate induced VSMCs and aortic ring calcification through inhibiting calcium influx, downregulating Runx2 expression and attenuating osteogenic differentiation.

Hemodynamics in an Aorta with Bicuspid and Trileaflet Valves

NASA Astrophysics Data System (ADS)

Gilmanov, Anvar; Sotiropoulos, Fotis

2015-11-01

Bicuspid aortic valve (BAV) is a congenital heart defect that has been associated with serious aortopathies, such as ascending aortic aneurysm, aortic stenosis, aortic regurgitation, infective endocarditis, aortic dissection, calcific aortic valve and dilatation of ascending aorta. Two main hypotheses - the genetic and the hemodynamic are discussed in literature to explain the development and progression of aortopathies in patients with BAV. In this study we seek to investigate the possible role of hemodynamic factors as causes of BAV-associated aortopathy. We employ the Curvilinear Immersed Boundary (CURVIB) method coupled with an efficient thin-shell finite element (TS-FE) formulation for tissues to carry out fluid-structure interaction simulations of a healthy tri-leaflet aortic valve (TAV) and a BAV placed in the same anatomic aorta. The computed results reveal major differences between the TAV and BAV flow patterns. These include: the dynamics of the aortic valve vortex ring formation and break up; the large scale flow patterns in the ascending aorta; and the shear stress magnitude on the aortic wall. The computed results are in qualitative agreement with in vivo Magnetic Resonance Imaging (MRI) data and suggest that the linkages between BAV aortopathy and hemodynamics deserve further investigation. This work is supported by the Lillehei Heart Institute at the University of Minnesota and the Minnesota Supercomputing Institute.

Anomalous origin of the left innominate (brachiocephalic) artery in the right aortic arch: How can it be anomalous when the left innominate artery is absent?

PubMed

Raimondi, Francesca; Bonnet, Damien; Geva, Tal; Sanders, Stephen P

2016-01-01

An unusual case of a rare vascular ring, which has been called right aortic arch with aberrant left innominate artery, is presented. The appearance of this case led to the realization that there is really no innominate artery present in this anomaly but only the left dorsal aorta. We present a clarification of the nature and likely development of the vessels present.

Reduced L-Carnitine Transport in Aortic Endothelial Cells from Spontaneously Hypertensive Rats

PubMed Central

Salsoso, Rocío; Guzmán-Gutiérrez, Enrique; Arroyo, Pablo; Salomón, Carlos; Zambrano, Sonia; Ruiz-Armenta, María Victoria; Blanca, Antonio Jesús; Pardo, Fabián; Leiva, Andrea; Mate, Alfonso; Sobrevia, Luis; Vázquez, Carmen María

2014-01-01

Impaired L-carnitine uptake correlates with higher blood pressure in adult men, and L-carnitine restores endothelial function in aortic rings from spontaneously hypertensive rat (SHR). Thus, endothelial dysfunction in hypertension could result from lower L-carnitine transport in this cell type. L-Carnitine transport is mainly mediated by novel organic cation transporters 1 (Octn1, Na+-independent) and 2 (Octn2, Na+-dependent); however, their kinetic properties and potential consequences in hypertension are unknown. We hypothesize that L-carnitine transport kinetic properties will be altered in aortic endothelium from spontaneously hypertensive rats (SHR). L-Carnitine transport was measured at different extracellular pH (pHo 5.5–8.5) in the absence or presence of sodium in rat aortic endothelial cells (RAECs) from non-hypertensive Wistar-Kyoto (WKY) rats and SHR. Octn1 and Octn2 mRNA relative expression was also determined. Dilation of endothelium-intact or denuded aortic rings in response to calcitonine gene related peptide (CGRP, 0.1–100 nmol/L) was measured (myography) in the absence or presence of L-carnitine. Total L-carnitine transport was lower in cells from SHR compared with WKY rats, an effect due to reduced Na+-dependent (Na+ dep) compared with Na+-independent (Na+ indep) transport components. Saturable L-carnitine transport kinetics show maximal velocity (V max), without changes in apparent K m for Na+ indep transport in SHR compared with WKY rats. Total and Na+ dep component of transport were increased, but Na+ indep transport was reduced by extracellular alkalization in WKY rats. However, alkalization reduced total and Na+ indep transport in cells from SHR. Octn2 mRNA was higher than Octn-1 mRNA expression in cells from both conditions. Dilation of artery rings in response to CGRP was reduced in vessels from SHR compared with WKY rats. CGRP effect was endothelium-dependent and restored by L-carnitine. All together these results suggest that reduced L-carnitine transport (likely via Na+-dependent Octn2) could limit this compound's potential beneficial effects in RAECs from SHR. PMID:24587332

Effect of nabumetone treatment on vascular responses of the thoracic aorta in rat experimental arthritis.

PubMed

Ulker, S; Onal, A; Hatip, F B; Sürücü, A; Alkanat, M; Koşay, S; Evinç, A

2000-04-01

Nabumetone is a nonsteroidal anti-inflammatory (NSAI) drug which is known to cause less gastrointestinal damage than other NSAI drugs. This study was performed to evaluate whether nabumetone treatment might alter the vascular aberrations related to inflammation in a rat model of adjuvant-induced arthritis. Nabumetone treatment (120 or 240 mg x kg(-1) x day(-1), orally) was initiated on the 15th day of adjuvant inoculation and continued for 14 days. Arthritic lesions, vascular contractile and relaxant responses and gastroduodenal histopathological preparations were evaluated 29 days after adjuvant inoculation. The contractile responses of aortic rings to phenylephrine and KCl were increased in grade 2 arthritic rats. In grade 3 arthritis only the phenylephrine contractility was decreased. The relaxant responses to acetylcholine and sodium nitroprusside were decreased in grades 2 and 3. In healthy rats, nabumetone did not change the vascular responses. After treatment of arthritic rats with nabumetone, both the contractile and relaxant response of the aortic rings returned to normal, and arthritic score and paw swelling were reduced. Gastroduodenal histopathology did not show erosions or ulcers in any of the groups. In conclusion, nabumetone improved the systemic signs and vascular alterations in experimental arthritis without showing any gastrointestinal side effects. Copyright 2000 S. Karger AG, Basel.

Comparative hemodynamics in an aorta with bicuspid and trileaflet valves

NASA Astrophysics Data System (ADS)

Gilmanov, Anvar; Sotiropoulos, Fotis

2016-04-01

Bicuspid aortic valve (BAV) is a congenital heart defect that has been associated with serious aortopathies, such as aortic stenosis, aortic regurgitation, infective endocarditis, aortic dissection, calcific aortic valve and dilatation of ascending aorta. There are two main hypotheses to explain the increase prevalence of aortopathies in patients with BAV: the genetic and the hemodynamic. In this study, we seek to investigate the possible role of hemodynamic factors as causes of BAV-associated aortopathy. We employ the curvilinear immersed boundary method coupled with an efficient thin-shell finite-element formulation for tissues to carry out fluid-structure interaction simulations of a healthy trileaflet aortic valve (TAV) and a BAV placed in the same anatomic aorta. The computed results reveal major differences between the TAV and BAV flow patterns. These include: the dynamics of the aortic valve vortex ring formation and break up; the large-scale flow patterns in the ascending aorta; the shear stress magnitude, directions, and dynamics on the heart valve surfaces. The computed results are in qualitative agreement with in vivo magnetic resonance imaging data and suggest that the linkages between BAV aortopathy and hemodynamics deserve further investigation.

Antioxidant effect of lidocaine and procaine on reactive oxygen species-induced endothelial dysfunction in the rabbit abdominal aorta

PubMed Central

Lee, Jae Myeong; Jeong, Ji Seon; Cho, Sang Yun; Kim, Dong Won

2010-01-01

Background Reactive oxygen species (ROS) induce lipid peroxidation and tissue damage in the endothelium. We tested the antioxidant effect of lidocaine and procaine on ROS-induced endothelial damage in the rabbit aorta. Methods Aortic rings isolated from rabbits were suspended in an organ bath filled with Krebs-Henseleit (K-H) solution bubbled with 5% CO2 and 95% O2 at 37.5℃. After precontraction with phenylephrine (PE, 10-6 M), changes in tension were recorded following a cumulative administration of acetylcholine (ACh 3 × 10-8 to 10-6 M). Differences were measured as percentages of ACh-induced relaxation of aortic rings before and after exposure to ROS as generated by electrolysis of the K-H solution. The aortic rings were pretreated with lidocaine or procaine (10-5 M to 3 × 10-3 M) to compare their effects, as well as ROS scavengers, catalase, mannitol, sodium salicylate, and deferoxamine, and a catalase inhibitor, 3-amino-1,2,4-triazole (3AT). Results Lidocaine and procaine dose-dependently maintained endothelium-dependent relaxation induced by ACh despite ROS activity (P < 0.05 vs control value). The 3AT pretreated procaine (3 × 10-3 M) group decreased more significantly than the un-pretreated procaine group (P < 0.05). Conclusions These findings suggest that lidocaine and procaine dose-dependently preserve endothelium-dependent vasorelaxation against ROS attack, potentially via hydrogen peroxide scavenging. PMID:20740215

Vasorelaxant effect of formononetin in the rat thoracic aorta and its mechanisms.

PubMed

Zhao, Yan; Chen, Bai-Nian; Wang, Shou-Bao; Wang, Shao-Hua; Du, Guan-Hua

2012-01-01

The purpose of the present study was to investigate the effect of formononetin and the related mechanisms on isolated rat thoracic aorta. Formononetin concentration dependently relaxed aortic rings precontracted with norepinephrine (NE, 1 μM) or KCl (80 mM). Pretreatment with formononetin noncompetitively inhibited contractile responses of aortas to NE and KCl. The vasorelaxant effect of formononetin partially relied on intact endothelia, which was significantly attenuated by incubation with N(ω)-nitro-L-arginine methyl ester (100 μM). In endothelium-denuded rings, glibenclamide (10 μM) and tetraethylammonium (5 mM) showed slight reduction in the vasorelaxant effect of formononetin. Moreover, formononetin reduced NE-induced transient contraction in Ca²⁺-free solution and inhibited the vasocontraction induced by increasing external calcium in medium plus 80 mM KCl. Our results suggested that formononetin induced relaxation in rat aortic rings through an endothelium-dependent manner via nitric oxide synthesis pathway, and also involving an endothelium-independent vasodilatation by the blockade of Ca²⁺ channels. The opening of K⁺ channels might also be one of the mechanisms of formononetin-induced vasorelaxation.

Effects of Hindlimb Unweighting on Arterial Contractile Responses in Mice

NASA Technical Reports Server (NTRS)

Ma, Jia; Ren, Xin-Ling; Purdy, Ralph E.

2003-01-01

The aim of this work was to determine if hindlimb unweighting in mice alters arterial contractile responses. Sixteen male C57B/6 mice and 16 male Chinese Kunming mice were divided into control and 3 weeks hindlimb unweighting groups, respectively. Using isolated arterial rings from different arteries of mouse, effects of 3 weeks hindlimb unweighting on arterial contractile responsiveness were examined in vitro. The results showed that, in arterial rings from both C57B/6 and Chinese Kunming mice, maximum isometric contractile tensions evoked by either KCl or phenylephrine were significantly lower in abdominal aortic, mesenteric arterial and femoral arterial rings from hindlimb unweighting, compared to control mice. However, the maximal contractile responses of common carotid rings to KCl and PE were not significantly different between control and hindlimb unweighting groups. The sensitivity (EC(sub 50)) of all arteries to KCl or PE showed no significant differences between control and hindlimb unweighting mice. These data indicated that 3 weeks hindlimb unweighting results in a reduced capacity of the arterial smooth muscle of the hindquarter to develop tension. In addition, the alterations in arterial contractile responses caused by hindlimb unweighting in mice are similar as those in rats. Our work suggested that hindlimb unweighting mouse model may be used as a model for the study of postflight cardiovascular deconditioning.

Activity of a new hydrogen sulfide-releasing aspirin (ACS14) on pathological cardiovascular alterations induced by glutathione depletion in rats.

PubMed

Rossoni, Giuseppe; Manfredi, Barbara; Tazzari, Valerio; Sparatore, Anna; Trivulzio, Silvio; Del Soldato, Piero; Berti, Ferruccio

2010-12-01

We investigated the effects of the hydrogen sulfide (H₂S)-releasing derivatives of aspirin (ACS14) and salicylic acid (ACS21) in a rat model of metabolic syndrome induced by glutathione (GSH) depletion, causing hypertension and other pathological cardiovascular alterations. GSH depletion was induced in normal rats by the GSH-synthase inhibitor buthionine sulfoximine (BSO, 30 mmol/L day for seven days in the drinking water). Systolic blood pressure and heart rate were measured daily by the tail-cuff method, and plasma thromboxane B₂, 6-keto-prostaglandin F(2α), 8-isoprostane, GSH, insulin and glucose were determined at the end of the seven-day BSO schedule. In addition, ischemia/reperfusion-induced myocardial dysfunction and endothelial dysfunction were assayed on isolated heart and aortic rings, respectively. Unlike aspirin and salicylic acid, ACS14 and ACS21 reduced BSO-induced hypertension, also lowering plasma levels of thromboxane B₂, 8-isoprostane and insulin, while GSH remained in the control range. Neither ACS14 nor ACS21 caused gastric lesions. Both restored the endothelial dysfunction observed in aortic rings from BSO-treated rats, and in ischemia/reperfusion experiments they lowered left ventricular end-diastolic pressure, consequently improving the developed pressure and the maximum rise and fall of left ventricular pressure. Together with this improvement of heart mechanics there were reductions in the activity of creatine kinase and lactate dehydrogenase in the cardiac perfusate. This implies that H₂S released by both ACS14 and ACS21 was involved in protecting the heart from ischemia/reperfusion, and significantly limited vascular endothelial dysfunction in aortic tissue and the related hypertension. Copyright © 2010 Elsevier B.V. All rights reserved.

Aortic arch syndrome

MedlinePlus

... including: Congenital absence of a branch of the aorta Isolation of the subclavian arteries Vascular rings An ... Braverman AC. Diseases of the aorta. In: Bonow RO, Mann DL, Zipes DP, ... Heart Disease: A Textbook of Cardiovascular Medicine . 10th ...

Vasomodulatory effect of novel peroxovanadate compounds on rat aorta: Role of rho kinase and nitric oxide/cGMP pathway.

PubMed

Khanna, Vivek; Jain, Manish; Barthwal, Manoj Kumar; Kalita, Diganta; Boruah, Jeena Jyoti; Das, Siva Prasad; Islam, Nashreen S; Ramasarma, Tangirala; Dikshit, Madhu

2011-09-01

The present study was undertaken to assess the role of reactive oxygen species (ROS) in rat aortic ring vasoreactivity and integrity by using various peroxovanadate (pV) compounds. All the pV compounds (1nM-300 μM) used in the present study exerted concentration-dependent contractions on endothelium intact rat aortic rings. All compounds with an exception of DPV-asparagine (DPV-asn) significantly altered vascular integrity as shown by diminished KCl responses. Phenylephrine (PE)-mediated contractions (3nM-300 μM) were unaltered in the presence of these compounds. Acetylcholine (Ach)-mediated relaxation in PE (1μM) pre-contracted rings was significantly reduced in presence of diperoxovanadate (DPV), poly (sodium styrene sulfonate-co-maleate)-pV (PSS-CoM-pV) and poly (sodium styrene 4-sulfonate)-pV (PSS-pV). However, no significant change in Ach-mediated responses was observed in the presence of poly (acrylate)-pV (PAA-pV) and DPV-asn. DPV-asn was thus chosen to further elucidate mechanism involved in peroxide mediated modulation of vasoreactivity. DPV-asn (30nM - 300 μM) exerted significantly more stable contractions, that was found to be catalase (100U/ml) resistant in comparison with H(2)O(2) (30nM-300 μM) in endothelium intact aortic rings. These contractile responses were found to be dependent on extracellular Ca(2+) and were significantly inhibited in presence of ROS scavenger N-acetylcysteine (100 μM). Intracellular calcium chelation by BAPTA-AM (10μM) had no significant effect on DPV-asn (30nM-300 μM) mediated contraction. Pretreatment of aortic rings by rho-kinase inhibitor Y-27632 (10μM) significantly inhibited DPV-asn-mediated vasoconstriction indicating role of voltage-dependent Ca(2+) influx and downstream activation of rho-kinase. The small initial relaxant effect obtained on addition of DPV-asn (30nM-1 μM) in PE (1 μM) pre-contracted endothelium intact rings, was prevented in the presence of guanylate cyclase inhibitor, methylene blue (10 μM) and/or nitric oxide synthase (NOS) inhibitor, l-NAME (100 μM) suggesting involvement of nitric oxide and cGMP. DPV-asn, like H(2)O(2), exerted a response of vasoconstriction in normal arteries and vasodilation at low concentrations (30nM-1 μM) in PE-pre contracted rings with overlapping mechanisms. These findings suggest usefulness of DPV-asn having low toxicity, in exploring the peroxide-mediated effects on various vascular beds. The present study also convincingly demonstrates role of H(2)O(2) in the modulation of vasoreactivity by using stable peroxide DPV-asn and warrants future studies on peroxide mediated signaling from a newer perspective. 2011 Published by Elsevier Ltd.

Vasodilator effects and putative guanylyl cyclase stimulation by 2-nitro-1-phenylethanone and 2-nitro-2-phenyl-propane-1,3-diol on rat aorta.

PubMed

Vasconcelos, Thiago Brasileiro de; Ribeiro-Filho, Helder Veras; Lahlou, Saad; Pereira, José Geraldo de Carvalho; Oliveira, Paulo Sérgio Lopes de; Magalhães, Pedro Jorge Caldas

2018-07-05

Compounds containing a nitro group may reveal vasodilator properties. Several nitro compounds have a NO 2 group in a short aliphatic chain connected to an aromatic group. In this study, we evaluated in rat aorta the effects of two nitro compounds, with emphasis on a putative recruitment of the soluble guanylate cyclase (sGC) pathway to induce vasodilation. Isolated aortic rings were obtained from male Wistar rats to compare the effects induced by 2-nitro-1-phenylethanone (NPeth) or 2-nitro-2-phenyl-propane-1,3-diol (NPprop). In aortic preparations contracted with phenylephrine or KCl, NPeth and NPprop induced vasorelaxant effects that did not depend on the integrity of vascular endothelium. NPeth had a lesser vasorelaxant efficacy than NPprop and only the NPprop effects were inhibited by pretreatment with the sGC inhibitors, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) or methylene blue. In an ODQ-preventable manner, NPprop inhibited the contractile component of the phenylephrine-induced response mediated by intracellular Ca 2+ release or by extracellular Ca 2+ recruitment through receptor- or voltage-operated Ca 2+ channels. In contrast, NPprop was inert against the transient contraction induced by caffeine in Ca 2+ -free medium. In an ODQ-dependent manner, NPprop inhibited the contraction induced by the protein kinase C activator phorbol 12,13-dibutyrate or by the tyrosine phosphatase inhibitor sodium orthovanadate. In silico docking analysis of a sGC homologous protein revealed preferential site for NPprop. In conclusion, the nitro compounds NPeth and NPprop induced vasorelaxation in rat aortic rings. Aliphatic chain substituents selectively interfered in the ability of these compounds to induce vasorelaxant effects, and only NPprop relaxed aortic rings via a sGC pathway. Copyright © 2018 Elsevier B.V. All rights reserved.

Double aortic arch and persistent left vena cava in a white lion cub (Panthera leo).

PubMed

Goldin, J P; Lambrechts, N E

1999-03-01

A 4-mo-old female white lion (Panthera leo) cub was presented with a 2-wk history of persistent postprandial regurgitation, mild dyspnea, and poor weight gain. The cub was weak and thin but otherwise alert. Survey and contrast radiography revealed a large dilated esophagus cranial to the heart base, with an esophageal filling defect present at the level of the fourth thoracic vertebra. A vascular ring anomaly was tentatively diagnosed. Exploratory thoracotomy revealed a double aortic arch and a persistent left vena cava. The left aortic arch was ligated and divided, and recovery was uneventful. A single episode of regurgitation occurred within the first postoperative month, and the cub gained 5.5 kg in weight during the same time period. Neither double aortic arch nor persistent left vena cava has been reported in a nondomestic felid.

Sildenafil restores endothelial function in the apolipoprotein E knockout mouse

PubMed Central

2013-01-01

Background Atherosclerosis is an inflammatory process of the arterial walls and is initiated by endothelial dysfunction accompanied by an imbalance in the production of reactive oxygen species (ROS) and nitric oxide (NO). Sildenafil, a selective phosphodiesterase-5 (PDE5) inhibitor used for erectile dysfunction, exerts its cardiovascular effects by enhancing the effects of NO. The aim of this study was to investigate the influence of sildenafil on endothelial function and atherosclerosis progression in apolipoprotein E knockout (apoE−/−) mice. Methods ApoE−/− mice treated with sildenafil (Viagra®, 40 mg/kg/day, for 3 weeks, by oral gavage) were compared to the untreated apoE−/− and the wild-type (WT) mice. Aortic rings were used to evaluate the relaxation responses to acetylcholine (ACh) in all of the groups. In a separate set of experiments, the roles of NO and ROS in the relaxation response to ACh were evaluated by incubating the aortic rings with L-NAME (NO synthase inhibitor) or apocynin (NADPH oxidase inhibitor). In addition, the atherosclerotic lesions were quantified and superoxide production was assessed. Results Sildenafil restored the vasodilator response to acetylcholine (ACh) in the aortic rings of the apoE−/− mice. Treatment with L-NAME abolished the vasodilator responses to ACh in all three groups of mice and revealed an augmented participation of NO in the endothelium-dependent vasodilation in the sildenafil-treated animals. The normalized endothelial function in sildenafil-treated apoE−/− mice was unaffected by apocynin highlighting the low levels of ROS production in these animals. Moreover, morphological analysis showed that sildenafil treatment caused approximately a 40% decrease in plaque deposition in the aorta. Conclusion This is the first study demonstrating the beneficial effects of chronic treatment with sildenafil on endothelial dysfunction and atherosclerosis in a model of spontaneous hypercholesterolemia. These data indicate that the main mechanism of the beneficial effect of sildenafil on the endothelial function appears to involve an enhancement of the NO pathway along with a reduction in oxidative stress. PMID:23289368

Dependence of endotoxin-induced vascular hyporeactivity on extracellular L-arginine.

PubMed

Schott, C A; Gray, G A; Stoclet, J C

1993-01-01

1. The dependence on extracellular L-arginine of vascular hyporeactivity induced by bacterial lipopolysaccharide (LPS) was studied in vivo in rats infused with LPS and in vitro in endothelium-denuded rat thoracic aortic rings exposed to LPS. 2. Infusion of LPS during 50 min at a dose of 10 mg kg-1 h-1 produced a significant impairment of the pressor effect of noradrenaline, while in tissues collected 60 min after the start of LPS infusion, no significant alteration in either plasma arginine concentration or aortic arginine content was found compared to saline-infused controls (where plasma arginine was 78.5 +/- 7 microM and aortic arginine 394 +/- 124 nmol g-1 tissue). 3. Incubation of isolated, endothelium-denuded aortic rings with LPS (10 micrograms ml-1) in the absence of L-arginine for 4 h at 37 degrees C produced a 6 fold (P < 0.01) rightward shift in the noradrenaline concentration-effect curve compared to polymyxin B (1 micrograms ml-1, a LPS neutralizing agent) and reduced by 15% the maximum observed tension. 4. The presence of L-arginine (100 microM) during the incubation with LPS and throughout the following contraction experiments caused a 15 fold (P < 0.01) increase in the EC50 of noradrenaline and greater depression (45%) of the maximum observed tension compared to polymyxin B-treated controls. Responses in control, non LPS-treated rings were unaffected by the presence of L-arginine. 5. The addition of L-arginine to rings incubated with LPS in the absence of L-arginine and maximally precontracted with noradrenaline (10 microM) induced a dose-dependent relaxation. The EC50 of L-arginine was 8.0+/-0.3mu.6. The reactivity of LPS-treated rings to noradrenaline both in the absence and presence of L-arginine was restored to control levels by N0-nitro-L-arginine methyl ester (L-NAME, 300 mu), an inhibitor of NO production and by methylene blue (3 JAM), an inhibitor of guanylate cyclase.7. Incubation of isolated aortae in the absence of L-arginine did not significantly decrease the tissue arginine content, whether LPS (10 fg ml-') was present or not. Similarly, the presence of L-arginine(100 mu) in the incubation medium did not modify the tissue arginine content.8. These results show that the LPS-induced impairment of vasoconstriction elicited by noradrenaline is dependent on extracellular L-arginine, although the tissue arginine content is not depleted after LPS pretreatment, and that circulating L-arginine is sufficient to activate maximally the vascular L-arginine/NO pathway in endotoxaemic rats.

Asymptomatic strut fracture in DeBakey-Surgitool aortic valves: incidence, management, and metallurgic aspects.

PubMed

Von Der Emde J, J; Eberlein, U; Breme J, J

1990-01-01

From August 1971 through November 1972, we implanted 62 Model 2 DeBakey-Surgitool aortic valve prostheses in 62 patients, 4 of whom later had clinically asymptomatic strut fractures. In 1 case, the patient died suddenly, and autopsy revealed detachment of the ball-cage; in each of the other 3 cases, fractures of 2 struts close to the base of the prosthesis were diagnosed fluoroscopically, and the patients underwent successful reoperation. The interval between implantation and reoperation ranged from 11 months to 16 years, 9 months. In 1 patient, retrospective study of chest radiographs revealed that the fracture had been present for 2(1/2) years. Larger valves (>/= A6) were affected significantly more often than smaller ones. We performed metallurgic analysis of 1 prosthesis: results revealed strut wear from fatigue cracking and secondary abrasion. Strut fracture was also promoted by suspension of the cage at right angles to the prosthetic ring and by use of a pyrolytic carbon ball in a titanium cage (i.e., an occluder harder than its holder). Patients with DeBakey-Surgitool aortic valve prostheses should undergo annual radiologic examinations to enable early detection of strut fractures. Prophylactic valve replacement is not indicated.

Use of 3D models of vascular rings and slings to improve resident education.

PubMed

Jones, Trahern W; Seckeler, Michael D

2017-09-01

Three-dimensional (3D) printing is a manufacturing method by which an object is created in an additive process, and can be used with medical imaging data to generate accurate physical reproductions of organs and tissues for a variety of applications. We hypothesized that using 3D printed models of congenital cardiovascular lesions to supplement an educational lecture would improve learners' scores on a board-style examination. Patients with normal and abnormal aortic arches were selected and anonymized to generate 3D printed models. A cohort of pediatric and combined pediatric/emergency medicine residents were then randomized to intervention and control groups. Each participant was given a subjective survey and an objective board-style pretest. Each group received the same 20-minutes lecture on vascular rings and slings. During the intervention group's lecture, 3D printed physical models of each lesion were distributed for inspection. After each lecture, both groups completed the same subjective survey and objective board-style test to assess their comfort with and postlecture knowledge of vascular rings. There were no differences in the basic demographics of the two groups. After the lectures, both groups' subjective comfort levels increased. Both groups' scores on the objective test improved, but the intervention group scored higher on the posttest. This study demonstrated a measurable gain in knowledge about vascular rings and pulmonary artery slings with the addition of 3D printed models of the defects. Future applications of this teaching modality could extend to other congenital cardiac lesions and different learners. © 2017 Wiley Periodicals, Inc.

Design, synthesis and biological evaluation of novel ring-opened cromakalim analogues with relaxant effects on vascular and respiratory smooth muscles and as stimulators of elastin synthesis.

PubMed

Bouhedja, Mourad; Peres, Basile; Fhayli, Wassim; Ghandour, Zeinab; Boumendjel, Ahcène; Faury, Gilles; Khelili, Smail

2018-01-20

Two new series of ring-opened analogues of cromakalim bearing sulfonylurea moieties (series A: with N-unmethylated sulfonylureas, series B: with N-methylated sulfonylureas) were synthesized and tested as relaxants of vascular and respiratory smooth muscles (rat aorta and trachea, respectively). Ex vivo biological evaluations indicated that the most active compounds, belonging to series B, displayed a marked vasorelaxant activity on endothelium-intact aortic rings and the trachea. A majority of series B compounds exhibited a higher vasorelaxant activity (EC 50  < 22 μM) than that of the reference compound diazoxide (EC 50  = 24 μM). Interestingly, several tested compounds of series B also presented stronger relaxant effects on the trachea than the reference compound cromakalim (EC 50  = 124 μM), in particular compounds B4, B7 and B16 (EC 50  < 10 μM). By contrast, series A derivatives were poorly active on aortic rings (EC 50  > 57 μM for all, and EC 50  > 200 μM for a majority of them), but some of them showed an interesting relaxing effect on trachea (i.e. A15 and A33, EC 50  = 30 μM). The most potent compounds of both series, i.e. A15, A33 and B16, tested on aortic rings in the presence of glibenclamide or 80 mM KCl, suggested that they acted as voltage-gated Ca 2+ channel blockers, like verapamil, instead of being ATP-potassium channel activators, as is cromakalim, the parent molecule. Further investigations on cultured vascular smooth muscle cells showed a strong stimulating effect on elastin synthesis, especially compound B16, which was more active at 20 μM than diazoxide, a reference ATP-sensitive potassium channel activator. Taken together, our results show that the N-methylation of the sulfonylurea moieties of ring-opened cromakalim analogues led to new compounds blocking calcium-gated channels, which had a major impact on the arterial and tracheal activities as well as selectivity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Effect of prolonged incubation with copper on endothelium-dependent relaxation in rat isolated aorta

PubMed Central

Chiarugi, Alberto; Pitari, Giovanni Mario; Costa, Rosa; Ferrante, Margherita; Villari, Loredana; Amico-Roxas, Matilde; Godfraind, Théophile; Bianchi, Alfredo; Salomone, Salvatore

2002-01-01

We investigated the effects of prolonged exposure to copper (Cu2+) on vascular functioning of isolated rat aorta. Aortic rings were exposed to CuSO4 (3–24 h) in Dulbecco's modified Eagle medium with or without 10% foetal bovine serum (FBS) and then challenged with vasoconstrictors or vasodilators in the absence of Cu2+. Exposure to 2 μM Cu2+ in the absence of FBS did not modify the response to phenylephrine (PE) or acetylcholine (ACh) in aortic rings incubated for 24 h. Identical exposure in the presence of FBS increased the contractile response to 1 μM PE by 30% (P<0.05) and impaired the relaxant response to 3 μM ACh or 1 μM A23187 (ACh, from 65.7±7.1 to 6.2±1.1%, n=8; A23187, from 74.6±8.2 to 12.0±0.8%, n=6; P<0.01 for both). Cu2+ exposure did not affect the relaxant response to NO-donors. Impairment of vasorelaxation appeared 3 h after incubation with 2 μM Cu2+ and required 12 h to attain a steady state. Vasorelaxation to ACh was partially restored by 1 mM tiron (intracellular scavenger of superoxide ions; maximum relaxation 34.2±6.4%, n=10, P<0.01 vs Cu2+ alone), whereas catalase, superoxide dismutase or cycloheximide were ineffective. Twenty-four hour-exposure to 2 μM Cu2+ did not affect endothelium integrity or eNOS expression, and increased the Cu content in arterial rings from 6.8±1.1 to 18.9±2.9 ng mg−1 wet weight, n=8; P<0.01. Our results show that, in the presence of FBS, prolonged exposure to submicromolar concentrations of Cu2+ impaired endothelium-dependent vasorelaxation in aortic rings, probably through an intracellular generation of superoxide ions. PMID:12163352

Endothelial TWIST1 Promotes Pathological Ocular Angiogenesis

PubMed Central

Li, Jie; Liu, Chi-Hsiu; Sun, Ye; Gong, Yan; Fu, Zhongjie; Evans, Lucy P.; Tian, Katherine T.; Juan, Aimee M.; Hurst, Christian G.; Mammoto, Akiko; Chen, Jing

2014-01-01

Purpose. Pathological neovessel formation impacts many blinding vascular eye diseases. Identification of molecular signatures distinguishing pathological neovascularization from normal quiescent vessels is critical for developing new interventions. Twist-related protein 1 (TWIST1) is a transcription factor important in tumor and pulmonary angiogenesis. This study investigated the potential role of TWIST1 in modulating pathological ocular angiogenesis in mice. Methods. Twist1 expression and localization were analyzed in a mouse model of oxygen-induced retinopathy (OIR). Pathological ocular angiogenesis in Tie2-driven conditional Twist1 knockout mice were evaluated in both OIR and laser-induced choroidal neovascularization models. In addition, the effects of TWIST1 on angiogenesis and endothelial cell function were analyzed in sprouting assays of aortic rings and choroidal explants isolated from Twist1 knockout mice, and in human retinal microvascular endothelial cells treated with TWIST1 small interfering RNA (siRNA). Results. TWIST1 is highly enriched in pathological neovessels in OIR retinas. Conditional Tie2-driven depletion of Twist1 significantly suppressed pathological neovessels in OIR without impacting developmental retinal angiogenesis. In a laser-induced choroidal neovascularization model, Twist1 deficiency also resulted in significantly smaller lesions with decreased vascular leakage. In addition, loss of Twist1 significantly decreased vascular sprouting in both aortic ring and choroid explants. Knockdown of TWIST1 in endothelial cells led to dampened expression of vascular endothelial growth factor receptor 2 (VEGFR2) and decreased endothelial cell proliferation. Conclusions. Our study suggests that TWIST1 is a novel regulator of pathologic ocular angiogenesis and may represent a new molecular target for developing potential therapeutic treatments to suppress pathological neovascularization in vascular eye diseases. PMID:25414194

Purified anthocyanin supplementation improves endothelial function via NO-cGMP activation in hypercholesterolemic individuals.

PubMed

Zhu, Yanna; Xia, Min; Yang, Yan; Liu, Fengqiong; Li, Zhongxia; Hao, Yuantao; Mi, Mantian; Jin, Tianru; Ling, Wenhua

2011-11-01

Anthocyanins have been shown to improve endothelial function in animal models. However, whether these compounds have similar beneficial effects in humans is largely unknown. In a short-term crossover study, 12 hypercholesterolemic individuals were given oral anthocyanins (320 mg) isolated from berries or placebo. Brachial artery flow-mediated dilation (FMD) was assessed before and after the intervention. In a long-term intervention trial (12 weeks), 150 hypercholesterolemic individuals were given anthocyanins (320 mg/day, n = 75) or placebo (n = 75), after which we measured FMD, plasma cGMP, and other serum biomarkers. Another short-term intervention was conducted in the presence of NO-cGMP inhibitors in 6 people and in a rat aortic ring model (n = 8). Significant increases of FMD from 8.3% (0.6%) at baseline to 11.0% (0.8%) at 1 h and 10.1% (0.9%) at 2 h were observed after short-term anthocyanin consumption, concomitantly with increases of plasma anthocyanin concentrations (P < 0.05). In the study participants who received long-term anthocyanin intervention, compared with the control group, we observed significant increases in the FMD (28.4% vs 2.2%), cGMP (12.6% vs -1.2%), and HDL-cholesterol concentrations, but decreases in the serum soluble vascular adhesion molecule-1 and LDL cholesterol concentrations (P < 0.05). The changes in the cGMP and HDL cholesterol concentrations positively correlated with FMD in the anthocyanin group (P < 0.05). In the presence of NO-cGMP inhibitors, the effects of anthocyanin on endothelial function were abolished in human participants and in a rat aortic ring model. Anthocyanin supplementation improves endothelium-dependent vasodilation in hypercholesterolemic individuals. This effect involves activation of the NO-cGMP signaling pathway, improvements in the serum lipid profile, and decreased inflammation.

Mesenchymal stem cell-based HSP70 promoter-driven VEGFA induction by resveratrol promotes angiogenesis in a mouse model.

PubMed

Chen, Young-Bin; Lan, Ying-Wei; Hung, Tsai-Hsien; Chen, Lih-Geeng; Choo, Kong-Bung; Cheng, Winston T K; Lee, Hsuan-Shu; Chong, Kowit-Yu

2015-07-01

Several studies of stem cell-based gene therapy have indicated that long-lasting regeneration following vessel ischemia may be stimulated through VEGFA gene therapy and/or MSC transplantation for reduction of ischemic injury in limb ischemia and heart failure. The therapeutic potential of MSC transplantation can be further improved by genetically modifying MSCs with genes which enhance angiogenesis following ischemic injury. In the present study, we aimed to develop an approach in MSC-based therapy for repair and mitigation of ischemic injury and regeneration of damaged tissues in ischemic disease. HSP70 promoter-driven VEGFA expression was induced by resveratrol (RSV) in MSCs, and in combination with known RSV biological functions, the protective effects of our approach were investigated by using ex vivo aortic ring coculture system and a 3D scaffolds in vivo model. Results of this investigation demonstrated that HSP promoter-driven VEGFA expression in MSC increased approximately 2-fold over the background VEGFA levels upon HSP70 promoter induction by RSV. Exposure of HUVEC cells to medium containing MSC in which VEGFA had been induced by cis-RSV enhanced tube formation in the treated HUVEC cells. RSV-treated MSC cells differentiated into endothelial-like phenotypes, exhibiting markedly elevated expression of endothelial cell markers. These MSCs also induced aortic ring sprouting, characteristic of neovascular formation from pre-existing vessels, and additionally promoted neovascularization at the MSC transplantation site in a mouse model. These observations support a hypothesis that VEGFA expression induced by cis-RSV acting on the HSP70 promoter in transplanted MSC augments the angiogenic effects of stem cell gene therapy. The use of an inducible system also vastly reduces possible clinical risks associated with constitutive VEGFA expression.

Mechanism of vasorelaxation induced by Tridax procumbens extract in rat thoracic aorta

PubMed Central

Salahdeen, Hussein Mofomosara; Idowu, Gbolahan O; Salami, Shakiru A; Murtala, Babatunde A; Alada, AbdulRasak A

2016-01-01

Background/Aim: Tridax procumbens (Linn) (Asteraceae) is one of the herbs widely distributed in many parts of the world. Its leaves have long been used for the treatment of hypertension in Nigeria. Previous studies have shown that aqueous leaves of T. procumbens extract (TPE) lowers blood pressure through endothelium-dependent and -independent mechanism in the aortic rings isolated from normotensive rats. The aim of the present study was to further investigate mechanisms of TPE-induced relaxation in the aortic artery by assessing its mechanistic interactions with nitric oxide (NO) synthase, cyclic guanosine monophosphate (cGMP), and cyclic adenosine monophosphate (cAMP). Materials and Methods: The aortic artery isolated from healthy, young adult normotensive Wistar albino rats (250-300 g) were pre-contracted with phenylephrine (PE) (10–7 M) and KCl (60 mM) and were treated with various concentrations of aqueous extract of TPE (0.5-9.0 mg/ml). The changes in arterial tension were recorded using Ugo Basile model 7004 coupled to data capsule acquisition system model 17400. The interaction between TPE with cAMP and cGMP inhibitors was also evaluated. Results: The results showed that the TPE (0.5-9.0 mg/ml) significantly (P < 0.05) reduced the contraction induced by PE in a concentration-dependent manner. The vasorelaxant effect caused by the TPE was significantly (P < 0.05) attenuated with pre-incubation of cGMP (Rp-8Br PET cGMPS) and cAMP (Rp-AMP) inhibitor, respectively. Conclusion: These results suggest that TPE causes vasodilatory effects in a concentration-dependent manner in the isolated rat aortic artery. The mechanism of action of TPE is complex. A part of its relaxing effect is mediated directly by blocking or modulating cGMP and cAMP. PMID:27104039

Mechanism of vasorelaxation induced by Tridax procumbens extract in rat thoracic aorta.

PubMed

Salahdeen, Hussein Mofomosara; Idowu, Gbolahan O; Salami, Shakiru A; Murtala, Babatunde A; Alada, AbdulRasak A

2016-01-01

Tridax procumbens (Linn) (Asteraceae) is one of the herbs widely distributed in many parts of the world. Its leaves have long been used for the treatment of hypertension in Nigeria. Previous studies have shown that aqueous leaves of T. procumbens extract (TPE) lowers blood pressure through endothelium-dependent and -independent mechanism in the aortic rings isolated from normotensive rats. The aim of the present study was to further investigate mechanisms of TPE-induced relaxation in the aortic artery by assessing its mechanistic interactions with nitric oxide (NO) synthase, cyclic guanosine monophosphate (cGMP), and cyclic adenosine monophosphate (cAMP). The aortic artery isolated from healthy, young adult normotensive Wistar albino rats (250-300 g) were pre-contracted with phenylephrine (PE) (10-7 M) and KCl (60 mM) and were treated with various concentrations of aqueous extract of TPE (0.5-9.0 mg/ml). The changes in arterial tension were recorded using Ugo Basile model 7004 coupled to data capsule acquisition system model 17400. The interaction between TPE with cAMP and cGMP inhibitors was also evaluated. The results showed that the TPE (0.5-9.0 mg/ml) significantly (P < 0.05) reduced the contraction induced by PE in a concentration-dependent manner. The vasorelaxant effect caused by the TPE was significantly (P < 0.05) attenuated with pre-incubation of cGMP (Rp-8Br PET cGMPS) and cAMP (Rp-AMP) inhibitor, respectively. These results suggest that TPE causes vasodilatory effects in a concentration-dependent manner in the isolated rat aortic artery. The mechanism of action of TPE is complex. A part of its relaxing effect is mediated directly by blocking or modulating cGMP and cAMP.

Thiopental inhibits nitric oxide production in rat aorta.

PubMed

Castillo, C; Asbun, J; Escalante, B; Villalón, C M; López, P; Castillo, E F

1999-12-01

We studied whether thiopental affects endothelial nitric oxide dependent vasodilator responses and nitrite production (an indicator of nitric oxide production) elicited by acetylcholine, histamine, and A23187 in rat aorta (artery in which nitric oxide is the main endothelial relaxant factor). In addition, we evaluated the barbiturate effect on nitric oxide synthase (NOS) activity in both rat aorta and kidney homogenates. Thiopental (10-100 microg/mL) reversibly inhibited the endothelium-dependent relaxation elicited by acetylcholine, histamine, and A23187. On the contrary, this anesthetic did not modify the endothelium-independent but cGMP-dependent relaxation elicited by sodium nitroprusside (1 nM - 1 microM) and nitroglycerin (1 nM - 1 microM), thus excluding an effect of thiopental on guanylate cyclase of vascular smooth muscle. Thiopental (100 microg/mL) inhibited both basal (87.8+/-14.3%) and acetylcholine- or A23187-stimulated (78.6+/-3.9 and 39.7+/-5.6%, respectively) production of nitrites in aortic rings. In addition the barbiturate inhibited (100 microg/mL) the NOS (45+/-4 and 42.8+/-9%) in aortic and kidney homogenates, respectively (measured as 14C-labeled citrulline production). In conclusion, thiopental inhibition of endothelium-dependent relaxation and nitrite production in aortic rings strongly suggests an inhibitory effect on NOS. Thiopental inhibition of the NOS provides further support to this contention.

Cardiovascular effects of Urtica dioica L. (Urticaceae) roots extracts: in vitro and in vivo pharmacological studies.

PubMed

Testai, Lara; Chericoni, Silvio; Calderone, Vincenzo; Nencioni, Giulia; Nieri, Paola; Morelli, Ivano; Martinotti, Enrica

2002-06-01

Urtica dioica (Urticaceae) is a plant principally used in the traditional medicine of oriental Marocco as antihypertensive remedy (J. Ethnopharmacol., 58 (1997), 45). The aim of this work was to evaluate a possible direct cardiovascular action of the plant and to investigate its mechanism of action. In aortic preparations with intact and functional endothelial layer, pre-contracted with KCl 20 mM or norepinephrine 3 microM, the crude aqueous and methanolic extracts of the plant roots, as well as purified fractions elicited a vasodilator action. Nevertheless, the vasodilator activity was not present in aortic rings without endothelial layer. In aortic rings with intact endothelial layer, the vasorelaxing effect was abolished by L-NAME, a NO-biosynthesis inhibitor, and ODQ, a guanylate cyclase inhibitor. Furthermore, potassium channel blockers (TEA, 4-aminopyridine, quinine, but not glybenclamide) antagonized the vasodilator action of the purified fraction F1W of U. dioica. The same fraction produced a marked decrease of inotropic activity, in spontaneously beating atria of guinea-pig, and a marked, but transient, hypotensive activity on the blood pressure of anaesthetized rats. It is concluded that U. dioica can produce hypotensive responses, through a vasorelaxing effect mediated by the release of endothelial nitric oxide and the opening of potassium channels, and through a negative inotropic action.

SUBCOMMISSURAL IMPLANTATION OF AORTIC PROSTHESES WITH THE USE OF THE NONCORONARY SINUS AND THE FIBROUS TRIGONES

PubMed Central

Liotta, Domingo; Haller, Jordan D.; Pisanu, Amadeo; Bracco, Daniel; Bertolozzi, Enrique

1979-01-01

The technique described here permits insertion of a large prosthesis into a small aortic annulus and avoids the necessity of additional procedures for enlarging the aortic ring. Inspection of the fibrous skeleton of the heart reveals that the large intervalvular trigone and the noncoronary sinus of Valsalva are remarkably elastic. Full advantage of this natural elasticity is achieved by suturing the prosthesis to the base of these structures from outside the aorta. Sutures are placed in the sinuses of the right and left cusps in the usual manner. Judicious application of this procedure allows the implantation of a No. 23 or No. 24 prosthesis in cases that would require a No. 19 or No. 21 with the use of conventional methods. Images PMID:15216322

Involvement of thromboxane A2 in the endothelium-dependent contractions induced by myricetin in rat isolated aorta

PubMed Central

Jiménez, Rosario; Andriambeloson, Emile; Duarte, Juan; Andriantsitohaina, Ramaroson; Jiménez, José; Pérez-Vizcaino, Francisco; Zarzuelo, Antonio; Tamargo, Juan

1999-01-01

The present study was undertaken to analyse the mechanism of the contractile response induced by the bioflavonoid myricetin in isolated rat aortic rings.Myricetin induced endothelium-dependent contractile responses (maximal value=21±2% of the response induced by 80 mM KCl and pD2=5.12±0.03). This effect developed slowly, reached a peak within 6 min and then declined progressively.Myricetin-induced contractions were almost abolished by the phospholipase A2 (PLA2) inhibitor, quinacrine (10 μM), the cyclo-oxygenase inhibitor, indomethacin (10 μM), the thromboxane synthase inhibitor, dazoxiben (100 μM), the putative thromboxane A2 (TXA2)/prostaglandin endoperoxide receptor antagonist, ifetroban (3 μM). These contractions were abolished in Ca2+-free medium but were not affected by the Ca2+ channel blocker verapamil (10 μM).In cultured bovine endothelial cells (BAEC), myricetin (50 μM) produced an increase in cytosolic free calcium ([Ca2+]i) which peaked within 1 min and remained sustained for 6 min, as determined by the fluorescent probe fura 2. This rise in [Ca2+]i was abolished after removal of extracellular Ca2+ in the medium.Myricetin (50 μM) significantly increased TXB2 production both in aortic rings with and without endothelium and in BAEC. These increases were abolished both by Ca2+-free media and by indomethacin.Taken together, these results suggests that myricetin stimulates Ca2+ influx and subsequently triggers the activation of the PLA2 and cyclo-oxygenase pathways releasing TXA2 from the endothelium to contract rat aortic rings. The latter response occurs via the activation of Tp receptors on vascular smooth muscle cells. PMID:10455307

Metformin exaggerates phenylephrine-induced AMPK phosphorylation independent of CaMKKβ and attenuates contractile response in endothelium-denuded rat aorta

PubMed Central

Pyla, Rajkumar; Osman, Islam; Pichavaram, Prahalathan; Hansen, Paul; Segar, Lakshman

2014-01-01

Metformin, a widely prescribed antidiabetic drug, has been shown to reduce the risk of cardiovascular disease, including hypertension. Its beneficial effect toward improved vasodilation results from its ability to activate AMPK and enhance nitric oxide formation in the endothelium. To date, metformin regulation of AMPK has not been fully studied in intact arterial smooth muscle, especially during contraction evoked by G protein-coupled receptor (GPCR) agonists. In the present study, ex vivo incubation of endothelium-denuded rat aortic rings with 3 mM metformin for 2 hours resulted in significant accumulation of metformin (~600 pmoles/mg tissue), as revealed by LC-MS/MS MRM analysis. However, metformin did not show significant increase in AMPK phosphorylation under these conditions. Exposure of aortic rings to a GPCR agonist (e.g., phenylephrine) resulted in enhanced AMPK phosphorylation by ~2.5-fold. Importantly, in metformin-treated aortic rings, phenylephrine challenge showed an exaggerated increase in AMPK phosphorylation by ~9.7-fold, which was associated with an increase in AMP/ATP ratio. Pretreatment with compound C (AMPK inhibitor) prevented AMPK phosphorylation induced by phenylephrine alone and also that induced by phenylephrine after metformin treatment. However, pretreatment with STO-609 (CaMKKβ inhibitor) diminished AMPK phosphorylation induced by phenylephrine alone but not that induced by phenylephrine after metformin treatment. Furthermore, attenuation of phenylephrine-induced contraction (observed after metformin treatment) was prevented by AMPK inhibition but not by CaMKKβ inhibition. Together, these findings suggest that, upon endothelial damage in the vessel wall, metformin uptake by the underlying vascular smooth muscle would accentuate AMPK phosphorylation by GPCR agonists independent of CaMKKβ to promote vasorelaxation. PMID:25179145

MMP-9-Dependent Serum-Borne Bioactivity Caused by Multiwalled Carbon Nanotube Exposure Induces Vascular Dysfunction via the CD36 Scavenger Receptor

PubMed Central

Aragon, Mario; Erdely, Aaron; Bishop, Lindsey; Salmen, Rebecca; Weaver, John; Liu, Jim; Hall, Pamela; Eye, Tracy; Kodali, Vamsi; Zeidler-Erdely, Patti; Stafflinger, Jillian E.; Ottens, Andrew K.; Campen, Matthew J.

2016-01-01

Inhalation of multiwalled carbon nanotubes (MWCNT) causes systemic effects including vascular inflammation, endothelial dysfunction, and acute phase protein expression. MWCNTs translocate only minimally beyond the lungs, thus cardiovascular effects thereof may be caused by generation of secondary biomolecular factors from MWCNT-pulmonary interactions that spill over into the systemic circulation. Therefore, we hypothesized that induced matrix metalloproteinase-9 (MMP-9) is a generator of factors that, in turn, drive vascular effects through ligand-receptor interactions with the multiligand pattern recognition receptor, CD36. To test this, wildtype (WT; C57BL/6) and MMP-9−/− mice were exposed to varying doses (10 or 40 µg) of MWCNTs via oropharyngeal aspiration and serum was collected at 4 and 24 h postexposure. Endothelial cells treated with serum from MWCNT-exposed WT mice exhibited significantly reduced nitric oxide (NO) generation, as measured by electron paramagnetic resonance, an effect that was independent of NO scavenging. Serum from MWCNT-exposed WT mice inhibited acetylcholine (ACh)-mediated relaxation of aortic rings at both time points. Absence of CD36 on the aortic rings (obtained from CD36-deficient mice) abolished the serum-induced impairment of vasorelaxation. MWCNT exposure induced MMP-9 protein levels in both bronchoalveolar lavage and whole lung lysates. Serum from MMP-9−/− mice exposed to MWCNT did not diminish the magnitude of vasorelaxation in naïve WT aortic rings, although a modest right shift of the ACh dose–response curve was observed in both MWCNT dose groups relative to controls. In conclusion, pulmonary exposure to MWCNT leads to elevated MMP-9 levels and MMP-9-dependent generation of circulating bioactive factors that promote endothelial dysfunction and decreased NO bioavailability via interaction with vascular CD36. PMID:26801584

Blueberry juice causes potent relaxation of rat aortic rings via the activation of potassium channels and the H₂S pathway.

PubMed

Horrigan, Louise A; Holohan, Catherine A; Lawless, Gráinne A; Murtagh, Melissa A; Williams, Carmel T; Webster, Christina M

2013-02-26

The objective of this study was to investigate the in vitro effects of blueberry juice on healthy rat aortic rings, and to explore the roles of potassium channels and of the hydrogen sulphide (H(2)S) pathway in mediating the effects of blueberry juice. Firstly, the antioxidant capacity of blueberry juice was compared to other popular juice drinks using the Folin-Ciocalteu and the DPPH assays. Blueberry juice had significantly higher total polyphenol content than any of the other drinks studied (p < 0.01). The effect of blueberry juice on noradrenaline-contracted aortic rings was then observed, and the juice caused significant inhibition of noradrenaline-induced contractions (p < 0.01). Voltage-gated potassium channel (Kv) blockers 4-aminopyridine (1 mM) and 3,4-diaminopyridine (1 mM), as well as the cystathionine γ-lysase (CSE) inhibitor d,l-propargylglycine (2 mM) were then utilised to elucidate the role of Kv channels and the CSE/H(2)S pathway. Kv channel blocker 3,4-diaminopyridine caused significant blockade at 1/100 and 1/50 dilutions of juice (p < 0.01), whilst 4-aminopyridine caused significant blockade of the 1/100 dilution of blueberry juice (p < 0.05). In addition, d,l-propargylglycine potently inhibited the effect of 1/100 and 1/50 dilutions of blueberry juice (p < 0.01). This study indicates that blueberry juice has potent vasorelaxing properties, and thus may be a useful dietary agent for the prevention and treatment of hypertension. This study also provides strong evidence that Kv channels and the CSE/H(2)S pathway may be responsible, at least in part, for mediating the effects of blueberry juice.

Ruthenium Complex Improves the Endothelial Function in Aortic Rings From Hypertensive Rats

PubMed Central

Vatanabe, Izabela Pereira; Rodrigues, Carla Nascimento dos Santos; Buzinari, Tereza Cristina; de Moraes, Thiago Francisco; da Silva, Roberto Santana; Rodrigues, Gerson Jhonatan

2017-01-01

Background The endothelium is a monolayer of cells that extends on the vascular inner surface, responsible for the modulation of vascular tone. By means of the release of nitric oxide (NO), the endothelium has an important protective function against cardiovascular diseases. Objective Verify if cis- [Ru(bpy)2(NO2)(NO)](PF6)2 (BPY) improves endothelial function and the sensibility of conductance (aorta) and resistance (coronary) to vascular relaxation induced by BPY. Methods Normotensive (2K) and hypertensive (2K-1C) Wistar rats were used. For vascular reactivity study, thoracic aortas were isolated, rings with intact endothelium were incubated with: BPY(0.01 to10 µM) and concentration effect curves to acetylcholine were performed. In addition, cumulative concentration curves were performed to BPY (1.0 nM to 0.1 µM) in aortic and coronary rings, with intact and denuded endothelium. Results In aorta from 2K-1C animals, the treatment with BPY 0.1µM increased the potency of acetylcholine-induced relaxation and it was able to revert the endothelial dysfunction. The presence of the endothelium did not modify the effect of BPY in inducing the relaxation in aortas from 2K and 2K-1C rats. In coronary, the endothelium potentiated the vasodilator effect of BPY in vessels from 2K and 2K-1C rats. Conclusion Our results suggest that 0.1 µM of BPY is able to normalize the relaxation endothelium dependent in hypertensive rats, and the compound BPY induces relaxation in aortic from normotensive and hypertensive rats with the same potency. The endothelium potentiate the relaxation effect induced by BPY in coronary from normotensive and hypertensive rats, with lower effect on coronary from hypertensive rats. PMID:28678930

Composition and biological activities of the aqueous extracts of three scleractinian corals from the Mexican Caribbean: Pseudodiploria strigosa, Porites astreoides and Siderastrea siderea.

PubMed

García-Arredondo, Alejandro; Rojas-Molina, Alejandra; Ibarra-Alvarado, César; Lazcano-Pérez, Fernando; Arreguín-Espinosa, Roberto; Sánchez-Rodríguez, Judith

2016-01-01

Scleractinian corals (stony corals) are the most abundant reef-forming cnidarians found in coral reefs throughout the world. Despite their abundance and ecological importance, information about the diversity of their toxins and their biological activities is very scarce. In this study, the chemical composition and the biological activities of the aqueous extracts of Pseudodiploria strigosa , Porites astreoides and Siderastrea siderea , three scleractinian corals from the Mexican Caribbean, have been assessed for the first time. Toxicity of the extracts was assessed in crickets; the presence of cytolysins was detected by the hemolysis assay; the vasoconstrictor activity was determined by the isolated rat aortic ring assay; the nociceptive activity was evaluated by the formalin test. The presence of phospholipases A 2 (PLA 2 ), serine proteases, and hyaluronidases was determined by enzymatic methods. Low-molecular-weight fractions were obtained by gel filtration chromatography and ultrafiltration. Extracts from the three species were toxic to crickets, induced hemolysis in human and rat erythrocytes, produced vasoconstriction on isolated rat aortic rings, and presented phospholipase A 2 and serine-protease activity. Despite the fact that these corals are not considered to be harmless to humans, the extracts generated significant nociceptive responses. The matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry analysis of the low-molecular-weight fractions revealed the presence of peptides within a mass range of 3000 to 6000 Da. These fractions were toxic to crickets and two of them induced a transitory vasoconstrictor effect on isolated rat aortic rings. This study suggests that scleractinian corals produce low-molecular-weight peptides that are lethal to crickets and induce vasoconstriction.

Effect of ketorolac and diclofenac on the impairment of endothelium-dependent relaxation induced by reactive oxygen species in rabbit abdominal aorta

PubMed Central

Lee, Seung Yoon; Choi, Jin Hwa; Jeon, Woo Jae; Cheong, Mi Ae

2010-01-01

Background Reactive oxygen species (ROS) induce lipid peroxidation and tissue damage in endothelium. We studied the influences of ketorolac and diclofenac on ROS effects using the endothelium of rabbit abdominal aorta. Methods Isolated rabbit aortic rings were suspended in an organ bath filled with Krebs-Henseleit (K-H) solution bubbled with 5% CO2 and 95% O2 at 37.5℃. After being stimulated to contract with phenylephrine (PE, 10-6 M), changes in arterial tension were recorded following the cumulative administration of acetylcholine (ACh, 3 × 10-8 to 10-6 M). The percentages of ACh-induced relaxation of aortic rings before and after exposure to ROS, generated by electrolysis of K-H solution, were used as the control and experimental values, respectively. The aortic rings were pretreated with ketorolac or diclofenac at the same concentrations (10-5 M to 3 × 10-4 M), and the effects of these agents were compared with the effects of ROS scavengers: catalase, mannitol, sodium salicylate and deferoxamine and the catalase inhibitor, 3-amino-1,2,4-triazole (3AT). Results Both ketorolac and diclofenac maintained endothlium-dependent relaxation induced by ACh in a dose-related manner inspite of ROS attack (P < 0.05 vs. control value). The 3AT pretreated ketorolac (3 × 10-3 M) group was decreased more significantly than un-pretreated ketorolac (P < 0.05). Conclusions These findings suggest that ketorlac and diclofenac preserve the endothelium-dependent vasorelaxation against the attack of ROS, in a concentration-related manner. One of the endothelial protection mechanisms of ketorolac may be hydrogen peroxide scavenging. PMID:20877705

Improvement of endothelial function in a murine model of mild cholesterol-induced atherosclerosis by mineralocorticoid antagonism.

PubMed

Kratz, Mario T; Schirmer, Stephan H; Baumhäkel, Magnus; Böhm, Michael

2016-08-01

The renin-angiotensin-aldosterone-system (RAAS) plays a role in endothelial dysfunction and atherosclerosis. During treatment with RAAS-inhibitors, elevated aldosterone may sustain "aldosterone escape". We investigated the effects of treatment with the mineralocorticoid antagonist eplerenone (Ep) compared with ramipril (Rami) or the combination of both on oxidative stress, plaque formation and endothelial function, in atherosclerotic apolipoprotein E deficient mice (ApoE(-/-)-mice). ApoE(-/-)-mice were fed a cholesterol rich diet (21% fat, 19.5% casein, 1.25% cholesterol) for 8 weeks to produce mild atherosclerosis (i.e. plaque load 20-30%). ApoE(-/-)-mice (control), ApoE(-/-)-mice treated with Ep (25 mg/kg/day), Rami (2.5 mg/kg/day) and their combination were compared. Heart rate (HR) and blood pressure (BP) were measured using the tail-cuff-method. Endothelial function was measured in aortic rings and corpora cavernosal strips (CCs). Atherosclerotic plaque burden, collagen content, oxidative stress (Dihydroethidium (DHE) staining) and macrophages were determined. Treatments had no effects on HR and slightly reduced BP in ApoE(-/-)-mice treated with the combination of eplerenone and ramipril. Endothelium-dependent relaxation of aortic rings and CCs with carbachol was significantly improved in animals treated with Ep, Rami or their combination (p = 0.05 - p = 0.001). DHE-stained penile and aortic sections revealed a significant reduction in superoxide production in all treated groups (p = 0.035 - p = 0.001). In parallel, aortic and penile collagen content in ApoE(-/-)-mice was significantly decreased (p = 0.035 - p < 0.001) in animals treated with Ep, Rami or their combination. In agreement, there was a trend towards a reduction of aortic plaque area by treatment with Ep (-9.0 ± 3.2%) and Rami (-11.9 ± 4%). Only the treatment with the combination induced a significant reduction of the atherosclerotic plaque burden (p = 0.045). Moreover, the treatment of ApoE(-/-)-mice with Ep, Rami and their combination significantly reduced the count macrophage count in atherosclerotic plaque lesions. Ep restored endothelial function by reduction of oxidative stress, atherosclerotic macrophage content, atherosclerotic lesion size and fibrosis to the same extent as treatment with Rami or the combination. Mineralocorticoid antagonism provides vasculoprotective effects and should be clinically evaluated for vascular disease such as erectile dysfunction. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cardiovascular effects of Persea americana Mill (Lauraceae) (avocado) aqueous leaf extract in experimental animals.

PubMed

Ojewole, J A O; Kamadyaapa, D R; Gondwe, M M; Moodley, K; Musabayane, C T

2007-01-01

The cardiovascular effects of Persea americana Mill (Lauraceae) aqueous leaf extract (PAE) have been investigated in some experimental animal paradigms. The effects of PAE on myocardial contractile performance was evaluated on guinea pig isolated atrial muscle strips, while the vasodilatory effects of the plant extract were examined on isolated portal veins and thoracic aortic rings of healthy normal Wistar rats in vitro. The hypotensive (antihypertensive) effect of the plant extract was examined in healthy normotensive and hypertensive Dahl salt-sensitive rats in vivo. P americana aqueous leaf extract (25-800 mg/ml) produced concentration-dependent, significant (p < 0.05-0.001), negative inotropic and negative chronotropic effects on guinea pig isolated electrically driven left and spontaneously beating right atrial muscle preparations, respectively. Moreover, PAE reduced or abolished, in a concentration-dependent manner, the positive inotropic and chronotropic responses of guinea pig isolated atrial muscle strips induced by noradrenaline (NA, 10(-10)-10(-5) M), and calcium (Ca(2+), 5-40 mM). PAE (50-800 mg/ml) also significantly reduced (p < 0.05-0.001) or abolished, in a concentration-dependent manner, the rhythmic, spontaneous, myogenic contractions of portal veins isolated from healthy normal Wistar rats. Like acetylcholine (ACh, 10(-8)-10(-5) M), the plant extract (25- 800 mg/ml) produced concentration-related relaxations of isolated endothelium-containing thoracic aortic rings pre-contracted with noradrenaline. The vasorelaxant effects of PAE in the isolated, endothelium-intact aortic rings were markedly inhibited or annulled by N(G)-nitro-L-arginine methyl ester (L-NAME, 10(-5) M), a nitric oxide synthase inhibitor. Furthermore, PAE (25-400 mg/kg iv) caused dose-related, transient but significant reductions (p < 0.05-0.001) in the systemic arterial blood pressure and heart rates of the anaesthetised normotensive and hypertensive rats used. The results of this laboratory animal study indicate that PAE caused bradycardia, vasorelaxation and hypotension in the mammalian experimental models used. The vasorelaxant action of PAE was endothelium dependent, and was, therefore, possibly dependent on the synthesis and release of nitric oxide (NO). The vasorelaxant effects of PAE appeared to contribute significantly to the hypotensive (antihypertensive) effects of the plant extract. However, the findings of this study tend to suggest that P americana leaf could be used as a natural supplementary remedy in essential hypertension and certain cases of cardiac dysfunctions in some rural Africa communities.

Endothelium-Dependent Vasorelaxant Effect of Butanolic Fraction from Caryocar brasiliense Camb. Leaves in Rat Thoracic Aorta

PubMed Central

de Oliveira, Lais Moraes; Rodrigues, Aline Gabriela; da Silva, Elaine Fernanda; Cerqueira, Letícia Bonancio; Castro, Carlos Henrique; Pedrino, Gustavo Rodrigues; de Carvalho, Maria Helena Catelli; Pontarolo, Roberto; Costa, Elson Alves; Campos, Francinete Ramos; Filgueira, Fernando Paranaiba; Ghedini, Paulo César

2012-01-01

Caryocar brasiliense Camb. “pequi” is a native plant from the Cerrado region of Brazil that contains bioactive components reported to be antioxidant agents. Previous work has demonstrated that dietary supplementation with pequi decreased the arterial pressure of volunteer athletes. We found that the crude hydroalcoholic extract (CHE) of C. brasiliense leaves relaxed, in a concentration-dependent manner, rat aortic rings precontracted with phenylephrine, and that the butanolic fraction (BF) produced an effect similar to that of the CHE. Aortic relaxation induced by BF was abolished by endothelium removal, by incubation of the nitric oxide synthase inhibitor L-NAME, or the soluble guanylatecyclase inhibitor ODQ. However, incubation with atropine and pyrilamine had no effect on the BF-induced vasorelaxation. Moreover, this effect was not inhibited by indomethacin and tetraethylammonium. The concentration-response curve to calcium in denuded-endothelium rings was not modified after incubation with BF, and the vasorelaxation by BF in endothelium-intact rings precontracted with KCl was abolished after incubation with L-NAME. In addition, administration of BF in anesthetized rats resulted in a reversible hypotension. The results reveal that C. brasiliense possesses both in vivo and in vitro activities and that the vascular effect of BF involves stimulation of the nitric oxide/cyclic GMP pathway. PMID:22927883

Relationship of aortic annular eccentricity and paravalvular regurgitation post transcatheter aortic valve implantation with CoreValve.

PubMed

Wong, Dennis T L; Bertaso, Angela G; Liew, Gary Y H; Thomson, Viji S; Cunnington, Michael S; Richardson, James D; Gooley, Robert; Lockwood, Siobhan; Meredith, Ian T; Worthley, Matthew I; Worthley, Stephen G

2013-04-01

Significant paravalvular aortic regurgitation (PAR) after transcatheter aortic valve implantation (TAVI) is associated with negative clinical consequences. We hypothesize that increased eccentricity of the aortic annulus is associated with greater PAR. Patients with severe aortic stenosis underwent multidetector computed tomography (MDCT) before successful TAVI with the Medtronic CoreValve bioprosthesis. The smallest (D(min)) and largest (D(max)) orthogonal diameters in the basal ring of the aortic annulus were determined. We defined circularity of aortic annulus using the eccentricity index (1 - D(min)/D(max)). The primary endpoint was early occurrence of significant PAR, defined as > grade II PAR by postprocedural aortography. Eighty-four patients, mean age 83 ± 4 years with a mean aortic valve area of 0.7 ± 0.2 cm² were included. Twenty patients had postprocedural PAR > grade II. Using a receiver operating characteristic (ROC) analysis, eccentricity index correlated with significant PAR (AUC = 0.834; P=.034). A retrospectively determined eccentricity index cut-off of >0.25 was related to significant PAR with a sensitivity of 80%, specificity of 86%, and negative predictive value of 95% (P<.001). On univariate logistic regression, eccentricity index of >0.25 (P<.001) and device implantation depth (P=.015) correlated with significant PAR, while other parameters such as annular calcification and cover index did not. On multivariate analysis including only parameters with P<.1 on univariate analysis, eccentricity index >0.25 was the sole independent predictor of significant PAR. Eccentricity index is related to significant PAR after TAVI with Medtronic CoreValve. Further larger studies are required to determine the utility of this novel index in screening suitable patients for this procedure.

Vasorelaxant and cardiovascular properties of the essential oil of Pogostemon elsholtzioides.

PubMed

Shiva Kumar, Arumugasamy; Jeyaprakash, Karnan; Chellappan, David Raj; Murugan, Ramar

2017-03-06

Pogostemon elsholtzioides Benth. (Lamiaceae) is an aromatic shrub, endemic to eastern Himalaya region. The leaves are used for treating goiter and high blood pressure (BP) by indigenous people in Arunachal Pradesh, India. Young leaves are used as vegetable and leaf decoction is also used for cough, cold and headache by some indigenous communities in Northeast India. This species is used for treating hypertension and the genus Pogostemon is rich in essential oil. Therefore, the present study was aimed at investigation of the chemical constituents, vasorelaxant and cardiovascular effects of the essential oil of P. elsholtzioides. P. elsholtzioides was collected from Pasighat, Arunachal Pradesh, India and essential oil was extracted from shade dried leaves. Essential oil was analyzed by GC-FID and GC-MS and the volatile constituents were identified. Vasorelaxant and cardiovascular properties of the essential oil were studied against phenylephrine induced contraction in isolated endothelium intact aortic preparations and by measuring systolic and diastolic BP, mean arterial pressure (MAP) and heart rate (HR) after carotid artery cannulation in Wistar rats. The essential oil was rich in sesquiterpenes and curzerene, benzophenone, α-cadinol and germacrone were major constituents. The essential oil exhibited significant vasodilation effect in phenylephrine induced contracted aortic rings. Vasorelaxant effect of the essential oil was also observed both in the presence and absence of Nitro-L-arginine methyl ester against phenylephrine-contracted aortic rings. It also induced reduction of systolic and diastolic BP, MAP and HR. Essential oil of P. elsholtzioides exhibited significant vasorelaxant effect against endothelium intact aortic preparation mediated through nitric oxide dependent pathway and also reduced BP. However, further study is needed to screen the role of calcium ions in both intracellular and extracellular pathway. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Cross-talk between toll-like receptor 4 (TLR4) and proteinase-activated receptor 2 (PAR(2) ) is involved in vascular function.

PubMed

Bucci, M; Vellecco, V; Harrington, L; Brancaleone, V; Roviezzo, F; Mattace Raso, G; Ianaro, A; Lungarella, G; De Palma, R; Meli, R; Cirino, G

2013-01-01

Proteinase-activated receptors (PARs) and toll-like receptors (TLRs) are involved in innate immune responses. The aim of this study was to evaluate the possible cross-talk between PAR(2) and TLR4 in vessels in physiological condition and how it varies following stimulation of TLR4 by using in vivo and ex vivo models. Thoracic aortas were harvested from both naïve and endotoxaemic rats for in vitro studies. Arterial blood pressure was monitored in anaesthetized rats in vivo. LPS was used as a TLR4 agonist while PAR(2) activating peptide (AP) was used as a PAR(2) agonist. Aortas harvested from TLR4(-/-) mice were also used to characterize the PAR(2) response. PAR(2) , but not TLR4, expression was enhanced in aortas of endotoxaemic rats. PAR(2) AP-induced vasorelaxation was increased in aortic rings of LPS-treated rats. TLR4 inhibitors, curcumine and resveratrol, reduced PAR(2) AP-induced vasorelaxation and PAR(2) AP-induced hypotension in both naïve and endotoxaemic rats. Finally, in aortic rings from TLR4(-/-) mice, the expression of PAR(2) was reduced and the PAR(2) AP-induced vasodilatation impaired compared with those from wild-type mice and both resveratrol and curcumine were ineffective. Cross-talk between PAR(2) and TLR4 contributes to vascular homeostasis. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Cross-talk between toll-like receptor 4 (TLR4) and proteinase-activated receptor 2 (PAR2) is involved in vascular function

PubMed Central

Bucci, M; Vellecco, V; Harrington, L; Brancaleone, V; Roviezzo, F; Mattace Raso, G; Ianaro, A; Lungarella, G; De Palma, R; Meli, R; Cirino, G

2013-01-01

Background and Purpose Proteinase-activated receptors (PARs) and toll-like receptors (TLRs) are involved in innate immune responses. The aim of this study was to evaluate the possible cross-talk between PAR2 and TLR4 in vessels in physiological condition and how it varies following stimulation of TLR4 by using in vivo and ex vivo models. Experimental Approach Thoracic aortas were harvested from both naïve and endotoxaemic rats for in vitro studies. Arterial blood pressure was monitored in anaesthetized rats in vivo. LPS was used as a TLR4 agonist while PAR2 activating peptide (AP) was used as a PAR2 agonist. Aortas harvested from TLR4–/– mice were also used to characterize the PAR2 response. Key Results PAR2, but not TLR4, expression was enhanced in aortas of endotoxaemic rats. PAR2AP-induced vasorelaxation was increased in aortic rings of LPS-treated rats. TLR4 inhibitors, curcumine and resveratrol, reduced PAR2AP-induced vasorelaxation and PAR2AP-induced hypotension in both naïve and endotoxaemic rats. Finally, in aortic rings from TLR4–/– mice, the expression of PAR2 was reduced and the PAR2AP-induced vasodilatation impaired compared with those from wild-type mice and both resveratrol and curcumine were ineffective. Conclusions and Implications Cross-talk between PAR2 and TLR4 contributes to vascular homeostasis. PMID:22957757

Ultrafine particulate matter exposure in vitro impairs vasorelaxant response in superoxide dismutase 2 deficient and aged murine aortic rings

EPA Science Inventory

Epidemiological studies positively associate exposure to inhaled ultrafine particulate matter (UFPM) and adverse cardiovascular events. PM-induced oxidative stress is believed to be a key mechanism contributing to the adverse short-term vascular effects of air pollution exposure....

Aortic annulus and root characteristics in severe aortic stenosis due to bicuspid aortic valve and tricuspid aortic valves: implications for transcatheter aortic valve therapies.

PubMed

Philip, Femi; Faza, Nadine Nadar; Schoenhagen, Paul; Desai, Milind Y; Tuzcu, E Murat; Svensson, Lars G; Kapadia, Samir R

2015-08-01

Patients with severe aortic stenosis due to BAV are excluded from transcatheter aortic valve replacement (TAVR) due to concern for asymmetric expansion and valve dysfunction. We sought to characterize the aortic root and annulus in bicuspid aortic valve (BAV) and tricuspid aortic valves (TAV). We identified patients with severe AS who underwent multi-detector computed tomographic (MDCT) imaging prior to surgical aortic valve replacement (SAVR, n = 200) for BAV and TAVR (n = 200) for TAV from 2010 to 2013. The presence of a BAV was confirmed on surgical and pathological review. Annulus measurements of the basal ring (short- and long-axis, area-derived diameter), coronary ostia height, sinus area (SA), sino-tubular junction area (STJ), calcification and eccentricity index (EI, 1-short axis/long axis) were made. Patients with TAV were older (78.8 years vs. 57.8 years, P = 0.04) than those with BAV. The aortic annulus area (5.21 ± 2.1 cm(2) vs. 4.63 ± 2.0 cm(2) , P = 0.0001), sinus of Valsalva diameter (3.7 ± 0.9 cm vs. 3.1 ± 0.1 cm, P = 0.001) and ascending aorta diameter (3.5 ± 0.7 cm vs. 2.97 ± 0.6 cm, P = 0.001) were significantly larger with BAV. Bicuspid aortic annuli were significantly less elliptical (EI, 1.24 ± 0.1 vs. 1.29 ± 0.1, P = 0.006) and more circular (39% vs. 4%, P < 0.001) compared to the TAV annulus. There was more eccentric annular calcification in BAV vs. TAV (68% vs. 32%, P < 0.001). The mean distance from the aortic annulus to the left main coronary ostium was less than the right coronary ostium. Less than 10% of the BAV annuli would not fit a currently available valved stents. Bicuspid aortic valves have a larger annulus size, sinus of Valsalva and ascending aorta dimensions. In addition, the BAV aortic annuli appear circular and most will fit currently available commercial valved stents. © 2015 Wiley Periodicals, Inc.

Effect of choline magnesium trisalicylate on prostacyclin production by isolated vascular tissue of the rat.

PubMed

Levy, J V

1983-01-15

Choline Magnesium Trisalicylate (Trilisate), in therapeutic concentrations of 5, 10, 15 and 30 mg/100 ml, did not significantly affect production of prostacyclin-like (PGI2) substance by rat aortic tissue in vitro. The ED50 for inhibition of aorta PGI2-like substance production by Trilisate was 1,200 mg/100 ml. This is approximately 40 times the maximum therapeutic blood concentration achieved in humans. Choline or Magnesium salicylate produced slight but insignificant inhibition of PGI2-like substance production by rat aortic tissue in vitro. The ED50 for ibuprofen (Motrin) for inhibition of PGI2-like production of rat aortic rings was 0.65-0.92 mg/100 ml. Injection of Choline Magnesium Trisalicylate into rats (124, 250, 500 mg/kg I.P.) did not affect the normal production of PGI2-like substance of aortic tissue obtained one hour after in vivo treatment. These results suggest this anti-inflammatory salicylate does not adversely affect PGI2-like production by blood vessels, in concentrations associated with therapeutic effects in man.

Computer-aided design of the human aortic root.

PubMed

Ovcharenko, E A; Klyshnikov, K U; Vlad, A R; Sizova, I N; Kokov, A N; Nushtaev, D V; Yuzhalin, A E; Zhuravleva, I U

2014-11-01

The development of computer-based 3D models of the aortic root is one of the most important problems in constructing the prostheses for transcatheter aortic valve implantation. In the current study, we analyzed data from 117 patients with and without aortic valve disease and computed tomography data from 20 patients without aortic valvular diseases in order to estimate the average values of the diameter of the aortic annulus and other aortic root parameters. Based on these data, we developed a 3D model of human aortic root with unique geometry. Furthermore, in this study we show that by applying different material properties to the aortic annulus zone in our model, we can significantly improve the quality of the results of finite element analysis. To summarize, here we present four 3D models of human aortic root with unique geometry based on computational analysis of ECHO and CT data. We suggest that our models can be utilized for the development of better prostheses for transcatheter aortic valve implantation. Copyright © 2014 Elsevier Ltd. All rights reserved.

A geometric approach to aortic root surgical anatomy.

PubMed

Contino, Monica; Mangini, Andrea; Lemma, Massimo Giovanni; Romagnoni, Claudia; Zerbi, Pietro; Gelpi, Guido; Antona, Carlo

2016-01-01

The aim of this study was the analysis of the geometrical relationships between the different structures constituting the aortic root, with particular attention to interleaflet triangles, haemodynamic ventriculo-arterial junction and functional aortic annulus in normal subjects. Sixteen formol-fixed human hearts with normal aortic roots were studied. The aortic root was isolated, sectioned at the midpoint of the non-coronary sinus, spread apart and photographed by a high-resolution digital camera. After calibration and picture resizing, the software AutoCAD 2004 was used to identify and measure all the elements of the interleaflets triangles and of the aortic root that were objects of our analysis. Multiple comparisons were performed with one-way analysis of variance for continuous data and with Kruskal-Wallis analysis for non-continuous data. Linear regression and Pearson's product correlation were used to correlate root element dimensions when appropriate. Student's t-test was used to compare means for unpaired data. Heron's formula was applied to estimate the functional aortic annular diameters. The non coronary-left coronary interleaflets triangles were larger, followed by inter-coronary and right-non-coronary ones. The apical angle is <60° and its standard deviation can be considered an asymmetry index. The sinu-tubular junction was shown to be 10% larger than the virtual basal ring (VBR). The mathematical relationship between the haemodynamic ventriculo-arterial junction and the VBR calculated by linear regression and expressed in terms of the diameter was: haemodynamic ventriculo-arterial junction = 2.29 VBR (diameter) + 47. Conservative aortic surgery is based on a better understanding of aortic root anatomy and physiology. The relationships among its elements are of paramount importance during aortic valve repair/sparing procedures and they can be useful also in echocardiographic analysis and in computed tomography reconstruction. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Immersed boundary-finite element model of fluid-structure interaction in the aortic root

NASA Astrophysics Data System (ADS)

Flamini, Vittoria; DeAnda, Abe; Griffith, Boyce E.

2016-04-01

It has long been recognized that aortic root elasticity helps to ensure efficient aortic valve closure, but our understanding of the functional importance of the elasticity and geometry of the aortic root continues to evolve as increasingly detailed in vivo imaging data become available. Herein, we describe a fluid-structure interaction model of the aortic root, including the aortic valve leaflets, the sinuses of Valsalva, the aortic annulus, and the sinotubular junction, that employs a version of Peskin's immersed boundary (IB) method with a finite element description of the structural elasticity. As in earlier work, we use a fiber-based model of the valve leaflets, but this study extends earlier IB models of the aortic root by employing an incompressible hyperelastic model of the mechanics of the sinuses and ascending aorta using a constitutive law fit to experimental data from human aortic root tissue. In vivo pressure loading is accounted for by a backward displacement method that determines the unloaded configuration of the root model. Our model yields realistic cardiac output at physiological pressures, with low transvalvular pressure differences during forward flow, minimal regurgitation during valve closure, and realistic pressure loads when the valve is closed during diastole. Further, results from high-resolution computations indicate that although the detailed leaflet and root kinematics show some grid sensitivity, our IB model of the aortic root nonetheless produces essentially grid-converged flow rates and pressures at practical grid spacings for the high Reynolds number flows of the aortic root. These results thereby clarify minimum grid resolutions required by such models when used as stand-alone models of the aortic valve as well as when used to provide models of the outflow valves in models of left-ventricular fluid dynamics.

Arginase reciprocally regulates nitric oxide synthase activity and contributes to endothelial dysfunction in aging blood vessels

NASA Technical Reports Server (NTRS)

Berkowitz, Dan E.; White, Ron; Li, Dechun; Minhas, Khalid M.; Cernetich, Amy; Kim, Soonyul; Burke, Sean; Shoukas, Artin A.; Nyhan, Daniel; Champion, Hunter C.;

Endothelial Estrogen Receptor-α Does Not Protect Against Vascular Stiffness Induced by Western Diet in Female Mice.

PubMed

Manrique, Camila; Lastra, Guido; Ramirez-Perez, Francisco I; Haertling, Dominic; DeMarco, Vincent G; Aroor, Annayya R; Jia, Guanghong; Chen, Dongqing; Barron, Brady J; Garro, Mona; Padilla, Jaume; Martinez-Lemus, Luis A; Sowers, James R

2016-04-01

Consumption of a diet high in fat and refined carbohydrates (Western diet [WD]) is associated with obesity and insulin resistance, both major risk factors for cardiovascular disease (CVD). In women, obesity and insulin resistance abrogate the protection against CVD likely afforded by estrogen signaling through estrogen receptor (ER)α. Indeed, WD in females results in increased vascular stiffness, which is independently associated with CVD. We tested the hypothesis that loss of ERα signaling in the endothelium exacerbates WD-induced vascular stiffening in female mice. We used a novel model of endothelial cell (EC)-specific ERα knockout (EC-ERαKO), obtained after sequential crossing of the ERα double floxed mice and VE-Cadherin Cre-recombinase mice. Ten-week-old females, EC-ERαKO and aged-matched genopairs were fed either a regular chow diet (control diet) or WD for 8 weeks. Vascular stiffness was measured in vivo by pulse wave velocity and ex vivo in aortic explants by atomic force microscopy. In addition, vascular reactivity was assessed in isolated aortic rings. Initial characterization of the model fed a control diet did not reveal changes in whole-body insulin sensitivity, aortic vasoreactivity, or vascular stiffness in the EC-ERαKO mice. Interestingly, ablation of ERα in ECs reduced WD-induced vascular stiffness and improved endothelial-dependent dilation. In the setting of a WD, endothelial ERα signaling contributes to vascular stiffening in females. The precise mechanisms underlying the detrimental effects of endothelial ERα in the setting of a WD remain to be elucidated.

Decreased expression of γ-carboxylase in diabetes-associated arterial stiffness: impact on matrix Gla protein.

PubMed

Doyon, Marielle; Mathieu, Patrick; Moreau, Pierre

2013-02-01

Arterial stiffness is accelerated in type 1 diabetic patients. Medial artery calcification (MAC) contributes to the development of arterial stiffness. Vitamin K oxidoreductase (VKOR) reduces the vitamin K required by γ-carboxylase to activate matrix γ-carboxyglutamic acid (Gla) protein (MGP), an inhibitor of vascular calcification. This study aimed to evaluate the hypothesis that diabetes reduces the γ-carboxylation of MGP in the aortic wall, leading to increased vascular calcification, and the role of γ-carboxylase and VKOR in this γ-carboxylation deficit. Type 1 diabetes was induced in male Wistar rats with a single ip injection of streptozotocin. Augmentation of arterial stiffness in diabetic rats was shown by a 44% increase in aortic pulse wave velocity. Aortic and femoral calcification were increased by 26 and 56%, respectively. γ-Carboxylated MGP (cMGP, active) was reduced by 36% and the aortic expression of γ-carboxylase was reduced by 58%. Expression of γ-carboxylase correlated with cMGP (r= 0.59) and aortic calcification (r = -0.57). VKOR aortic expression and activity were not modified by diabetes. Vitamin K plasma concentrations were increased by 191% in diabetic rats. In ex vivo experiments with aortic rings, vitamin K supplementation prevented the glucose-induced decrease in γ-carboxylase expression. Our results suggest that reduced cMGP, through an impaired expression of γ-carboxylase, is involved in the early development of MAC in diabetes, and therefore, in the acceleration of arterial stiffness. A defect in vitamin K uptake by target cells could also be involved.

Vascular smooth muscle cell polyploidy and cardiomyocyte hypertrophy due to chronic NOS inhibition in vivo.

PubMed

Devlin, A M; Brosnan, M J; Graham, D; Morton, J J; McPhaden, A R; McIntyre, M; Hamilton, C A; Reid, J L; Dominiczak, A F

1998-01-01

To assess the vascular and cardiac response to NO (nitric oxide) synthase (NOS) blockade in vivo, Wistar-Kyoto rats (WKY) were treated for 3 wk with NG-nitro-L-arginine methyl ester (L-NAME; 10 mg.kg-1.day-1). L-NAME treatment induced hypertension that was associated with increased plasma renin activity. Flow cytometry cell cycle DNA analysis showed that aortic vascular smooth muscle cells (VSMC) from L-NAME-treated WKY had a significantly higher polyploid population compared with WKY controls. Using organ bath experiments, we have shown that aortic rings from L-NAME-treated WKY have an increased contractile response to phenylephrine and impaired relaxation to carbachol compared with control rings. NOS blockade in vivo caused a significant increase in cardiac and left ventricular hypertrophy. Northern mRNA analysis of the myocardium showed that L-NAME treatment caused reexpression of the fetal skeletal alpha-actin isoform without alterations in collagen type I expression, a pattern indicating true hypertrophy of the cardiomyocytes. These studies provide further insight to confirm that NO deficiency in vivo results in the development of vascular and cardiac hypertrophy.

Vasorelaxation induced by common edible tropical plant extracts in isolated rat aorta and mesenteric vascular bed.

PubMed

Runnie, I; Salleh, M N; Mohamed, S; Head, R J; Abeywardena, M Y

2004-06-01

In this study, the vasodilatory actions of nine edible tropical plant extracts were investigated. Ipomoea batatas (sweet potato leaf), Piper betle (betel leaf), Anacardium occidentale (cashew leaf), Gynandropsis gynandra (maman leaf), Carica papaya (papaya leaf), and Mentha arvensis (mint leaf) extracts exhibited more than 50% relaxing effect on aortic ring preparations, while Piper betle and Cymbopogon citratus (lemongrass stalk) showed comparable vasorelaxation on isolated perfused mesenteric artery preparation. The vascular effect on the aortic ring preparations were mainly endothelium-dependent, and mediated by nitric oxide (NO) as supported by the inhibition of action in the presence of N(omega)-nitro-L-arginine (NOLA), an nitric oxide synthase (NOS) inhibitor, or by the removal of endothelium. In contrast, vasodilatory actions in resistance vessels (perfused mesenteric vascular beds) appear to involve several biochemical mediators, including NO, prostanoids, and endothelium-dependent hyperpolarizing factors (EDHFs). Total phenolic contents and antioxidant capacities varied among different extracts and found to be independent of vascular relaxation effects. This study demonstrates that many edible plants common in Asian diets to possess potential health benefits, affording protection at the vascular endothelium level.

Vasorelaxant and antihypertensive effects of methanolic fraction of the essential oil of Alpinia zerumbet.

PubMed

da Cunha, Gilmara Holanda; de Moraes, Manoel Odorico; Fechine, Francisco Vagnaldo; Frota Bezerra, Fernando Antônio; Silveira, Edilberto Rocha; Canuto, Kirley Marques; de Moraes, Maria Elisabete Amaral

2013-01-01

Alpinia zerumbet is used in folk medicine in Brazil to treat hypertension. However, several pathways involved in the mechanism of vasorelaxation are still unclear. This study was designed to verify the antihypertensive effect of the methanolic fraction of the essential oil of A. zerumbet (MFEOAz) and to characterize its mechanism of action. The thoracic aortic rings from the Wistar rats were perfused in the organ chambers filled with Kreb's solution, where the tension of each ring was measured. The antihypertensive effect of MFEOAz was assessed in rats submitted to chronic hypertension by inhibition of nitric oxide synthesis by indirect measurement of blood pressure with indirect tail cuff method. MFEOAz relaxed phenylephrine and KCl-induced contraction of either endothelium-intact or endothelium-denuded rat aortic rings in a concentration-dependent manner. Pre-incubation with MFEOAz (100 and 300 μg/mL) in Ca(2+)-free Krebs solution attenuated phenylephrine- or caffeine-induced contraction. Pre-incubation with L-NAME, ODQ, wortmannin, atropine, indomethacin, catalase, SOD, TEA, 4-aminopyridine, glibenclamide, apamin, charybdotoxin, or iberiotoxin did not affect MFEOAz-induced relaxation. The intragastric administration of MFEOAz induced an antihypertensive effect. MFEOAz it seems inhibited the calcium influx via voltage-operated calcium channels and receptor-operated calcium channels, as well as inhibition of calcium mobilization from intracellular stores. Copyright © 2013 Elsevier Inc. All rights reserved.

Mechanisms underlying the antihypertensive properties of Urtica dioica.

PubMed

Qayyum, Rahila; Qamar, Hafiz Misbah-Ud-Din; Khan, Shamim; Salma, Umme; Khan, Taous; Shah, Abdul Jabbar

2016-09-01

Urtica dioica has traditionally been used in the management of cardiovascular disorders especially hypertension. The aim of this study was to explore pharmacological base of its use in hypertension. Crude methanolic extract of U. dioica (Ud.Cr) and its fractions (Ud.EtAc, Ud.nHex, Ud.Chl and Ud.Aq) were tested in vivo on normotensive and hypertensive rats under anesthesia for blood pressure lowering effect. In-vitro experiments on rat and rabbit aortae were employed to probe the vasorelaxation mechanism(s). The responses were measured using pressure and force transducers connected to PowerLab Data Acquisition System. Ud.Cr and fractions were found more effective antihypertensive in hypertensive rats than normotensive with remarkable potency exhibited by the ethyl acetate fraction. The effect was same in the presence of atropine. In isolated rat aortic rings, Ud.Cr and all its fractions exhibited L-NAME sensitive endothelium-dependent vasodilator effect and also inhibit K(+) (80 mM)-induced pre-contractions. In isolated rabbit thoracic aortic rings Ud.Cr and its fractions induced relaxation with more potency against K(+) (80 mM) than phenylephrine (1 µM) like verapamil, showing Ud.EtAc fraction the most potent one. Pre-incubation of aortic rings with Ud.Cr and its fractions exhibited Ca(2+) channel blocking activity comparable with verapamil by shifting Ca(2+) concentration response curves to the right. Ud.Cr and its fractions also ablated the intracellular Ca(2+) release by suppressing PE peak formation in Ca(2+) free medium. When tested on basal tension, the crude extract and all fractions were devoid of any vasoconstrictor effect. These data indicate that crude methanolic extract and its fractions possess antihypertensive effect. Identification of NO-mediated vasorelaxation and calcium channel blocking effects explain the antihypertensive potential of U. dioica and provide a potential pharmacological base to its medicinal use in the management of hypertension.

Closed transventricular dilation of discrete subvalvular aortic stenosis in dogs.

PubMed

Linn, K; Orton, E C

1992-01-01

Discrete subvalvular aortic stenosis with peak systolic pressure gradients of more than 60 mm Hg was treated by closed transventricular dilation in six young dogs. Peak systolic pressure gradients were measured by direct catheterization before surgery, immediately after dilation, and 3 months after surgery. Maximum instantaneous pressure gradients were measured by continuous wave Doppler echocardiography before surgery and 6 weeks to 9 months after surgery. All dogs survived the procedure, and two dogs were clinically normal after 9 and 14 months. Two dogs died at week 6 and month 7. One dog was receiving medication for pulmonary edema 15 months after surgery. One dog underwent open resection of the subvalvular ring at month 3, and was clinically normal 6 months after the second procedure. Complications included intraoperative ventricular fibrillation in one dog, and mild postoperative aortic insufficiency in one dog. Closed transventricular dilation resulted in an immediate 83% decrease in the peak systolic pressure gradient from a preoperative mean of 97 +/- 22 mm Hg to a mean of 14 +/- 15 mm Hg. However, systolic pressure gradients measured by direct catheterization at month 3 (77 +/- 26 mm Hg), and by Doppler echocardiography at week 6 to month 9 (85 +/- 32 mm Hg) were not significantly different from preoperative values, which suggested recurrence of the aortic stenosis. Closed transventricular dilation should not be considered a definitive treatment for discrete subvalvular aortic stenosis in dogs, but may be useful in young dogs with critical aortic stenosis as a bridge to more definitive surgery.

Phosphate binding reduces aortic angiotensin-converting enzyme and enhances nitric oxide bioactivity in experimental renal insufficiency.

PubMed

Eräranta, Arttu; Törmänen, Suvi; Kööbi, Peeter; Vehmas, Tuija I; Lakkisto, Päivi; Tikkanen, Ilkka; Moilanen, Eeva; Niemelä, Onni; Mustonen, Jukka; Pörsti, Ilkka

2014-01-01

Disturbed calcium-phosphorus metabolism is associated with increased kidney angiotensin-converting enzyme (ACE) in experimental chronic renal insufficiency (CRI). However, information about the effects of phosphate binding and loading on vascular ACE is lacking. Fifteen weeks after 5/6 nephrectomy (NX), rats were placed on a phosphate-binding (NX+Ca, 3.0% Ca), phosphate-loading (NX+Pi, 1.5% Pi), or control diet for 12 weeks (NX and sham). Aortic ACE, blood pressure, plasma phosphate, and parathyroid hormone were increased in the NX and NX+Pi groups, but were reduced with phosphate binding. Endothelium-mediated relaxations of isolated mesenteric conduit artery rings to acetylcholine were impaired in the NX and NX+Pi groups, but did not differ from sham in NX+Ca rats. Experiments with nitric oxide (NO) synthase inhibition in vitro suggested that the NO-mediated component of acetylcholine response was lower in the NX and NX+Pi groups, but did not differ from sham in NX+Ca rats. In all NX groups, aortic endothelial NO synthase (eNOS) was reduced, while plasma and urine concentrations of NO metabolites were increased. Aortic nitrated proteins and calcification were increased in the NX and NX+Pi groups when compared with the NX+Ca and sham groups. Hypertension in the NX model of CRI was associated with reduced vasorelaxation, decreased eNOS, and increased ACE and nitrated proteins in the aorta. Phosphate binding with calcium carbonate enhanced vasorelaxation via endogenous NO and suppressed elevation of ACE and nitrated proteins, suggesting reduced vascular oxidative stress. Our findings support the view that correction of the calcium-phosphorus balance prevents CRI-induced vascular pathophysiology.

HZE ⁵⁶Fe-ion irradiation induces endothelial dysfunction in rat aorta: role of xanthine oxidase.

PubMed

Soucy, Kevin G; Lim, Hyun Kyo; Kim, Jae Hyung; Oh, Young; Attarzadeh, David O; Sevinc, Baris; Kuo, Maggie M; Shoukas, Artin A; Vazquez, Marcelo E; Berkowitz, Dan E

2011-10-01

Ionizing radiation has been implicated in the development of significant cardiovascular complications. Since radiation exposure is associated with space exploration, astronauts are potentially at increased risk of accelerated cardiovascular disease. This study investigated the effect of high atomic number, high-energy (HZE) iron-ion radiation on vascular and endothelial function as a model of space radiation. Rats were exposed to a single whole-body dose of iron-ion radiation at doses of 0, 0.5 or 1 Gy. In vivo aortic stiffness and ex vivo aortic tension responses were measured 6 and 8 months after exposure as indicators of chronic vascular injury. Rats exposed to 1 Gy iron ions demonstrated significantly increased aortic stiffness, as measured by pulse wave velocity. Aortic rings from irradiated rats exhibited impaired endothelial-dependent relaxation consistent with endothelial dysfunction. Acute xanthine oxidase (XO) inhibition or reactive oxygen species (ROS) scavenging restored endothelial-dependent responses to normal. In addition, XO activity was significantly elevated in rat aorta 4 months after whole-body irradiation. Furthermore, XO inhibition, initiated immediately after radiation exposure and continued until euthanasia, completely inhibited radiation-dependent XO activation. ROS production was elevated after 1 Gy irradiation while production of nitric oxide (NO) was significantly impaired. XO inhibition restored NO and ROS production. Finally, dietary XO inhibition preserved normal endothelial function and vascular stiffness after radiation exposure. These results demonstrate that radiation induced XO-dependent ROS production and nitroso-redox imbalance, leading to chronic vascular dysfunction. As a result, XO is a potential target for radioprotection. Enhancing the understanding of vascular radiation injury could lead to the development of effective methods to ameliorate radiation-induced vascular damage.

JS-K has potent anti-angiogenic activity in vitro and inhibits tumour angiogenesis in a multiple myeloma model in vivo.

PubMed

Kiziltepe, Tanyel; Anderson, Kenneth C; Kutok, Jeffery L; Jia, Lee; Boucher, Kenneth M; Saavedra, Joseph E; Keefer, Larry K; Shami, Paul J

2010-01-01

Glutathione S-transferases (GSTs) play an important role in multidrug resistance and are upregulated in multiple cancers. We have designed a prodrug class that releases nitric oxide on metabolism by GST. O(2)-(2,4-Dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K, a member of this class) has potent antineoplastic activity. We studied the effect of JS-K on angiogenesis in human umbilical vein endothelial cells (HUVECs), OPM1 multiple myeloma cells, chick aortic rings and in mice. JS-K inhibited the proliferation of HUVECs with a 50% inhibitory concentration (IC50) of 0.432, 0.466 and 0.505 microm at 24, 48 and 72 h, respectively. In the cord formation assay, JS-K led to a decrease in the number of cord junctions and cord length with an IC50 of 0.637 and 0.696 microm, respectively. JS-K inhibited cell migration at 5 h using VEGF as a chemoattractant. Migration inhibition occurred with an IC50 of 0.493 microm. In the chick aortic ring assay using VEGF or FGF-2 for vessel growth stimulation, 0.5 microm JS-K completely inhibited vessel growth. JS-K inhibited tumour angiogenesis in vivo in NIH III mice implanted subcutaneously with OPM1 multiple myeloma cells. JS-K is a potent inhibitor of angiogenesis in vitro and tumour vessel growth in vivo. As such, it establishes a new class of antineoplastic agent that targets the malignant cells directly as well as their microenvironment.

Inhibition of angiogenesis: a novel antitumor mechanism of the herbal compound arctigenin.

PubMed

Gu, Yuan; Scheuer, Claudia; Feng, Dilu; Menger, Michael D; Laschke, Matthias W

2013-09-01

Arctigenin, a functional ingredient of several traditional Chinese herbs, has been reported to have potential antitumor activity. However, its mechanisms of action are still not well elucidated. Because the establishment and metastatic spread of tumors is crucially dependent on angiogenesis, here we investigated whether arctigenin inhibits tumor growth by disturbing blood vessel formation. For this purpose, human dermal microvascular endothelial cells were exposed to different arctigenin doses to study their viability, proliferation, protein expression, migration, and tube formation compared with vehicle-treated controls. In addition, arctigenin action on vascular sprouting was analyzed in an aortic ring assay. Furthermore, we studied direct arctigenin effects on CT26.WT colon carcinoma cells. Spheroids of these tumor cells were transplanted into the dorsal skinfold chamber of arctigenin-treated and vehicle-treated BALB/c mice for the in-vivo analysis of tumor vascularization and growth by intravital fluorescence microscopy, histology, and immunohistochemistry. We found that noncytotoxic doses of arctigenin dose dependently reduced the proliferation of human dermal microvascular endothelial cells without affecting their migratory and tube-forming capacity. Arctigenin treatment also resulted in a decreased cellular expression of phosphorylated serine/threonine protein kinase AKT, vascular endothelial growth factor receptor 2, and proliferating cell nuclear antigen and inhibited vascular sprouting from aortic rings. In addition, proliferation, but not secretion of vascular endothelial growth factor, was decreased in arctigenin-treated tumor cells. Finally, arctigenin suppressed the vascularization and growth of engrafting CT26.WT tumors in the dorsal skinfold chamber model. Taken together, these results show for the first time an antiangiogenic action of arctigenin, which may contribute considerably toward its antitumor activity.

Gerbode defect and multivalvular dysfunction: Complex complications in adult congenital heart disease.

PubMed

Ruivo, Catarina; Guardado, Joana; Montenegro Sá, Fernando; Saraiva, Fátima; Antunes, Alexandre; Correia, Joana; Morais, João

2017-07-01

We report a clinical case of a 40-year-old male with surgically corrected congenital heart disease (CHD) 10 years earlier: closure of ostium primum, mitral annuloplasty, and aortic valve and root surgery. The patient was admitted with acute heart failure. Transesophageal echocardiography (TEE) revealed a dysmorphic and severely incompetent aortic valve, a partial tear of the mitral valve cleft repair and annuloplasty ring dehiscence. A true left ventricular-to-right atrial shunt confirmed a direct Gerbode defect. The authors aim to discuss the diagnostic challenge of adult CHD, namely the key role of TEE on septal defects and valve regurgitations description. © 2017, Wiley Periodicals, Inc.

Treatment of aortic stenosis with aortic valve bypass (apicoaortic conduit) surgery: an assessment using computational modeling.

PubMed

Balaras, Elias; Cha, K S; Griffith, Bartley P; Gammie, James S

2009-03-01

Aortic valve bypass surgery treats aortic valve stenosis with a valve-containing conduit that connects the left ventricular apex to the descending thoracic aorta. After aortic valve bypass, blood is ejected from the left ventricle via both the native stenotic aortic valve and the conduit. We performed computational modeling to determine the effects of aortic valve bypass on aortic and cerebral blood flow, as well as the effect of conduit size on relative blood flow through the conduit and the native valve. The interaction of blood flow with the vascular boundary was modeled using a hybrid Eurelian-Lagrangian formulation, where an unstructured Galerkin finite element method was coupled with an immersed boundary approach. Our model predicted native (stenotic) valve to conduit flow ratios of 45:55, 52:48, and 60:40 for conduits with diameters of 20, 16, and 10 mm, respectively. Mean gradients across the native aortic valve were calculated to be 12.5, 13.8, and 17.6 mm Hg, respectively. Post-aortic valve bypass cerebral blood flow was unchanged from preoperative aortic valve stenosis configurations and was constant across all conduit sizes. In all cases modeled, cerebral blood flow was completely supplied by blood ejected across the native aortic valve. An aortic valve bypass conduit as small as 10 mm results in excellent relief of left ventricular outflow tract obstruction in critical aortic valve stenosis. The presence of an aortic valve bypass conduit has no effect on cerebral blood flow. All blood flow to the brain occurs via antegrade flow across the native stenotic valve; this configuration may decrease the long-term risk of cerebral thromboembolism.

Optimal Surgical Therapy in a Porcine (Sus scrofa) Model of Extra-Thoracic Penetrating Trauma Resulting in Hemorrhagic Shock: ED Thoracotomy vs. Immediate Trans-Abdominal Vascular Control. A Porcine Model for Evaluating the Management of Non-Compressible Torso Hemorrhage

DTIC Science & Technology

2010-11-08

celiac aortic clamping (n=6), direct vascular control (n=6), and endovascular aortic occlusion n=6). This study presents a large animal model of class...including thoracic aortic clamping, supra- celiac aortic clamping, direct vascular control, and proximal endovascular balloon occlusion. Following vascular...subsequently underwent non-compressible hemorrhage with thoracic aortic clamping (n=6), supra- celiac aortic clamping (n=6), direct vascular control (n=6

Predictive risk models for proximal aortic surgery

PubMed Central

Díaz, Rocío; Pascual, Isaac; Álvarez, Rubén; Alperi, Alberto; Rozado, Jose; Morales, Carlos; Silva, Jacobo; Morís, César

2017-01-01

Predictive risk models help improve decision making, information to our patients and quality control comparing results between surgeons and between institutions. The use of these models promotes competitiveness and led to increasingly better results. All these virtues are of utmost importance when the surgical operation entails high-risk. Although proximal aortic surgery is less frequent than other cardiac surgery operations, this procedure itself is more challenging and technically demanding than other common cardiac surgery techniques. The aim of this study is to review the current status of predictive risk models for patients who undergo proximal aortic surgery, which means aortic root replacement, supracoronary ascending aortic replacement or aortic arch surgery. PMID:28616348

Modelling of aortic aneurysm and aortic dissection through 3D printing.

PubMed

Ho, Daniel; Squelch, Andrew; Sun, Zhonghua

2017-03-01

The aim of this study was to assess if the complex anatomy of aortic aneurysm and aortic dissection can be accurately reproduced from a contrast-enhanced computed tomography (CT) scan into a three-dimensional (3D) printed model. Contrast-enhanced cardiac CT scans from two patients were post-processed and produced as 3D printed thoracic aorta models of aortic aneurysm and aortic dissection. The transverse diameter was measured at five anatomical landmarks for both models, compared across three stages: the original contrast-enhanced CT images, the stereolithography (STL) format computerised model prepared for 3D printing and the contrast-enhanced CT of the 3D printed model. For the model with aortic dissection, measurements of the true and false lumen were taken and compared at two points on the descending aorta. Three-dimensional printed models were generated with strong and flexible plastic material with successful replication of anatomical details of aortic structures and pathologies. The mean difference in transverse vessel diameter between the contrast-enhanced CT images before and after 3D printing was 1.0 and 1.2 mm, for the first and second models respectively (standard deviation: 1.0 mm and 0.9 mm). Additionally, for the second model, the mean luminal diameter difference between the 3D printed model and CT images was 0.5 mm. Encouraging results were achieved with regards to reproducing 3D models depicting aortic aneurysm and aortic dissection. Variances in vessel diameter measurement outside a standard deviation of 1 mm tolerance indicate further work is required into the assessment and accuracy of 3D model reproduction. © 2017 The Authors. Journal of Medical Radiation Sciences published by John Wiley & Sons Australia, Ltd on behalf of Australian Society of Medical Imaging and Radiation Therapy and New Zealand Institute of Medical Radiation Technology.

Echocardiographic features of the normofunctional Labcor-Santiago pericardial bioprosthesis.

PubMed

Gonzalez-Juanatey, J R; Garcia-Bengoechea, J B; Vega, M; Rubio, J; Sierra, J; Duran, D; Amaro, A; Gil, M

1994-09-01

Echocardiography was performed in 94 patients with a total of 99 normally functioning Labcor-Santiago bioprostheses, 62 in the aortic and 37 in the mitral position. The following variables were measured: peak and mean transvalvular velocities, peak and mean instantaneous pressure gradients as calculated from the modified Bernoulli equation, pressure half-time, cardiac index, stroke volume and effective orifice area (using continuity and Hatle equations). Regurgitation patterns were sought by transthoracic echocardiography (all valves) and, for selected mitral bioprostheses, by transesophageal echocardiography. Calculated mean aortic pressure gradient ranged from six to 10 mmHg and calculated effective aortic orifice area increased with ring diameter, with means of 1.27 cm2 for the 19 mm valve and 2.58 cm2 for the 27 mm valve. For mitral bioprostheses, mean pressure gradient ranged from 3.0 to 4.5 mmHg and calculated effective orifice area from 2.27 to 2.73 cm2. Only central regurgitation was observed. The Labcor-Santiago pericardial bioprostheses created little resistance to forward flow. In the small aortic root their hemodynamic performance was as good or better than that of other currently available devices. It is hoped that this new design will contribute increased in vivo mechanical durability.

Successful surgical treatment of intramural aortoatrial fistula, severe aortic regurgitation, mitral prolapse, and tricuspid insufficiency in a patient with Ehlers-Danlos syndrome type IV.

PubMed

Jiang, Shengli; Gao, Changqing; Ren, Chonglei; Zhang, Tao

2012-06-01

Patients with Ehlers-Danlos syndrome (EDS) type IV, an inherited connective tissue disorder, are predisposed to vascular and digestive ruptures, and arterial ruptures account for the majority of deaths. A 31-year-old man with EDS presented with an intramural aortoatrial fistula, severe aortic regurgitation, mitral valve prolapse, and severe tricuspid valve insufficiency combined with a severely dilated left ventricle. Determining the best surgical option for the patient was not easy, especially regarding the course of action for the aortic root with a tear in the sinus of Valsalva. The fistula tract was closed at the aorta with suture and with a patch in the right atrium, the mitral valve was repaired with edge-to-edge suture and then annuloplasty with a Cosgrove ring, the aortic valve was replaced with a mechanical prosthesis, and a modified De Vega technique was used for the tricuspid valvuloplasty. The postoperative course was uncomplicated, and the patient was discharged 2 weeks later. The considerations made to arrive at the chosen surgical course of action in this complex case are reviewed.

[Simultaneous interventions on the ascending portion, arch of the aorta and cardiac valves in patients with Marfan's syndrome].

PubMed

Belov, Iu V; Stepanenko, A B; Gens, A P; Charchian, E R; Savichev, D D

2007-01-01

Simultaneous surgical interventions on the aorta and valvular system of the heart were performed in four patients presenting with aortic dissections and aneurysms conditioned by Marfan's syndrome. The following reconstructive operations were carried out: 1) prosthetic repair of the aortic valve and the ascending portion of the aorta by means of a valve-containing conduit with replantation of the openings of the coronary arteries into the side of the prosthesis according to the Benthall - De Bono technique, annuloplasty of the tricuspid valve according to the De Vega technique, valvuloplasty of the mitral valve by the Alferi technique; 2) grafting of the aortic valve and the ascending portion of the aorta by means of a valve-containing conduit with replantation of the openings of the coronary arteries according to the Kabrol's technique, plasty of the tricuspid valve by the De Vega technique; 3) prosthetic repair of the aortic arch with distal wedge-like excision of the membrane of the dissection and directing the blood flow along the both channels, plasty of the mitral valve, plasty of the aortic valve and the ascending portion of the aorta with a valve-containing conduit, accompanied by replantation of the openings of the coronary arteries into the side of the graft according to the Benthall - De Bono technique; (4) plasty of the mitral valve with a disk graft through the fibrous ring of the aortic valve, prosthetic repair of the aortic valve and the ascending portion of the aorta with a valve-containing conduit, accompanied by replantation of the openings of the coronary arteries into the side according to the Benthall-De Bono technique.

Increased vascular sensitivity and connexin43 expression after sympathetic denervation.

PubMed

Slovut, David P; Mehta, Shyamal H; Dorrance, Anne M; Brosius, Frank C; Watts, Stephanie W; Webb, R Clinton

2004-05-01

Following denervation, arteries demonstrate a heightened sensitivity to alpha-adrenergic agonists and increased oscillatory contractions that may partly result from increased gap junction expression. Hence, we wanted to study the effect of sympathetic denervation on connexin43 (Cx43) expression and agonist-induced contractility in the vascular smooth muscle (VSM). Effects of denervation with reserpine (3 mg/kg/day, i.p.) or topical 5% phenol-glycerol on VSM contractions and expression of the gap junction Cx43 mRNA by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting for Cx43 protein were examined. Wistar-Kyoto (WKY) rat tail arteries were exposed to norepinephrine (NE) (10(-9)-10(-5) M). Reactivity was also examined in the carotid arteries and thoracic aortas from Cx43 heterozygote deficient (KO) mice. The concentration for NE-induced contraction was lower in reserpine- and phenol-treated vessels than controls (p<0.05). NE-induced oscillatory activity (OA) was seen in 5/5 reserpine- and 5/8 phenol-treated vessels vs. 0/12 controls (p<0.05). Spontaneous OA was observed more frequently in carotid and aortic rings from WT than Cx43 KO rings. Cumulative OA in response to alpha-adrenergic stimulation was significantly greater in WT carotid (429+/-101 vs. 128+/-7 mN s, p<0.05) and aortic rings (337+/-85 vs. 134+/-11 mN s, p<0.05) than in Cx43 KO rings. Following denervation, RT-PCR showed significantly increased levels of Cx43 mRNA (p<0.05). Western blot analysis revealed near doubling of Cx43 protein (p<0.05). We conclude that sympathetic denervation results in increased expression of Cx43, which in turn, contributes to increased spontaneous and agonist-induced OA in VSM.

Chronic inhibition of nitric-oxide synthase potentiates endothelium-dependent contractions in the rat aorta by augmenting the expression of cyclooxygenase-2.

PubMed

Qu, Chen; Leung, Susan W S; Vanhoutte, Paul M; Man, Ricky Y K

2010-08-01

Acute inhibition of nitric-oxide synthase (NOS) unmasks the release of endothelium-derived contracting factors (EDCFs). The present study investigated whether chronic inhibition of NOS modulates endothelium-dependent contractions. Eighteen-week-old male Sprague-Dawley rats were treated by daily gavage for 6 weeks with the NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) (60 mg/kg) or vehicle (distilled water; 1 ml/kg). Chronic treatment with L-NAME increased arterial blood pressure. Isometric tension was measured in aortic rings with or without endothelium. Endothelium-dependent relaxations to acetylcholine and the calcium ionophore 5-(methylamino)-2-[(2R,3R,6S,8S,9R,11R)-3,9,11-trimethyl-8-[(1S)-1-methyl-2-oxo-2-(1H-pyrrol-2-yl)-ethyl]-1,7-dioxaspiro[5.5]undec-2-yl]methyl]-4-benzoxazolecarboxylic acid (A23187) were reduced in preparations from L-NAME-treated rats. The reduction in relaxation to A23187 was partially reversed by L-arginine (1 mM). In quiescent aortic rings, A23187 caused contractions in the presence of L-NAME and intact endothelium. The A23187-induced contractions were greater in rings from the L-NAME-treated rats than in those from the control group. These contractions were abolished by the cyclooxygenase (COX)-2 inhibitor N-[2-cyclohexyloxy-4-nitrophenyl]methanesulfonamide (NS-398) and the thromboxane-prostanoid (TP) receptor antagonist 3-((6R)-6-{[(4-chlorophenyl)sulfonyl]amido}-2-methyl-5,6,7,8-tetrahydronaphthalen-1-yl)propanoate (S18886), but not by the COX-1 inhibitor 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole (SC-560). Chronic L-NAME treatment reduced the level of nitric oxide in the plasma but increased COX activity in the aortic rings. Western blotting and immunohistochemical staining showed that endothelial NOS expression was reduced in the aortae of the chronic L-NAME-treated group. COX-1 expression was augmented slightly, whereas COX-2 expression was up-regulated markedly. The TP receptor expression was comparable with control. These experiments demonstrate that chronic NOS inhibition increases endothelium-dependent contractions of the rat aorta by inducing COX-2 expression and augmenting the production of EDCF.

The influence of methionine-5-enkephalin on calcium uptake by the bovine aortic media.

PubMed

Kokkas, B; Kotoula, M; Kouyoumtzis, A; Kouvelas, D; Papadopoulos, K; Paradelis, A G

1990-04-01

The influence of methionine-5-enkephalin (M-5-E), an endogenous opioid receptor agonist, on calcium uptake by bovine aortic media was investigated in vitro. 45Ca was used and radioactivity was counted in a beta scintillation counter. M-5-E increases Ca2+ uptake by the preparation. This action is inhibited by naloxone and that is proof that an opioid receptor is stimulated. A comparative study showed that phenylephrine, an alpha-adrenoceptor agonist, exhibits the same action as M-5-E, whereas morphine's action is negligible. Phenylephrine contracts the deendotheliazed ring of the bovine aorta, whereas M-5-E fails to do so. It is concluded that an opioid receptor was identified at the bovine aortic smooth muscle. This receptor is stimulated by M-5-E resulting in an increase of the extracellular Ca2+ entrance. Although no relationship was observed between the receptor and the contraction mechanism, a possible role of M-5-E in the maintenance of the vascular tone cannot be excluded.

Augmented vascular smooth muscle cell stiffness and adhesion when hypertension is superimposed on aging.

PubMed

Sehgel, Nancy L; Sun, Zhe; Hong, Zhongkui; Hunter, William C; Hill, Michael A; Vatner, Dorothy E; Vatner, Stephen F; Meininger, Gerald A

2015-02-01

Hypertension and aging are both recognized to increase aortic stiffness, but their interactions are not completely understood. Most previous studies have attributed increased aortic stiffness to changes in extracellular matrix proteins that alter the mechanical properties of the vascular wall. Alternatively, we hypothesized that a significant component of increased vascular stiffness in hypertension is due to changes in the mechanical and adhesive properties of vascular smooth muscle cells, and that aging would augment the contribution from vascular smooth muscle cells when compared with the extracellular matrix. Accordingly, we studied aortic stiffness in young (16-week-old) and old (64-week-old) spontaneously hypertensive rats and Wistar-Kyoto wild-type controls. Systolic and pulse pressures were significantly increased in young spontaneously hypertensive rats when compared with young Wistar-Kyoto rats, and these continued to rise in old spontaneously hypertensive rats when compared with age-matched controls. Excised aortic ring segments exhibited significantly greater elastic moduli in both young and old spontaneously hypertensive rats versus Wistar-Kyoto rats. were isolated from the thoracic aorta, and stiffness and adhesion to fibronectin were measured by atomic force microscopy. Hypertension increased both vascular smooth muscle cell stiffness and vascular smooth muscle cell adhesion, and these increases were both augmented with aging. By contrast, hypertension did not affect histological measures of aortic collagen and elastin, which were predominantly changed by aging. These findings support the concept that stiffness and adhesive properties of vascular smooth muscle cells are novel mechanisms contributing to the increased aortic stiffness occurring with hypertension superimposed on aging. © 2014 American Heart Association, Inc.

In vitro and ex vivo angiogenic effects of roxarsone on rat endothelial cells.

PubMed

Zhu, Jiaqiao; Cui, Weibo; Liu, Xue; Ying, Jun; Hu, Chengyun; Zhang, Yumei

2013-11-25

Roxarsone, a feed additive, is being used worldwide to promote animal growth. However, the potential effect of roxarsone on angiogenesis has not been extensively characterized. We examined the ability of roxarsone to promote angiogenesis of rat endothelial cells in vitro and from rat aorta rings ex vivo. Endothelial cells from rats were exposed to 0.01-10.00μM roxarsone, 5ng/mL vascular endothelial growth factor (VEGF) as a positive control or phosphate buffer saline (PBS) as a negative control. Cell proliferation was measured by MTT assay, and the content of VEGF in supernatants was measured by enzyme-linked immunosorbent assay and Western blotting. A Matrigel-induced tube formation assay was used to evaluate the effects of roxarsone on endothelial cells. Additionally, the total number and length of microvessels sprouted from rat aortic rings were measured for ex vivo investigation of angiogenesis. Results showed that the cell viability and total number and length of capillary-like tube formations after roxarsone treatment was significantly higher than that of negative (P<0.05), with a maximum effect at 1.00μM exposure. Furthermore, the number of microvessels sprouted from aortic rings treated for 4h with 0.1-10.0μM roxarsone was significantly higher than that of PBS treatment, with a peak value of 1.0μM. These results further demonstrate the potential of roxarsone to promote angiogenesis in vitro and ex vivo. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Anti-angiogenic and cytotoxicity studies of some medicinal plants.

PubMed

Ng, Kwok-Wen; Salhimi, Salizawati Muhamad; Majid, Amin Malik; Chan, Kit-Lam

2010-06-01

Angiogenesis plays an important role in tumor formation and proliferation. The development of anti-angiogenic agents to block new blood vessel growth will inhibit metastasis and induce apoptosis of the cancer cells. Nine medicinal plants, Strobilanthes crispus, Phyllanthus niruri, Phyllanthus pulcher, Phyllanthus urinaria, Ailanthus malabarica, Irvingia malayana, Smilax myosotiflora, Tinospora crispa and blumea balsamifera were screened for anti-angiogenic properties using the rat aortic ring assay. Of these, the methanol extracts of Phyllanthus species and Irvingia malayana exhibited the highest activity. At 100 microg/mL, P. pulcher, P. niruri, P. urinaria and I. malayana recorded an inhibition of 78.8 %, 59.5 %, 56.7 % and 46.4 %, respectively, against rat aortic vascular growth. Their activities were further investigated by the tube formation assay involving human umbilical vein endothelial cells (HUVEC) on Matrigel. I. malayana, P. niruri and P. urinaria showed a significant decrease of 45.5, 37.9 and 35.6 %, respectively, whilst P. pulcher showed a much lower decrease of 15.5 % when compared with that of the rat aortic ring assay. All the plant extracts were evaluated for cytotoxicity on a panel of human cancer cell lines using the MTT assay. None of them displayed acute cytotoxicity. The HPLC of P. niruri, P. urinaria and P. pulcher indicated the extracts contained some identical chromatographic peaks of lignans. Further fractionation of I. malayana yielded betulinic acid reported in this plant for the first time and at 100 microg/mL it exhibited a 67.3 % inhibition of vessel outgrowth and 46.5 % inhibition of tube formation. Georg Thieme Verlag KG Stuttgart-New York.

Ergothioneine prevents endothelial dysfunction induced by mercury chloride.

PubMed

Gökçe, Göksel; Arun, Mehmet Zuhuri; Ertuna, Elif

2018-06-01

Exposure to mercury has detrimental effects on the cardiovascular system, particularly the vascular endothelium. The present study aimed to investigate the effects of ergothioneine (EGT) on endothelial dysfunction induced by low-dose mercury chloride (HgCl 2 ). Agonist-induced contractions and relaxations were evaluated in isolated aortic rings from 3-month-old male Wistar rats treated by intra-muscular injection to caudal hind leg muscle with HgCl 2 (first dose, 4.6 µg/kg; subsequent doses, 0.07 µg/kg/day for 15 days) and optionally with EGT (2 µg/kg for 30 days). Reactive oxygen species (ROS) in aortic rings were measured by means of lucigenin- and luminol-enhanced chemiluminescence. The protein level of endothelial nitric oxide synthase was evaluated by ELISA. Blood glutathione (GSH) and catalase levels, lipid peroxidation and total nitrite were measured spectrophotometrically. The results indicated that low-dose HgCl 2 administration impaired acetylcholine (ACh)-induced relaxation and potentiated phenylephrine- and serotonin-induced contractions in rat aortas. In addition, HgCl 2 significantly increased the levels of ROS in the aortic tissue. EGT prevented the loss of ACh-induced relaxations and the increase in contractile responses. These effects were accompanied by a significant decrease in ROS levels. EGT also improved the ratio of reduced GSH to oxidized GSH and catalase levels with a concomitant decrease in lipid peroxidation. In conclusion, to the best of our knowledge, the present study was the first to report that EGT prevents endothelial dysfunction induced by low-dose HgCl 2 administration. EGT may serve as a therapeutic tool to reduce mercury-associated cardiovascular complications via improving the antioxidant status.

[Correction of the endothelial function damaged by gamma-irradiation with free and liposomal quercetin].

PubMed

Kyslova, O V; Sapatyĭ, A L; Kupnovyts'ka, I H; Moĭbenko, O O

2007-01-01

It has been investigation the action of solubil quercetin (corvitin) and quercetin filled liposomes (lipoflavon) on endothelium--dependent r-irradiated isolated rats aortic rings relaxations to acetylcholine. It has been showed, that corvitin addition directly to the buffer solution (0.1 mg/ml) increase endothelium--dependent vascular responses to acetylcholine on 35%, lipoflavon addition--on 25%.

Allopurinol prevents nitroglycerin-induced tolerance in rat thoracic aorta.

PubMed

Azarmi, Yadollah; Babaei, Hossein; Alizadeh, Fatemeh; Gharebageri, Afsaneh; Fouladi, Daniel F; Nikkhah, Elhameh

2014-02-01

Xanthine oxidase is an important source of reactive oxygen species; so, it may play a role in the pathogenesis of endothelium dysfunction and its consequences. Allopurinol, a purine analog, is a famous xanthine oxidase inhibitor. This study aimed to investigate possible effects of allopurinol on nitroglycerin tolerance, vasoconstriction, and vasorelaxation in rat aortic ring. Using thoracic aortic rings obtained from male Wistar rats, the effect of allopurinol was examined on nitroglycerin-induced tolerance. In addition, changes of vasoconstriction (by using KCl and phenylephrine) and vasorelaxation (by using carbachol, sodium nitroprusside, and nitroglycerin) were also measured and compared between tissues treated with and without allopurinol. All 3 concentrations of allopurinol (50, 100, and 150 μM) significantly acted against the development of nitroglycerin-induced tolerance in comparison with controls. In terms of vasoconstriction and vasorelaxation, the effect of allopurinol was significant only on carbachol-induced (endothelium related) vasorelaxation in a dose-dependent manner. In conclusion, although allopurinol had no significant effect on the contractile response of the aorta, in accord with the previous data, it significantly intensified endothelium-dependent vasodilation. The inhibitory effect of allopurinol against the development of nitrate-induced tolerance may suggest its clinical benefit and is worth to be studied more extensively.

A C-terminal fragment of fibulin-7 interacts with endothelial cells and inhibits their tube formation in culture.

PubMed

de Vega, Susana; Suzuki, Nobuharu; Nonaka, Risa; Sasaki, Takako; Forcinito, Patricia; Arikawa-Hirasawa, Eri; Yamada, Yoshihiko

2014-03-01

We have previously demonstrated that fibulin-7 (Fbln7) is expressed in teeth by pre-odontoblast and odontoblast cells, localized in the basement membrane and dentin matrices, and is an adhesion molecule for dental mesenchyme cells and odontoblasts. Fbln7 is also expressed in blood vessels by endothelial cells. In this report, we show that a recombinant C-terminal Fbln7 fragment (Fbln7-C) bound to Human Umbilical Vein Endothelial Cells (HUVECs) but did not promote cell spreading and actin stress fiber formation. Fbln7-C binding to HUVECs induced integrin clustering at cell adhesion sites with other focal adhesion molecules, and sustained activation of FAK, p130Cas, and Rac1. In addition, RhoA activation was inhibited, thereby preventing HUVEC spreading. As endothelial cell spreading is an important step for angiogenesis, we examined the effect of Fbln7-C on angiogenesis using in vitro assays for endothelial cell tube formation and vessel sprouting from aortic rings. We found that Fbln7-C inhibited the HUVEC tube formation and the vessel sprouting in aortic ring assays. Our findings suggest potential anti-angiogenic activity of the Fbln7 C-terminal region. Published by Elsevier Inc.

Chemical Composition, Toxicity and Vasodilatation Effect of the Flowers Extract of Jasminum sambac (L.) Ait. "G. Duke of Tuscany".

PubMed

Kunhachan, Phanukit; Banchonglikitkul, Chuleratana; Kajsongkram, Tanwarat; Khayungarnnawee, Amonrat; Leelamanit, Wichet

2012-01-01

Phytochemical analysis of the ethanolic Jasmine flower extract of Jasminum sambac (L.) Ait. "G. Duke of Tuscany" revealed the mixtures of coumarins, cardiac glycosides, essential oils, flavonoids, phenolics, saponins, and steroids. However, alkaloids, anthraquinones, and tannins were not detected. By intravenous injection at a single dose of 0.5 mL/mouse (15 mg) of the flower extract, no systemic biological toxicity demonstrated in ICR mice was observed. In Wistar rats, the LD(50) of the extract was higher than 5,000 mg/kg BW by oral administration. Vasodilatation effect of the 95% ethanolic extract on isolated aortic rats was also investigated. Compared with the control group, the Jasmine flowers extract in 0.05% DMSO clearly reduced tonus of isolated endothelium thoracic aortic rings preconstricted with phenylephrine (10(-6) M), as a dose-dependent manner. Nevertheless, this pharmacological effect disappeared after the preincubation of the rings with atropine (10(-6) M) or with N(ω)-nitro-L-arginine (10(-4) M). These are possibly due to the actions of the active components on the vessel muscarinic receptors or by causing the release of nitric oxide.

Changes of imidazoline receptors in spontaneously hypertensive rats

PubMed Central

Mar, Guang-Yuan; Chou, Ming-Ting; Chung, Hsien-Hui; Chiu, Nien-Hua; Chen, Mei-Fen; Cheng, Juei-Tang

2013-01-01

The role of imidazoline receptors in the regulation of vascular function remains unclear. In this study, we evaluated the effect of agmatine, an imidazoline receptor agonist, on systolic blood pressure (SBP) in spontaneously hypertensive rats (SHRs) and investigated the expressions of imidazoline receptors by Western blot. The isometric tension of aortic rings isolated from male SHRs was also estimated. Agmatine decreased SBP in a dose-dependent manner in SHRs but not in the normal group [Wistar–Kyoto (WKY) rats]. This reduction in SBP in SHRs was abolished by BU224, a selective antagonist of imidazoline I2-receptors. Higher expression of imidazoline receptors in SHR was observed. Moreover, agmatine-induced relaxation in isolated aortic rings precontracted with phenylephrine or KCl. This relaxation was also abolished by BU224 but was not modified by efaroxan, an imidazoline I1-receptor antagonist. Agmatine-induced relaxation was also attenuated by PNU 37883, a selective blocker of vascular ATP-sensitive potassium (KATP) channels. Additionally, vasodilatation by agmatine was reduced by an inhibitor of protein kinase A (PKA). We suggest that agmatine can lower blood pressure in SHRs through activation of the peripheral imidazoline I2-receptor, which is expressed more highly in SHRs. PMID:23176371

Anti-angiogenic and vascular disrupting effects of C9, a new microtubule-depolymerizing agent

PubMed Central

Ren, Xuan; Dai, Mei; Lin, Li-Ping; Li, Pui-Kai; Ding, Jian

2009-01-01

Background and purpose: The critical role of blood supply in the growth of solid tumours makes blood vessels an ideal target for anti-tumour drug discovery. The anti-angiogenic and vascular disrupting activities of C9, a newly synthesized microtubule-depolymerizing agent, were investigated with several in vitro and in vivo models. Possible mechanisms involved in its activity were also assessed. Experimental approach: Microtubule-depolymerizing actions were assessed by surface plasmon resonance binding, competitive inhibition and cytoskeleton immunofluorescence. Anti-angiogenic and vascular disrupting activities were tested on proliferation, migration, tube formation with human umbilical vein endothelial cells, and in rat aortic ring, chick chorioallantoic membrane and Matrigel plug assays. Western blots and Rho activation assays were employed to examine the role of Raf-MEK-ERK (mitogen-activated ERK kinase, extracellular signal-regulated kinase) and Rho/Rho kinase signalling. Key results: C9 inhibited proliferation, migration and tube formation of endothelial cells and inhibited angiogenesis in aortic ring and chick chorioallantoic membrane assays. C9 induced disassembly of microtubules in endothelial cells and down-regulated Raf-MEK-ERK signalling activated by pro-angiogenic factors. In addition, C9 disrupted capillary-like networks and newly formed vessels in vitro and rapidly decreased perfusion of neovasculature in vivo. Endothelial cell contraction and membrane blebbing induced by C9 in neovasculature was dependent on the Rho/Rho kinase pathway. Conclusions and implications: Anti-angiogenic and vascular disruption by C9 was associated with changes in morphology and function of endothelial cells, involving the Raf-MEK-ERK and Rho/Rho kinase signalling pathways. These findings strongly suggest that C9 is a new microtubule-binding agent that could effectively target tumour vasculature. PMID:19302593

Homocysteine impaired endothelial function through compromised vascular endothelial growth factor/Akt/endothelial nitric oxide synthase signalling.

PubMed

Yan, Ting-Ting; Li, Qian; Zhang, Xuan-Hong; Wu, Wei-Kang; Sun, Juan; Li, Lin; Zhang, Quan; Tan, Hong-Mei

2010-11-01

1. Hyperhomocysteinaemia (HHcy) is associated with endothelial dysfunction and has been recognized as a risk factor of cardiovascular disease. The present study aimed to investigate the effect of homocysteine (Hcy) on endothelial function in vivo and in vitro, and the underlying signalling pathways. 2. The HHcy animal model was established by intragastric administration with l-methionine in rats. Plasma Hcy and nitric oxide (NO) concentration were measured by fluorescence immunoassay or nitrate reductase method, respectively. Vasorelaxation in response to acetylcholine and sodium nitroprusside were carried out on aortic rings. Human umbilical vein endothelial cells (HUVEC) were treated with indicated concentrations of Hcy in the in vitro experiments. Intracellular NO level and NO concentration in culture medium were assayed. The alterations of possible signalling proteins were detected by western blot analysis. 3. l-methionine administration induced a significant increase in plasma Hcy and decrease in plasma NO. Endothelium-dependent relaxation of aortic rings in response to acetylcholine was impaired in l-methionine-administrated rats. The in vitro study showed that Hcy reduced both intracellular and culture medium NO levels. Furthermore, Hcy decreased phosphorylation of endothelial nitric oxide synthase (eNOS) at serine-1177 and phosphorylation of Akt at serine-473. Hcy-induced dephosphorylation of eNOS at Ser-1177 was partially reversed by insulin (Akt activator) and GF109203X (PKC inhibitor). Furthermore, Hcy reduced vascular endothelial growth factor (VEGF) expression in a dose-dependent manner. 4. In conclusion, Hcy impaired endothelial function through compromised VEGF/Akt/endothelial nitric oxide synthase signalling. These findings will be beneficial for further understanding the role of Hcy in cardiovascular disease. © 2010 Blackwell Publishing Asia Pty Ltd.

IRAP inhibition using HFI419 prevents moderate to severe acetylcholine mediated vasoconstriction in a rabbit model.

PubMed

El-Hawli, Aisha; Qaradakhi, Tawar; Hayes, Alan; Rybalka, Emma; Smith, Renee; Caprnda, Martin; Opatrilova, Radka; Gazdikova, Katarina; Benckova, Maria; Kruzliak, Peter; Zulli, Anthony

2017-02-01

Coronary artery vasospasm (constriction) caused by reduced nitric oxide bioavailability leads to myocardial infarction. Reduced endothelial release of nitric oxide by the neurotransmitter acetylcholine, leads to paradoxical vasoconstriction as it binds to smooth muscle cell M3 receptors. Thus, inhibition of coronary artery vasospasm will improve clinical outcomes. Inhibition of insulin regulated aminopeptidase has been shown to improve vessel function, thus we tested the hypothesis that HFI419, an inhibitor of insulin regulated aminopeptidase, could reduce blood vessel constriction to acetylcholine. The abdominal aorta was excised from New Zealand white rabbits (n=15) and incubated with 3mM Hcy to induce vascular dysfunction in vitro for 1h. HFI419 was added 5min prior to assessment of vascular function by cumulative doses of acetylcholine. In some rings, vasoconstriction to acetylcholine was observed in aortic rings after pre-incubation with 3mM homocysteine. Incubation with HFI419 inhibited the vasoconstrictive response to acetylcholine, thus improving, but not normalizing, vascular function (11.5±8.9% relaxation vs 79.2±37% constriction, p<0.05). Similarly, in another group with mild vasoconstriction, HFI419 inhibited this effect (34.9±4.6% relaxation vs 11.1±5.2%, constriction, p<0.05). HFI419 had no effect on control aorta or aorta with mild aortic dysfunction. The present study shows that HFI419 prevents acetylcholine mediated vasoconstriction in dysfunctional blood vessels. HFI419 had no effect on normal vasodilation. Our results indicate a therapeutic potential of HFI419 in reducing coronary artery vasospasm. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

A low-dose atorvastatin and losartan combination directly improves aortic ring relaxation and diminishes ischaemic-reperfusion injury in isolated rat hearts

PubMed Central

Lunder, Mojca; Janić, Miodrag; Žiberna, Lovro; Drevenšek, Gorazd; Šabovič, Mišo

2012-01-01

Summary Background The cardiovascular pleiotropic effects of statins and angiotensin receptor blockers (ARBs) could be of interest for innovative preventive approaches. We aimed to investigate whether low-dose atorvastatin and losartan, separately not possessing protective cardiovascular pleiotropic effects, express them when combined. Material/Methods Forty-five adult male Wistar rats were anaesthetized and their thoracic aortas and hearts were isolated. Relaxation of aortic rings, coronary flow rate and the extent of myocardial ischaemic-reperfusion injury were measured. Different concentrations (0.01, 0.1, 1.0 μM) of atorvastatin and losartan added to a perfusion medium were first tested. The separate drugs, which were ineffective, were then combined at the same concentrations and the concentration was tested in the same model. Results Low concentrations of atorvastatin or losartan (0.1 and 1 μM, respectively) produced no effects in isolated aorta. However, surprisingly, when these drug concentrations were combined, a significantly improved endothelium-dependent relaxation of the thoracic aorta was observed. Similarly, when combining individually ineffective concentrations of atorvastatin or losartan (0.01 and 0.1 μM, respectively), significantly increased coronary flow and a decreased extent of myocardial injury were observed. By using a nitric oxide-synthase inhibitor, we demonstrated that the vasodilatory effects obtained were nitric oxide-dependent. The degree of effectiveness by the combination was comparable to that obtained by 10-fold (atorvastatin) or 100-fold (losartan) higher concentrations of the separate drugs. Conclusions Our results revealed that remarkable additive/synergistic effects exist between low-doses of a statin (atorvastatin) and an ARB (losartan), resulting in important cardiovascular protection. This new concept could be valuable in cardiovascular prevention. PMID:22936187

Anti-Cancer Properties of a Novel Class of Tetrafluorinated Thalidomide Analogs

PubMed Central

Beedie, Shaunna L.; Peer, Cody J.; Pisle, Steven; Gardner, Erin R.; Mahony, Chris; Barnett, Shelby; Ambrozak, Agnieszka; Gütschow, Michael; Chau, Cindy H.; Vargesson, Neil; Figg, William D.

2015-01-01

Thalidomide has demonstrated clinical activity in various malignancies affecting immunomodulatory and angiogenesis pathways. The development of novel thalidomide analogs with improved efficacy and decreased toxicity is an ongoing research effort. We recently designed and synthesized a new class of compounds, consisting of both tetrafluorinated thalidomide analogs (Gu973 and Gu998) and tetrafluorobenzamides (Gu1029 and Gu992). In this study, we demonstrate the anti-angiogenic properties of these newly synthesized compounds. We examined the specific anti-angiogenic characteristics in vitro using rat aortic rings with carboxyamidotriazole as a positive control. Additionally, further in vitro efficacy was evaluated using HUVECs and PC3 cells treated with 5μM and 10μM doses of each compound. All compounds were seen to reduce microvessel outgrowth in rat aortic rings as well as inhibit HUVECs to a greater extent, at lower concentrations than previously tested thalidomide analogs. The anti-angiogenic properties of the compounds was also examined in vivo in fli1:EGFP zebrafish embryos, where all compounds were seen to inhibit the extent of outgrowth of newly developing blood vessels. In addition, Gu1029 and Gu973 reduced the anti-inflammatory response in mpo:GFP zebrafish embryos, while Gu998 and Gu992 showed no difference. The compounds anti-tumor effects were also explored in vivo using the human prostate cancer PC3 xenograft model. All four compounds were also screened in vivo in chicken embryos to investigate their teratogenic potential. This study establishes these novel thalidomide analogs as a promising immunomodulatory class with anti-cancer effects that warrant further development to characterize their mechanisms of action. PMID:26269604

Vascular mechanisms underlying the hypotensive effect of Rumex acetosa.

PubMed

Qamar, Hafiz Misbah-Ud-Din; Qayyum, Rahila; Salma, Umme; Khan, Shamim; Khan, Taous; Shah, Abdul Jabbar

2018-12-01

Rumex acetosa L. (Polygonaceae) is well known in traditional medicine for its therapeutic efficacy as an antihypertensive. The study investigates antihypertensive potential of crude methanol extract (Ra.Cr) and fractions of Rumex acetosa in normotensive and hypertensive rat models and probes the underlying vascular mechanisms. Ra.Cr and its fractions were tested in vivo on normotensive and hypertensive Sprague-Dawley rats under anaesthesia for blood pressure lowering effect. In vitro experiments on rat and Oryctolagus cuniculus rabbit aortae were employed to probe the underlying vasorelaxant mechanism. In normotensive rats under anaesthesia, Ra.Cr caused fall in MAP (40 mmHg) at 50 mg/kg with % fall of 27.88 ± 4.55. Among the fractions tested, aqueous fraction was more potent at the dose of 50 mg/kg with % fall of 45.63 ± 2.84. In hypertensive rats under similar conditions, extract and fractions showed antihypertensive effect at same doses while aqueous fraction being more potent, exhibited 68.53 ± 4.45% fall in MAP (70 mmHg). In isolated rat aortic rings precontracted with phenylephrine (PE), Ra.Cr and fractions induced endothelium-dependent vasorelaxation, which was partially blocked in presence of l-NAME, indomethacin and atropine. In isolated rabbit aortic rings pre-contracted with PE and K + -(80 mM), Ra.Cr induced vasorelaxation and shifted Ca 2+ concentration-response curves to the right and suppressed PE peak formation, similar to verapamil, in Ca 2+ -free medium. The data indicate that l-NAME and atropine-sensitive endothelial-derived NO and COX enzyme inhibitors and Ca 2+ entry blocking-mediated vasodilator effect of the extract explain its antihypertensive potential.

OPC-28326, a selective femoral arterial vasodilator, augments ischemia induced angiogenesis.

PubMed

Sumi, Makoto; Sata, Masataka; Hashimoto, Ayako; Imaizumi, Takashi; Yanaga, Katsuhiko; Ohki, Takao; Mori, Toyoki; Nagai, Ryozo

2007-05-01

OPC-28326, 4-(N-methyl-2-phenylethylamino)-1-(3,5-dimethyl-4-propionyl-aminobenzoyl) piperidine hydrochloride monohydrate, is a newly developed selective peripheral vasodilator and increases blood flow to lower extremities with alpha2-adrenergic antagonist property. Here, we investigated the effect of OPC-28326 on ischemia-induced angiogenesis. OPC-28326 enhanced tube formation by human aortic endothelial cells (HAECs). Moreover, OPC-28326 enhanced the number of microvessels sprouting from aortic rings embedded in collagen gel. OPC-28326 markedly induced phosphorylation of endothelial nitric oxide synthase (eNOS) in HAECs via phosphatidylinositol-3 kinase PI3K/Akt (PI3K/Akt) pathway. Next, the angiogenic effect of OPC-28326 was evaluated in a mouse hindlimb ischemia model. Blood flow recovery to the ischemic leg was significantly enhanced by OPC-28326. Furthermore, anti-CD31 immunostaining revealed that OPC-28326 increased capillary density in the ischemic muscle. However, OPC-28326 failed to promote blood flow recovery in ischemic hindlimb in eNOS-deficient mice. These results suggest that OPC-28326 promotes angiogenesis, which was associated with activation of eNOS via PI3K/Akt pathway. OPC-28326 might be promising to treat patients with ischemic vascular diseases.

Obtaining the biomechanical behavior of ascending aortic aneurysm via the use of novel speckle tracking echocardiography.

PubMed

Alreshidan, Mohammed; Shahmansouri, Nastaran; Chung, Jennifer; Lash, Vynka; Emmott, Alexander; Leask, Richard L; Lachapelle, Kevin

2017-04-01

Ex vivo measurement of ascending aortic biomechanical properties may help understand the risk for rupture or dissection of dilated ascending aortas. A validated in vivo method that can predict aortic biomechanics does not exist. Speckle tracking transesophageal echocardiography (TEE) has been used to measure ventricular stiffness; we sought to determine whether speckle TEE could be adapted to estimate aortic stiffness in vivo and compare these findings with those obtained by ex vivo tissue measurements. A total of 17 patients undergoing ascending aortic resection were recruited to with a mean aortic diameter was 56.16 ± 15 mm. Intraoperative speckle TEE tracking analysis was used to calculate aortic stiffness index using the following equation: β2=ln(SBP/DBP)/AoS, where β2 is the stiffness index; SBP is systolic blood pressure; DBP is diastolic blood pressure; and AoS is the circumferential strain. Ex vivo stiffness was obtained by mechanical tissue testing according to previously described methods. The aortic ring at the pulmonary trunk was divided into 4 equal quadrants. The in vivo stiffness index for the inner curvature, anterior wall, outer curvature, and posterior wall were 0.0544 ± 0.0490, 0.0295 ± 0.0199, 0.0411 ± 0.0328, and 0.0502 ± 0.0320, respectively. The mean ex vivo 25% apparent stiffness for inner curvature, anterior wall, outer curvature, and posterior wall were 0.0616 ± 0.0758 MPa, 0.0352 ± 0.00992 MPa, 0.0405 ± 0.0199 MPa, and 0.0327 ± 0.0106 MPa, respectively. The patient-matched ex vivo 25% apparent stiffness and in vivo stiffness index were not significantly different (P = .8617, 2-way analysis of variance with repeated measures). The use of speckle TEE appears to be a promising technique to estimate ex vivo mechanical properties of the ascending aortic tissue. Copyright © 2016 The American Association for Thoracic Surgery. All rights reserved.

Impact of magnesium:calcium ratio on calcification of the aortic wall.

PubMed

Villa-Bellosta, Ricardo

2017-01-01

An inverse relationship between serum magnesium concentration and vascular calcification has been reported following observational clinical studies. Moreover, several studies have been suggesting a protective effect of magnesium on the vascular calcification. However, the exact mechanism remains elusive, and investigators have speculated among a myriad of potential actions. The effect of magnesium on calcification of the aortic wall is yet to be investigated. In the present study, the effects of magnesium and calcium on the metabolism of extracellular PPi, the main endogenous inhibitor of vascular calcification, were investigated in the rat aorta. Calcium and magnesium have antagonist effects on PPi hydrolysis in the aortic wall. Km and Ki values for PPi hydrolysis in rat aortic rings were 1.1 mmol/L magnesium and 32 μmol/L calcium, respectively, but ATP hydrolysis was not affected with calcium. Calcium deposition in the rat aortic wall dramatically increased when the magnesium concentration was increased (ratio of Mg:Ca = 1:1; 1.5 mmol/L calcium and 1.5 mmol/L magnesium) respect to low magnesium concentration (ratio Mg:Ca = 1:3, 1.5 mmol/L calcium and 0.75 mmol/L magnesium). Data from observational clinical studies showing that the serum magnesium concentration is inversely correlated with vascular calcification could be reinterpreted as a compensatory regulatory mechanism that reduces both PPi hydrolysis and vascular calcification. The impact of magnesium in vascular calcification in humans could be studied in association with calcium levels, for example, as the magnesium:calcium ratio.

Cardiovascular effects of Helichrysum ceres S Moore [Asteraceae] ethanolic leaf extract in some experimental animal paradigms.

PubMed

Musabayane, Cephas T; Kamadyaapa, Dave R; Gondwe, Mavuto; Moodley, Kogi; Ojewole, John A O

2008-01-01

The aim of this study was to examine some in vivo and in vitro cardiovascular effects of Helichrysum ceres leaf ethanolic extract (HCE) in experimental animal paradigms. The acute effects of HCE on blood pressure were studied in anaesthetised normotensive male Wistar rats challenged with intravenous hypotonic saline infusion after a 3.5-hour equilibration for four hours of one-hour control, 1.5-hour treatment and 1.5-hour recovery periods. HCE was added to the infusate during the treatment period. Sub-chronic hypotensive effects of HCE were examined in weanling Dahl saltsensitive (DSS) genetically hypertensive rats, which progressively develop hypertension with age, treated with HCE (80 mg/kg) every third consecutive day for seven weeks. Isolated atrial muscle strips, portal veins and descending thoracic aortic rings of healthy normotensive Wistar rats were used to investigate the vascular effects of HCE. Acute HCE administration caused a significant (p < 0.05) fall in blood pressure in the normotensive anaesthetised Wistar rats. DSS hypertensive rats treated with HCE displayed low arterial blood pressure and heart rate values from weeks five to seven. HCE produced concentrationdependent negative inotropic and chronotropic effects on rat isolated electrically driven left, and spontaneously beating right atrial muscle preparations, respectively. HCE also evoked concentration-dependent relaxation responses of endothelium-intact aortic rings and portal veins isolated from healthy normotensive Wistar rats. The vasorelaxant effects of HCE in intact aortic rings were significantly reduced, but not completely abolished by adding endothelial- derived factor (EDRF) inhibitor, L-NAME, suggesting that the vasorelaxant effect of the extract is mediated via EDRF-dependent and independent mechanisms. The results of the study suggest that the hypotensive action of HCE is elicited, in part, directly by decreasing myocardial contractile performance and total peripheral vascular resistance due to its negative inotropic and chronotropic effects on rat isolated atrial muscle strips; and vasorelaxant effects on isolated vascular smooth muscles. The observed cardiovascular effects of HCE partly support the basis for its use in the management of high blood pressure in folkloric medicine.

Cardiovascular effects of Helichrysum ceres S Moore [Asteraceae] ethanolic leaf extract in some experimental animal paradigms

PubMed Central

Musabayane, Cephas T; Kamadyaapa, Dave R; Gondwe, Mavuto; Moodley, Kogi; Ojewole, John AO

2008-01-01

Summary Summary The aim of this study was to examine some in vivo and in vitro cardiovascular effects of Helichrysum ceres leaf ethanolic extract (HCE) in experimental animal paradigms. The acute effects of HCE on blood pressure were studied in anaesthetised normotensive male Wistar rats challenged with intravenous hypotonic saline infusion after a 3.5-hour equilibration for four hours of one-hour control, 1.5-hour treatment and 1.5-hour recovery periods. HCE was added to the infusate during the treatment period. Sub-chronic hypotensive effects of HCE were examined in weanling Dahl salt-sensitive (DSS) genetically hypertensive rats, which progressively develop hypertension with age, treated with HCE (80 mg/kg) every third consecutive day for seven weeks. Isolated atrial muscle strips, portal veins and descending thoracic aortic rings of healthy normotensive Wistar rats were used to investigate the vascular effects of HCE. Acute HCE administration caused a significant (p < 0.05) fall in blood pressure in the normotensive anaesthetised Wistar rats. DSS hypertensive rats treated with HCE displayed low arterial blood pressure and heart rate values from weeks five to seven. HCE produced concentration-dependent negative inotropic and chronotropic effects on rat isolated electrically driven left, and spontaneously beating right atrial muscle preparations, respectively. HCE also evoked concentration-dependent relaxation responses of endothelium-intact aortic rings and portal veins isolated from healthy normotensive Wistar rats. The vasorelaxant effects of HCE in intact aortic rings were significantly reduced, but not completely abolished by adding endothelial-derived factor (EDRF) inhibitor, L-NAME, suggesting that the vasorelaxant effect of the extract is mediated via EDRF-dependent and independent mechanisms. The results of the study suggest that the hypotensive action of HCE is elicited, in part, directly by decreasing myocardial contractile performance and total peripheral vascular resistance due to its negative inotropic and chronotropic effects on rat isolated atrial muscle strips; and vasorelaxant effects on isolated vascular smooth muscles. The observed cardiovascular effects of HCE partly support the basis for its use in the management of high blood pressure in folkloric medicine. PMID:18997985

Altitude negates the benefits of aerobic training on the vascular adaptations in rats.

PubMed

Reboul, Cyril; Tanguy, Stephane; Dauzat, Michel; Obert, Philippe

2005-06-01

This study questioned the effect of living and training at moderate altitude on aortic vasoreactivity. Considering that chronic hypoxia exposure and endurance training are able to generate opposite effects on the systemic vascular reactivity, it was hypothesized that endurance training benefits on the vascular function could be limited by chronic hypoxia. Sea-level native rats were randomly assigned to N (living in normoxia), NT (living and training 5 d.wk for 5 wk in normoxia), CH (living in hypoxia, 2800 m), and CHT (living and training 5 d.wk for 5 wk in hypoxia, 2800 m) groups. Concentration response curves to epinephrine, norepinephrine, endothelin-1, acetylcholine, and sodium nitro-prusside were assessed on aortic isolated rings. Left ventricular resting and maximal (during Tyrode's infusion) stroke volumes were evaluated by Doppler-echocardiography and used as indexes of chronic aortic volume overload. The main finding was that favorable aortic vasoreactivity adaptations consecutive to sea-level training were not observed when training was conducted at altitude. An improvement in the endothelium-dependent vasorelaxation (maximal relaxation, R(max), N = 60.4 +/- 10.0 vs NT = 91.7 +/- 3.2%; P < 0.05) and a reduced sensitivity to ET-1 were observed in NT rats. Such an enhancement in endothelium-dependent vasorelaxation was not found in CHT rats (R(max): 48.4 +/- 7.8%). Moreover, a higher sensitivity to ET-1 was reported in this group. Altitude-induced limitation in aortic blood flow and shear stress could play a major role in the explanation of these specific altitude-training adaptations. If extrapolated to the peripheral vascular bed, our results have practical significance for aerobic performance as aortic vasoreactivity adaptations after altitude training could contribute to limit blood delivery to exercising muscles.

Cardiovascular effects in vitro of aqueous extract of wild strawberry (Fragaria vesca, L.) leaves.

PubMed

Mudnic, I; Modun, D; Brizic, I; Vukovic, J; Generalic, I; Katalinic, V; Bilusic, T; Ljubenkov, I; Boban, M

2009-05-01

In contrast to the strawberry fruits, strawberry leaves as a source of bioactive compounds with potentially beneficial biological effects have been largely overlooked. In this study we examined direct, dose-dependent effects of wild strawberry (Fragaria vesca, L.) leaves aqueous extract, in two experimental models and animal species, the isolated guinea pig hearts and rat aortic rings. Vasodilatory potential of the wild strawberry leaves extract was compared with vasodilatory activity of aqueous extract of hawthorn (Crataegus oxycantha, L) leaves with flowers, which can be regarded as a reference plant extract with a marked vasodilatory activity. The extracts were analysed by their "phenolic fingerprints", total phenolic content and antioxidative capacity. Their vasodilatory activity was determined and compared in the isolated aortic rings from 24 rats that were exposed to the extracts doses of 0.06, 0.6, 6, and 60 mg/100ml. Both extracts induced similar, dose-dependent vasodilation. Maximal relaxation was 72.2+/-4.4% and 81.3+/-4.5%, induced by the strawberry and hawthorn extract, respectively. To determine vasodilatory mechanisms of the wild strawberry leaves extract, endothelium-denuded and intact rings exposed to nitric oxide (NO) synthase inhibitor L-NAME or cyclooxygenase inhibitor indomethacin were used. Removal of the endothelium prevented and exposure to L-NAME or indomethacin strongly diminished the vasodilatatory response to the extract. In the isolated hearts (n=12), the wild strawberry extract was applied at concentrations of 0.06, 0.18, 0.6, and 1.8 mg/100ml. Each dose was perfused for 3.5 min with 15 min of washout periods. Heart contractility, electrophysiological activity, coronary flow and oxygen consumption were continuously monitored. The extract did not significantly affect heart rate and contractility, main parameters of the cardiac action that determine oxygen demands, while coronary flow increased up to 45% over control value with a simultaneous decrease of oxygen extraction by 34%. The results indicate that the aqueous extract of wild strawberry leaves is a direct, endothelium-dependent vasodilator, action of which is mediated by NO and cyclooxygenase products and which potency is similar to that of the hawthorn aqueous extract.

ATP sensitive K+ channel subunits (Kir6.1, Kir6.2) are the candidate mediators regulating ameliorating effects of pulsed magnetic field on aortic contractility in diabetic rats.

PubMed

Ocal, Isil; Yilmaz, Mehmet B; Kocaturk-Sel, Sabriye; Tufan, Turan; Erkoc, Mehmet A; Comertpay, Gamze; Oksuz, Hale; Barc, Esma D

2018-05-01

Diabetes mellitus is a metabolic disease that causes increased morbidity and mortality in developed and developing countries. With recent advancements in technology, alternative treatment methods have begun to be investigated in the world. This study aims to evaluate the effect of pulsed magnetic field (PMF) on vascular complications and contractile activities of aortic rings along with Kir6.1 and Kir6.2 subunit expressions of ATP-sensitive potassium channels (K ATP ) in aortas of controlled-diabetic and non-controlled diabetic rats. Controlled-diabetic and non-controlled diabetic adult male Wistar rats were exposed to PMF for a period of 6 weeks according to the PMF application protocol (1 h/day; intensity: 1.5 mT; consecutive frequency: 1, 10, 20, and 40 Hz). After PMF exposure, body weight and blood glucose levels were measured. Then, thoracic aorta tissue was extracted for relaxation-contraction and Kir6.1 and Kir6.2 expression experiments. Blood plasma glucose levels, body weight, and aortic ring contraction percentage decreased in controlled-diabetic rats but increased in non-controlled diabetic rats. PMF therapy repressed Kir6.1 mRNA expression in non-controlled diabetic rats but not in controlled diabetic rats. Conversely, Kir6.2 mRNA expressions were repressed both in controlled diabetic and non-controlled diabetic rats by PMF. Our findings suggest that the positive therapeutic effects of PMF may act through (K ATP ) subunits and may frequently occur in insulin-free conditions. Bioelectromagnetics. 39:299-311, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Yoda1 analogue (Dooku1) which antagonizes Yoda1‐evoked activation of Piezo1 and aortic relaxation

PubMed Central

Evans, Elizabeth L; Cuthbertson, Kevin; Endesh, Naima; Rode, Baptiste; Blythe, Nicola M; Hyman, Adam J; Hall, Sally J; Gaunt, Hannah J; Ludlow, Melanie J

2018-01-01

Background and Purpose The mechanosensitive Piezo1 channel has important roles in vascular physiology and disease. Yoda1 is a small‐molecule agonist, but the pharmacology of these channels is otherwise limited. Experimental Approach Yoda1 analogues were generated by synthetic chemistry. Intracellular Ca2+ and Tl+ measurements were made in HEK 293 or CHO cell lines overexpressing channel subunits and in HUVECs, which natively express Piezo1. Isometric tension recordings were made from rings of mouse thoracic aorta. Key Results Modification of the pyrazine ring of Yoda1 yielded an analogue, which lacked agonist activity but reversibly antagonized Yoda1. The analogue is referred to as Dooku1. Dooku1 inhibited 2 μM Yoda1‐induced Ca2+‐entry with IC50s of 1.3 μM (HEK 293 cells) and 1.5 μM (HUVECs) yet failed to inhibit constitutive Piezo1 channel activity. It had no effect on endogenous ATP‐evoked Ca2+ elevation or store‐operated Ca2+ entry in HEK 293 cells or Ca2+ entry through TRPV4 or TRPC4 channels overexpressed in CHO and HEK 293 cells. Yoda1 caused dose‐dependent relaxation of aortic rings, which was mediated by an endothelium‐ and NO‐dependent mechanism and which was antagonized by Dooku1 and analogues of Dooku1. Conclusion and Implications Chemical antagonism of Yoda1‐evoked Piezo1 channel activity is possible, and the existence of a specific chemical interaction site is suggested with distinct binding and efficacy domains. PMID:29498036

Prosthetic Aortic Valve Fixation Study: 48 Replacement Valves Analyzed Using Digital Pressure Mapping.

PubMed

Lee, Candice Y; Wong, Joshua K; Ross, Ronald E; Liu, David C; Khabbaz, Kamal R; Martellaro, Angelo J; Gorea, Heather R; Sauer, Jude S; Knight, Peter A

Prostheses attachment is critical in aortic valve replacement surgery, yet reliable prosthetic security remains a challenge. Accurate techniques to analyze prosthetic fixation pressures may enable the use of fewer sutures while reducing the risk of paravalvular leaks (PVL). Customized digital thin film pressure transducers were sutured between aortic annulus models and 21-mm bioprosthetic valves with 15 × 4-mm, 12 × 4-mm, or 9 × 6-mm-wide pledgeted mattress sutures. Simulating open and minimally invasive access, 4 surgeons, blinded to data acquisition, each secured 12 valves using manual knot-tying (hand-tied [HT] or knot-pusher [KP]) or automated titanium fasteners (TFs). Real-time pressure measurements and times were recorded. Two-dimensional (2D) and 3D pressure maps were generated for all valves. Pressures less than 80 mm Hg were considered at risk for PVL. Pressures under each knot (intrasuture) fell less than 80 mm Hg for 12 of 144 manual knots (5/144 HT, 7/144 KP) versus 0 of 288 TF (P < 0.001). Pressures outside adjacent sutures (extrasuture) were less than 80 mm Hg in 10 of 60 HT, zero of 60 KP, and zero of 120 TF sites for 15 × 4-mm valves; 17 of 48 HT, 25 of 48 KP, and 12 of 96 TF for 12 × 4-mm valves; and 15 of 36 HT, 17 of 36 KP, and 9 and 72 TF for 9 × 6-mm valves; P < 0.001 all manual versus TF. Annular areas with pressures less than 80 mm Hg ranged from 0% of the sewing-ring area (all open TF) to 31% (12 × 4 mm, KP). The average time per manual knot, 46 seconds (HT, 31 seconds; KP, 61 seconds), was greater than TF, 14 seconds (P < 0.005). Reduced operative times and PVL risk would fortify the advantages of surgical aortic valve replacement. This research encourages continued exploration of technical factors in optimizing prosthetic valve security.

An augmented magnetic navigation system for Transcatheter Aortic Valve Implantation.

PubMed

Luo, Zhe; Cai, Junfeng; Nie, Yuanyuan; Wang, Guotai; Gu, Lixu

2013-01-01

This research proposes an augmented magnetic navigation system for Transcatheter Aortic Valve Implantation (TAVI) employing a magnetic tracking system (MTS) combined with a dynamic aortic model and intra-operative ultrasound (US) images. The dynamic 3D aortic model is constructed based on the preoperative 4D computed tomography (CT), which is animated according to the real time electrocardiograph (ECG) input of patient. And a preoperative planning is performed to determine the target position of the aortic valve prosthesis. The temporal alignment is performed to synchronize the ECG signals, intra-operative US image and tracking information. Afterwards, with the assistance of synchronized ECG signals, the contour of aortic root automatic extracted from short axis US image is registered to the dynamic aortic model by a feature based registration intra-operatively. Then the augmented MTS guides the interventionist to confidently position and deploy the aortic valve prosthesis to target. The system was validated by animal studies on three porcine subjects, the deployment and tilting errors of which are 3.17 ± 0.91 mm and 7.40 ± 2.89° respectively.

Nitrate decreases xanthine oxidoreductase-mediated nitrite reductase activity and attenuates vascular and blood pressure responses to nitrite.

PubMed

Damacena-Angelis, Célio; Oliveira-Paula, Gustavo H; Pinheiro, Lucas C; Crevelin, Eduardo J; Portella, Rafael L; Moraes, Luiz Alberto B; Tanus-Santos, Jose E

2017-08-01

Nitrite and nitrate restore deficient endogenous nitric oxide (NO) production as they are converted back to NO, and therefore complement the classic enzymatic NO synthesis. Circulating nitrate and nitrite must cross membrane barriers to produce their effects and increased nitrate concentrations may attenuate the nitrite influx into cells, decreasing NO generation from nitrite. Moreover, xanthine oxidoreductase (XOR) mediates NO formation from nitrite and nitrate. However, no study has examined whether nitrate attenuates XOR-mediated NO generation from nitrite. We hypothesized that nitrate attenuates the vascular and blood pressure responses to nitrite either by interfering with nitrite influx into vascular tissue, or by competing with nitrite for XOR, thus inhibiting XOR-mediated NO generation. We used two independent vascular function assays in rats (aortic ring preparations and isolated mesenteric arterial bed perfusion) to examine the effects of sodium nitrate on the concentration-dependent responses to sodium nitrite. Both assays showed that nitrate attenuated the vascular responses to nitrite. Conversely, the aortic responses to the NO donor DETANONOate were not affected by sodium nitrate. Further confirming these results, we found that nitrate attenuated the acute blood pressure lowering effects of increasing doses of nitrite infused intravenously in freely moving rats. The possibility that nitrate could compete with nitrite and decrease nitrite influx into cells was tested by measuring the accumulation of nitrogen-15-labeled nitrite ( 15 N-nitrite) by aortic rings using ultra-performance liquid chromatography tandem mass-spectrometry (UPLC-MS/MS). Nitrate exerted no effect on aortic accumulation of 15 N-nitrite. Next, we used chemiluminescence-based NO detection to examine whether nitrate attenuates XOR-mediated nitrite reductase activity. Nitrate significantly shifted the Michaelis Menten saturation curve to the right, with a 3-fold increase in the Michaelis constant. Together, our results show that nitrate inhibits XOR-mediated NO production from nitrite, and this mechanism may explain how nitrate attenuates the vascular and blood pressure responses to nitrite. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fiorim, Jonaina, E-mail: nanafiorim@hotmail.com; Ribeiro Júnior, Rogério Faustino, E-mail: faustino43@oi.com.br; Azevedo, Bruna Fernades, E-mail: brunafernandes.azevedo@gmail.com

Seven day exposure to a low concentration of lead acetate increases nitric oxide bioavailability suggesting a putative role of K{sup +} channels affecting vascular reactivity. This could be an adaptive mechanism at the initial stages of toxicity from lead exposure due to oxidative stress. We evaluated whether lead alters the participation of K{sup +} channels and Na{sup +}/K{sup +}-ATPase (NKA) on vascular function. Wistar rats were treated with lead (1st dose 4 μg/100 g, subsequent doses 0.05 μg/100 g, im, 7 days) or vehicle. Lead treatment reduced the contractile response of aortic rings to phenylephrine (PHE) without changing the vasodilatormore » response to acetylcholine (ACh) or sodium nitroprusside (SNP). Furthermore, this treatment increased basal O{sub 2}{sup −} production, and apocynin (0.3 μM), superoxide dismutase (150 U/mL) and catalase (1000 U/mL) reduced the response to PHE only in the treated group. Lead also increased aortic functional NKA activity evaluated by K{sup +}-induced relaxation curves. Ouabain (100 μM) plus L-NAME (100 μM), aminoguanidine (50 μM) or tetraethylammonium (TEA, 2 mM) reduced the K{sup +}-induced relaxation only in lead-treated rats. When aortic rings were precontracted with KCl (60 mM/L) or preincubated with TEA (2 mM), 4-aminopyridine (4-AP, 5 mM), iberiotoxin (IbTX, 30 nM), apamin (0.5 μM) or charybdotoxin (0.1 μM), the ACh-induced relaxation was more reduced in the lead-treated rats. Additionally, 4-AP and IbTX reduced the relaxation elicited by SNP more in the lead-treated rats. Results suggest that lead treatment promoted NKA and K{sup +} channels activation and these effects might contribute to the preservation of aortic endothelial function against oxidative stress. -- Highlights: ► Increased free radicals production ► Increased Na{sup +}/K{sup +} ATPase activity ► Promotes activation of the K{sup +} channels and reduced vascular reactivity ► These effects preserve endothelial function against oxidative stress. ► Low concentrations constitute environmental cardiovascular risk factor.« less

Chemical Composition, Toxicity and Vasodilatation Effect of the Flowers Extract of Jasminum sambac (L.) Ait. “G. Duke of Tuscany”

PubMed Central

Kunhachan, Phanukit; Banchonglikitkul, Chuleratana; Kajsongkram, Tanwarat; Khayungarnnawee, Amonrat; Leelamanit, Wichet

2012-01-01

Phytochemical analysis of the ethanolic Jasmine flower extract of Jasminum sambac (L.) Ait. “G. Duke of Tuscany” revealed the mixtures of coumarins, cardiac glycosides, essential oils, flavonoids, phenolics, saponins, and steroids. However, alkaloids, anthraquinones, and tannins were not detected. By intravenous injection at a single dose of 0.5 mL/mouse (15 mg) of the flower extract, no systemic biological toxicity demonstrated in ICR mice was observed. In Wistar rats, the LD50 of the extract was higher than 5,000 mg/kg BW by oral administration. Vasodilatation effect of the 95% ethanolic extract on isolated aortic rats was also investigated. Compared with the control group, the Jasmine flowers extract in 0.05% DMSO clearly reduced tonus of isolated endothelium thoracic aortic rings preconstricted with phenylephrine (10−6 M), as a dose-dependent manner. Nevertheless, this pharmacological effect disappeared after the preincubation of the rings with atropine (10−6 M) or with Nω-nitro-L-arginine (10−4 M). These are possibly due to the actions of the active components on the vessel muscarinic receptors or by causing the release of nitric oxide. PMID:22536286

Vasodilatory effects and underlying mechanisms of the ethyl acetate extracts from Gastrodia elata.

PubMed

Dai, Rong; Wang, Ting; Si, Xiaoqin; Jia, Yuanyuan; Wang, Lili; Yuan, Yan; Lin, Qing; Yang, Cui

2017-05-01

The objective of this study was to assess the ethyl acetate extracts of Gastrodia elata Blume (GEB) on vascular tone and the mechanisms involved. GEB was extracted with 95% EtOH followed by a further extraction with ethyl acetate. The effects of GEB and its ingredients on the isometric tensions of the aortic rings from rats were measured. The ethyl acetate extract of GEB induced a vasodilatory effect on rat aorta, which was partially dependent on endothelium. Four chemical compounds isolated from GEB were identified as 3,4-dihydroxybenzaldehyde (DB), 4-hydroxybenzaldehyde (HB), 4-methoxybenzyl alcohol (MA), and 4,4'-dihydroxydiphenyl methane (DM), respectively. All of these compounds induced vasodilatations, which were dependent on the endothelium to different degrees. After pretreatment with N ω -nitro-l-arginine methyl ester, indomethacin, or methylene blue, the vasodilatations induced by DB, HB, and MA were significantly decreased. In addition, the contractions of the rat aortic rings due to Ca 2+ influx and intracellular Ca 2+ release were also inhibited by DM. Furthermore, the administration of DB significantly enhanced the productions of nitric oxide (NO) and the activities of the endothelial NO synthase in aorta and in endothelial cells. Thus, GEB may play an important role in the amelioration of hypertension by modulating vascular tones.

Endothelial cell-fatty acid binding protein 4 promotes angiogenesis: role of stem cell factor/c-kit pathway

PubMed Central

Elmasri, Harun; Ghelfi, Elisa; Yu, Chen-wei; Traphagen, Samantha; Cernadas, Manuela; Cao, Haiming; Shi, Guo-Ping; Plutzky, Jorge; Sahin, Mustafa; Hotamisligil, Gokhan; Cataltepe, Sule

2013-01-01

Fatty acid binding protein 4 (FABP4) plays an important role in regulation of glucose and lipid homeostasis as well as inflammation through its actions in adipocytes and macrophages. FABP4 is also expressed in a subset of endothelial cells, but its role in this cell type is not known. We found that FABP4-deficient human umbilical vein endothelial cells (HUVECs) demonstrate a markedly increased susceptibility to apoptosis as well as decreased migration and capillary network formation. Aortic rings from FABP4−/− mice demonstrated decreased angiogenic sprouting, which was recovered by reconstitution of FABP4. FABP4 was strongly regulated by mTORC1 and inhibited by Rapamycin. FABP4 modulated activation of several important signaling pathways in HUVECs, including downregulation of P38, eNOS, and stem cell factor (SCF)/c-kit signaling. Of these, the SCF/c-kit pathway was found to have a major role in attenuated angiogenic activity of FABP4-deficient ECs as provision of exogenous SCF resulted in a significant recovery in cell proliferation, survival, morphogenesis, and aortic ring sprouting. These data unravel a novel pro-angiogenic role for endothelial cell-FABP4 and suggest that it could be exploited as a potential target for diseases associated with pathological angiogenesis. PMID:22562362

Biomechanical properties of the Marfan's aortic root and ascending aorta before and after personalised external aortic root support surgery.

PubMed

Singh, S D; Xu, X Y; Pepper, J R; Treasure, T; Mohiaddin, R H

2015-08-01

Marfan syndrome is an inherited systemic connective tissue disease which may lead to aortic root disease causing dilatation, dissection and rupture of the aorta. The standard treatment is a major operation involving either an artificial valve and aorta or a complex valve repair. More recently, a personalised external aortic root support (PEARS) has been used to strengthen the aorta at an earlier stage of the disease avoiding risk of both rupture and major surgery. The aim of this study was to compare the stress and strain fields of the Marfan aortic root and ascending aorta before and after insertion of PEARS in order to understand its biomechanical implications. Finite element (FE) models were developed using patient-specific aortic geometries reconstructed from pre and post-PEARS magnetic resonance images in three Marfan patients. For the post-PEARS model, two scenarios were investigated-a bilayer model where PEARS and the aortic wall were treated as separate layers, and a single-layer model where PEARS was incorporated into the aortic wall. The wall and PEARS materials were assumed to be isotropic, incompressible and linearly elastic. A static load on the inner wall corresponding to the patients' pulse pressure was applied. Results from our FE models with patient-specific geometries show that peak aortic stresses and displacements before PEARS were located at the sinuses of Valsalva but following PEARS surgery, these peak values were shifted to the aortic arch, particularly at the interface between the supported and unsupported aorta. Further studies are required to assess the statistical significance of these findings and how PEARS compares with the standard treatment. Copyright © 2015 IPEM. Published by Elsevier Ltd. All rights reserved.

Inhibitory effects of vitamin K3 on DNA polymerase and angiogenesis.

PubMed

Matsubara, Kiminori; Kayashima, Tomoko; Mori, Masaharu; Yoshida, Hiromi; Mizushina, Yoshiyuki

2008-09-01

Vitamins play essential roles in cellular reactions and maintain human health. Recent studies have revealed that some vitamins including D3, B6 and K2 and their derivatives have an anti-cancer effect. As a mechanism, their inhibitory effect on cancer-related angiogenesis has been demonstrated. Vitamin K2 (menaquinones) has an anti-cancer effect in particular for hepatic cancer and inhibits angiogenesis. In the current study, we demonstrated that sole vitamin K3 (menadione) selectively inhibits the in vitro activity of eukaryotic DNA polymerase gamma, which is a mitochondrial DNA polymerase, and suppresses angiogenesis in a rat aortic ring model. The anti-angiogenic effect of vitamin K3 has been shown in angiogenesis models using human umbilical vein endothelial cells (HUVECs) with regard to HUVEC growth, tube formation on reconstituted basement membrane and chemotaxis. These results suggest that vitamin K3 may be a potential anti-cancer agent like vitamin K2.

Effects of carvedilol on structural and functional outcomes and plasma biomarkers in the mouse transverse aortic constriction heart failure model.

PubMed

Hampton, Caryn; Rosa, Raymond; Szeto, Daphne; Forrest, Gail; Campbell, Barry; Kennan, Richard; Wang, Shubing; Huang, Chin-Hu; Gichuru, Loise; Ping, Xiaoli; Shen, Xiaolan; Small, Kersten; Madwed, Jeffrey; Lynch, Joseph J

2017-01-01

Despite the widespread use of the mouse transverse aortic constriction heart failure model, there are no reports on the characterization of the standard-of-care agent carvedilol in this model. Left ventricular pressure overload was produced in mice by transverse aortic constriction between the innominate and left common carotid arteries. Carvedilol was administered at multiple dose levels (3, 10 and 30 mg/kg/day per os ; yielding end-study mean plasma concentrations of 0.002, 0.015 and 0.044 µM, respectively) in a therapeutic design protocol with treatment initiated after the manifestation of left ventricular remodeling at 3 weeks post transverse aortic constriction and continued for 10 weeks. Carvedilol treatment in transverse aortic constriction mice significantly decreased heart rate and left ventricular dP/dt (max) at all dose levels consistent with β-adrenoceptor blockade. The middle dose of carvedilol significantly decreased left ventricular weight, whereas the higher dose decreased total heart, left and right ventricular weight and wet lung weight compared to untreated transverse aortic constriction mice. The higher dose of carvedilol significantly increased cardiac performance as measured by ejection fraction and fractional shortening and decreased left ventricular end systolic volume consistent with the beneficial effect on cardiac function. End-study plasma sST-2 and Gal-3 levels did not differ among sham, transverse aortic constriction control and transverse aortic constriction carvedilol groups. Plasma b rain natriuretic peptide concentrations were elevated significantly in transverse aortic constriction control animals (~150%) compared to shams in association with changes in ejection fraction and heart weight and tended to decrease (~30%, p = 0.10-0.12) with the mid- and high-dose carvedilol treatment. A comparison of carvedilol hemodynamic and structural effects in the mouse transverse aortic constriction model versus clinical use indicates a strong agreement in effect profiles preclinical versus clinical, providing important translational validation for this widely used animal model. The present plasma brain natriuretic peptide biomarker findings support the measurement of plasma natriuretic peptides in the mouse transverse aortic constriction model to extend the translational utility of the model.

Effects of carvedilol on structural and functional outcomes and plasma biomarkers in the mouse transverse aortic constriction heart failure model

PubMed Central

Hampton, Caryn; Rosa, Raymond; Szeto, Daphne; Forrest, Gail; Campbell, Barry; Kennan, Richard; Wang, Shubing; Huang, Chin-Hu; Gichuru, Loise; Ping, Xiaoli; Shen, Xiaolan; Small, Kersten; Madwed, Jeffrey; Lynch, Joseph J

2017-01-01

Introduction: Despite the widespread use of the mouse transverse aortic constriction heart failure model, there are no reports on the characterization of the standard-of-care agent carvedilol in this model. Methods: Left ventricular pressure overload was produced in mice by transverse aortic constriction between the innominate and left common carotid arteries. Carvedilol was administered at multiple dose levels (3, 10 and 30 mg/kg/day per os; yielding end-study mean plasma concentrations of 0.002, 0.015 and 0.044 µM, respectively) in a therapeutic design protocol with treatment initiated after the manifestation of left ventricular remodeling at 3 weeks post transverse aortic constriction and continued for 10 weeks. Results: Carvedilol treatment in transverse aortic constriction mice significantly decreased heart rate and left ventricular dP/dt (max) at all dose levels consistent with β-adrenoceptor blockade. The middle dose of carvedilol significantly decreased left ventricular weight, whereas the higher dose decreased total heart, left and right ventricular weight and wet lung weight compared to untreated transverse aortic constriction mice. The higher dose of carvedilol significantly increased cardiac performance as measured by ejection fraction and fractional shortening and decreased left ventricular end systolic volume consistent with the beneficial effect on cardiac function. End-study plasma sST-2 and Gal-3 levels did not differ among sham, transverse aortic constriction control and transverse aortic constriction carvedilol groups. Plasma brain natriuretic peptide concentrations were elevated significantly in transverse aortic constriction control animals (~150%) compared to shams in association with changes in ejection fraction and heart weight and tended to decrease (~30%, p = 0.10–0.12) with the mid- and high-dose carvedilol treatment. Conclusion: A comparison of carvedilol hemodynamic and structural effects in the mouse transverse aortic constriction model versus clinical use indicates a strong agreement in effect profiles preclinical versus clinical, providing important translational validation for this widely used animal model. The present plasma brain natriuretic peptide biomarker findings support the measurement of plasma natriuretic peptides in the mouse transverse aortic constriction model to extend the translational utility of the model. PMID:28491305

Transesophageal echocardiographic strain imaging predicts aortic biomechanics: Beyond diameter.

PubMed

Emmott, Alexander; Alzahrani, Haitham; Alreishidan, Mohammed; Therrien, Judith; Leask, Richard L; Lachapelle, Kevin

2018-03-11

Clinical guidelines recommend resection of ascending aortic aneurysms at diameters 5.5 cm or greater to prevent rupture or dissection. However, approximately 40% of all ascending aortic dissections occur below this threshold. We propose new transesophageal echocardiography strain-imaging moduli coupled with blood pressure measurements to predict aortic dysfunction below the surgical threshold. A total of 21 patients undergoing aortic resection were recruited to participate in this study. Transesophageal echocardiography imaging of the aortic short-axis and invasive radial blood pressure traces were taken for 3 cardiac cycles. By using EchoPAC (GE Healthcare, Madison, Wis) and postprocessing in MATLAB (MathWorks, Natick, Mass), circumferential stretch profiles were generated and combined with the blood pressure traces. From these data, 2 in vivo stiffness moduli were calculated: the Cardiac Cycle Pressure Modulus and Cardiac Cycle Stress Modulus. From the resected aortic ring, testing squares were isolated for ex vivo mechanical analysis and histopathology. Each square underwent equibiaxial tensile testing to generate stress-stretch profiles for each patient. Two ex vivo indices were calculated from these profiles (energy loss and incremental stiffness) for comparison with the Cardiac Cycle Pressure Modulus and Cardiac Cycle Stress Modulus. The echo-derived stiffness moduli demonstrate positive significant covariance with ex vivo tensile biomechanical indices: energy loss (vs Cardiac Cycle Pressure Modulus: R 2  = 0.5873, P < .0001; vs Cardiac Cycle Stress Modulus: R 2  = 0.6401, P < .0001) and apparent stiffness (vs Cardiac Cycle Pressure Modulus: R 2  = 0.2079, P = .0378; vs Cardiac Cycle Stress Modulus: R 2  = 0.3575, P = .0042). Likewise, these transesophageal echocardiography-derived moduli are highly predictive of the histopathologic composition of collagen and elastin (collagen/elastin ratio vs Cardiac Cycle Pressure Modulus: R 2  = 0.6165, P < .0001; vs Cardiac Cycle Stress Modulus: R 2  = 0.6037, P < .0001). Transesophageal echocardiography-derived stiffness moduli correlate strongly with aortic wall biomechanics and histopathology, which demonstrates the added benefit of using simple echocardiography-derived biomechanics to stratify patient populations. Copyright © 2018. Published by Elsevier Inc.

Orthogonal Rings, Fiducial Markers, and Overlay Accuracy When Image Fusion is Used for EVAR Guidance.

PubMed

Koutouzi, G; Sandström, C; Roos, H; Henrikson, O; Leonhardt, H; Falkenberg, M

2016-11-01

Evaluation of orthogonal rings, fiducial markers, and overlay accuracy when image fusion is used for endovascular aortic repair (EVAR). This was a prospective single centre study. In 19 patients undergoing standard EVAR, 3D image fusion was used for intra-operative guidance. Renal arteries and targeted stent graft positions were marked with rings orthogonal to the respective centre lines from pre-operative computed tomography (CT). Radiopaque reference objects attached to the back of the patient were used as fiducial markers to detect patient movement intra-operatively. Automatic 3D-3D registration of the pre-operative CT with an intra-operative cone beam computed tomography (CBCT) as well as 3D-3D registration after manual alignment of nearby vertebrae were evaluated. Registration was defined as being sufficient for EVAR guidance if the deviation of the origin of the lower renal artery was less than 3 mm. For final overlay registration, the renal arteries were manually aligned using aortic calcification and vessel outlines. The accuracy of the overlay before stent graft deployment was evaluated using digital subtraction angiography (DSA) as direct comparison. Fiducial markers helped in detecting misalignment caused by patient movement during the procedure. Use of automatic intensity based registration alone was insufficient for EVAR guidance. Manual registration based on vertebrae L1-L2 was sufficient in 7/19 patients (37%). Using the final adjusted registration as overlay, the median alignment error of the lower renal artery marking at pre-deployment DSA was 2 mm (0-5) sideways and 2 mm (0-9) longitudinally, mostly in a caudal direction. 3D image fusion can facilitate intra-operative guidance during EVAR. Orthogonal rings and fiducial markers are useful for visualization and overlay correction. However, the accuracy of the overlaid 3D image is not always ideal and further technical development is needed. Copyright © 2016 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

A mechanistic model on the role of “radially-running” collagen fibers on dissection properties of human ascending thoracic aorta

PubMed Central

Pal, Siladitya; Tsamis, Alkiviadis; Pasta, Salvatore; D'Amore, Antonio; Gleason, Thomas G.; Vorp, David A.; Maiti, Spandan

2014-01-01

Aortic dissection (AoD) is a common condition that often leads to life-threatening cardiovaular emergency. From a biomechanics viewpoint, AoD involves failure of load-bearing microstructural components of the aortic wall, mainly elastin and collagen fibers. Delamination strength of the aortic wall depends on the load-bearing capacity and local micro-architecture of these fibers, which may vary with age, disease and aortic location. Therefore, quantifying the role of fiber micro-architecture on the delamination strength of the aortic wall may lead to improved understanding of AoD. We present an experimentally-driven modeling paradigm towards this goal. Specifically, we utilize collagen fiber microarchitecture, obtained in a parallel study from multi-photon microopy, in a predictive mechanistic framework to characterize the delamination strength. We then validate our model against peel test experiments on human aortic strips and utilize the model to predict the delamination strength of separate aortic strips and compare with experimental findings. We observe that the number density and failure energy of the radially-running collagen fibers control the peel strength. Furthermore, our model suggests that the lower delamination strength previously found for the circumferential direction in human aorta is related to a lower number density of radially-running collagen fibers in that direction. Our model sets the stage for an expanded future study that could predict AoD propagation in patient-specific aortic geometries and better understand factors that may influence propensity for occurrence. PMID:24484644

3D Printing Based on Cardiac CT Assists Anatomic Visualization Prior to Transcatheter Aortic Valve Replacement

PubMed Central

Ripley, Beth; Kelil, Tatiana; Cheezum, Michael K.; Goncalves, Alexandra; Di Carli, Marcelo F.; Rybicki, Frank J.; Steigner, Mike; Mitsouras, Dimitrios; Blankstein, Ron

2017-01-01

Background 3D printing is a promising technique that may have applications in medicine, and there is expanding interest in the use of patient-specific 3D models to guide surgical interventions. Objective To determine the feasibility of using cardiac CT to print individual models of the aortic root complex for transcatheter aortic valve replacement (TAVR) planning as well as to determine the ability to predict paravalvular aortic regurgitation (PAR). Methods This retrospective study included 16 patients (9 with PAR identified on blinded interpretation of post-procedure trans-thoracic echocardiography and 7 age, sex, and valve size-matched controls with no PAR). 3D printed models of the aortic root were created from pre-TAVR cardiac computed tomography data. These models were fitted with printed valves and predictions regarding post-implant PAR were made using a light transmission test. Results Aortic root 3D models were highly accurate, with excellent agreement between annulus measurements made on 3D models and those made on corresponding 2D data (mean difference of −0.34 mm, 95% limits of agreement: ± 1.3 mm). The 3D printed valve models were within 0.1 mm of their designed dimensions. Examination of the fit of valves within patient-specific aortic root models correctly predicted PAR in 6 of 9 patients (6 true positive, 3 false negative) and absence of PAR in 5 of 7 patients (5 true negative, 2 false positive). Conclusions Pre-TAVR 3D-printing based on cardiac CT provides a unique patient-specific method to assess the physical interplay of the aortic root and implanted valves. With additional optimization, 3D models may complement traditional techniques used for predicting which patients are more likely to develop PAR. PMID:26732862

Impact of magnesium:calcium ratio on calcification of the aortic wall

PubMed Central

2017-01-01

Objective An inverse relationship between serum magnesium concentration and vascular calcification has been reported following observational clinical studies. Moreover, several studies have been suggesting a protective effect of magnesium on the vascular calcification. However, the exact mechanism remains elusive, and investigators have speculated among a myriad of potential actions. The effect of magnesium on calcification of the aortic wall is yet to be investigated. In the present study, the effects of magnesium and calcium on the metabolism of extracellular PPi, the main endogenous inhibitor of vascular calcification, were investigated in the rat aorta. Approach and results Calcium and magnesium have antagonist effects on PPi hydrolysis in the aortic wall. Km and Ki values for PPi hydrolysis in rat aortic rings were 1.1 mmol/L magnesium and 32 μmol/L calcium, respectively, but ATP hydrolysis was not affected with calcium. Calcium deposition in the rat aortic wall dramatically increased when the magnesium concentration was increased (ratio of Mg:Ca = 1:1; 1.5 mmol/L calcium and 1.5 mmol/L magnesium) respect to low magnesium concentration (ratio Mg:Ca = 1:3, 1.5 mmol/L calcium and 0.75 mmol/L magnesium). Conclusion Data from observational clinical studies showing that the serum magnesium concentration is inversely correlated with vascular calcification could be reinterpreted as a compensatory regulatory mechanism that reduces both PPi hydrolysis and vascular calcification. The impact of magnesium in vascular calcification in humans could be studied in association with calcium levels, for example, as the magnesium:calcium ratio. PMID:28570619

Dietary copper supplements modulate aortic superoxide dismutase, nitric oxide and atherosclerosis.

PubMed

Lamb, David J; Tickner, Michelle L; Hourani, Susanna M O; Ferns, Gordon A A

2005-08-01

The objective was to test the hypothesis that dietary copper inhibits atherosclerosis by inducing superoxide dismutase (SOD) and potentiating nitric oxide (NO). New Zealand White rabbits were fed either a cholesterol diet (n = 8) or a cholesterol diet containing 0.02% copper acetate (n = 8) for 13 weeks. We found that the intimal area was significantly smaller in the animals supplemented with copper (P < 0.005), although integrated plasma cholesterol levels were not significantly different. This was associated with a significant increase in aortic copper content (P < 0.05), SOD activity (P < 0.05) and Cu/Zn SOD mRNA (P < 0.05) and a significant decrease in nitrotyrosine content (P < 0.05). Furthermore, there was a positive correlation between aortic copper content and SOD activity (P < 0.005, R(2) = 0.83) and a negative correlation between aortic superoxide dimutase activity and nitrotyrosine content (P < 0.005, R(2) = 0.93). In organ bath experiments, the relaxation of precontracted carotid artery rings to calcium ionophore was greater in animals supplemented with copper. No difference in response to sodium nitroprusside was observed. These data suggest that in the cholesterol-fed rabbit, copper supplements inhibit the progression of atherosclerosis by increasing SOD expression, thereby reducing the interaction of NO with superoxide, and hence potentiating NO-mediated pathways that may protect against atherosclerosis.

Dietary copper supplements modulate aortic superoxide dismutase, nitric oxide and atherosclerosis

PubMed Central

Lamb, David J; Tickner, Michelle L; Hourani, Susanna M O; Ferns, Gordon A A

2005-01-01

The objective was to test the hypothesis that dietary copper inhibits atherosclerosis by inducing superoxide dismutase (SOD) and potentiating nitric oxide (NO). New Zealand White rabbits were fed either a cholesterol diet (n = 8) or a cholesterol diet containing 0.02% copper acetate (n = 8) for 13 weeks. We found that the intimal area was significantly smaller in the animals supplemented with copper (P < 0.005), although integrated plasma cholesterol levels were not significantly different. This was associated with a significant increase in aortic copper content (P < 0.05), SOD activity (P < 0.05) and Cu/Zn SOD mRNA (P < 0.05) and a significant decrease in nitrotyrosine content (P < 0.05). Furthermore, there was a positive correlation between aortic copper content and SOD activity (P < 0.005, R2 = 0.83) and a negative correlation between aortic superoxide dimutase activity and nitrotyrosine content (P < 0.005, R2 = 0.93). In organ bath experiments, the relaxation of precontracted carotid artery rings to calcium ionophore was greater in animals supplemented with copper. No difference in response to sodium nitroprusside was observed. These data suggest that in the cholesterol-fed rabbit, copper supplements inhibit the progression of atherosclerosis by increasing SOD expression, thereby reducing the interaction of NO with superoxide, and hence potentiating NO-mediated pathways that may protect against atherosclerosis. PMID:16045547

The risk for type B aortic dissection in Marfan syndrome.

PubMed

den Hartog, Alexander W; Franken, Romy; Zwinderman, Aeilko H; Timmermans, Janneke; Scholte, Arthur J; van den Berg, Maarten P; de Waard, Vivian; Pals, Gerard; Mulder, Barbara J M; Groenink, Maarten

2015-01-27

Aortic dissections involving the descending aorta are a major clinical problem in patients with Marfan syndrome. The purpose of this study was to identify clinical parameters associated with type B aortic dissection and to develop a risk model to predict type B aortic dissection in patients with Marfan syndrome. Patients with the diagnosis of Marfan syndrome and magnetic resonance imaging or computed tomographic imaging of the aorta were followed for a median of 6 years for the occurrence of type B dissection or the combined end point of type B aortic dissection, distal aortic surgery, and death. A model using various clinical parameters as well as genotyping was developed to predict the risk for type B dissection in patients with Marfan syndrome. Between 1998 and 2013, 54 type B aortic dissections occurred in 600 patients with Marfan syndrome (mean age 36 ± 14 years, 52% male). Independent variables associated with type B aortic dissection were prior prophylactic aortic surgery (hazard ratio: 2.1; 95% confidence interval: 1.2 to 3.8; p = 0.010) and a proximal descending aorta diameter ≥27 mm (hazard ratio: 2.2; 95% confidence interval: 1.1 to 4.3; p = 0.020). In the risk model, the 10-year occurrence of type B aortic dissection in low-, moderate-, and high-risk patients was 6%, 19%, and 34%, respectively. Angiotensin II receptor blocker therapy was associated with fewer type B aortic dissections (hazard ratio: 0.3; 95% confidence interval: 0.1 to 0.9; p = 0.030). Patients with Marfan syndrome with prior prophylactic aortic surgery are at substantial risk for type B aortic dissection, even when the descending aorta is only slightly dilated. Angiotensin II receptor blocker therapy may be protective in the prevention of type B aortic dissections. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Ascending aortic curvature as an independent risk factor for type A dissection, and ascending aortic aneurysm formation: a mathematical model.

PubMed

Poullis, Michael P; Warwick, Richard; Oo, Aung; Poole, Robert J

2008-06-01

To develop a mathematical model to demonstrate that ascending aortic curvature is an independent risk factor for type A dissections, in addition to hypertension, bicuspid aortic valve, aneurysm of ascending aorta, and intrinsic aortic tissue abnormalities, like Marfan's syndrome. A steady state one-dimensional flow analysis was performed, utilising Newton's third law of motion. Five different clinical scenarios were evaluated: (1) effect of aortic curvature; (2) effect of beta-blockers, (3) effect of patient size, (4) forces on a Marfan's aorta, and (5) site of entry flap in aortic dissection. Aortic curvature increases the forces exerted on the ascending aorta by a factor of over 10-fold. Aortic curvature can cause patients with a systolic blood pressure of 8 0mmHg to have greater forces exerted on their aorta despite smaller diameters and lower cardiac outputs, than patients with systolic blood pressures of 120 mmHg. In normal diameter aortas, beta-blockers have minimal effect compared with aortic curvature. Aortic curvature may help to explain why normal diameter aortas can dissect, and also that the point of the entry tear may be potentially predictable. Aortic curvature has major effects on the forces exerted on the aorta in patients with Marfan's syndrome. Aortic curvature is relatively more important that aortic diameter, blood pressure, cardiac output, beta-blocker use, and patient size with regard to the force acting on the aortic wall. This may explain why some patients with normal diameter ascending aortas with or without Marfan's syndrome develop type A dissections and aneurysms. Aortic curvature may also help to explain the site of entry tear in acute type A dissection. Further clinical study is needed to validate this study's finding.

A model for predicting aortic dynamic response to -G sub z impact acceleration.

NASA Technical Reports Server (NTRS)

Advani, S. H.; Tarnay, T. J.; Byars, E. F.; Love, J. S.

1972-01-01

A steady state dynamic response model for the radial motion of the aorta is developed from in vivo pressure-displacement and nerve stimulation experiments on canines. The model represented by a modified Van der Pol wave motion oscillator closely predicts steady state and perturbed response results. The applicability of the steady state canine aortic model to tailward acting impact forces is studied by means of the perturbed phase plane of the oscillator. The backflow through the aortic arch resulting from a specified acceleration-time profile is computed and an analysis for predicting the forced motion aortic response is presented.

Hit to lead account of the discovery of bisbenzamide and related ureidobenzamide inhibitors of Rho kinase.

PubMed

Morwick, Tina; Büttner, Frank H; Cywin, Charles L; Dahmann, Georg; Hickey, Eugene; Jakes, Scott; Kaplita, Paul; Kashem, Mohammed A; Kerr, Steven; Kugler, Stanley; Mao, Wang; Marshall, Daniel; Paw, Zofia; Shih, Cheng-Kon; Wu, Frank; Young, Erick

2010-01-28

A highly selective series of bisbenzamide inhibitors of Rho-associated coiled-coil forming protein kinase (ROCK) and a related ureidobenzamide series, both identified by high throughput screening (HTS), are described. Details of the hit validation and lead generation process, including structure-activity relationship (SAR) studies, a selectivity assessment, target-independent profiling (TIP) results, and an analysis of functional activity using a rat aortic ring assay are discussed.

Potassium Inhibits Dietary Salt-Induced Transforming Growth Factor-β Production

PubMed Central

Ying, Wei-Zhong; Aaron, Kristal; Wang, Pei-Xuan; Sanders, Paul W.

2009-01-01

Human and animal studies demonstrate an untoward effect of excess dietary NaCl (salt) intake on cardiovascular function and life span. The endothelium in particular augments the production of transforming growth factor (TGF)-β, a fibrogenic growth factor, in response to excess dietary salt intake. This study explored the initiating mechanism that regulates salt-induced endothelial cell production of TGF-β. Male Sprague-Dawley rats were given diets containing different amounts of NaCl and potassium for 4 days. A bioassay for TGF-β demonstrated increased (35.2%) amounts of active TGF-β in the medium of aortic ring segments from rats on the high-salt diet compared with rats maintained on a 0.3% NaCl diet. Inhibition of the large-conductance, calcium-activated potassium channel inhibited dietary salt-induced vascular production of TGF-β but did not affect production of TGF-β by ring segments from rats on the low-salt diet. Immunohistochemical and Western analyses demonstrated the α subunit of the calcium-activated potassium channel in endothelial cells. Increasing medium [K+] inhibited production of dietary salt-induced vascular production levels of total and active TGF-β but did not alter TGF-β production by aortic rings from rats on the 0.3% NaCl diet. Increasing dietary potassium content decreased urinary active TGF-β in animals receiving the high-salt diet but did not change urinary active TGF-β in animals receiving the low-salt diet. The findings demonstrated an interesting interaction between the dietary intake of potassium and excess NaCl and further showed the fundamental role of the endothelial calcium-activated potassium channel in the vascular response to excess salt intake. PMID:19738156

Murine study of portal hypertension associated endothelin-1 hypo-response.

PubMed

Theodorakis, Nicholas; Maluccio, Mary; Skill, Nicholas

2015-04-28

To investigate endothelin-1 hypo-responsive associated with portal hypertension in order to improve patient treatment outcomes. Wild type, eNOS(-/-) and iNOS(-/-) mice received partial portal vein ligation surgery to induce portal hypertension or sham surgery. Development of portal hypertension was determined by measuring the splenic pulp pressure, abdominal aortic flow and portal systemic shunting. To measure splenic pulp pressure, a microtip pressure transducer was inserted into the spleen pulp. Abdominal aortic flow was measured by placing an ultrasonic Doppler flow probe around the abdominal aorta between the diaphragm and celiac artery. Portal systemic shunting was calculated by injection of fluorescent microspheres in to the splenic vein and determining the percentage accumulation of spheres in liver and pulmonary beds. Endothelin-1 hypo-response was evaluated by measuring the change in abdominal aortic flow in response to endothelin-1 intravenous administration. In addition, thoracic aorta endothelin-1 contraction was measured in 5 mm isolated thoracic aorta rings ex-vivo using an ADI small vessel myograph. In wild type and iNOS(-/-) mice splenic pulp pressure increased from 7.5 ± 1.1 mmHg and 7.2 ± 1 mmHg to 25.4 ± 3.1 mmHg and 22 ± 4 mmHg respectively. In eNOS(-/-) mice splenic pulp pressure was increased after 1 d (P = NS), after which it decreased and by 7 d was not significantly elevated when compared to 7 d sham operated controls (6.9 ± 0.6 mmHg and 7.3 ± 0.8 mmHg respectively, P = 0.3). Abdominal aortic flow was increased by 80% and 73% in 7 d portal vein ligated wild type and iNOS when compared to shams, whereas there was no significant difference in 7 d portal vein ligated eNOS(-/-) mice when compared to shams. Endothelin-1 induced a rapid reduction in abdominal aortic blood flow in wild type, eNOS(-/-) and iNOS(-/-) sham mice (50% ± 8%, 73% ± 9% and 47% ± 9% respectively). Following portal vein ligation endothelin-1 reduction in blood flow was significantly diminished in each mouse group. Abdominal aortic flow was reduced by 19% ± 9%, 32% ± 10% and 9% ± 9% in wild type, eNOS(-/-) and iNOS(-/-) mice respectively. Aberrant endothelin-1 response in murine portal hypertension is NOS isoform independent. Moreover, portal hypertension in the portal vein ligation model is independent of ET-1 function.

[Status of aortic valve reconstruction and Ross operation in aortic valve diseases].

PubMed

Sievers, Hans H

2002-08-01

At first glance the aortic valve is a relative simple valve mechanism connecting the left ventricle and the ascending aorta. Detailed analysis of the different components of the aortic valve including the leaflets and sinuses revealed a complex motion of each part leading to a perfect durable valve mechanism at rest and during exercise. Theoretically, the reconstruction or imitation of these structures in patients with aortic valve disease should lead to optimal results. Prerequisite is the exact knowledge of the important functional characteristics of the aortic valve. The dynamic behavior of the aortic root closely harmonizing with the leaflets not only warrants stress minimizing and valve durability, but also optimizes coronary flow, left ventricular function and aortic impedance. The newly discovered contractile capacity of the leaflets and the root components are important for tuning the dynamics. Isolated reconstruction of the aortic valve such as decalcification, commissurotomy, plication of ring or leaflets of a tricuspid aortic valve and cusp extension are seldom indicated in contrast to the reconstruction of the bicuspid insufficient valve. Proper indication and skilled techniques lead to excellent hemodynamic and clinical intermediate-term result up to 7 years after reconstruction. Latest follow-up revealed a mean aortic insufficiency of 0.7, maximal pressure gradient of 11.4 +/- 8.5 mm Hg with zero hospital or late mortality, reoperation or thromboembolic events in 22 patients. The reconstructive techniques for aortic root aneurysm and/or type A dissection according to David or Yacoub have become routine procedures in the last 10 years. The hemodynamic and clinical results are excellent with low reoperation rate and very low risk of thromboembolism. Generally, a maximal diameter of the root of 5 cm is indicative for performing the operation. In patients with Marfan's syndrome the reconstruction should be advanced even with smaller diameters especially if these are progressive and combined with aortic insufficiency. ROSS-OPERATION: The Ross-Operation includes the replacement of the diseased aortic valve with the pulmonary autograft and reconstruction of the right ventricular outflow tract using a homograft. The hemodynamic results are excellent regarding the autograft and also the clinical results with very low thromboembolic risk and acceptable reoperation rate. This method is especially indicated for active young patients, women, who desire children, athletes and patients in general, who like to avoid long-term anticoagulation. In some cases the homograft may develop a dysfunction predominantly a pulmonary stenosis requiring reoperation. In the author's series of 245 Ross-operations in 12 years the homograft had to be replaced in 4 cases without letality. Innovative, decellularized homografts with the potential to repopulate with autologeous cells show promising results after 1 year of clinical implantation without signs of antibody development. Probably these tissue-engineered modification may improve the homograft results. The reconstructive techniques of the aortic valve and the Ross-operation have a certain risk of reoperation that must be weighed against the advantages of very low hospital and late valve related death, excellent hemodynamics, very low risk of macro- and microembolism as well as bleeding, lack of long-term anticoagulation and unrestricted life-style.

Influences of prostanoids and nitric oxide on post-suspension hypotension in female Sprague-Dawley rats

NASA Technical Reports Server (NTRS)

Eatman, D.; Listhrop, R. A.; Beasley, A. S.; Socci, R. R.; Abukhalaf, I.; Bayorh, M. A.

2003-01-01

Impairment in cardiovascular functions sometimes manifested in astronauts during standing postflight, may be related to the diminished autonomic function and/or excessive production of endothelium-dependent relaxing factors. In the present study, using the 30 degrees head-down tilt (HDT) model, we compared the cardiovascular and biochemical effects of 7 days of suspension and a subsequent 6-h post-suspension period between suspended and non-suspended conscious female Sprague-Dawley rats. Mean arterial pressure (MAP) and heart rate were measured prior to suspension (basal), daily thereafter, and every 2h post-suspension. Following 7 days of suspension, MAP was not different from their basal values, however, upon release from suspension, MAP was significantly reduced compared to the non-suspended rats. Nitric oxide levels were elevated while thromboxane A(2) levels declined significantly in both plasma and tissue samples following post-suspension. The levels of prostacyclin following post-suspension remained unaltered in plasma and aortic rings but was significantly elevated in carotid arterial rings. Therefore, the post-suspension reduction in mean arterial pressure is due mostly to overproduction of nitric oxide and to a lesser extent prostacyclin.

Tracheal reconstruction with a composite graft: fascial flap-wrapped allogenic aorta with external cartilage-ring support

PubMed Central

Wurtz, Alain; Hysi, Ilir; Kipnis, Eric; Zawadzki, Christophe; Hubert, Thomas; Jashari, Ramadan; Copin, Marie-Christine; Jude, Brigitte

2013-01-01

OBJECTIVES Animal and clinical studies have demonstrated the feasibility of tracheal replacement by silicone-stented allogenic aortas. In clinical trials, however, this graft did not show mature cartilage regeneration into the grafts as was observed in animal models. To solve this issue, we investigated tracheal replacement with a composite graft based on a fascial flap-wrapped allogenic aorta with external cartilage-ring support in a rabbit model. METHODS Seven male 'Géant des Flandres' and 'New Zealand' rabbits served as donors of aortas and cartilage rings, respectively. Nineteen female 'New Zealand' rabbits were used as recipients. First, in nine animals, neoangiogenesis of the composite graft following a wrap using a pedicled lateral thoracic fascial flap and implantation under the skin of the chest wall was investigated. Animal sacrifice was scheduled at regular intervals up to 38 days. Second, 10 animals underwent tracheal replacement with the composite graft after a 7-to-9 day revascularization period, and were followed-up to death. Macroscopic and microscopic examinations were used to study the morphology, stiffness and viability of the construct. RESULTS There was one operative death after tracheal replacement. The first group of animals was found to have a satisfactory tubular morphology and stiffness of their construct associated with preserved histological structure of cartilages and moderate to severe aortic ischaemic lesions. In the group of rabbits having undergone tracheal replacement, the anatomical results were characterized by a discrepancy between the severity of ischaemic lesions involving both allogenic aorta and cartilage rings and the satisfactory biomechanical characteristics of the graft in 7 of 10 animals, probably due to cartilage calcification deposits associated with inflammatory scar tissue ensuring the stiffness of the construct. CONCLUSIONS Our investigations demonstrate the feasibility of the replacement of circumferential tracheal defects using our composite graft. Future experiments using therapeutic bronchoscopy tools are required to draw conclusions regarding the effectiveness of this tracheal substitute in the long-term. PMID:23049080

3D printing based on cardiac CT assists anatomic visualization prior to transcatheter aortic valve replacement.

PubMed

Ripley, Beth; Kelil, Tatiana; Cheezum, Michael K; Goncalves, Alexandra; Di Carli, Marcelo F; Rybicki, Frank J; Steigner, Mike; Mitsouras, Dimitrios; Blankstein, Ron

2016-01-01

3D printing is a promising technique that may have applications in medicine, and there is expanding interest in the use of patient-specific 3D models to guide surgical interventions. To determine the feasibility of using cardiac CT to print individual models of the aortic root complex for transcatheter aortic valve replacement (TAVR) planning as well as to determine the ability to predict paravalvular aortic regurgitation (PAR). This retrospective study included 16 patients (9 with PAR identified on blinded interpretation of post-procedure trans-thoracic echocardiography and 7 age, sex, and valve size-matched controls with no PAR). 3D printed models of the aortic root were created from pre-TAVR cardiac computed tomography data. These models were fitted with printed valves and predictions regarding post-implant PAR were made using a light transmission test. Aortic root 3D models were highly accurate, with excellent agreement between annulus measurements made on 3D models and those made on corresponding 2D data (mean difference of -0.34 mm, 95% limits of agreement: ± 1.3 mm). The 3D printed valve models were within 0.1 mm of their designed dimensions. Examination of the fit of valves within patient-specific aortic root models correctly predicted PAR in 6 of 9 patients (6 true positive, 3 false negative) and absence of PAR in 5 of 7 patients (5 true negative, 2 false positive). Pre-TAVR 3D-printing based on cardiac CT provides a unique patient-specific method to assess the physical interplay of the aortic root and implanted valves. With additional optimization, 3D models may complement traditional techniques used for predicting which patients are more likely to develop PAR. Copyright © 2016 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

Evaluation of prosthetic valve obstruction on electrocardiographically gated multidetector-row computed tomography--identification of subprosthetic pannus in the aortic position.

PubMed

Ueda, Tomohiro; Teshima, Hideki; Fukunaga, Shuji; Aoyagi, Shigeaki; Tanaka, Hiroyuki

2013-01-01

This study was performed to evaluate the diagnostic role of electrocardiographically gated multidetector-row computed tomography (MDCT) for prosthetic valve obstruction (PVO) in the aortic position. Between 2002 and 2006, 9 patients were diagnosed with PVO of an aortic bileaflet mechanical valve based on echocardiographic and cineradiographic criteria. These 9 patients were examined using MDCT before replacement of the mechanical valve, and intraoperative findings were compared to morphologic periprosthetic abnormalities observed on MDCT. CT attenuation (Hounsfield units; HU) of the periprosthetic abnormalities was measured to investigate the underlying cause of the PVO. MDCT showed subprosthetic masses extending beyond the prosthetic ring into the orifice of the valve. At reoperation, presence of subprosthetic pannus was confirmed in all of the 9 patients, but no periprosthetic thrombus was found. The mean CT attenuation of the subprosthetic pannus was 170 HU, and it was significantly greater than that obtained from the interventricular septum (108 HU; P<0.0001). MDCT can be used to clearly visualize subprosthetic pannus causing PVO and the mean CT attenuation of subprosthetic pannus is significantly higher than that of the interventricular septum on MDCT.

Detrimental Effects of Testosterone Addition to Estrogen Therapy Involve Cytochrome P-450-Induced 20-HETE Synthesis in Aorta of Ovariectomized Spontaneously Hypertensive Rat (SHR), a Model of Postmenopausal Hypertension

PubMed Central

Costa, Tiago J.; Ceravolo, Graziela S.; Echem, Cinthya; Hashimoto, Carolina M.; Costa, Beatriz P.; Santos-Eichler, Rosangela A.; Oliveira, Maria Aparecida; Jiménez-Altayó, Francesc; Akamine, Eliana H.; Dantas, Ana Paula; Carvalho, Maria Helena C.

2018-01-01

Postmenopausal period has been associated to different symptoms such as hot flashes, vulvovaginal atrophy, hypoactive sexual desire disorder (HSDD) and others. Clinical studies have described postmenopausal women presenting HSDD can benefit from the association of testosterone to conventional hormonal therapy. Testosterone has been linked to development of cardiovascular diseases including hypertension and it also increases cytochrome P-450-induced 20-HETE synthesis which in turn results in vascular dysfunction. However, the effect of testosterone plus estrogen in the cardiovascular system is still very poorly studied. The aim of the present study is to evaluate the role of cytochrome P-450 pathway in a postmenopausal hypertensive female treated with testosterone plus estrogen. For that, hypertensive ovariectomized rats (OVX-SHR) were used as a model of postmenopausal hypertension and four groups were created: SHAM-operated (SHAM), ovariectomized SHR (OVX), OVX treated for 15 days with conjugated equine estrogens [(CEE) 9.6 μg/Kg/day/po] or CEE associated to testosterone [(CEE+T) 2.85 mg/kg/weekly/im]. Phenylephrine-induced contraction and generation of reactive oxygen species (ROS) were markedly increased in aortic rings from OVX-SHR compared to SHAM rats which were restored by CEE treatment. On the other hand, CEE+T abolished vascular effects by CEE and augmented both systolic and diastolic blood pressure of SHR. Treatment of aortic rings with the CYP/20-HETE synthesis inhibitor HET0016 (1 μM) reduced phenylephrine hyperreactivity and the augmented ROS generation in the CEE+T group. These results are paralleled by the increased CYP4F3 protein expression and activity in aortas of CEE+T. In conclusion, we showed that association of testosterone to estrogen therapy produces detrimental effects in cardiovascular system of ovariectomized hypertensive females via CYP4F3/20-HETE pathway. Therefore, our findings support the standpoint that the CYP/20-HETE pathway is an important therapeutic target for the prevention of cardiovascular disease in menopausal women in the presence of high levels of testosterone. PMID:29867542

Detrimental Effects of Testosterone Addition to Estrogen Therapy Involve Cytochrome P-450-Induced 20-HETE Synthesis in Aorta of Ovariectomized Spontaneously Hypertensive Rat (SHR), a Model of Postmenopausal Hypertension.

PubMed

Costa, Tiago J; Ceravolo, Graziela S; Echem, Cinthya; Hashimoto, Carolina M; Costa, Beatriz P; Santos-Eichler, Rosangela A; Oliveira, Maria Aparecida; Jiménez-Altayó, Francesc; Akamine, Eliana H; Dantas, Ana Paula; Carvalho, Maria Helena C

2018-01-01

Postmenopausal period has been associated to different symptoms such as hot flashes, vulvovaginal atrophy, hypoactive sexual desire disorder (HSDD) and others. Clinical studies have described postmenopausal women presenting HSDD can benefit from the association of testosterone to conventional hormonal therapy. Testosterone has been linked to development of cardiovascular diseases including hypertension and it also increases cytochrome P -450-induced 20-HETE synthesis which in turn results in vascular dysfunction. However, the effect of testosterone plus estrogen in the cardiovascular system is still very poorly studied. The aim of the present study is to evaluate the role of cytochrome P -450 pathway in a postmenopausal hypertensive female treated with testosterone plus estrogen. For that, hypertensive ovariectomized rats (OVX-SHR) were used as a model of postmenopausal hypertension and four groups were created: SHAM-operated (SHAM), ovariectomized SHR (OVX), OVX treated for 15 days with conjugated equine estrogens [(CEE) 9.6 μg/Kg/day/po] or CEE associated to testosterone [(CEE+T) 2.85 mg/kg/weekly/im]. Phenylephrine-induced contraction and generation of reactive oxygen species (ROS) were markedly increased in aortic rings from OVX-SHR compared to SHAM rats which were restored by CEE treatment. On the other hand, CEE+T abolished vascular effects by CEE and augmented both systolic and diastolic blood pressure of SHR. Treatment of aortic rings with the CYP/20-HETE synthesis inhibitor HET0016 (1 μM) reduced phenylephrine hyperreactivity and the augmented ROS generation in the CEE+T group. These results are paralleled by the increased CYP4F3 protein expression and activity in aortas of CEE+T. In conclusion, we showed that association of testosterone to estrogen therapy produces detrimental effects in cardiovascular system of ovariectomized hypertensive females via CYP4F3/20-HETE pathway. Therefore, our findings support the standpoint that the CYP/20-HETE pathway is an important therapeutic target for the prevention of cardiovascular disease in menopausal women in the presence of high levels of testosterone.

DW10075, a novel selective and small-molecule inhibitor of VEGFR, exhibits antitumor activities both in vitro and in vivo

PubMed Central

Li, Meng-yuan; Lv, Yong-cong; Tong, Lin-jiang; Peng, Ting; Qu, Rong; Zhang, Tao; Sun, Yi-ming; Chen, Yi; Wei, Li-xin; Geng, Mei-yu; Duan, Wen-hu; Xie, Hua; Ding, Jian

2016-01-01

Aim: Targeting the VEGF/VEGF receptor (VEGFR) pathway has proved to be an effective antiangiogenic approach for cancer treatment. Here, we identified 6-((2-((3-acetamidophenyl)amino)pyrimidin-4-yl)oxy)-N-phenyl-1-naphthamide (designated herein as DW10075) as a novel and highly selective inhibitor of VEGFRs. Methods: In vitro tyrosine kinase activity was measured using ELISA, and intracellular signaling pathway proteins were detected by Western blot analysis. Endothelial cell proliferation was examined with CCK-8 assays, and tumor cell proliferation was determined with SRB assays. Cell migration, tube formation and rat aortic ring assays were used to detect antiangiogenic activity. Antitumor efficacy was further evaluated in U87-MG human glioblastoma xenograft tumors in nude mice receiving DW10075 (500 mg·kg−1·d−1, po) for two weeks. Results: Among a panel of 21 kinases tested, DW10075 selectively inhibited VEGFR-1, VEGFR-2 and VEGFR-3 (the IC50 values were 6.4, 0.69 and 5.5 nmol/L, respectively), but did not affect 18 other kinases including FGFR and PDGFR at 10 μmol/L. DW10075 significantly blocked VEGF-induced activation of VEGFR and its downstream signaling transduction in primary human umbilical vein endothelial cells (HUVECs), thus inhibited VEGF-induced HUVEC proliferation. DW10075 (1–100 nmol/L) dose-dependently inhibited VEGF-induced HUVEC migration and tube formation and suppressed angiogenesis in both the rat aortic ring model and the chicken chorioallantoic membrane model. Furthermore, DW10075 exhibited anti-proliferative activity against 22 different human cancer cell lines with IC50 values ranging from 2.2 μmol/L (for U87-MG human glioblastoma cells) to 22.2 μmol/L (for A375 melanoma cells). In U87-MG xenograft tumors in nude mice, oral administration of DW10075 significantly suppressed tumor growth, and reduced the expression of CD31 and Ki67 in the tumor tissues. Conclusion: DW10075 is a potent and highly selective inhibitor of VEGFR that deserves further development. PMID:26806300

Effects of aortic root motion on wall stress in the Marfan aorta before and after personalised aortic root support (PEARS) surgery.

PubMed

Singh, S D; Xu, X Y; Pepper, J R; Izgi, C; Treasure, T; Mohiaddin, R H

2016-07-05

Aortic root motion was previously identified as a risk factor for aortic dissection due to increased longitudinal stresses in the ascending aorta. The aim of this study was to investigate the effects of aortic root motion on wall stress and strain in the ascending aorta and evaluate changes before and after implantation of personalised external aortic root support (PEARS). Finite element (FE) models of the aortic root and thoracic aorta were developed using patient-specific geometries reconstructed from pre- and post-PEARS cardiovascular magnetic resonance (CMR) images in three Marfan patients. The wall and PEARS materials were assumed to be isotropic, incompressible and linearly elastic. A static load on the inner wall corresponding to the patients' pulse pressure was applied. Cardiovascular MR cine images were used to quantify aortic root motion, which was imposed at the aortic root boundary of the FE model, with zero-displacement constraints at the distal ends of the aortic branches and descending aorta. Measurements of the systolic downward motion of the aortic root revealed a significant reduction in the axial displacement in all three patients post-PEARS compared with its pre-PEARS counterparts. Higher longitudinal stresses were observed in the ascending aorta when compared with models without the root motion. Implantation of PEARS reduced the longitudinal stresses in the ascending aorta by up to 52%. In contrast, the circumferential stresses at the interface between the supported and unsupported aorta were increase by up to 82%. However, all peak stresses were less than half the known yield stress for the dilated thoracic aorta. Copyright © 2016 Elsevier Ltd. All rights reserved.

Rabbit aortic aneurysm model with enlarging diameter capable of better mimicking human aortic aneurysm disease.

PubMed

Bi, Yonghua; Chen, Hongmei; Li, Yahua; Yu, Zepeng; Han, Xinwei; Ren, Jianzhuang

2018-01-01

The self-healing phenomenon can be found in the elastase-induced abdominal aortic aneurysm (AAA) model, and an enlarging AAA model was successfully induced by coarctation. Unfortunately, aortic coarctation in these enlarging models is generally not found in human AAA disease. This study aimed to create an experiment model of enlarging AAA in rabbits to better mimic human aortic aneurysm disease. Eighty-four male New Zealand white rabbits were randomly divided into three equal groups: two aneurysm groups (A and B) and a SHAM group. Aneurysm group rabbits underwent extrinsic aortic stenosis below the right renal artery and received a 10-minute incubation of 60 μl elastase (1 unit/μl). Absorbable suture was used in Group A and nonabsorbable cotton thread was used in Group B. A sham operation was performed in the SHAM group. Aortic diameter was measured after 1, 3, 7, and 15 weeks; thereafter animals were sacrificed for histopathological, immunohistochemical and quantitative studies. Two rabbits died at 29 and 48 days, respectively, after operation in Group B. All aneurysms formed and enlarged progressively by 3 weeks in the Aneurysm groups. However, diameter enlargement in Group A was significantly lower than that in Group B at 7 weeks. Aneurysm groups developed intimal hyperplasia; intima-media thickness (IMT) increased significantly by week 7, and aortic media thickness and intima-media ratio (IMR) increased significantly by week 15. Marked destruction of elastin fibers and smooth muscle cells (SMCs) occurred 1 week later and increased progressively thereafter. Intimal hyperplasia and SMCs content in Group A increased significantly by week 15 compared with Group B. Aneurysm groups exhibited strong expression of matrix metalloproteinases 2 and 9 and RAM11 by week 1, and decreased progressively thereafter. In conclusion, this novel rabbit AAA model enlarges progressively without coarctation and is capable of better mimicking human aortic aneurysm disease.

High Fat Diet Attenuates the Anticontractile Activity of Aortic PVAT via a Mechanism Involving AMPK and Reduced Adiponectin Secretion

PubMed Central

Almabrouk, Tarek A. M.; White, Anna D.; Ugusman, Azizah B.; Skiba, Dominik S.; Katwan, Omar J.; Alganga, Husam; Guzik, Tomasz J.; Touyz, Rhian M.; Salt, Ian P.; Kennedy, Simon

2018-01-01

Background and aim: Perivascular adipose tissue (PVAT) positively regulates vascular function through production of factors such as adiponectin but this effect is attenuated in obesity. The enzyme AMP-activated protein kinase (AMPK) is present in PVAT and is implicated in mediating the vascular effects of adiponectin. In this study, we investigated the effect of an obesogenic high fat diet (HFD) on aortic PVAT and whether any changes involved AMPK. Methods: Wild type Sv129 (WT) and AMPKα1 knockout (KO) mice aged 8 weeks were fed normal diet (ND) or HFD (42% kcal fat) for 12 weeks. Adiponectin production by PVAT was assessed by ELISA and AMPK expression studied using immunoblotting. Macrophages in PVAT were identified using immunohistochemistry and markers of M1 and M2 macrophage subtypes evaluated using real time-qPCR. Vascular responses were measured in endothelium-denuded aortic rings with or without attached PVAT. Carotid wire injury was performed and PVAT inflammation studied 7 days later. Key results: Aortic PVAT from KO and WT mice was morphologically indistinct but KO PVAT had more infiltrating macrophages. HFD caused an increased infiltration of macrophages in WT mice with increased expression of the M1 macrophage markers Nos2 and Il1b and the M2 marker Chil3. In WT mice, HFD reduced the anticontractile effect of PVAT as well as reducing adiponectin secretion and AMPK phosphorylation. PVAT from KO mice on ND had significantly reduced adiponectin secretion and no anticontractile effect and feeding HFD did not alter this. Wire injury induced macrophage infiltration of PVAT but did not cause further infiltration in KO mice. Conclusions: High-fat diet causes an inflammatory infiltrate, reduced AMPK phosphorylation and attenuates the anticontractile effect of murine aortic PVAT. Mice lacking AMPKα1 phenocopy many of the changes in wild-type aortic PVAT after HFD, suggesting that AMPK may protect the vessel against deleterious changes in response to HFD. PMID:29479319

Smooth muscle-dependent changes in aortic wall dynamics during intra-aortic counterpulsation in an animal model of acute heart failure.

PubMed

Cabrera Fischer, Edmundo I; Bia, Daniel; Zócalo, Yanina; Armentano, Ricardo L

2009-06-01

Intra-aortic balloon pumping (IABP) may modify arterial biomechanics; however, its effects on arterial wall properties during acute cardio-depression have not yet been fully explored. This dynamical study was designed to characterize the effects of IABP on aortic wall mechanics in an in vivo animal model of acute heart failure. Aortic pressure, diameter and blood flow were measured in six anesthetized sheep with acute cardio-depression by halothane (4%), before and during IABP (1:2). Aortic characteristic impedance and aortic wall stiffness indexes were calculated. acute experimental cardio-depression resulted in a reduction in mean aortic pressure (p<0.05) and an increase in the characteristic impedance (p<0.005), incremental elastic modulus (p<0.05), stiffness index (p<0.05) and Peterson elastic modulus (p<0.05). IABP caused an increase in the cardiac output (p<0.005) and a reduction in the systemic vascular resistances (p<0.05). In addition, the aortic impedance, incremental elastic modulus, stiffness index and Peterson modulus were significantly reduced during IABP (p<0.05). Our findings show that IABP caused changes in aortic wall impedance and intrinsic wall properties, improving the arterial functional capability and the left ventricular afterload by a reduction in both. Systemic vascular resistances and aortic stiffness were also improved by means of smooth muscle-dependent mechanisms.

Glutathione metabolic status in the aged rabbit aorta.

PubMed

Lapenna, Domenico; Ciofani, Giuliano; Giamberardino, Maria Adele

2017-05-01

It is not known whether aging alters glutathione metabolic status of the mammalian arterial tissue favoring vascular oxidative stress and dysfunction. Thus we assessed total, reduced and oxidized glutathione (TG, GSH and GSSG, respectively), the glutathione redox ratio (GRR, namely [GSSG]/[GSH+2GSSG]×100), and the activities of the glutathione status-regulating enzymes glutathione reductase (GSSG-Red), γ-glutamylcysteine synthetase (γ-GCS) and γ-glutamyl transpeptidase (γ-GT) in the aortic tissue of 9 young adult control rabbits (YACR, about 4months old) and 9 aged rabbits (AR, about 4.5years old); aortic lipid and protein oxidation and H 2 O 2 were also determined as oxidative stress indicators. Vascular function was assessed on aortic ring preparations. TG and GSH concentrations, together with γ-GCS and γ-GT activities, were significantly lower, while GSSG content and the GRR higher, in the AR than in the YACR aortas; GSSG-Red activity did not differ significantly between the two groups. Heightened levels of lipid and protein oxidation and H 2 O 2 occurred in the AR aortas, indicating age-dependent vascular oxidative stress. Moreover, in the whole population of 18 rabbits, the aortic values of GSH and related enzyme activities were inversely and significantly correlated with those of lipid and protein oxidation and H 2 O 2 , highlighting the antioxidant role of GSH and related enzymes in the vascular tissue. Aortic endothelium-dependent vasodilation was lower in the AR than in the YACR. In conclusion, glutathione metabolic status is altered in the aged rabbit aorta reflecting depressed γ-GCS- and γ-GT-related GSH biosynthesis and GSSG burden eventually favoring vascular oxidative stress and dysfunction. Copyright © 2017 Elsevier Inc. All rights reserved.

Ca2+ mobilization in the aortic endothelium in streptozotocin-induced diabetic and cholesterol-fed mice.

PubMed

Kamata, K; Nakajima, M

1998-04-01

1. Experiments were performed to compare Ca2+ mobilization in the aortic endothelium in streptozotocin (STZ)-induced diabetic and cholesterol-fed mice with that in age-matched controls. 2. The intracellular free Ca2+ ([Ca2+]i) in the fura PE-3 loaded endothelium of aortic rings was dose-dependently increased by cumulative administration of acetylcholine (ACh). ACh caused a transient rise in [Ca2+]i in Ca2+-free medium. The ACh-induced increase in [Ca2+]i in normal or Ca2+-free medium was significantly weaker in both STZ-induced diabetic and cholesterol-fed mice. 3. The weaker [Ca2+]i response in Ca2+-containing medium in STZ-induced diabetic and cholesterol-fed mice was normalized by chronic administration of cholestyramine. 4. The increased low density lipoprotein (LDL) levels seen in both STZ-induced diabetic and cholesterol-fed mice were normalized by the same chronic administration of cholestyramine (300 mg kg(-1), p.o. daily for 10 weeks). Chronic administration of cholestyramine had no effect on the plasma glucose level. 5. Lysophosphatidylcholine (LPC) decreased the [Ca2+]i responses to ACh in the aortic endothelium from normal mice. 6. These results suggest that ACh increases both Ca2+ influx and Ca2+ release from storage in the aortic endothelium. The weaker [Ca2+]i influx seen in the endothelium of aortae from both STZ-induced diabetic and cholesterol-fed mice was improved by the chronic administration of cholestyramine, and we suggest that this improvement is due, at least in part, to a lowering of the plasma LDL level. It is further suggested that LPC may have an important influence over Ca2+ mobilization in the endothelium.

Mild aerobic exercise blocks elastin fiber fragmentation and aortic dilatation in a mouse model of Marfan syndrome associated aortic aneurysm.

PubMed

Gibson, Christine; Nielsen, Cory; Alex, Ramona; Cooper, Kimbal; Farney, Michael; Gaufin, Douglas; Cui, Jason Z; van Breemen, Cornelis; Broderick, Tom L; Vallejo-Elias, Johana; Esfandiarei, Mitra

2017-07-01

Regular low-impact physical activity is generally allowed in patients with Marfan syndrome, a connective tissue disorder caused by heterozygous mutations in the fibrillin-1 gene. However, being above average in height encourages young adults with this syndrome to engage in high-intensity contact sports, which unfortunately increases the risk for aortic aneurysm and rupture, the leading cause of death in Marfan syndrome. In this study, we investigated the effects of voluntary (cage-wheel) or forced (treadmill) aerobic exercise at different intensities on aortic function and structure in a mouse model of Marfan syndrome. Four-week-old Marfan and wild-type mice were subjected to voluntary and forced exercise regimens or sedentary lifestyle for 5 mo. Thoracic aortic tissue was isolated and subjected to structural and functional studies. Our data showed that exercise improved aortic wall structure and function in Marfan mice and that the beneficial effect was biphasic, with an optimum at low intensity exercise (55-65% V̇o 2max ) and tapering off at a higher intensity of exercise (85% V̇o 2max ). The mechanism underlying the reduced elastin fragmentation in Marfan mice involved reduction of the expression of matrix metalloproteinases 2 and 9 within the aortic wall. These findings present the first evidence of potential beneficial effects of mild exercise on the structural integrity of the aortic wall in Marfan syndrome associated aneurysm. Our finding that moderate, but not strenuous, exercise protects aortic structure and function in a mouse model of Marfan syndrome could have important implications for the medical care of young Marfan patients. NEW & NOTEWORTHY The present study provides conclusive scientific evidence that daily exercise can improve aortic health in a mouse model of Marfan syndrome associated aortic aneurysm, and it establishes the threshold for the exercise intensity beyond which exercise may not be as protective. These findings establish a platform for a new focus on promoting regular exercise in Marfan patients at an optimum intensity and create a paradigm shift in clinical care of Marfan patients suffering from aortic aneurysm complications. Copyright © 2017 the American Physiological Society.

Supravalvar mitral ring with a parachute mitral valve and subcoarctation of the aorta in a child with hemodynamically significant VSD. A study of the morphology, echocardiographic diagnostics and surgical therapy.

PubMed

Mądry, Wojciech; Karolczak, Maciej A; Grabowski, Krzysztof

2017-09-01

The authors present a case of echocardiographic diagnosis of supravalvar mitral ring (a fibromembranous structure that arose from the atrial surface of the mitral leaflets) in a child with a parachute mitral valve, a ventricular septal defect, and mild narrowing of the aortic isthmus. The supravalvar mitral stenosis is a typical but very infrequently detected element of the complex of anatomical abnormalities located within the left heart and the proximal aorta, called the Shone's complex (syndrome). Diagnosing an additional, hemodynamically significant anatomic defect during echocardiography was possible thanks to the detection of marked mobility limitation of the ring-adjacent part of the mitral valve mural leaflet as well as of an atypical image of turbulence occurring during the inflow from the left atrium to the left ventricle. The early diagnosis made it possible to perform complete correction of this complex congenital defect within a single operation.

Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kesavan, Manickam; Sarath, Thengumpallil Sasindran; Kannan, Kandasamy

We evaluated whether atorvastatin, an extensively prescribed statin for reducing the risks of cardiovascular diseases, can reduce the risk of arsenic-induced vascular dysfunction and inflammation in rats and whether the modulation could be linked to improvement in vascular NO signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91{sup st} day, blood was collected for measuring serum C-reactive protein. Thoracic aorta was isolated for assessing reactivity to phenylephrine, sodium nitroprusside and acetylcholine; evaluating eNOSmore » and iNOS mRNA expression and measuring NO production, while abdominal aorta was used for ELISA of cytokines, chemokine and vascular cell adhesion molecules. Histopathology was done in aortic arches. Arsenic did not alter phenylephrine-elicited contraction. Atorvastatin inhibited E{sub max} of phenylephrine, but it augmented the contractile response in aortic rings from arsenic-exposed animals. Sodium nitroprusside-induced relaxation was not altered with any treatment. However, arsenic reduced acetylcholine-induced relaxation and affected aortic eNOS at the levels of mRNA expression, protein concentration, phosphorylation and NO production. Further, it increased aortic iNOS mRNA expression, iNOS-derived NO synthesis, production of pro-inflammatory mediators (IL-1β, IL-6, MCP-1, VCAM, sICAM) and serum C-reactive protein and aortic vasculopathic lesions. Atorvastatin attenuated these arsenic-mediated functional, biochemical and structural alterations. Results show that atorvastatin has the potential to ameliorate arsenic-induced vascular dysfunction and inflammation by restoring endothelial function with improvement in NO signaling and attenuating production of pro-inflammatory mediators and cell adhesion molecules. - Highlights: • We evaluated if atorvastatin reduce arsenic-induced vascular dysfunction. • Arsenic reduced ACh-induced aortic relaxation but didn’t alter response to SNP and PE. • Arsenic affected aortic NO signalling and production of inflammatory mediators. • Arsenic produced vasculopathic lesions in aorta. • Atorvastatin restored arsenic-induced functional, biochemical and structural changes.« less

Calcium-dependent mechanisms mediate the vasorelaxant effects of Tridax procumbens (Lin) aqueous leaf extract in rat aortic ring.

PubMed

Salahdeen, Hussein M; Idowu, Gbolahan O; Yemitan, Omoniyi K; Murtala, Babatunde A; Alada, Abdul-Rasak A

2014-05-01

Tridax procumbens leaf extract has a folk reputation as an antihypertensive agent in Nigeria. Evidence suggests that it has a relaxant effect on smooth muscles. The present study was designed to investigate the role of calcium in the vasorelaxant effect of this extract. Concentration-response studies with noradrenaline (NA), KCl and CaCl2 were carried out in rat aortic rings with and without the extract in physiological salt solution (PSS) (n=6 each). Also, the role of intracellular calcium mobilization was studied by measuring the phasic response to NA in Ca2+-free N,N-ethylene glycol tetraacetic acid (EGTA) PSS (n=6). The results showed that the contractile responses to either NA or KCl were attenuated (p<0.05) in the presence of the extract. Also, the extract attenuated the contractile response to CaCl2 in the presence of NA or KCl (p<0.05) in the Ca2+-free EGTA PSS, while the phasic response to NA was significantly (p<0.05) diminished. These results suggest that the vasorelaxant effect of T. procumbens leaf extract may be mediated by a non-specific, non-competitive inhibition of Ca2+ influx as well as by inhibition of Ca2+ mobilization from intracellular stores. This implies that it may contain vasorelaxant agents that may have calcium antagonistic potential.

Dimethylarginine dimethylaminohydrolase 1 modulates endothelial cell growth through NO and Akt

PubMed Central

Zhang, Ping; Hu, Xinli; Xu, Xin; Chen, Yingjie; Bache, Robert J.

2011-01-01

Objective Dimethylarginine dimethylaminohydrolase 1 (DDAH1) modulates NO production by degrading the endogenous NO synthase (NOS) inhibitors ADMA and L-NMMA. This study examined whether, in addition to degrading ADMA, DDAH1 exerts ADMA independent effects that influence endothelial function. Methods and Results Using selective gene silencing of DDAH1 with small interfering RNA and overexpression of DDAH1 in HUVEC, we found that DDAH1 acts to promote endothelial cell proliferation, migration and tube formation both by Akt phosphorylation as well as through the traditional role of degrading ADMA. Incubation of HUVEC with the NOS inhibitors L-NAME or ADMA, the soluble guanylyl cyclase inhibitor ODQ, or the cGMP analog 8-pCPT-cGMP had no effect on p-AktSer473, indicating that the increase of p-AktSer473 produced by DDAH1 was independent of the NO-cGMP signaling pathway. DDAH1 formed a protein complex with Ras, and DDAH1 overexpression increased Ras activity. The Ras inhibitor manumycin-A or dominant-negative Ras significantly attenuated the DDAH1-induced increase of p-AktSer473. Furthermore, DDAH1 knockout impaired endothelial sprouting from cultured aortic rings, and overexpression of constitutively active Akt or DDAH1 rescued endothelial sprouting in the aortic rings from these mice. Conclusions DDAH1 exerts a unique role in activating Akt that affects endothelial function independent of degrading endogenous NOS inhibitors. PMID:21212404

Investigation of terpinen-4-ol effects on vascular smooth muscle relaxation.

PubMed

Maia-Joca, Rebeca Peres Moreno; Joca, Humberto Cavalcante; Ribeiro, Francisca Jéssica Penha; do Nascimento, Renata Vieira; Silva-Alves, Kerly Shamyra; Cruz, Jader S; Coelho-de-Souza, Andrelina Noronha; Leal-Cardoso, José Henrique

2014-10-12

This study investigated the mechanisms underlying the vascular effects of terpinen-4-ol in isolated rat aortic ring preparations. The thoracic aortae of healthy rats were submitted to isometric tension recording. Membrane resting potential and input membrane resistance were measured by conventional microelectrode technique. Terpinen-4-ol reversibly relaxed endothelium-containing preparations pre-contracted with high K(+) and phenylephrine with IC50 values of 421.43 μM and 802.50 μM, respectively. These effects were significantly reduced by vascular endothelium removal. In Ca(2+)-free and high K(+) (80 mM) medium, the contractions produced by Ba(2+) were reduced by terpinen-4-ol (100-1000 μM) in a concentration-dependent manner. In aortic rings maintained under Ca(2+)-free conditions, terpinen-4-ol significantly reduced the contractions induced by either phenylephrine (1 μM) or phorbol 12,13-dibutyrate (1 μM). Terpinen-4-ol (10-1000 μM) also relaxed the contractions evoked by BAYK-8644 (3 μM) with an IC50 of 454.23 μM. Neither membrane resting potential nor input resistance of smooth muscle cells was altered by terpinen-4-ol exposure. The present results suggest that terpinen-4-ol induced vascular smooth muscle relaxation that was preferentially due to the inhibition of electromechanical pathways related to calcium influx through voltage-operated calcium channels. Copyright © 2014 Elsevier Inc. All rights reserved.

Dietary soy modulates endothelium-dependent relaxation in aged male rats: Increased agonist-induced endothelium-derived hyperpolarising factor and basal nitric oxide activity

PubMed Central

Knock, Greg A.; Mahn, Katharina; Mann, Giovanni E.; Ward, Jeremy P.T.; Aaronson, Philip I.

2018-01-01

We examined the effects of dietary soy on the contributions of endothelium-derived hyperpolarising factor (EDHF), nitric oxide (NO), and oxidative stress to vascular tone in isolated aortic rings and small mesenteric and pulmonary arteries in vitro. Male Wistar rats were either continuously fed a soy-deficient diet (SD) or switched from a soy-deficient diet to a soy-rich one for 6 months (SW). Contractile responses were generally smaller in arteries from SW rats. In mesenteric arteries, this difference was blunted by L-NAME, but not by charybdotoxin and apamin. Preconstricted SW mesenteric arteries were more sensitive to acetylcholine (ACh) than SD ones. This difference was unaffected by L-NAME but was abolished by charybdotoxin and apamin. Exogenous superoxide dismutase (SOD) and catalase induced powerful relaxations in aortic rings, which were smaller in those from SW rats. In mesenteric and pulmonary arteries, however, they partially inhibited ACh-mediated relaxation, and enhanced PGF2α–mediated contraction, respectively. Our results suggest that feeding aging male rats a soy-rich diet results in improved agonist-mediated EDHF production and a generalized reduction in contractile force, which is partly due to elevated basal NO. Our data also suggest a prorelaxant role for endogenous H2O2 in small arteries, which is modulated by a soy diet. PMID:16895793

Potentiation of vasoconstriction and pressor response by low concentration of monomethylarsonous acid (MMA(III)).

PubMed

Lim, Kyung-Min; Shin, Yoo-Sun; Kang, Seojin; Noh, Ji-Yoon; Kim, Keunyoung; Chung, Seung-Min; Yun, Yeo-Pyo; Chung, Jin-Ho

2011-09-10

A close link between arsenic exposure and hypertension has been well-established through many epidemiological reports, yet the mechanism underlying it remains unclear. Here we report that nanomolar concentrations of monomethylarsonous acid (MMA(III)), a toxic trivalent methylated arsenic metabolite, can potentiate agonist-induced vasoconstriction and pressor responses. In freshly isolated rat aortic ring, exposure to nanomolar MMA(III) (100-500 nM) potentiated phenylephrine (PE)-induced vasoconstriction while at higher concentrations (≥2.5 μM), suppression of vasoconstriction and apoptosis of vascular smooth muscle were observed. Potentiation of agonist-induced vasoconstriction was also observed with other contractile agonists and it was retained in endothelium-denuded aortic rings, suggesting that these events are agonist-independent and smooth muscle cell dependent. Interestingly, exposure to MMA(III) resulted in increased myosin light chain phosphorylation while PE-induced Ca2+ influx was not affected, reflecting that Ca2+ sensitization is involved. In line with this, MMA(III) enhanced agonist-induced activation of small GTPase RhoA, a key contributor to Ca2+ sensitization. Of note, treatment of MMA(III) to rats induced significantly higher pressor responses in vivo, demonstrating that this event can occur in vivo indeed. We believe that RhoA-mediated Ca2+ sensitization and the resultant potentiation of vasoconstriction by MMA(III) may shed light on arsenic-associated hypertension. Copyright © 2011. Published by Elsevier Ireland Ltd.

3D analysis of vortical structures in an abdominal aortic aneurysm by stereoscopic PIV

NASA Astrophysics Data System (ADS)

Deplano, Valérie; Guivier-Curien, Carine; Bertrand, Eric

2016-11-01

The present work presents an experimental in vitro three-dimensional analysis of the flow dynamics in an abdominal aortic aneurysm (AAA) through stereoscopic particle image velocimetry (SPIV) measurements. The experimental set-up mimics the pathophysiological context involving a shear thinning blood analogue fluid, compliant AAA and aorto-iliac bifurcation walls and controlled inlet and outlet flow rate and pressure waveforms as well as working fluid temperature. SPIV was carefully calibrated and conducted to assess the three velocity components in the AAA volume. For the first time in the literature, the 3D vortex ring genesis, propagation, and vanishing in the AAA bulge are experimentally described and quantified. In comparison with classical 2-component PIV measurements (2C PIV), the third component of the velocity vector was shown to be of importance in such a geometry, especially, during the deceleration phase of the flow rate. The 3D velocity magnitude reached up more than 20 % of the 2D one showing that 2C PIV are definitively not accurate enough to provide a complete description of flow behaviour in an AAA. In addition to potential clinical implications of a full 3D vortex ring description in AAA evolution, the 3D in vitro experimental quantification of the flow dynamics carried out in the present study offers an interesting tool for the validation of fluid-structure interaction numerical studies dealing with AAA.

Multi-Carotenoids at Physiological Levels Inhibit VEGF-Induced Tube Formation of Endothelial Cells and the Possible Mechanisms of Action Both In Vitro and Ex Vivo.

PubMed

Huang, Chien-Hao; Huang, Chin-Shiu; Hu, Miao-Lin; Chuang, Cheng-Hung

2018-01-01

Carotenoids have been shown to exhibit antiangiogenic activities. Several studies have indicated that carotenoids used in combination were more effective on antioxidation and anticancer actions than carotenoids used singly. However, it is unclear whether multi-carotenoids have antiangiogenic effects. We investigated the effects of multi-carotenoids at physiological plasma levels of Taiwanese (abbreviated as MCT, with a total of 1.4 μM) and Americans (abbreviated as MCA, with a total of 1.8 μM), and of post-supplemental plasma levels (abbreviated as HMC with a total of 3.55 μM) on vascular endothelial growth factor (VEGF)-induced tube formation in human umbilical vein endothelial cells (HUVECs) and rat aortic rings. MCT, MCA, and HMC inhibited VEGF-induced migration, invasion, and tube formation of HUVECs as well as new vessels formation in rat aortic rings. MCT, MCA, and HMC inhibited activities o\\f matrix metalloproteinase (MMP)-2, urokinase plasminogen activator, and phosphorylation of VEGF receptor 2 induced by VEGF. Moreover, MCT, MCA, and HMC significantly upregulated protein expression of tissue inhibitors of MMP-2 and plasminogen activator inhibitor-1. These results demonstrate the antiangiogenic effect of multi-carotenoids both in vitro and ex vivo with possible mechanistic actions involving attenuation of VEGF receptor 2 phosphorylation and extracellular matrix degradation.

Effects of hindlimb unweighting on the mechanical and structure properties of the rat abdominal aorta

NASA Technical Reports Server (NTRS)

Papadopoulos, Anthony; Delp, Michael D.

2003-01-01

Previous studies have shown that hindlimb unweighting of rats, a model of microgravity, reduces evoked contractile tension of peripheral conduit arteries. It has been hypothesized that this diminished contractile tension is the result of alterations in the mechanical properties of these arteries (e.g., active and passive mechanics). Therefore, the purpose of this study was to determine whether the reduced contractile force of the abdominal aorta from 2-wk hindlimb-unweighted (HU) rats results from a mechanical function deficit resulting from structural vascular alterations or material property changes. Aortas were isolated from control (C) and HU rats, and vasoconstrictor responses to norepinephrine (10(-9)-10(-4) M) and AVP (10(-9)-10(-5) M) were tested in vitro. In a second series of tests, the active and passive Cauchy stress-stretch relations were determined by incrementally increasing the uniaxial displacement of the aortic rings. Maximal Cauchy stress in response to norepinephrine and AVP were less in aortic rings from HU rats. The active Cauchy stress-stretch response indicated that, although maximum stress was lower in aortas from HU rats (C, 8.1 +/- 0.2 kPa; HU, 7.0 +/- 0.4 kPa), it was achieved at a similar hoop stretch. There were also no differences in the passive Cauchy stress-stretch response or the gross vascular morphology (e.g., medial cross-sectional area: C, 0.30 +/- 0.02 mm(2); HU, 0.32 +/- 0.01 mm(2)) between groups and no differences in resting or basal vascular tone at the displacement that elicits peak developed tension between groups (resting tension: C, 1.71 +/- 0.06 g; HU, 1.78 +/- 0.14 g). These results indicate that HU does not alter the functional mechanical properties of conduit arteries. However, the significantly lower active Cauchy stress of aortas from HU rats demonstrates a true contractile deficit in these arteries.

The effect of tetrathiomolybdate on cytokine expression, angiogenesis, and tumor growth in squamous cell carcinoma of the head and neck.

PubMed

Teknos, Theodoros N; Islam, Mozaffarul; Arenberg, Douglas A; Pan, Quintin; Carskadon, Shannon L; Abarbanell, Aaron M; Marcus, Benjamin; Paul, Supriti; Vandenberg, Curtis D; Carron, Michael; Nor, Jacques E; Merajver, Sofia D

2005-03-01

To assess the effect of tetrathiomolybdate on cytokine expression, angiogenesis, and tumor growth rate in human squamous cell carcinoma (SCC). Three human SCC cell lines were used in this study for both in vitro and in vivo investigations. Conditioned media from untreated and tetrathiomolybdate-treated cell lines were compared with regard to cytokine levels, endothelial cell chemotaxis, endothelial cell tubule formation, and migration and the ability to induce angiogenesis in a rat aortic ring array. In vivo UM-SCC-38 was seeded onto tissue-engineered scaffolds and surgically implanted into the flanks of immunodeficient mice. Tumor growth rates and the level of angiogenesis were compared after 2 weeks of therapy. A tertiary care facility. In this study, we demonstrate that tetrathiomolybdate significantly decreases the secretion of interleukin 6 and basic fibroblast growth factor by head and neck SCC (HNSCC) cell lines in vitro. Furthermore, we demonstrate that tetrathiomolybdate significantly decreases the secretion of interleukin 6 and basic fibroblast growth factor by HNSCC cell lines in vitro. Furthermore, tetrathiomolybdate treatment of HNSCC cell lines results in significantly decreased endothelial cell chemotaxis, tubule formation, and neovascularization in a rat aortic ring assay. This in vitro evidence of decreased angiogenesis by tetrathiomolybdate is confirmed in vivo by using a severe combined immunodeficiency disorder mouse model in which tetrathiomolybdate therapy is shown to prevent human blood vessel formation. Finally, human HNSCC implanted into immunodeficient mice grow to a much larger size in untreated mice compared with those treated with 0.7 mL/kg per day of oral tetrathiomolybdate. These findings illustrate the ability of tetrathiomolybdate to down-regulate proinflammatory and proangiogenic cytokines in HNSCC. These observations are potentially exciting from a clinical perspective because a global decrease in these cytokines may decrease tumor aggressiveness and reverse the resistance to chemotherapy and radiation therapy seen in this tumor type.

Neonatal piglet model of intraaortic balloon pumping: improved efficacy using echocardiographic timing.

PubMed

Minich, L L; Tani, L Y; Pantalos, G M; Bolland, B L; Knorr, B K; Hawkins, J A

1998-11-01

Pediatric intraaortic balloon pumping (IABP) has met with little success because of technical difficulty in tracking rapid heart rates. This study was designed to evaluate the efficacy of M-mode echocardiography for IABP timing in a neonatal piglet model. Two groups of piglets underwent mitral valve avulsion to create a model of shock. Group 1 (n = 8; mean weight, 7.7+/-1.8 kg) underwent IABP timed with both the ascending aortic pressure and M-mode echocardiogram. Group 2 (n = 6; mean weight, 7.5+/-1.4 kg) underwent two separate periods of IABP: one with echocardiographic timing and the second using standard timing points from the femoral arterial pressure tracing and electrocardiogram. Measurements included ascending aortic flow, left anterior descending arterial flow, ascending aortic pressure, left atrial pressure, and heart rate. Mitral valve avulsion produced a shock model with a significant decrease in mean aortic pressure and aortic flow and a significant increase in left atrial pressure and heart rate. Compared with the shock state, IABP in group 1 animals resulted in a significant increase in aortic flow (353+/-152 versus 454+/-109 mL/min; p < 0.05) and a significant decrease in left atrial pressure (23+/-6 versus 17+/-7 mm Hg; p < 0.05). Group 2 animals with echocardiogram-timed IABP had significantly increased aortic flow (365+/-106 versus 458+/-107 mL/min; p < 0.05) and mean aortic pressure (43+/-11 versus 52+/-8 mm Hg; p < 0.05). However, standard-timed IABP failed to show any improvement. In piglets with rapid heart rates, echocardiogram-timed IABP results in increased aortic flow and pressure and decreased left atrial pressure compared with standard-timed IABP.

Advanced technologies for cardiac valvular replacement, transcatheter innovations and reconstructive surgery.

PubMed

Jamieson, W R Eric

2006-01-01

Since the 2002 Surgical Technology International monograph on valvular prostheses, there have been significant developmental and investigative advances. Aortic bioprostheses and mechanical prostheses have undergone design changes to optimize hemodynamics and prevent patient-prosthesis mismatch to have a potential satisfactory influence on survival. There has been continual technological improvements striving to bring forward advances that improve the durability of bioprostheses and reduce the thrombogenicity of mechanical prostheses. There also has been a continuance to preserve biological tissue with glutaraldehyde, rather than clinically evaluate other cross-linking technologies, by controlling or retarding calcification with therapies to control phospholipids and residual aldehydes. The techniques of mitral valve reconstruction have now been well established and new annuloplasty rings have been designed for the potential of maintaining the anatomical and physiological characteristics of the mitral annulus. Several objectives exist for annuloplasty, namely remodeling of the length and shape of the dilated annulus, prevention of dilatation of the annulus, and support for the potentially fragile area after partial-leaflet resection. Currently, there exists an emergence of catheter-based therapies for management of aortic stenosis and mitral regurgitation. For management of selected populations with critical aortic stenosis, techniques for aortic valve substitution have been developed for both antegrade and retrograde catheter techniques, as well as apical transventricular implantation. Mitral regurgitation has been addressed by experimental transcoronary sinus, stent-like devices and transventricular, edge-to-edge leaflet devices. The devices, descriptions and pictorial images comprise this monograph.

Quantitative assessment of paravalvular leakage after transcatheter aortic valve replacement using a patient-specific pulsatile flow model.

PubMed

Tanaka, Yutaka; Saito, Shigeru; Sasuga, Saeko; Takahashi, Azuma; Aoyama, Yusuke; Obama, Kazuto; Umezu, Mitsuo; Iwasaki, Kiyotaka

2018-05-01

Quantitative assessment of post-transcatheter aortic valve replacement (TAVR) aortic regurgitation (AR) remains challenging. We developed patient-specific anatomical models with pulsatile flow circuit and investigated factors associated with AR after TAVR. Based on pre-procedural computed tomography (CT) data of the six patients who underwent transfemoral TAVR using a 23-mm SAPIEN XT, anatomically and mechanically equivalent aortic valve models were developed. Forward flow and heart rate of each patient in two days after TAVR were duplicated under mean aortic pressure of 80mmHg. Paravalvular leakage (PVL) volume in basal and additional conditions was measured for each model using an electromagnetic flow sensor. Incompletely apposed tract between the transcatheter and aortic valves was examined using a micro-CT. PVL volume in each patient-specific model was consistent with each patient's PVL grade, and was affected by hemodynamic conditions. PVL and total regurgitation volume increased with the mean aortic pressure, whereas closing volume did not change. In contrast, closing volume increased proportionately with heart rate, but PVL did not change. The minimal cross-sectional gap had a positive correlation with the PVL volumes (r=0.89, P=0.02). The gap areas typically occurred in the vicinity of the bulky calcified nodules under the native commissure. PVL volume, which could be affected by hemodynamic conditions, was significantly associated with the minimal cross-sectional gap area between the aortic annulus and the stent frame. These data may improve our understanding of the mechanism of the occurrence of post-TAVR PVL. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Patient-specific simulation of guidewire deformation during transcatheter aortic valve implantation.

PubMed

Vy, Phuoc; Auffret, Vincent; Castro, Miguel; Badel, Pierre; Rochette, Michel; Haigron, Pascal; Avril, Stéphane

2018-06-01

Transcatheter aortic valve implantation is a recent mini-invasive procedure to implant an aortic valve prosthesis. Prosthesis positioning in transcatheter aortic valve implantation appears as an important aspect for the success of the intervention. Accordingly, we developed a patient-specific finite element framework to predict the insertion of the stiff guidewire, used to position the aortic valve. We simulated the guidewire insertion for 2 patients based on their pre-operative CT scans. The model was designed to primarily predict the position and the angle of the guidewires in the aortic valve, and the results were successfully compared with intraoperative images. The present paper describes extensively the numerical model, which was solved by using the ANSYS software with an implicit resolution scheme, as well as the stabilization techniques which were used to overcome numerical instabilities. We performed sensitivity analysis on the properties of the guidewire (curvature angle, curvature radius, and stiffness) and the conditions of insertion (insertion force and orientation). We also explored the influence of the model parameters. The accuracy of the model was quantitatively evaluated as the distance and the angle difference between the simulated guidewires and the intraoperative ones. A good agreement was obtained between the model predictions and intraoperative views available for 2 patient cases. In conclusion, we showed that the shape of the guidewire in the aortic valve was mainly determined by the geometry of the patient's aorta and by the conditions of insertion (insertion force and orientation). Copyright © 2018 John Wiley & Sons, Ltd.

No Beneficial Effect of General and Specific Anti-Inflammatory Therapies on Aortic Dilatation in Marfan Mice

PubMed Central

den Hartog, Alexander W.; Radonic, Teodora; de Vries, Carlie J. M.; Zwinderman, Aeilko H.; Groenink, Maarten; Mulder, Barbara J. M.; de Waard, Vivian

2014-01-01

Aims Patients with Marfan syndrome have an increased risk of life-threatening aortic complications, mostly preceded by aortic dilatation. In the FBN1 C1039G/+ Marfan mouse model, losartan decreases aortic root dilatation. We recently confirmed this beneficial effect of losartan in adult patients with Marfan syndrome. The straightforward translation of this mouse model to man is reassuring to test novel treatment strategies. A number of studies have shown signs of inflammation in aortic tissue of Marfan patients. This study examined the efficacy of anti-inflammatory therapies in attenuating aortic root dilation in Marfan syndrome and compared effects to the main preventative agent, losartan. Methods and Results To inhibit inflammation in FBN1 C1039G/+ Marfan mice, we treated the mice with losartan (angiotensin II receptor type 1 inhibitor), methylprednisolone (corticosteroid) or abatacept (T-cell-specific inhibitor). Treatment was initiated in adult Marfan mice with already existing aortic root dilatation, and applied for eight weeks. Methylprednisolone- or abatacept-treated mice did not reveal a reduction in aortic root dilatation. In this short time frame, losartan was the only treatment that significantly reduced aorta inflammation, transforming growth factor-beta (TGF-β) signaling and aortic root dilatation rate in these adult Marfan mice. Moreover, the methylprednisolone-treated mice had significantly more aortic alcian blue staining as a marker for aortic damage. Conclusion Anti-inflammatory agents do not reduce the aortic dilatation rate in Marfan mice, but possibly increase aortic damage. Currently, the most promising therapeutic drug in Marfan syndrome is losartan, by blocking the angiotensin II receptor type 1 and thereby inhibiting pSmad2 signaling. PMID:25238161

Modelling and numerical simulation of the in vivo mechanical response of the ascending aortic aneurysm in Marfan syndrome.

PubMed

García-Herrera, Claudio M; Celentano, Diego J; Herrera, Emilio A

2017-03-01

Marfan syndrome (MFS) is a genetic disorder that affects connective tissue, impairing cardiovascular structures and function, such as heart valves and aorta. Thus, patients with Marfan disease have a higher risk of developing circulatory problems associated with mitral and aortic valves prolapse, manifested as dilated aorta and aortic aneurysm. However, little is known about the biomechanical characteristics of these structures affected with MFS. This study presents the modelling and simulation of the mechanical response of human ascending aortic aneurysms in MFS under in vivo conditions with intraluminal pressures within normotensive and hypertensive ranges. We obtained ascending aortic segments from five adults with MFS subjected to a vascular prosthesis implantation replacing an aortic aneurysm. We characterised the arterial samples via ex vivo tensile test measurements that enable fitting the material parameters of a hyperelastic isotropic constitutive model. Then, these material parameters were used in a numerical simulation of an ascending aortic aneurysm subjected to in vivo normotensive and hypertensive conditions. In addition, we assessed different constraints related to the movement of the aortic root. Overall, our results provide not only a realistic description of the mechanical behaviour of the vessel, but also useful data about stress/stretch-based criteria to predict vascular rupture. This knowledge may be included in the clinical assessment to determine risk and indicate surgical intervention.

Computer model analysis of the radial artery pressure waveform.

PubMed

Schwid, H A; Taylor, L A; Smith, N T

1987-10-01

Simultaneous measurements of aortic and radial artery pressures are reviewed, and a model of the cardiovascular system is presented. The model is based on resonant networks for the aorta and axillo-brachial-radial arterial system. The model chosen is a simple one, in order to make interpretation of the observed relationships clear. Despite its simplicity, the model produces realistic aortic and radial artery pressure waveforms. It demonstrates that the resonant properties of the arterial wall significantly alter the pressure waveform as it is propagated from the aorta to the radial artery. Although the mean and end-diastolic radial pressures are usually accurate estimates of the corresponding aortic pressures, the systolic pressure at the radial artery is often much higher than that of the aorta due to overshoot caused by the resonant behavior of the radial artery. The radial artery dicrotic notch is predominantly dependent on the axillo-brachial-radial arterial wall properties, rather than on the aortic valve or peripheral resistance. Hence the use of the radial artery dicrotic notch as an estimate of end systole is unreliable. The rate of systolic upstroke, dP/dt, of the radial artery waveform is a function of many factors, making it difficult to interpret. The radial artery waveform usually provides accurate estimates for mean and diastolic aortic pressures; for all other measurements it is an inadequate substitute for the aortic pressure waveform. In the presence of low forearm peripheral resistance the mean radial artery pressure may significantly underestimate the mean aortic pressure, as explained by a voltage divider model.

Interaction in endothelium of non-muscular myosin light-chain kinase and the NF-κB pathway is critical to lipopolysaccharide-induced vascular hyporeactivity.

PubMed

Recoquillon, Sylvain; Carusio, Nunzia; Lagrue-Lakhal, Anne-Hélène; Tual-Chalot, Simon; Filippelli, Amelia; Andriantsitohaina, Ramaroson; Martinez, M Carmen

2015-10-01

During sepsis, endothelial barrier dysfunction contributes to cardiovascular failure, mainly through the release of oxidative metabolites by penetrant leukocytes. We reported the non-muscular isoform of myosin light chain kinase (nmMLCK) playing a pivotal role in endotoxin shock injury associated with oxidative and nitrative stresses, and vascular hyporeactivity. The present study was aimed at understanding the molecular mechanism of lipopolysaccharide (LPS)-induced vascular alterations as well as studying a probable functional association of nmMLCK with nuclear factor κ-light-chain enhancer of activated B cells (NF-κB). Aortic rings from mice were exposed in vitro to LPS and, then, vascular reactivity was measured. Human aortic endothelial cells (HAoECs) were incubated with LPS, and interaction of nmMLCK with NF-κB was analysed. We provide evidence that nmMLCK deletion prevents vascular hyporeactivity induced by in vitro LPS treatment but not endothelial dysfunction in the aorta. Deletion of nmMLCK inhibits LPS-induced NF-κB activation and increases nitric oxide (NO) release via induction of inducible NO synthase (iNOS) within the vascular wall. Also, removal of endothelium prevented both NF-κB and iNOS expression in aortic rings. Among the proinflammatory factors released by LPS-treated endothelial cells, interleukin-6 accounts for the induction of iNOS on smooth muscle cells in response to LPS. Of particular interest is the demonstration that, in HAoECs, LPS-induced NF-κB activation occurs via increased MLCK activity sensitive to the MLCK inhibitor, ML-7, and physical interactions between nmMLCK and NF-κB. We report for the first time on NF-κB as a novel partner of nmMLCK within endothelial cells. The present study demonstrates a pivotal role of nmMLCK in vascular inflammatory pathologies. © 2015 Authors; published by Portland Press Limited.

Chlorogenic acid improves ex vivo vessel function and protects endothelial cells against HOCl-induced oxidative damage, via increased production of nitric oxide and induction of Hmox-1.

PubMed

Jiang, Rujia; Hodgson, Jonathan M; Mas, Emilie; Croft, Kevin D; Ward, Natalie C

2016-01-01

Dietary polyphenols are potential contributors toward improved cardiovascular health. Coffee is one of the richest sources of dietary polyphenols in a coffee-drinking population, the most abundant form being chlorogenic acid (CGA). Endothelial dysfunction is an early and major risk factor for cardiovascular disease. Nitric oxide (NO) is a key factor in regulation of endothelial function. Heme oxygenase-1 (Hmox-1), an inducible isoform of heme oxygenase that is produced in response to stressors such as oxidative stress, may also play a role in vascular protection. The aim of this study was to investigate the effect of CGA on endothelial function with oxidant-induced damage in isolated aortic rings from C57BL mice. We further examine the mechanism by investigating cell viability, activation of eNOS and induction of Hmox-1 in human aortic endothelial cells (HAECs). We found that pretreatment of isolated aortic rings with 10-μM CGA-protected vessels against HOCl-induced endothelial dysfunction (P<0.05). Pretreatment of cultured HAECs with 10-μM CGA increased endothelial cell viability following exposure to HOCl (P<0.05). Moreover, CGA increased NO production in HAECs in a dose-dependent manner, peaking at 6 h (P<0.05). CGA at 5 μM and 10 μM increased eNOS dimerization at 6 h and induced Hmox-1 protein expression at 6 h and 24 h in HAECs. These results are consistent with the cardiovascular protective effects of coffee polyphenols and demonstrate that CGA can protect vessels and cultured endothelial cells against oxidant-induced damage. The mechanism behind the beneficial effect of CGA appears to be in part via increased production of NO and induction of Hmox-1. Copyright © 2015 Elsevier Inc. All rights reserved.

Outcomes of De Vega versus biodegradable ring annuloplasty in the surgical treatment of tricuspid regurgitation (mid-term results).

PubMed

Basel, Halil; Aydin, Unal; Kutlu, Hakan; Dostbil, Aysenur; Karadag, Melike; Odabasi, Dolunay; Aydin, Cemalettin

2010-08-01

The aim of this study was to compare De Vega semicircular annuloplasty and a new biodegradable ring annuloplasty technique in patients requiring surgical intervention for tricuspid valve disease with concomitant disease of the mitral valve. Between January 2004 and May 2008, 129 consecutive patients underwent annuloplasty procedures to correct tricuspid valve regurgitation during a concomitant mitral valve operation requiring replacement. Additionally, 24 patients underwent aortic valve replacement (AVR), 11 underwent coronary artery bypass grafting (CABG), 5 underwent AVR plus CABG, 3 underwent mitral valve replacement plus atrial septal defect (ASD) closure, and 2 underwent ASD closure. The patients in this study were assigned to 2 groups: Kalangos ring annuloplasty was performed in 67 patients (group 1), and De Vega semicircular annuloplasty was performed in the remaining 62 patients (group 2). Both tricuspid valve repair techniques produced a low rate of complications; however, the number of patients who developed residual tricuspid regurgitation was significantly lower in group 1. The biodegradable ring annuloplasty technique may be used easily and safely in moderate and severe cases of tricuspid regurgitation; however, larger clinical series are necessary to confirm our promising results.

Segmentation of the Aortic Valve Apparatus in 3D Echocardiographic Images: Deformable Modeling of a Branching Medial Structure

PubMed Central

Pouch, Alison M.; Tian, Sijie; Takabe, Manabu; Wang, Hongzhi; Yuan, Jiefu; Cheung, Albert T.; Jackson, Benjamin M.; Gorman, Joseph H.; Gorman, Robert C.; Yushkevich, Paul A.

2015-01-01

3D echocardiographic (3DE) imaging is a useful tool for assessing the complex geometry of the aortic valve apparatus. Segmentation of this structure in 3DE images is a challenging task that benefits from shape-guided deformable modeling methods, which enable inter-subject statistical shape comparison. Prior work demonstrates the efficacy of using continuous medial representation (cm-rep) as a shape descriptor for valve leaflets. However, its application to the entire aortic valve apparatus is limited since the structure has a branching medial geometry that cannot be explicitly parameterized in the original cm-rep framework. In this work, we show that the aortic valve apparatus can be accurately segmented using a new branching medial modeling paradigm. The segmentation method achieves a mean boundary displacement of 0.6 ± 0.1 mm (approximately one voxel) relative to manual segmentation on 11 3DE images of normal open aortic valves. This study demonstrates a promising approach for quantitative 3DE analysis of aortic valve morphology. PMID:26247062

Automated segmentation and geometrical modeling of the tricuspid aortic valve in 3D echocardiographic images.

PubMed

Pouch, Alison M; Wang, Hongzhi; Takabe, Manabu; Jackson, Benjamin M; Sehgal, Chandra M; Gorman, Joseph H; Gorman, Robert C; Yushkevich, Paul A

2013-01-01

The aortic valve has been described with variable anatomical definitions, and the consistency of 2D manual measurement of valve dimensions in medical image data has been questionable. Given the importance of image-based morphological assessment in the diagnosis and surgical treatment of aortic valve disease, there is considerable need to develop a standardized framework for 3D valve segmentation and shape representation. Towards this goal, this work integrates template-based medial modeling and multi-atlas label fusion techniques to automatically delineate and quantitatively describe aortic leaflet geometry in 3D echocardiographic (3DE) images, a challenging task that has been explored only to a limited extent. The method makes use of expert knowledge of aortic leaflet image appearance, generates segmentations with consistent topology, and establishes a shape-based coordinate system on the aortic leaflets that enables standardized automated measurements. In this study, the algorithm is evaluated on 11 3DE images of normal human aortic leaflets acquired at mid systole. The clinical relevance of the method is its ability to capture leaflet geometry in 3DE image data with minimal user interaction while producing consistent measurements of 3D aortic leaflet geometry.

The Effect of Infrarenal Aortic Balloon Occlusion on Weaning from Supraceliac Aortic Balloon Occlusion in a Porcine Model (Sus scrofa) of Hemorrhagic Shock

DTIC Science & Technology

2017-06-15

all animals , and continued for six hours. Half of the animals were randomly assigned to Zone-3 REBOA for an additional 45 minutes following Zone-1...concentration or resuscitation requirements.Conclusion: In an animal model of hemorrhagic shock and Zone-1 REBOA, subsequent Zone-3 aortic occlusion did not add

Physical Fitness and Aortic Stiffness Explain the Reduced Cognitive Performance Associated with Increasing Age in Older People.

PubMed

Kennedy, Greg; Meyer, Denny; Hardman, Roy J; Macpherson, Helen; Scholey, Andrew B; Pipingas, Andrew

2018-01-01

Greater physical fitness is associated with reduced rates of cognitive decline in older people; however, the mechanisms by which this occurs are still unclear. One potential mechanism is aortic stiffness, with increased stiffness resulting in higher pulsatile pressures reaching the brain and possibly causing progressive micro-damage. There is limited evidence that those who regularly exercise may have lower aortic stiffness. To investigate whether greater fitness and lower aortic stiffness predict better cognitive performance in older people and, if so, whether aortic stiffness mediates the relationship between fitness and cognition. Residents of independent living facilities, aged 60-90, participated in the study (N = 102). Primary measures included a computerized cognitive assessment battery, pulse wave velocity analysis to measure aortic stiffness, and the Six-Minute Walk test to assess fitness. Based on hierarchical regression analyses, structural equation modelling was used to test the mediation hypothesis. Both fitness and aortic stiffness independently predicted Spatial Working Memory (SWM) performance, however no mediating relationship was found. Additionally, the derived structural equation model shows that, in conjunction with BMI and sex, fitness and aortic stiffness explain 33% of the overall variation in SWM, with age no longer directly predicting any variation. Greater fitness and lower aortic stiffness both independently predict better SWM in older people. The strong effect of age on cognitive performance is totally mediated by fitness and aortic stiffness. This suggests that addressing both physical fitness and aortic stiffness may be important to reduce the rate of age associated cognitive decline.

A new beating-heart mitral and aortic valve assessment model with implications for valve intervention training.

PubMed

Bouma, Wobbe; Jainandunsing, Jayant S; Khamooshian, Arash; van der Harst, Pim; Mariani, Massimo A; Natour, Ehsan

2017-02-01

A thorough understanding of mitral and aortic valve motion dynamics is essential in mastering the skills necessary for performing successful valve intervention (open or transcatheter repair or replacement). We describe a reproducible and versatile beating-heart mitral and aortic valve assessment and valve intervention training model in human cadavers. The model is constructed by bilateral ligation of the pulmonary veins, ligation of the supra-aortic arteries, creating a shunt between the descending thoracic aorta and the left atrial appendage with a vascular prosthesis, anastomizing a vascular prosthesis to the apex and positioning an intra-aortic balloon pump (IABP) in the vascular prosthesis, cross-clamping the descending thoracic aorta, and finally placing a fluid line in the shunt prosthesis. The left ventricle is filled with saline to the desired pressure through the fluid line, and the IABP is switched on and set to a desired frequency (usually 60-80 bpm). Prerepair valve dynamic motion can be studied under direct endoscopic visualization. After assessment, the IABP is switched off, and valve intervention training can be performed using standard techniques. This high-fidelity simulation model has known limitations, but provides a realistic environment with an actual beating (human) heart, which is of incremental value. The model provides a unique opportunity to fill a beating heart with saline and to study prerepair mitral and aortic valve dynamic motion under direct endoscopic visualization. The entire set-up provides a versatile beating-heart mitral and aortic valve assessment model, which may have important implications for future valve intervention training. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

3D printing of the aortic annulus based on cardiovascular computed tomography: Preliminary experience in pre-procedural planning for aortic valve sizing.

PubMed

Faletti, Riccardo; Gatti, Marco; Cosentino, Aurelio; Bergamasco, Laura; Cura Stura, Erik; Garabello, Domenica; Pennisi, Giovanni; Salizzoni, Stefano; Veglia, Simona; Ottavio, Davini; Rinaldi, Mauro; Fonio, Paolo

2018-05-26

to determine reliability and reproducibility of measurements of aortic annulus in 3D models printed from cardiovascular computed tomography (CCT) images. Retrospective study on the records of 20 patients who underwent aortic valve replacement (AVR) with pre-surgery annulus assessment by CCT and intra-operative sizing by Hegar dilators (IOS). 3D models were fabricated by fused deposition modelling of thermoplastic polyurethane filaments. For each patient, two 3D models were independently segmented, modelled and printed by two blinded "manufacturers": a radiologist and a radiology technician. Two blinded cardiac surgeons performed the annulus diameter measurements by Hegar dilators on the two sets of models. Matched data from different measurements were analyzed with Wilcoxon test, Bland-Altmann plot and within-subject ANOVA. No significant differences were found among the measurements made by each cardiac surgeon on the same 3D model (p = 0.48) or on the 3D models printed by different manufacturers (p = 0.25); also, no intraobserver variability (p = 0.46). The annulus diameter measured on 3D models showed good agreement with the reference CCT measurement (p = 0.68) and IOH sizing (p = 0.11). Time and cost per model were: model creation ∼10-15 min; printing time ∼60 min; post-processing ∼5min; material cost ∼1€.
 CONCLUSION: 3D printing of aortic annulus can offer reliable, not expensive patient-specific information to be used in the pre-operative planning of AVR or transcatheter aortic valve implantation (TAVI). Copyright © 2018 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

Computational analysis of an aortic valve jet

NASA Astrophysics Data System (ADS)

Shadden, Shawn C.; Astorino, Matteo; Gerbeau, Jean-Frédéric

2009-11-01

In this work we employ a coupled FSI scheme using an immersed boundary method to simulate flow through a realistic deformable, 3D aortic valve model. This data was used to compute Lagrangian coherent structures, which revealed flow separation from the valve leaflets during systole, and correspondingly, the boundary between the jet of ejected fluid and the regions of separated, recirculating flow. Advantages of computing LCS in multi-dimensional FSI models of the aortic valve are twofold. For one, the quality and effectiveness of existing clinical indices used to measure aortic jet size can be tested by taking advantage of the accurate measure of the jet area derived from LCS. Secondly, as an ultimate goal, a reliable computational framework for the assessment of the aortic valve stenosis could be developed.

Vascular protective actions of a nitric oxide aspirin analog in both in vitro and in vivo models of diabetes mellitus.

PubMed

Pieper, Galen M; Siebeneich, Wolfgang; Olds, Cara L; Felix, Christopher C; Del Soldato, Piero

2002-06-01

Defective endothelium-dependent relaxation is observed in experimental and human diabetes mellitus. The nature of this defect is not fully understood but may involve decreased nitric oxide (NO) bioactivity due to enhanced production of reactive oxygen species (ROS). In this paper, we examine the benefits and actions of a novel NO-donating, antioxidant called 2-acetoxybenzoic acid 2-(2-nitrooxymethyl) phenyl ester, and denoted as NCX4016, on NO-mediated endothelium-dependent relaxation in normal arteries exposed to acute elevations in glucose or in arteries derived from chronic diabetic animals. Intrinsic free radical scavenging by NO-NSAIDs in solution were evaluated using electron paramagnetic resonance (EPR) spectroscopy and spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). In acute studies, normal rat aortas were exposed in tissue culture for 18 h to 5.5 mM or 40 mM in the presence or absence of NCX4016, a NO-donating NSAID unrelated to aspirin (NCX2216) or aspirin. Vascular reactivity of thoracic aortic rings to endothelium-dependent relaxation to acetylcholine in vitro was determined. For chronic hyperglycemia, diabetes was induced in rats by intravenous injection with streptozotocin. Vascular reactivity of thoracic aortic rings to endothelium-dependent relaxation to acetylcholine in vitro was determined after 8 wks in untreated animals or animals chronically-treated with NCX4016. Antioxidant efficacy in vivo was determined by measurement of plasma isoprostanes and by nuclear binding activity of NF-kappaB in nuclear fractions of aortae. Incubation with NCX4016 and NCX2216 produced a concentration-dependent inhibition of DMPO-OH formation indicating scavenging of hydroxyl radicals (HO(*)). In contrast, little efficacy to scavenge superoxide anion radicals was noted. Acute incubation of normal arteries with elevated glucose concentration caused inhibition of normal relaxation to acetylcholine. This impairment was prevented by co-incubation with NCX4106 but not by mannitol, the parent compound (aspirin) or by NCX2216. In addition, chronic treatment with NCX4016 prevented the development of defective endothelium-dependent relaxation to acetylcholine. This protection did not occur as a result to any changes in blood glucose concentration or hemoglobin glycation. Treatment with NCX4016 did decrease the elevation in plasma isoprostanes and normalized the diabetes-induced increase in NF-kappaB binding activity in nuclear fractions derived from aortic tissue. Collectively, these studies suggest that antioxidant interventions using NO-donating NSAIDs may provide an important novel therapeutic strategy to protect the diabetic endothelium.

The role of intraluminal thrombus on oxygen transport in abdominal aortic aneurysms

NASA Astrophysics Data System (ADS)

Madhavan, Sudharsan; Cherry Kemmerling, Erica

2017-11-01

Abdominal aortic aneurysm is ranked as the 13th leading cause of death in the United States. The presence of intraluminal thrombus is thought to cause hypoxia in the vessel wall eventually aggravating the condition. Our work investigates oxygen transport and consumption in a patient-specific model of an abdominal aortic aneurysm. The model includes intraluminal thrombus and consists of the abdominal aorta, renal arteries, and iliac arteries. Oxygen transport to and within the aortic wall layer was modeled, accounting for oxygen consumption and diffusion. Flow and transport in the lumen layer were modeled using coupled Navier-Stokes and scalar transport equations. The thrombus layer was assumed to be biomechanically inactive but permeable to oxygen transport in accordance with previously-measured diffusion coefficients. Plots of oxygen concentration through the layers illustrating reduced oxygen supply to the vessel walls in parts of the model that include thrombus will be presented.

Dispersive aortic cannulas reduce aortic wall shear stress affecting atherosclerotic plaque embolization.

PubMed

Assmann, Alexander; Gül, Fethi; Benim, Ali Cemal; Joos, Franz; Akhyari, Payam; Lichtenberg, Artur

2015-03-01

Neurologic complications during on-pump cardiovascular surgery are often induced by mobilization of atherosclerotic plaques, which is directly related to enhanced wall shear stress. In the present study, we numerically evaluated the impact of dispersive aortic cannulas on aortic blood flow characteristics, with special regard to the resulting wall shear stress profiles. An idealized numerical model of the human aorta and its branches was created and used to model straight as well as bent dispersive aortic cannulas with meshlike tips inserted in the distal ascending aorta. Standard cannulas with straight beveled or bent tips served as controls. Using a recently optimized computing method, simulations of pulsatile and nonpulsatile extracorporeal circulation were performed. Dispersive aortic cannulas reduced the maximum and average aortic wall shear stress values to approximately 50% of those with control cannulas, while the difference in local values was even larger. Moreover, under pulsatile circulation, dispersive cannulas shortened the time period during which wall shear stress values were increased. The turbulent kinetic energy was also diminished by utilizing dispersive cannulas, reducing the risk of hemolysis. In summary, dispersive aortic cannulas decrease aortic wall shear stress and turbulence during extracorporeal circulation and may therefore reduce the risk of endothelial and blood cell damage as well as that of neurologic complications caused by atherosclerotic plaque mobilization. Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Computational models of aortic coarctation in hypoplastic left heart syndrome: considerations on validation of a detailed 3D model.

PubMed

Biglino, Giovanni; Corsini, Chiara; Schievano, Silvia; Dubini, Gabriele; Giardini, Alessandro; Hsia, Tain-Yen; Pennati, Giancarlo; Taylor, Andrew M

2014-05-01

Reliability of computational models for cardiovascular investigations strongly depends on their validation against physical data. This study aims to experimentally validate a computational model of complex congenital heart disease (i.e., surgically palliated hypoplastic left heart syndrome with aortic coarctation) thus demonstrating that hemodynamic information can be reliably extrapolated from the model for clinically meaningful investigations. A patient-specific aortic arch model was tested in a mock circulatory system and the same flow conditions were re-created in silico, by setting an appropriate lumped parameter network (LPN) attached to the same three-dimensional (3D) aortic model (i.e., multi-scale approach). The model included a modified Blalock-Taussig shunt and coarctation of the aorta. Different flow regimes were tested as well as the impact of uncertainty in viscosity. Computational flow and pressure results were in good agreement with the experimental signals, both qualitatively, in terms of the shape of the waveforms, and quantitatively (mean aortic pressure 62.3 vs. 65.1 mmHg, 4.8% difference; mean aortic flow 28.0 vs. 28.4% inlet flow, 1.4% difference; coarctation pressure drop 30.0 vs. 33.5 mmHg, 10.4% difference), proving the reliability of the numerical approach. It was observed that substantial changes in fluid viscosity or using a turbulent model in the numerical simulations did not significantly affect flows and pressures of the investigated physiology. Results highlighted how the non-linear fluid dynamic phenomena occurring in vitro must be properly described to ensure satisfactory agreement. This study presents methodological considerations for using experimental data to preliminarily set up a computational model, and then simulate a complex congenital physiology using a multi-scale approach.

Wall stress on ascending thoracic aortic aneurysms with bicuspid compared with tricuspid aortic valve.

PubMed

Xuan, Yue; Wang, Zhongjie; Liu, Raymond; Haraldsson, Henrik; Hope, Michael D; Saloner, David A; Guccione, Julius M; Ge, Liang; Tseng, Elaine

2018-03-08

Guidelines for repair of bicuspid aortic valve-associated ascending thoracic aortic aneurysms have been changing, most recently to the same criteria as tricuspid aortic valve-ascending thoracic aortic aneurysms. Rupture/dissection occurs when wall stress exceeds wall strength. Recent studies suggest similar strength of bicuspid aortic valve versus tricuspid aortic valve-ascending thoracic aortic aneurysms; thus, comparative wall stress may better predict dissection in bicuspid aortic valve versus tricuspid aortic valve-ascending thoracic aortic aneurysms. Our aim was to determine whether bicuspid aortic valve-ascending thoracic aortic aneurysms had higher wall stresses than their tricuspid aortic valve counterparts. Patients with bicuspid aortic valve- and tricuspid aortic valve-ascending thoracic aortic aneurysms (bicuspid aortic valve = 17, tricuspid aortic valve = 19) greater than 4.5 cm underwent electrocardiogram-gated computed tomography angiography. Patient-specific 3-dimensional geometry was reconstructed and loaded to systemic pressure after accounting for prestress geometry. Finite element analyses were performed using the LS-DYNA solver (LSTC Inc, Livermore, Calif) with user-defined fiber-embedded material model to determine ascending thoracic aortic aneurysm wall stress. Bicuspid aortic valve-ascending thoracic aortic aneurysms 99th-percentile longitudinal stresses were 280 kPa versus 242 kPa (P = .028) for tricuspid aortic valve-ascending thoracic aortic aneurysms in systole. These stresses did not correlate to diameter for bicuspid aortic valve-ascending thoracic aortic aneurysms (r = -0.004) but had better correlation to tricuspid aortic valve-ascending thoracic aortic aneurysms diameter (r = 0.677). Longitudinal stresses on sinotubular junction were significantly higher in bicuspid aortic valve-ascending thoracic aortic aneurysms than in tricuspid aortic valve-ascending thoracic aortic aneurysms (405 vs 329 kPa, P = .023). Bicuspid aortic valve-ascending thoracic aortic aneurysm 99th-percentile circumferential stresses were 548 kPa versus 462 kPa (P = .033) for tricuspid aortic valve-ascending thoracic aortic aneurysms, which also did not correlate to bicuspid aortic valve-ascending thoracic aortic aneurysm diameter (r = 0.007). Circumferential and longitudinal stresses were greater in bicuspid aortic valve- than tricuspid aortic valve-ascending thoracic aortic aneurysms and were more pronounced in the sinotubular junction. Peak wall stress did not correlate with bicuspid aortic valve-ascending thoracic aortic aneurysm diameter, suggesting diameter alone in this population may be a poor predictor of dissection risk. Our results highlight the need for patient-specific aneurysm wall stress analysis for accurate dissection risk prediction. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Evaluation of simulation training in cardiothoracic surgery: the Senior Tour perspective.

PubMed

Fann, James I; Feins, Richard H; Hicks, George L; Nesbitt, Jonathan C; Hammon, John W; Crawford, Fred A

2012-02-01

The study objective was to introduce senior surgeons, referred to as members of the "Senior Tour," to simulation-based learning and evaluate ongoing simulation efforts in cardiothoracic surgery. Thirteen senior cardiothoracic surgeons participated in a 2½-day Senior Tour Meeting. Of 12 simulators, each participant focused on 6 cardiac (small vessel anastomosis, aortic cannulation, cardiopulmonary bypass, aortic valve replacement, mitral valve repair, and aortic root replacement) or 6 thoracic surgical simulators (hilar dissection, esophageal anastomosis, rigid bronchoscopy, video-assisted thoracoscopic surgery lobectomy, tracheal resection, and sleeve resection). The participants provided critical feedback regarding the realism and utility of the simulators, which served as the basis for a composite assessment of the simulators. All participants acknowledged that simulation may not provide a wholly immersive experience. For small vessel anastomosis, the portable chest model is less realistic compared with the porcine model, but is valuable in teaching anastomosis mechanics. The aortic cannulation model allows multiple cannulations and can serve as a thoracic aortic surgery model. The cardiopulmonary bypass simulator provides crisis management experience. The porcine aortic valve replacement, mitral valve annuloplasty, and aortic root models are realistic and permit standardized training. The hilar dissection model is subject to variability of porcine anatomy and fragility of the vascular structures. The realistic esophageal anastomosis simulator presents various approaches to esophageal anastomosis. The exercise associated with the rigid bronchoscopy model is brief, and adding additional procedures should be considered. The tracheal resection, sleeve resection, and video-assisted thoracoscopic surgery lobectomy models are highly realistic and simulate advanced maneuvers. By providing the necessary tools, such as task trainers and assessment instruments, the Senior Tour may be one means to enhance simulation-based learning in cardiothoracic surgery. The Senior Tour members can provide regular programmatic evaluation and critical analyses to ensure that proposed simulators are of educational value. Published by Mosby, Inc.

Three-dimensional thoracic aorta principal strain analysis from routine ECG-gated computerized tomography: feasibility in patients undergoing transcatheter aortic valve replacement.

PubMed

Satriano, Alessandro; Guenther, Zachary; White, James A; Merchant, Naeem; Di Martino, Elena S; Al-Qoofi, Faisal; Lydell, Carmen P; Fine, Nowell M

2018-05-02

Functional impairment of the aorta is a recognized complication of aortic and aortic valve disease. Aortic strain measurement provides effective quantification of mechanical aortic function, and 3-dimenional (3D) approaches may be desirable for serial evaluation. Computerized tomographic angiography (CTA) is routinely performed for various clinical indications, and offers the unique potential to study 3D aortic deformation. We sought to investigate the feasibility of performing 3D aortic strain analysis in a candidate population of patients undergoing transcatheter aortic valve replacement (TAVR). Twenty-one patients with severe aortic valve stenosis (AS) referred for TAVR underwent ECG-gated CTA and echocardiography. CTA images were analyzed using a 3D feature-tracking based technique to construct a dynamic aortic mesh model to perform peak principal strain amplitude (PPSA) analysis. Segmental strain values were correlated against clinical, hemodynamic and echocardiographic variables. Reproducibility analysis was performed. The mean patient age was 81±6 years. Mean left ventricular ejection fraction was 52±14%, aortic valve area (AVA) 0.6±0.3 cm 2 and mean AS pressure gradient (MG) 44±11 mmHg. CTA-based 3D PPSA analysis was feasible in all subjects. Mean PPSA values for the global thoracic aorta, ascending aorta, aortic arch and descending aorta segments were 6.5±3.0, 10.2±6.0, 6.1±2.9 and 3.3±1.7%, respectively. 3D PSSA values demonstrated significantly more impairment with measures of worsening AS severity, including AVA and MG for the global thoracic aorta and ascending segment (p<0.001 for all). 3D PSSA was independently associated with AVA by multivariable modelling. Coefficients of variation for intra- and inter-observer variability were 5.8 and 7.2%, respectively. Three-dimensional aortic PPSA analysis is clinically feasible from routine ECG-gated CTA. Appropriate reductions in PSSA were identified with increasing AS hemodynamic severity. Expanded study of 3D aortic PSSA for patients with various forms of aortic disease is warranted.

The influence of computational assumptions on analysing abdominal aortic aneurysm haemodynamics.

PubMed

Ene, Florentina; Delassus, Patrick; Morris, Liam

2014-08-01

The variation in computational assumptions for analysing abdominal aortic aneurysm haemodynamics can influence the desired output results and computational cost. Such assumptions for abdominal aortic aneurysm modelling include static/transient pressures, steady/transient flows and rigid/compliant walls. Six computational methods and these various assumptions were simulated and compared within a realistic abdominal aortic aneurysm model with and without intraluminal thrombus. A full transient fluid-structure interaction was required to analyse the flow patterns within the compliant abdominal aortic aneurysms models. Rigid wall computational fluid dynamics overestimates the velocity magnitude by as much as 40%-65% and the wall shear stress by 30%-50%. These differences were attributed to the deforming walls which reduced the outlet volumetric flow rate for the transient fluid-structure interaction during the majority of the systolic phase. Static finite element analysis accurately approximates the deformations and von Mises stresses when compared with transient fluid-structure interaction. Simplifying the modelling complexity reduces the computational cost significantly. In conclusion, the deformation and von Mises stress can be approximately found by static finite element analysis, while for compliant models a full transient fluid-structure interaction analysis is required for acquiring the fluid flow phenomenon. © IMechE 2014.

Virgin Coconut Oil Prevents Blood Pressure Elevation and Improves Endothelial Functions in Rats Fed with Repeatedly Heated Palm Oil

PubMed Central

Nurul-Iman, Badlishah Sham; Kamisah, Yusof; Jaarin, Kamsiah; Qodriyah, Hj Mohd Saad

2013-01-01

This study was performed to explore the effects of virgin coconut oil (VCO) in male rats that were fed with repeatedly heated palm oil on blood pressure, plasma nitric oxide level, and vascular reactivity. Thirty-two male Sprague-Dawley rats were divided into four groups: (i) control (basal diet), (ii) VCO (1.42 mL/kg, oral), (iii) five-times-heated palm oil (15%) (5HPO), and (iv) five-times-heated palm oil (15%) and VCO (1.42 mL/kg, oral) (5HPO + VCO). Blood pressure was significantly increased in the group that was given the 5HPO diet compared to the control group. Blood pressure in the 5HPO + VCO group was significantly lower than the 5HPO group. Plasma nitric oxide (NO) level in the 5HPO group was significantly lower compared to the control group, whereas in the 5HPO + VCO group, the plasma NO level was significantly higher compared to the 5HPO group. Aortic rings from the 5HPO group exhibited attenuated relaxation in response to acetylcholine and sodium nitroprusside as well as increased vasoconstriction to phenylephrine compared to the control group. Aortic rings from the 5HPO + VCO group showed only attenuated vasoconstriction to phenylephrine compared to the 5HPO group. In conclusion, VCO prevents blood pressure elevation and improves endothelial functions in rats fed with repeatedly heated palm oil. PMID:23861707

Virgin coconut oil prevents blood pressure elevation and improves endothelial functions in rats fed with repeatedly heated palm oil.

PubMed

Nurul-Iman, Badlishah Sham; Kamisah, Yusof; Jaarin, Kamsiah; Qodriyah, Hj Mohd Saad

2013-01-01

This study was performed to explore the effects of virgin coconut oil (VCO) in male rats that were fed with repeatedly heated palm oil on blood pressure, plasma nitric oxide level, and vascular reactivity. Thirty-two male Sprague-Dawley rats were divided into four groups: (i) control (basal diet), (ii) VCO (1.42 mL/kg, oral), (iii) five-times-heated palm oil (15%) (5HPO), and (iv) five-times-heated palm oil (15%) and VCO (1.42 mL/kg, oral) (5HPO + VCO). Blood pressure was significantly increased in the group that was given the 5HPO diet compared to the control group. Blood pressure in the 5HPO + VCO group was significantly lower than the 5HPO group. Plasma nitric oxide (NO) level in the 5HPO group was significantly lower compared to the control group, whereas in the 5HPO + VCO group, the plasma NO level was significantly higher compared to the 5HPO group. Aortic rings from the 5HPO group exhibited attenuated relaxation in response to acetylcholine and sodium nitroprusside as well as increased vasoconstriction to phenylephrine compared to the control group. Aortic rings from the 5HPO + VCO group showed only attenuated vasoconstriction to phenylephrine compared to the 5HPO group. In conclusion, VCO prevents blood pressure elevation and improves endothelial functions in rats fed with repeatedly heated palm oil.

[Vasodilator effect mediated by nitric oxide of the Zea mays L (andean purple corn) hydroalcoholic extract in aortic rings of rat].

PubMed

Moreno-Loaiza, Oscar; Paz-Aliaga, Azael

2010-01-01

To evaluate the vasodilator response of the hydroalcoholic extract of Zea mays L. (Andean purple corn) and to determine if this response is mediated by nitric oxide (NO). We obtained an extract by maceration for eight days of Andean purple corn cobs in 70% ethanol and subsequent concentration of the product. Thoracic aortic rings were evaluated in an isolated organ chamber, bathed with Krebs-Hensleit solution (KH), and vasomotor activity was recorded with an isometric tension transducer. Basal contraction was produced with 120 mM KCl and then, we proceeded to determinate the vasodilator effect of 3 doses of the extract: 0.1, 0.5, and 1.0 mg/mL. We used L-NG-Nitroarginin methyl ester (L-NAME) to verify that the vasodilation depends on nitric oxide sinteasa (NOs). Then we compared the inhibition of vascular contraction after incubation for 30 minutes, with purple corn extract and captopril 10-5 M. We observed a reduction in maximum contraction (100%) to 85.25 ± 2.60%, 77.76 ± 3.23%, and 73.3 ± 4.87% for doses of 0.1, 0.5 and 1,0 mg/mL respectively. The vasodilation was inhibited by prior incubation with L-NAME. Andean purple corn extract did not inhibit vascular contraction as captopril did (reduction to 75.27 ± 8.61%). The hydroalcoholic extract of Zea mays L produces NO dependent vasodilation.

Preliminary Studies of Acute Cadmium Administration Effects on the Calcium-Activated Potassium (SKCa and BKCa) Channels and Na+/K+-ATPase Activity in Isolated Aortic Rings of Rats.

PubMed

Vassallo, Dalton V; Almenara, Camila C P; Broseghini-Filho, Gilson Brás; Teixeira, Ariane Calazans; da Silva, David Chaves F; Angeli, Jhuli K; Padilha, Alessandra S

2018-06-01

Cadmium is an environmental pollutant closely linked with cardiovascular diseases that seems to involve endothelium dysfunction and reduced nitric oxide (NO) bioavailability. Knowing that NO causes dilatation through the activation of potassium channels and Na + /K + -ATPase, we aimed to determine whether acute cadmium administration (10 μM) alters the participation of K + channels, voltage-activated calcium channel, and Na + /K + -ATPase activity in vascular function of isolated aortic rings of rats. Cadmium did not modify the acetylcholine-induced relaxation. After L-NAME addition, the relaxation induced by acetylcholine was abolished in presence or absence of cadmium, suggesting that acutely, this metal did not change NO release. However, tetraethylammonium (a nonselective K + channels blocker) reduced acetylcholine-induced relaxation but this effect was lower in the preparations with cadmium, suggesting a decrease of K + channels function in acetylcholine response after cadmium incubation. Apamin (a selective blocker of small Ca 2+ -activated K + channels-SK Ca ), iberiotoxin (a selective blocker of large-conductance Ca 2+ -activated K + channels-BK Ca ), and verapamil (a blocker of calcium channel) reduced the endothelium-dependent relaxation only in the absence of cadmium. Finally, cadmium decreases Na + /K + -ATPase activity. Our results provide evidence that the cadmium acute incubation unaffected the calcium-activated potassium channels (SK Ca and BK Ca ) and voltage-calcium channels on the acetylcholine vasodilatation. In addition, acute cadmium incubation seems to reduce the Na + /K + -ATPase activity.

Honey promotes angiogeneic activity in the rat aortic ring assay.

PubMed

Rossiter, K; Cooper, A J; Voegeli, D; Lwaleed, B A

2010-10-01

To investigate possible effects of honey on angiogenesis, using in vitro analogues of angiogenesis and an endothelial proliferation assay. Using an in vitro rat aortic ring assay we compared pseudotubule formation by medicinal honey (Activon), supermarket honey (Rowse) and a honey-based ointment (Mesitran), with that of artificial honey (70% w/w sugar glucose/fructose). Pseudotubules were analysed using TCS Cellworks AngioSys software. The Angiokit sytem was used to validate the results. Using the MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium. Bromide] assay, toxicity was also assessed on human umbilical vein endothelial cells (HUVEC) directly adherent to plastic. All honey preparations stimulated pseudotubule formation, maximal at around 0.2% honey. Medicinal honeys were more active than Rowse. The effect was not attributable to the sugar content. Among the honeys tested, the Manuka-based Activon preparation reduced residual viable biomass compared with a sugar control at > 0.32% v/v concentration. Rowse had a similar effect only at 2.5%, the highest dose tested. The influence of honey constituents on angiogenesis in a wound dressing context is likely to be positive, but would depend on the effective dilution of the honey and the penetration of the active constituents against an osmotic gradient. The extent to which this occurs has yet to be established. This work was conceived, designed and executed by the authors. Medical honey preparations were supplied unconditionally but free of charge by the distributors.

Esophageal dysfunction in four alpaca crias and a llama cria with vascular ring anomalies.

PubMed

McKenzie, Erica C; Seguin, Bernard; Cebra, Christopher K; Margiocco, Marco L; Anderson, David E; Löhr, Christiane V

2010-08-01

3 alpaca crias and cadavers of an alpaca cria and a llama cria were evaluated for evidence of esophageal dysfunction. All 5 crias were between 3 and 5 months of age when clinical signs developed, and all had a thin body condition when examined. Clinical signs included coughing, regurgitation, and grossly visible esophageal peristaltic waves. A barium esophagram was used to diagnose esophageal obstruction, megaesophagus, and a vascular ring anomaly (VRA). Fluoroscopy was used to evaluate deglutition, esophageal peristalsis, and the extent of esophageal dilation in 1 alpaca cria. A persistent right aortic arch was identified in 1 alpaca cria, and a left aortic arch with right ductus arteriosus or ligamentum arteriosum and an aberrant right subclavian artery were identified in the 4 remaining crias. Surgical correction of the VRA was attempted in the 3 live alpaca crias. It was complicated by the conformation and location of each VRA and inaccurate anatomic diagnosis of the VRAs before surgery. Treatment was universally unsuccessful because of intraoperative complications and the persistence of clinical signs after surgery. Megaesophagus is typically an idiopathic condition in camelids. However, these findings suggested that camelids with esophageal dysfunction during the neonatal period may have a VRA. The prognosis is grave for camelids with VRA, and accurate anatomic diagnosis of the VRA via the use of advanced imaging techniques (eg, angiography, computed tomography, or magnetic resonance imaging) may improve the success of surgical intervention.

Rapid prototyping of compliant human aortic roots for assessment of valved stents.

PubMed

Kalejs, Martins; von Segesser, Ludwig Karl

2009-02-01

Adequate in-vitro training in valved stents deployment as well as testing of the latter devices requires compliant real-size models of the human aortic root. The casting methods utilized up to now are multi-step, time consuming and complicated. We pursued a goal of building a flexible 3D model in a single-step procedure. We created a precise 3D CAD model of a human aortic root using previously published anatomical and geometrical data and printed it using a novel rapid prototyping system developed by the Fab@Home project. As a material for 3D fabrication we used common house-hold silicone and afterwards dip-coated several models with dispersion silicone one or two times. To assess the production precision we compared the size of the final product with the CAD model. Compliance of the models was measured and compared with native porcine aortic root. Total fabrication time was 3 h and 20 min. Dip-coating one or two times with dispersion silicone if applied took one or two extra days, respectively. The error in dimensions of non-coated aortic root model compared to the CAD design was <3.0% along X, Y-axes and 4.1% along Z-axis. Compliance of a non-coated model as judged by the changes of radius values in the radial direction by 16.39% is significantly different (P<0.001) from native aortic tissue--23.54% at the pressure of 80-100 mmHg. Rapid prototyping of compliant, life-size anatomical models with the Fab@Home 3D printer is feasible--it is very quick compared to previous casting methods.

Impact of wall thickness and saccular geometry on the computational wall stress of descending thoracic aortic aneurysms.

PubMed

Shang, Eric K; Nathan, Derek P; Sprinkle, Shanna R; Fairman, Ronald M; Bavaria, Joseph E; Gorman, Robert C; Gorman, Joseph H; Jackson, Benjamin M

2013-09-10

Wall stress calculated using finite element analysis has been used to predict rupture risk of aortic aneurysms. Prior models often assume uniform aortic wall thickness and fusiform geometry. We examined the effects of including local wall thickness, intraluminal thrombus, calcifications, and saccular geometry on peak wall stress (PWS) in finite element analysis of descending thoracic aortic aneurysms. Computed tomographic angiography of descending thoracic aortic aneurysms (n=10 total, 5 fusiform and 5 saccular) underwent 3-dimensional reconstruction with custom algorithms. For each aneurysm, an initial model was constructed with uniform wall thickness. Experimental models explored the addition of variable wall thickness, calcifications, and intraluminal thrombus. Each model was loaded with 120 mm Hg pressure, and von Mises PWS was computed. The mean PWS of uniform wall thickness models was 410 ± 111 kPa. The imposition of variable wall thickness increased PWS (481 ± 126 kPa, P<0.001). Although the addition of calcifications was not statistically significant (506 ± 126 kPa, P=0.07), the addition of intraluminal thrombus to variable wall thickness (359 ± 86 kPa, P ≤ 0.001) reduced PWS. A final model incorporating all features also reduced PWS (368 ± 88 kPa, P<0.001). Saccular geometry did not increase diameter-normalized stress in the final model (77 ± 7 versus 67 ± 12 kPa/cm, P=0.22). Incorporation of local wall thickness can significantly increase PWS in finite element analysis models of thoracic aortic aneurysms. Incorporating variable wall thickness, intraluminal thrombus, and calcifications significantly impacts computed PWS of thoracic aneurysms; sophisticated models may, therefore, be more accurate in assessing rupture risk. Saccular aneurysms did not demonstrate a significantly higher normalized PWS than fusiform aneurysms.

Resveratrol Inhibits Aortic Root Dilatation in the Fbn1C1039G/+ Marfan Mouse Model.

PubMed

Hibender, Stijntje; Franken, Romy; van Roomen, Cindy; Ter Braake, Anique; van der Made, Ingeborg; Schermer, Edith E; Gunst, Quinn; van den Hoff, Maurice J; Lutgens, Esther; Pinto, Yigal M; Groenink, Maarten; Zwinderman, Aeilko H; Mulder, Barbara J M; de Vries, Carlie J M; de Waard, Vivian

2016-08-01

Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the fibrillin-1 gene. Patients with MFS are at risk of aortic aneurysm formation and dissection. Usually, blood pressure-lowering drugs are used to reduce aortic events; however, this is not sufficient for most patients. In the aorta of smooth muscle cell-specific sirtuin-1-deficient mice, spontaneous aneurysm formation and senescence are observed. Resveratrol is known to enhance sirtuin-1 activity and to reduce senescence, which prompted us to investigate the effectiveness of resveratrol in inhibition of aortic dilatation in the Fbn1(C1039G/+) MFS mouse model. Aortic senescence strongly correlates with aortic root dilatation rate in MFS mice. However, although resveratrol inhibits aortic dilatation, it only shows a trend toward reduced aortic senescence. Resveratrol enhances nuclear localization of sirtuin-1 in the vessel wall and, in contrast to losartan, does not affect leukocyte infiltration nor activation of SMAD2 and extracellular signal-regulated kinases 1/2 (ERK1/2). Interestingly, specific sirtuin-1 activation (SRT1720) or inhibition (sirtinol) in MFS mice does not affect aortic root dilatation rate, although senescence is changed. Resveratrol reduces aortic elastin breaks and decreases micro-RNA-29b expression coinciding with enhanced antiapoptotic Bcl-2 expression and decreased number of terminal apoptotic cells. In cultured smooth muscle cells, the resveratrol effect on micro-RNA-29b downregulation is endothelial cell and nuclear factor κB-dependent. Resveratrol inhibits aortic root dilatation in MFS mice by promoting elastin integrity and smooth muscle cell survival, involving downregulation of the aneurysm-related micro-RNA-29b in the aorta. On the basis of these data, resveratrol holds promise as a novel intervention strategy for patients with MFS. © 2016 The Authors.

Resveratrol Inhibits Aortic Root Dilatation in the Fbn1C1039G/+ Marfan Mouse Model

PubMed Central

Hibender, Stijntje; Franken, Romy; van Roomen, Cindy; ter Braake, Anique; van der Made, Ingeborg; Schermer, Edith E.; Gunst, Quinn; van den Hoff, Maurice J.; Lutgens, Esther; Pinto, Yigal M.; Groenink, Maarten; Zwinderman, Aeilko H.; Mulder, Barbara J.M.; de Vries, Carlie J.M.

2016-01-01

Objective— Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the fibrillin-1 gene. Patients with MFS are at risk of aortic aneurysm formation and dissection. Usually, blood pressure–lowering drugs are used to reduce aortic events; however, this is not sufficient for most patients. In the aorta of smooth muscle cell–specific sirtuin-1–deficient mice, spontaneous aneurysm formation and senescence are observed. Resveratrol is known to enhance sirtuin-1 activity and to reduce senescence, which prompted us to investigate the effectiveness of resveratrol in inhibition of aortic dilatation in the Fbn1C1039G/+ MFS mouse model. Approach and Results— Aortic senescence strongly correlates with aortic root dilatation rate in MFS mice. However, although resveratrol inhibits aortic dilatation, it only shows a trend toward reduced aortic senescence. Resveratrol enhances nuclear localization of sirtuin-1 in the vessel wall and, in contrast to losartan, does not affect leukocyte infiltration nor activation of SMAD2 and extracellular signal–regulated kinases 1/2 (ERK1/2). Interestingly, specific sirtuin-1 activation (SRT1720) or inhibition (sirtinol) in MFS mice does not affect aortic root dilatation rate, although senescence is changed. Resveratrol reduces aortic elastin breaks and decreases micro-RNA-29b expression coinciding with enhanced antiapoptotic Bcl-2 expression and decreased number of terminal apoptotic cells. In cultured smooth muscle cells, the resveratrol effect on micro-RNA-29b downregulation is endothelial cell and nuclear factor κB-dependent. Conclusions— Resveratrol inhibits aortic root dilatation in MFS mice by promoting elastin integrity and smooth muscle cell survival, involving downregulation of the aneurysm-related micro-RNA-29b in the aorta. On the basis of these data, resveratrol holds promise as a novel intervention strategy for patients with MFS. PMID:27283746

Percutaneous valved stent implantation in the ascending aorta for the treatment of very high-risk aortic regurgitation: an animal study.

PubMed

Zong, Gang-Jun; Jiang, Hai-Bin; Bai, Yuan; Wu, Gang-Yong; Ye, Guang-Ming; Chen, Jing-Kai; Qin, Yong-Wen; Zhao, Xian-xian

2013-12-01

We investigated the effects of percutaneous valved stent implantation in the ascending aorta as an alternative treatment for aortic regurgitation in a canine model. A total of 16 healthy dogs weighing an average of 18.3 ± 2.1 kg were used for the establishment of animal models of chronic aortic regurgitation by percutaneous aortic valve perforation and balloon dilation. At 2 mo after successful model establishment, all experimental animals underwent valved stent implantation in the ascending aorta and then were followed up for 3 mo. Experimental models of chronic aortic regurgitation were successfully established in 10 dogs. Surviving dogs underwent successful valved stent implantation in the ascending aorta and were subsequently followed up for 3 mo. The level of instantaneous aortic regurgitation at 3-mo follow-up was significantly reduced compared with that before valved stent implantation (2.4 ± 0.9 versus 10.6 ± 2.1 mL/s, P < 0.05). The left ventricular ejection fraction was significantly increased (53.8 ± 4.2% versus 37.8 ± 3.7%, P < 0.05), and the left ventricular end-diastolic volume was also significantly reduced (30.3 ± 2.2 versus 40.1 ± 3.6 mL, P < 0.05). No paravalvular leak, stroke, atrioventricular block, or other complications occurred in dogs undergoing valved stent implantation. Percutaneous valved stent implantation in the ascending aorta is feasible, effective, and safe as an alternative treatment for very high-risk aortic regurgitation in a canine model. Copyright © 2013 Elsevier Inc. All rights reserved.

Single-port gynecologic surgery with a novel surgical platform.

PubMed

Knight, Jason; Tunitsky-Britton, Elena; Muffly, Tyler; Michener, Chad M; Escobar, Pedro F

2012-09-01

Laparoendoscopic single-site surgery (LESS) allows better cosmesis and decreased pain when compared with traditional laparoscopy (TL). Instrument crowding and diminished triangulation are limitations. This study evaluates a novel single-port surgical platform (NSP) designed to facilitate the transition from TL to LESS (TransEnterix SPIDER, Durham, NC). NSP and TL were compared using standardized dry lab tasks. Feasibility of NSP in gynecology was assessed using the porcine model. Completion times with NSP were longer for ring transfer (P = .025) and trended longer for disc cutting (P = .074). Disc cutting accuracy was lower with NSP versus TL (P = .008). NSP operative times for hysterectomy, pelvic and para-aortic node dissection were 22.3, 13.3, and 26 minutes, respectively, without complications. Fatigue and lack of integrated bipolar cautery were limitations of NSP. While application of NSP to gynecology appears feasible, lower performance when compared with TL underscores the need for caution when applying NSP to humans.

Study of normal, fibrous and calcified aortic valve tissue by Raman and reflectance spectroscopy

NASA Astrophysics Data System (ADS)

Rodrigues, Kátia Calligaris; Munin, Egberto; Alves, Leandro P.; Silveira, Fabrício L.; Junior, Landulfo S.; De Lima, Carlos J.; Lázzaro, João C.; De Souza, Genivaldo C.; Piotto, José A. B.; Pacheco, Marcos T. T.; Zângaro, Renato A.

2007-02-01

Several studies have identified the degree of aortic valve calcification as a strong predictor both for the progression and outcome of aortic stenosis. In industrialized countries, aortic valve stenosis is most frequently caused by progressive calcification and degeneration of aortic cusps. However, there are no accurate methods to quantify the extent of aortic valve calcification. To provide a non-invasive alternative to biopsy, a range of optical methods have been investigated, including Raman and reflectance spectroscopy. A Raman spectrum can be used to access the molecular constitution of a particular tissue and classify it. Raman spectroscopy is largely used in the quantification and evaluation of human atherosclerosis, being a powerful technique for performing biochemical analysis without tissue removal. Nevertheless, increased thickness and disorganization of the collagen fibre network and extracellular matrix are known to affect the diffuse spectral reflectance of the tissue. A catheter with the "6 around 1" configuration, the central fiber transmit laser radiation to the sample and the scattered light is collected by the other six surrounding fibers, was used both for Raman and reflectance spectroscopy. A white light (krypton lamp, flashtube Model FX 1160 Perkin Elmer, USA) excitation was used for reflectance measurements. A Ti-sapphire (785nm, Spectra Physics, model 3900S, USA) laser, pumped by an argon laser (Spectra Physics, model Stabilite 2017, USA) was used as the near infrared Raman set up. Several ex-vivo spectra of aortic valve samples were analyzed. The results show a promising way to differentiate normal, fibrous and calcified tissue in aortic valve.

The aortic reservoir-wave as a paradigm for arterial haemodynamics: insights from three-dimensional fluid-structure interaction simulations in a model of aortic coarctation.

PubMed

Segers, Patrick; Taelman, Liesbeth; Degroote, Joris; Bols, Joris; Vierendeels, Jan

2015-03-01

The reservoir-wave paradigm considers aortic pressure as the superposition of a 'reservoir pressure', directly related to changes in reservoir volume, and an 'excess' component ascribed to wave dynamics. The change in reservoir pressure is assumed to be proportional to the difference between aortic inflow and outflow (i.e. aortic volume changes), an assumption that is virtually impossible to validate in vivo. The aim of this study is therefore to apply the reservoir-wave paradigm to aortic pressure and flow waves obtained from three-dimensional fluid-structure interaction simulations in a model of a normal aorta, aortic coarctation (narrowed descending aorta) and stented coarctation (stiff segment in descending aorta). We found no unequivocal relation between the intraaortic volume and the reservoir pressure for any of the simulated cases. When plotted in a pressure-volume diagram, hysteresis loops are found that are looped in a clockwise way indicating that the reservoir pressure is lower than the pressure associated with the change in volume. The reservoir-wave analysis leads to very high excess pressures, especially for the coarctation models, but to surprisingly little changes of the reservoir component despite the impediment of the buffer capacity of the aorta. With the observation that reservoir pressure is not related to the volume in the aortic reservoir in systole, an intrinsic assumption in the wave-reservoir concept is invalidated and, consequently, also the assumption that the excess pressure is the component of pressure that can be attributed to wave travel and reflection.

Evolution of the Proximal Sealing Rings of the Anaconda Stent-Graft After Endovascular Aneurysm Repair.

PubMed

Koenrades, Maaike A; Klein, Almar; Leferink, Anne M; Slump, Cornelis H; Geelkerken, Robert H

2018-04-01

To provide insight into the evolution of the saddle-shaped proximal sealing rings of the Anaconda stent-graft after endovascular aneurysm repair (EVAR). Eighteen abdominal aortic aneurysm patients were consecutively enrolled in a single-center, prospective, observational cohort study (LSPEAS; Trialregister.nl identifier NTR4276). The patients were treated electively using an Anaconda stent-graft with a mean 31% oversizing (range 17-47). According to protocol, participants were to be followed for 2 years, during which 5 noncontrast electrocardiogram-gated computed tomography scans would be conducted. Three patients were eliminated within 30 days (1 withdrew, 1 died, and a third was converted before stent-graft deployment), leaving 15 patients (mean age 72.8±3.7 years; 14 men) for this analysis. Evolution in size and shape (symmetry) of both proximal infrarenal sealing rings were assessed from discharge to 24 months using dedicated postprocessing algorithms. At 24 months, the mean diameters of the first and second ring stents had increased significantly (first ring: 2.2±1.0 mm, p<0.001; second ring: 2.7±1.1 mm, p<0.001). At 6 months, the first and second rings had expanded to a mean 96.6%±2.1% and 94.8%±2.7%, respectively, of their nominal diameter, after which the rings expanded slowly; ring diameters stabilized to near nominal size (first ring, 98.3%±1.1%; second ring, 97.2%±1.4%) at 24 months irrespective of initial oversizing. No type I or III endoleaks or aneurysm-, device-, or procedure-related adverse events were noted in follow-up. The difference in the diametric distances between the peaks and valleys of the saddle-shaped rings was marked at discharge but became smaller after 24 months for both rings (first ring: median 2.0 vs 1.2 mm, p=0.191; second ring: median 2.8 vs 0.8 mm; p=0.013). Irrespective of initial oversizing, the Anaconda proximal sealing rings radially expanded to near nominal size within 6 months after EVAR. Initial oval-shaped rings conformed symmetrically and became nearly circular through 24 months. These findings should be taken into account in planning and follow-up.

Shape-based diagnosis of the aortic valve

NASA Astrophysics Data System (ADS)

Ionasec, Razvan Ioan; Tsymbal, Alexey; Vitanovski, Dime; Georgescu, Bogdan; Zhou, S. Kevin; Navab, Nassir; Comaniciu, Dorin

2009-02-01

Disorders of the aortic valve represent a common cardiovascular disease and an important public-health problem worldwide. Pathological valves are currently determined from 2D images through elaborate qualitative evalu- ations and complex measurements, potentially inaccurate and tedious to acquire. This paper presents a novel diagnostic method, which identies diseased valves based on 3D geometrical models constructed from volumetric data. A parametric model, which includes relevant anatomic landmarks as well as the aortic root and lea ets, represents the morphology of the aortic valve. Recently developed robust segmentation methods are applied to estimate the patient specic model parameters from end-diastolic cardiac CT volumes. A discriminative distance function, learned from equivalence constraints in the product space of shape coordinates, determines the corresponding pathology class based on the shape information encoded by the model. Experiments on a heterogeneous set of 63 patients aected by various diseases demonstrated the performance of our method with 94% correctly classied valves.

Vasodilatory effects of ethanol extract of Radix Paeoniae Rubra and its mechanism of action in the rat aorta.

PubMed

Jin, Song Nan; Wen, Jin Fu; Wang, Ting Ting; Kang, Dae Gill; Lee, Ho Sub; Cho, Kyung Woo

2012-06-26

Radix Paeoniae Rubra (RPR) is an important traditional Chinese medicine (TCM) commonly used in clinic for a long history in China. RPR is the radix of either Paeonia lactiflora Pall. or Paeonia veitchii Lynch. RPR has a wide variety of pharmacological actions such as anti-thrombus, anti-coagulation, and anti-atherosclerotic properties, protecting heart and liver. However, the mechanisms involved are to be defined. The aim of the present study was to define the effect of Paeonia lactiflora Pall. extracts on vascular tension and responsible mechanisms in rat thoracic aortic rings. Ethanol extract of Paeonia lactiflora Pall. (EPL) was examined for their vascular relaxant effects in isolated phenylephrine-precontracted rat thoracic aorta. EPL induced relaxation of the phenylephrine-precontracted aortic rings in a concentration-dependent manner. Vascular relaxation induced by EPL was significantly inhibited by removal of the endothelium or pretreatment of the rings with N(G)-nitro-L-arginine methylester (L-NAME) or 1H-[1,2,4]-oxadiazolo-[4,3-α]-quinoxalin-1-one (ODQ). Extracellular Ca²⁺ depletion or diltiazem significantly attenuated EPL-induced vasorelaxation. Modulators of the store-operated Ca²⁺ entry (SOCE), thapsigargin, 2-aminoethyl diphenylborinate and Gd³⁺, and an inhibitor of Akt, wortmannin, markedly attenuated the EPL-induced vasorelaxation. Further, the EPL-induced vasorelaxation was significantly attenuated by pretreatment with tetraethylammonium, a non-selective K(Ca) channels blocker, or glibenclamide, an ATP-sensitive K⁺ channels inhibitor, respectively. Inhibition of cyclooxygenases with indomethacin, and adrenergic and muscarinic receptors blockade had no effects on the EPL-induced vasorelaxation. The present study suggests that EPL relaxes vascular smooth muscle via endothelium-dependent and Akt- and SOCE-eNOS-cGMP-mediated pathways through activation of both K(Ca) and K(ATP) channels and inhibition of L-type Ca²⁺ channels. Copyright © 2012. Published by Elsevier Ireland Ltd.

Effect of load alterations on the effective regurgitant orifice area in chronic aortic regurgitation.

PubMed

Kim, Y J; Jones, M; Shiota, T; Tsujino, H; Qin, J X; Bauer, F; Sitges, M; Kwan, J; Cardon, L A; Zetts, A D; Thomas, J D

2002-10-01

To evaluate the load dependence of effective regurgitant orifice area (ROA) in an animal model of chronic aortic regurgitation. Eight sheep were studied 10-20 weeks after the surgical creation of aortic regurgitation. After baseline studies, 500 ml of blood, angiotensin II, and nitroprusside were infused sequentially. Electromagnetic flow meters were used as reference standards to determine aortic regurgitation volume. The time-velocity integral was acquired using the continuous wave Doppler method. Baseline aortic regurgitant volume varied from 8 ml (regurgitant fraction 28%) to 29 ml (59%), with a mean (SD) value of 17 (8) ml; mean ROA was 0.15 (0.05) cm2. During angiotensin II infusion, aortic regurgitation volume (20 (8) ml) and mean diastolic aortoventricular pressure gradient (62 (18) mm Hg) increased by 26 (16)% and 48 (64)%, respectively (p < 0.01 for both). ROA did not change (0.16 (0.06) cm(2), p = 0.15). During nitroprusside infusion, aortic regurgitant volume (13 (7) ml, p = 0.05) and diastolic pressure gradient (25 (13) mm Hg, p < 0.05) decreased. ROA did not change (0.15 (0.05) cm2). When analysing 32 stages together, aortic regurgitant volume (r = 0.78, p < 0.01) and regurgitant fraction (r = 0.55, p < 0.01) correlated well with ROA. However, diastolic pressure gradient (r = 0.28) was not significantly correlated with ROA. In an animal model of chronic aortic regurgitation, ROA did not change with load alterations.

A novel sax-stent method in treatment of ascending aorta and aortic arch aneurysms evaluated by finite element simulations.

PubMed

Arokiaraj, M C; De Beule, M; De Santis, G

2017-02-01

A novel stent method to simplify treatment of proximal ascending aorta and aortic arch aneurysms was developed and investigated by finite element analysis. Therapy of ascending aortic and aortic arch aneurysms is difficult and challenging and is associated with various complications. A 55mm wide×120mm long stent was designed without the stent graft and the stent was deployed by an endovascular method in a virtual patient-specific aneurysm model. The stress-strain analysis and deployment characteristics were performed in a finite element analysis using the Abaqus software. The stent, when embedded in the aortic wall, significantly reduced aortic wall stresses, while preserving the side coronary ostia and side branches in the aortic arch. When tissue growth was modeled computationally over the stent struts the wall stresses in aorta was reduced. This effect became more pronounced when increasing the thickness of the tissue growth. There were no abnormal stresses in the aorta, coronary ostium and at the origin of aortic branches. The stent reduced aneurysm expansion cause by hypertensive condition from 2mm without stenting to 1.3mm after stenting and embedding. In summary, we uncovered a simple treatment method using a bare nitinol stent without stent graft in the treatment of the proximal aorta and aortic arch aneurysms, which could eventually replace the complex treatment methods for this disease. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Automated aortic calcification detection in low-dose chest CT images

NASA Astrophysics Data System (ADS)

Xie, Yiting; Htwe, Yu Maw; Padgett, Jennifer; Henschke, Claudia; Yankelevitz, David; Reeves, Anthony P.

2014-03-01

The extent of aortic calcification has been shown to be a risk indicator for vascular events including cardiac events. We have developed a fully automated computer algorithm to segment and measure aortic calcification in low-dose noncontrast, non-ECG gated, chest CT scans. The algorithm first segments the aorta using a pre-computed Anatomy Label Map (ALM). Then based on the segmented aorta, aortic calcification is detected and measured in terms of the Agatston score, mass score, and volume score. The automated scores are compared with reference scores obtained from manual markings. For aorta segmentation, the aorta is modeled as a series of discrete overlapping cylinders and the aortic centerline is determined using a cylinder-tracking algorithm. Then the aortic surface location is detected using the centerline and a triangular mesh model. The segmented aorta is used as a mask for the detection of aortic calcification. For calcification detection, the image is first filtered, then an elevated threshold of 160 Hounsfield units (HU) is used within the aorta mask region to reduce the effect of noise in low-dose scans, and finally non-aortic calcification voxels (bony structures, calcification in other organs) are eliminated. The remaining candidates are considered as true aortic calcification. The computer algorithm was evaluated on 45 low-dose non-contrast CT scans. Using linear regression, the automated Agatston score is 98.42% correlated with the reference Agatston score. The automated mass and volume score is respectively 98.46% and 98.28% correlated with the reference mass and volume score.

Human Thiel-Embalmed Cadaveric Aortic Model with Perfusion for Endovascular Intervention Training and Medical Device Evaluation.

PubMed

McLeod, Helen; Cox, Ben F; Robertson, James; Duncan, Robyn; Matthew, Shona; Bhat, Raj; Barclay, Avril; Anwar, J; Wilkinson, Tracey; Melzer, Andreas; Houston, J Graeme

2017-09-01

The purpose of this investigation was to evaluate human Thiel-embalmed cadavers with the addition of extracorporeal driven ante-grade pulsatile flow in the aorta as a model for simulation training in interventional techniques and endovascular device testing. Three human cadavers embalmed according to the method of Thiel were selected. Extracorporeal pulsatile ante-grade flow of 2.5 L per min was delivered directly into the aorta of the cadavers via a surgically placed connection. During perfusion, aortic pressure and temperature were recorded and optimized for physiologically similar parameters. Pre- and post-procedure CT imaging was conducted to plan and follow up thoracic and abdominal endovascular aortic repair as it would be in a clinical scenario. Thoracic endovascular aortic repair (TEVAR) and endovascular abdominal repair (EVAR) procedures were conducted in simulation of a clinical case, under fluoroscopic guidance with a multidisciplinary team present. The Thiel cadaveric aortic perfusion model provided pulsatile ante-grade flow, with pressure and temperature, sufficient to conduct a realistic simulation of TEVAR and EVAR procedures. Fluoroscopic imaging provided guidance during the intervention. Pre- and post-procedure CT imaging facilitated planning and follow-up evaluation of the procedure. The human Thiel-embalmed cadavers with the addition of extracorporeal flow within the aorta offer an anatomically appropriate, physiologically similar robust model to simulate aortic endovascular procedures, with potential applications in interventional radiology training and medical device testing as a pre-clinical model.

Impaired Vascular Contractility and Aortic Wall Degeneration in Fibulin-4 Deficient Mice: Effect of Angiotensin II Type 1 (AT1) Receptor Blockade

PubMed Central

Moltzer, Els; te Riet, Luuk; Swagemakers, Sigrid M. A.; van Heijningen, Paula M.; Vermeij, Marcel; van Veghel, Richard; Bouhuizen, Angelique M.; van Esch, Joep H. M.; Lankhorst, Stephanie; Ramnath, Natasja W. M.; de Waard, Monique C.; Duncker, Dirk J.; van der Spek, Peter J.; Rouwet, Ellen V.; Danser, A. H. Jan; Essers, Jeroen

2011-01-01

Medial degeneration is a key feature of aneurysm disease and aortic dissection. In a murine aneurysm model we investigated the structural and functional characteristics of aortic wall degeneration in adult fibulin-4 deficient mice and the potential therapeutic role of the angiotensin (Ang) II type 1 (AT1) receptor antagonist losartan in preventing aortic media degeneration. Adult mice with 2-fold (heterozygous Fibulin-4+/R) and 4-fold (homozygous Fibulin-4R/R) reduced expression of fibulin-4 displayed the histological features of cystic media degeneration as found in patients with aneurysm or dissection, including elastin fiber fragmentation, loss of smooth muscle cells, and deposition of ground substance in the extracellular matrix of the aortic media. The aortic contractile capacity, determined by isometric force measurements, was diminished, and was associated with dysregulation of contractile genes as shown by aortic transcriptome analysis. These structural and functional alterations were accompanied by upregulation of TGF-β signaling in aortas from fibulin-4 deficient mice, as identified by genome-scaled network analysis as well as by immunohistochemical staining for phosphorylated Smad2, an intracellular mediator of TGF-β. Tissue levels of Ang II, a regulator of TGF-β signaling, were increased. Prenatal treatment with the AT1 receptor antagonist losartan, which blunts TGF-β signaling, prevented elastic fiber fragmentation in the aortic media of newborn Fibulin-4R/R mice. Postnatal losartan treatment reduced haemodynamic stress and improved lifespan of homozygous knockdown fibulin-4 animals, but did not affect aortic vessel wall structure. In conclusion, the AT1 receptor blocker losartan can prevent aortic media degeneration in a non-Marfan syndrome aneurysm mouse model. In established aortic aneurysms, losartan does not affect aortic architecture, but does improve survival. These findings may extend the potential therapeutic application of inhibitors of the renin-angiotensin system to the preventive treatment of aneurysm disease. PMID:21858106

Sex, pregnancy and aortic disease in Marfan syndrome.

PubMed

Renard, Marjolijn; Muiño-Mosquera, Laura; Manalo, Elise C; Tufa, Sara; Carlson, Eric J; Keene, Douglas R; De Backer, Julie; Sakai, Lynn Y

2017-01-01

Sex-related differences as well as the adverse effect of pregnancy on aortic disease outcome are well-established phenomena in humans with Marfan syndrome (MFS). The underlying mechanisms of these observations are largely unknown. In an initial (pilot) step we aimed to confirm the differences between male and female MFS patients as well as between females with and without previous pregnancy. We then sought to evaluate whether these findings are recapitulated in a pre-clinical model and performed in-depth cardiovascular phenotyping of mutant male and both nulliparous and multiparous female Marfan mice. The effect of 17β-estradiol on fibrillin-1 protein synthesis was compared in vitro using human aortic smooth muscle cells and fibroblasts. Our small retrospective study of aortic dimensions in a cohort of 10 men and 20 women with MFS (10 pregnant and 10 non-pregnant) confirmed that aortic root growth was significantly increased in the pregnant group compared to the non-pregnant group (0.64mm/year vs. 0.12mm/year, p = 0.018). Male MFS patients had significantly larger aortic root diameters compared to the non-pregnant and pregnant females at baseline and follow-up (p = 0.002 and p = 0.007, respectively), but no significant increase in aortic root growth was observed compared to the females after follow-up (p = 0.559 and p = 0.352). In the GT-8/+ MFS mouse model, multiparous female Marfan mice showed increased aortic diameters when compared to nulliparous females. Aortic dilatation in multiparous females was comparable to Marfan male mice. Moreover, increased aortic diameters were associated with more severe fragmentation of the elastic lamellae. In addition, 17β-estradiol was found to promote fibrillin-1 production by human aortic smooth muscle cells. Pregnancy-related changes influence aortic disease severity in otherwise protected female MFS mice and patients. There may be a role for estrogen in the female sex protective effect.

[Late outlet strut fracture of an aortic Björk-Shiley and embolization of the prosthetic disc].

PubMed

Brochet, E; Bougis de Brux, M A; Assayag, P; Benacin, Y; Gamerman, G; Guerot, C; Valère, P E

1988-09-01

A new case of late fracture of an outlet strut in a convexo-concave Björk-Shiley valve is reported. The fracture occurred 6 years after aortic implantation of the valve and was responsible for aorto-iliac embolization by the prosthetic disc and death of the patient from cardiogenic shock. This not uncommon complication of the Björk-Shiley valve prosthesis is usually ascribed to the relative fragility of its outlet strut welded to the metallic ring and subjected to strong pressures. Although most cases were observed within the first two years of prosthetic valve insertion, and mainly with valves manufactured in 1981 and 1982, our case and a few others demonstrate the possibility of late rupture. Cardiologists must be aware of this possible complication, since in some favourable cases it can be diagnosed at an early stage and the patient's life can be saved by an emergency operation.

Aortic reactivity and electrophysiology in normotensive rats, spontaneously hypertensive rats and rats made hypertensive with desoxycorticosterone plus salt

PubMed Central

Massingham, R.; Shevde, S.

1971-01-01

The mechanical and electrophysiological activity of rings and strips of thoracic aortic smooth muscle taken from normotensive, DOCA-hypertensive and New Zealand spontaneously hypertensive (A.S. strain) rats have been compared. Aortae from A.S.-hypertensive rats developed less tension in the presence of noradrenaline and K+ than those isolated from normotensive and DOCA-hypertensive rats. Aortae from DOCA-hypertensive rats developed the same tension in response to K+ as normotensive rats but were less reactive to noradrenaline. Measurements of resting membrane potentials from the three groups of rats demonstrated that whereas normotensive and DOCA-hypertensive rats had similar resting membrane potentials, those from A.S.-hypertensive rats were significantly lower (P<0.001). It is suggested that the enhanced responsiveness of intact vascular beds in A.S.-hypertensive rats is a consequence of a change in the geometry of the blood vessels rather than an increase in the contractor response of the smooth muscle cells. PMID:5152033

Low molecular weight fucoidan ameliorates streptozotocin-induced hyper-responsiveness of aortic smooth muscles in type 1 diabetes rats.

PubMed

Liang, Zhengyang; Zheng, Yuanyuan; Wang, Jing; Zhang, Quanbin; Ren, Shuang; Liu, Tiantian; Wang, Zhiqiang; Luo, Dali

2016-09-15

Low molecular weight fucoidan (LMWF) was prepared from Laminaria japonica Areschoug, a popular seafood and medicinal plant consumed in Asia. Chinese have long been using it as a traditional medicine for curing hypertension and edema. This study was intent to investigate the possible beneficial effect of LMWF on hyper-responsiveness of aortic smooth muscles instreptozotocin (STZ)-induced type 1 diabetic rats. Sprague-Dawley rats were made diabetic by injection of STZ, followed by the administration of LMWF (50 or 100mg/kg/day) or probucol (100mg/kg/day) for 12 weeks. Body weight, blood glucose level, basal blood pressure, serum lipid profiles, oxidative stress, prostanoids production, and vasoconstriction response of endothelium-denuded aorta rings to phenylephrine were measured by Real time-PCR, Western blots, ELISA assay, and force myograph, respectively. LMWF (100mg/kg/day)-treated group showed robust improvements on STZ-induced body weight-loss, hypertension, and hyperlipidaemia as indicated by decreased serum level of total cholesterol, triglyceride, and low density lipoprotein cholesterol; while probucol, a lipid-modifying drug with antioxidant properties, displayed mild effects. In addition, LMWF appreciably ameliorated STZ-elicited hyper-responsiveness and oxidative stress in aortic smooth muscles as indicated by decreased superoxide level, increased glutathione content and higher superoxide dismutase activity. Furthermore, administration with LMWF dramatically prevented cyclooxygenase-2 stimulation and restored the up-regulation of thromboxane synthase and down-regulation of 6-keto-PGF1α (a stable metabolic product of prostaglandin I2) in the STZ-administered rats. This study demonstrates for the first time that LMWF can protect against hyperlipidaemia, hypertension, and hyper-responsiveness of aortic smooth muscles in type 1 diabetic rat via, at least in part, amelioration of oxidative stress and restoration of prostanoids levels in aortic smooth muscles. Therefore, LMWF can be a potential adjuvant treatment against cardiovascular complications in type 1 diabetes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

In vitro evaluation of the effect of aortic compliance on pediatric intra-aortic balloon pumping.

PubMed

Minich, L L; Tani, L Y; Hawkins, J A; Bartkowiak, R R; Royall, M L; Pantalos, G M

2001-04-01

OBJECTIVES: To evaluate the effect of aortic compliance on pediatric intra-aortic balloon pumping (IABP). DESIGN: In vitro study using a mechanical model of the pediatric left heart circulation. SETTING: Cardiovascular fluid dynamics research laboratory. SUBJECT: Pulsatile flow system simulating the pediatric left heart circulation and two different aortas with compliances comparable to those of the pediatric aorta (0.12 and 0.07 mL/mm Hg). INTERVENTIONS: Measurements were made at a baseline peak aortic flow of 4 L/min, at simulated shock (1.7 L/min), and with 1:1 IABP (rates, 130 and 150 bpm; balloon volumes, 2.5 and 5.0 mL). MEASUREMENTS AND MAIN RESULTS: Peak flow rates were measured in the ascending aorta, coronary arterial system, and brachiocephalic arterial systems. Aortic pressure was measured in the ascending aorta. For both aortas (0.12 and 0.07 mL/mm Hg), IABP resulted in diastolic augmentation (38 +/- 8 and 43 +/- 16 mm Hg) and afterload reduction (4 +/- 2 and 6 +/- 3 mm Hg). For both aortas, compared to shock, IABP resulted in significant increases in coronary arterial and brachiocephalic arterial flow and aortic pressure for both aortas. Aortic flow significantly increased only in the less-compliant aorta. CONCLUSIONS: In a laboratory model of pediatric left heart circulation, IABP results in diastolic augmentation, afterload reduction, and improved hemodynamics, even in aortas of greater compliance.

The Value of Circulating Biomarkers in Bicuspid Aortic Valve-Associated Aortopathy.

PubMed

Naito, Shiho; Hillebrand, Mathias; Bernhardt, Alexander Martin Justus; Jagodzinski, Annika; Conradi, Lenard; Detter, Christian; Sydow, Karsten; Reichenspurner, Hermann; Kodolitsch, Yskert von; Girdauskas, Evaldas

2018-06-01

Traditional risk stratification model of bicuspid aortic valve (BAV) aortopathy is based on measurement of maximal cross-sectional aortic diameter, definition of proximal aortic shape, and aortic stiffness/elasticity parameters. However, conventional imaging-based criteria are unable to provide reliable information regarding the risk stratification in BAV aortopathy, especially considering the heterogeneous nature of BAV disease. Given those limitations of conventional imaging, there is a growing clinical interest to use circulating biomarkers in the screening process for thoracic aortic aneurysms as well as in the risk-assessment algorithms. We aimed to systematically review currently available biomarkers, which may be of value to predict the natural evolution of aortopathy in individuals with BAV. Georg Thieme Verlag KG Stuttgart · New York.

4D optical coherence tomography of aortic valve dynamics in a murine mouse model ex vivo

NASA Astrophysics Data System (ADS)

Schnabel, Christian; Jannasch, Anett; Faak, Saskia; Waldow, Thomas; Koch, Edmund

2015-07-01

The heart and its mechanical components, especially the heart valves and leaflets, are under enormous strain during lifetime. Like all highly stressed materials, also these biological components undergo fatigue and signs of wear, which impinge upon cardiac output and in the end on health and living comfort of affected patients. Thereby pathophysiological changes of the aortic valve leading to calcific aortic valve stenosis (AVS) as most frequent heart valve disease in humans are of particular interest. The knowledge about changes of the dynamic behavior during the course of this disease and the possibility of early stage diagnosis could lead to the development of new treatment strategies and drug-based options of prevention or therapy. ApoE-/- mice as established model of AVS versus wildtype mice were introduced in an ex vivo artificially stimulated heart model. 4D optical coherence tomography (OCT) in combination with high-speed video microscopy were applied to characterize dynamic behavior of the murine aortic valve and to characterize dynamic properties during artificial stimulation. OCT and high-speed video microscopy with high spatial and temporal resolution represent promising tools for the investigation of dynamic behavior and their changes in calcific aortic stenosis disease models in mice.

Impact of different aortic valve calcification patterns on the outcome of transcatheter aortic valve implantation: A finite element study.

PubMed

Sturla, Francesco; Ronzoni, Mattia; Vitali, Mattia; Dimasi, Annalisa; Vismara, Riccardo; Preston-Maher, Georgia; Burriesci, Gaetano; Votta, Emiliano; Redaelli, Alberto

2016-08-16

Transcatheter aortic valve implantation (TAVI) can treat symptomatic patients with calcific aortic stenosis. However, the severity and distribution of the calcification of valve leaflets can impair the TAVI efficacy. Here we tackle this issue from a biomechanical standpoint, by finite element simulation of a widely adopted balloon-expandable TAVI in three models representing the aortic root with different scenarios of calcific aortic stenosis. We developed a modeling approach realistically accounting for aortic root pressurization and complex anatomy, detailed calcification patterns, and for the actual stent deployment through balloon-expansion. Numerical results highlighted the dependency on the specific calcification pattern of the "dog-boning" of the stent. Also, local stent distortions were associated with leaflet calcifications, and led to localized gaps between the TAVI stent and the aortic tissues, with potential implications in terms of paravalvular leakage. High stresses were found on calcium deposits, which may be a risk factor for stroke; their magnitude and the extent of the affected regions substantially increased for the case of an "arc-shaped" calcification, running from commissure to commissure. Moreover, high stresses due to the interaction between the aortic wall and the leaflet calcifications were computed in the annular region, suggesting an increased risk for annular damage. Our analyses suggest a relation between the alteration of the stresses in the native anatomical components and prosthetic implant with the presence and distribution of relevant calcifications. This alteration is dependent on the patient-specific features of the calcific aortic stenosis and may be a relevant indicator of suboptimal TAVI results. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Load dependence of the effective regurgitant orifice area in a sheep model of aortic regurgitation.

PubMed

Reimold, S C; Byrne, J G; Caguioa, E S; Lee, C C; Laurence, R G; Peigh, P S; Cohn, L H; Lee, R T

1991-10-01

Treatment of patients with aortic regurgitation with vasodilators reduces regurgitant volume, ventricular dilation and left ventricular mass. Although these effects are presumably due to afterload reduction, it is also possible that the aortic regurgitant orifice area is not constant. To test the latter hypothesis, aortic regurgitation was created in 10 open chest sheep by partial resection of the noncoronary leaflet under direct visualization. Regurgitant flow was measured with an aortic supravalvular electromagnetic probe; aortic and left ventricular pressures were measured with catheter-tipped micromanometer pressure transducers. The effective regurgitant orifice area was calculated by a modification of the continuity equation in a manner similar to the Gorlin equation. The regurgitant orifice area was measured three times: after aortic regurgitation was created, after mean arterial pressure was increased by 15 to 25 mm Hg with intravenous dopamine and after mean arterial pressure was reduced by 15 to 25 mm Hg with intravenous sodium nitroprusside. Comparison of regurgitant volumes and areas obtained after creation of aortic regurgitation and at the conclusion of the experiment in the absence of dopamine or sodium nitroprusside demonstrated no significant change over time. Dopamine administration was associated with an 86 +/- 81% increase in regurgitant volume (p less than 0.01) and a 38 +/- 44% increase in regurgitant orifice area (p less than 0.01). Sodium nitroprusside administration resulted in a 51 +/- 14% decrease in regurgitant volume (p less than 0.001) and a 28 +/- 21% reduction in regurgitant orifice area (p = 0.007). In this model of acute aortic regurgitation, the effective regurgitant orifice area was altered by increasing or decreasing the aortic transvalvular pressure gradient.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic Study of Flow Remodeling Stent Graft for the Treatment of Highly Angulated Abdominal Aortic Aneurysm

PubMed Central

Yeow, Siang Lin; Leo, Hwa Liang

2016-01-01

This study investigates the effect of a novel flow remodeling stent graft (FRSG) on the hemodynamic characteristics in highly angulated abdominal aortic aneurysm based on computational fluid dynamics (CFD) approach. An idealized aortic aneurysm with varying aortic neck angulations was constructed and CFD simulations were performed on nonstented models and stented models with FRSG. The influence of FRSG intervention on the hemodynamic performance is analyzed and compared in terms of flow patterns, wall shear stress (WSS), and pressure distribution in the aneurysm. The findings showed that aortic neck angulations significantly influence the velocity flow field in nonstented models, with larger angulations shifting the mainstream blood flow towards the center of the aorta. By introducing FRSG treatment into the aneurysm, erratic flow recirculation pattern in the aneurysm sac diminishes while the average velocity magnitude in the aneurysm sac was reduced in the range of 39% to 53%. FRSG intervention protects the aneurysm against the impacts of high velocity concentrated flow and decreases wall shear stress by more than 50%. The simulation results highlighted that FRSG may effectively treat aneurysm with high aortic neck angulations via the mechanism of promoting thrombus formation and subsequently led to the resorption of the aneurysm. PMID:27247612

Particle Image Velocimetry studies of bicuspid aortic valve hemodynamics

NASA Astrophysics Data System (ADS)

Saikrishnan, Neelakantan; Yap, Choon-Hwai; Yoganathan, Ajit P.

2010-11-01

Bicuspid aortic valves (BAVs) are a congenital anomaly of the aortic valve with two fused leaflets, affecting about 1-2% of the population. BAV patients have much higher incidence of valve calcification & aortic dilatation, which may be related to altered mechanical forces from BAV hemodynamics. This study aims to characterize BAV hemodynamics using Particle Image Velocimetry(PIV). BAV models are constructed from normal explanted porcine aortic valves by suturing two leaflets together. The valves are mounted in an acrylic chamber with two sinuses & tested in a pulsatile flow loop at physiological conditions. 2D PIV is performed to obtain flow fields in three planes downstream of the valve. The stenosed BAV causes an eccentric jet, resulting in a very strong vortex in the normal sinus. The bicuspid sinus vortex appears much weaker, but more unstable. Unsteady oscillatory shear stresses are also observed, which have been associated with adverse biological response; characterization of the hemodynamics of BAVs will provide the first step to understanding these processes better. Results from multiple BAV models of varying levels of stenosis will be presented & higher stenosis corresponded to stronger jets & increased aortic wall shear stresses.

An in vitro experimental study of flow past aortic valve under varied pulsatile conditions

NASA Astrophysics Data System (ADS)

Zhang, Ruihang; Zhang, Yan

2017-11-01

Flow past aortic valve represents a complex fluid-structure interaction phenomenon that involves pulsatile, vortical, and turbulent conditions. The flow characteristics immediately downstream of the valve, such as the variation of pulsatile flow velocity, formation of vortices, distribution of shear stresses, are of particular interest to further elucidate the role of hemodynamics in various aortic diseases. However, the fluid dynamics of a realistic aortic valve is not fully understood. Particularly, it is unclear how the flow fields downstream of the aortic valve would change under varied pulsatile inlet boundary conditions. In this study, an in vitro experiment has been conducted to investigate the flow fields downstream of a silicone aortic valve model within a cardiovascular flow simulator. Phased-locked Particle Image Velocimetry measurements were performed to map the velocity fields and Reynolds normal and shear stresses at different phases in a cardiac cycle. Temporal variations of pressure across the valve model were measured using high frequency transducers. Results have been compared for different pulsatile inlet conditions, including varied frequencies (heart rates), magnitudes (stroke volumes), and cardiac contractile functions (shapes of waveforms).

Elective tracheostomy in intensive care unit: Looking between techniques, a three cases report

PubMed Central

Ferraro, Fausto; Marullo, Lucia; d’Elia, Anna; Izzo, Giuseppe

2014-01-01

There is no optimal tracheostomy (TS) technique, proved to be the best. For this reason, operators’ skills, clinical anatomical and physio-pathological features of the patient should be considered as discriminating factors in the choice of percutaneous dilation tracheostomy (PDT) technique. This article includes reports of three cases of PDT: In the first case distance between jugular notch and the first tracheal ring was too long, the second case involving a patient with mild ectasia of the ascending aorta and aortic regurgitation with De Musset's sign with great risk of perioperative bleeding and a third case, of tracheomalacia with inflammatory stenosis at the 4th tracheal ring. All together, this case series describes how decisions were made by an experienced staff, in which the patient characteristics were assessed and techniques best suited for each case were implemented. PMID:24963186

Risk model of thoracic aortic surgery in 4707 cases from a nationwide single-race population through a web-based data entry system: the first report of 30-day and 30-day operative outcome risk models for thoracic aortic surgery.

PubMed

Motomura, Noboru; Miyata, Hiroaki; Tsukihara, Hiroyuki; Takamoto, Shinichi

2008-09-30

The objective of this study was to collect integrated data from nationwide hospitals using a web-based national database system to build up our own risk model for the outcome from thoracic aortic surgery. The Japan Adult Cardiovascular Surgery Database was used; this involved approximately 180 hospitals throughout Japan through a web-based data entry system. Variables and definitions are almost identical to the STS National Database. After data cleanup, 4707 records were analyzed from 97 hospitals (between January 1, 2000, and December 31, 2005). Mean age was 66.5 years. Preoperatively, the incidence of chronic lung disease was 11%, renal failure was 9%, and rupture or malperfusion was 10%. The incidence of the location along the aorta requiring replacement surgery (including overlapping areas) was: aortic root, 10%; ascending aorta, 47%; aortic arch, 44%; distal arch, 21%; descending aorta, 27%; and thoracoabdominal aorta, 8%. Raw 30-day and 30-day operative mortality rates were 6.7% and 8.6%, respectively. Postoperative incidence of permanent stroke was 6.1%, and renal failure requiring dialysis was 6.7%. OR for 30-day operative mortality was as follows: emergency or salvage, 3.7; creatinine >3.0 mg/dL, 3.0; and unexpected coronary artery bypass graft, 2.6. As a performance metric of the risk model, C-index of 30-day and 30-day operative mortality was 0.79 and 0.78, respectively. This is the first report of risk stratification on thoracic aortic surgery using a nationwide surgical database. Although condition of these patients undergoing thoracic aortic surgery was much more serious than other procedures, the result of this series was excellent.

Early development of calcific aortic valve disease and left ventricular hypertrophy in a mouse model of combined dyslipidemia and type 2 diabetes mellitus.

PubMed

Le Quang, Khai; Bouchareb, Rihab; Lachance, Dominic; Laplante, Marc-André; El Husseini, Diala; Boulanger, Marie-Chloé; Fournier, Dominique; Fang, Xiang Ping; Avramoglu, Rita Kohen; Pibarot, Philippe; Deshaies, Yves; Sweeney, Gary; Mathieu, Patrick; Marette, André

2014-10-01

This study aimed to determine the potential impact of type 2 diabetes mellitus on left ventricular dysfunction and the development of calcified aortic valve disease using a dyslipidemic mouse model prone to developing type 2 diabetes mellitus. When compared with nondiabetic LDLr(-/-)/ApoB(100/100), diabetic LDLr(-/-)/ApoB(100/100)/IGF-II mice exhibited similar dyslipidemia and obesity but developed type 2 diabetes mellitus when fed a high-fat/sucrose/cholesterol diet for 6 months. LDLr(-/-)/ApoB(100/100)/IGF-II mice showed left ventricular hypertrophy versus C57BL6 but not LDLr(-/-)/ApoB(100/100) mice. Transthoracic echocardiography revealed significant reductions in both left ventricular systolic fractional shortening and diastolic function in high-fat/sucrose/cholesterol fed LDLr(-/-)/ApoB(100/100)/IGF-II mice when compared with LDLr(-/-)/ApoB(100/100). Importantly, we found that peak aortic jet velocity was significantly increased in LDLr(-/-)/ApoB(100/100)/IGF-II mice versus LDLr(-/-)/ApoB(100/100) animals on the high-fat/sucrose/cholesterol diet. Microtomography scans and Alizarin red staining indicated calcification in the aortic valves, whereas electron microscopy and energy dispersive x-ray spectroscopy further revealed mineralization of the aortic leaflets and the presence of inflammatory infiltrates in diabetic mice. Studies showed upregulation of hypertrophic genes (anp, bnp, b-mhc) in myocardial tissues and of osteogenic genes (spp1, bglap, runx2) in aortic tissues of diabetic mice. We have established the diabetes mellitus -prone LDLr(-/-)/ApoB(100/100)/IGF-II mouse as a new model of calcified aortic valve disease. Our results are consistent with the growing body of clinical evidence that the dysmetabolic state of type 2 diabetes mellitus contributes to early mineralization of the aortic valve and calcified aortic valve disease pathogenesis. © 2014 American Heart Association, Inc.

Assessment of Correlation of Distal Mean Arterial Pressure with Aortic Blood Flow during Partial Resuscitative Endovascular Balloon Aortic Occlusion (P-REBOA) in a Swine (Sus scrofa) Controlled Hemorrhage Model

DTIC Science & Technology

2017-11-06

60th Medical Group (AMC), Travis AFB, CA INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE (IACUC) FINAL REPORT SUMMARY (Please type all information. Use...Pressure with Aortic Blood Flow during Partial Resuscitative Endovascular Balloon Aortic Occlusion (P-REBOA) in a Swine (Sus scrofa) Controlled Hemorrhage...to Date Sus scrofa 8 8 2. PROTOCOL TYPE /CHARACTERISTICS: (Check all applicable terms in EACH column) _ Training: Live Animal Medical Readiness

Effects of intra-aortic counterpulsation on aortic wall energetics and damping: in vivo experiments.

PubMed

Fischer, Edmundo I Cabrera; Bia, Daniel; Camus, Juan M; Zócalo, Yanina; de Forteza, Eduardo; Armentano, Ricardo L

2008-01-01

Intra-aortic balloon pumping (IABP) could modify the arterial biomechanics; however, its effects on arterial wall properties have not been fully explored. This dynamical study was designed to characterize the pressure-dependent and smooth muscle-dependent effects of IABP on aortic wall energetics in an in vivo animal model. Intra-aortic balloon pumping (1:2) was performed in six anesthetized sheep in which aortic pressure and diameter signals were measured in basal, augmented (during balloon inflation), and assisted (postaugmented) beats. Energy dissipation values in augmented and assisted beats were significantly higher than those observed in basal state (p < 0.05). Assisted beats showed a significant increase of wall damping with respect to basal and augmented beats (p < 0.05). Intra-aortic balloon pumping resulted in a significant increase of pulse wave velocity (p < 0.05) in augmented beats with respect to basal state (6.3 +/- 0.8 vs. 5.2 +/- 0.5 m x s(-1)); whereas values observed in assisted beats were significantly (p < 0.05) lower than those observed in augmented beats (4.9 +/- 0.5 vs. 6.3 +/- 0.8 m x s(-1)). Our findings show that IABP determined the pressure and smooth muscle-dependent changes in arterial wall energetics and damping properties in this animal model.

Effect of the Antioxidant Lipoic Acid in Aortic Phenotype in a Marfan Syndrome Mouse Model.

PubMed

Guido, Maria C; Debbas, Victor; Salemi, Vera M; Tavares, Elaine R; Meirelles, Thayna; Araujo, Thaís L S; Nolasco, Patricia; Ferreira-Filho, Julio C A; Takimura, Celso K; Pereira, Lygia V; Laurindo, Francisco R

2018-01-01

Marfan syndrome (MFS) cardiovascular manifestations such as aortic aneurysms and cardiomyopathy carry substantial morbidity/mortality. We investigated the effects of lipoic acid, an antioxidant, on ROS production and aortic remodeling in a MFS mgΔ loxPneo mouse model. MFS and WT (wild-type) 1-month-old mice were allocated to 3 groups: untreated, treated with losartan, and treated with lipoic acid. At 6 months old, echocardiography, ROS production, and morphological analysis of aortas were performed. Aortic ROS generation in 6-month-old MFS animals was higher at advanced stages of disease in MFS. An unprecedented finding in MFS mice analyzed by OCT was the occurrence of focal inhomogeneous regions in the aortic arch, either collagen-rich extremely thickened or collagen-poor hypotrophic regions. MFS animals treated with lipoic acid showed markedly reduced ROS production and lower ERK1/2 phosphorylation; meanwhile, aortic dilation and elastic fiber breakdown were unaltered. Of note, lipoic acid treatment associated with the absence of focal inhomogeneous regions in MFS animals. Losartan reduced aortic dilation and elastic fiber breakdown despite no change in ROS generation. In conclusion, oxidant generation by itself seems neutral with respect to aneurysm progression in MFS; however, lipoic acid-mediated reduction of inhomogeneous regions may potentially associate with less anisotropy and reduced chance of dissection/rupture.

Creation of Abdominal Aortic Aneurysms in Sheep by Extrapolation of Rodent Models: Is It Feasible?

PubMed

Verbrugghe, Peter; Verhoeven, Jelle; Clijsters, Marnick; Vervoort, Dominique; Coudyzer, Walter; Verbeken, Eric; Meuris, Bart; Herijgers, Paul

2018-06-07

Abdominal aortic aneurysms (AAAs) are a potentially deathly disease, needing surgical or endovascular treatment. To evaluate potentially new diagnostic tools and treatments, a large animal model, which resembles not only the morphological characteristics but also the pathophysiological background, would be useful. Rodent animal aneurysm models were extrapolated to sheep. Four groups were created: intraluminal infusion with an elastase-collagenase solution (n = 4), infusion with elastase-collagenase solution combined with proximal stenosis (n = 7), aortic xenograft (n = 3), and elastase-collagenase-treated xenograft (n = 4). At fixed time intervals (6, 12, and 24 weeks), computer tomography and autopsy with histological evaluation were performed. The described models had a high perioperative mortality (45%), due to acute aortic thrombosis or fatale hemorrhage. A maximum aortic diameter increase of 30% was obtained in the protease-stenosis group. In the protease-treated groups, some histological features of human AAAs, such as inflammation, thinning of the media, and loss of elastin could be reproduced. In the xenotransplant groups, a pronounced inflammatory reaction was visible at the start. In all models, inflammation decreased and fibrosis occurred at long follow-up, 24 weeks postoperatively. None of the extrapolated small animal aneurysm models could produce an AAA in sheep with similar morphological features as the human disease. Some histological findings of human surgical specimens could be reproduced in the elastase-collagenase-treated groups. Long-term histological evaluation indicated stabilization and healing of the aortic wall months after the initial stimulus. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Mechanisms of Improved Aortic Stiffness by Arotinolol in Spontaneously Hypertensive Rats

PubMed Central

Zhou, Wugang; Hong, Mona; Zhang, Ke; Chen, Dongrui; Han, Weiqing; Shen, Weili; Zhu, Dingliang; Gao, Pingjin

2014-01-01

Objectives This study investigates the effects on aortic stiffness and vasodilation by arotinolol and the underlying mechanisms in spontaneously hypertensive rats (SHR). Methods The vasodilations of rat aortas, renal and mesenteric arteries were evaluated by isometric force recording. Nitric oxide (NO) was measured in human aortic endothelial cells (HAECs) by fluorescent probes. Sixteen-week old SHRs were treated with metoprolol (200 mg·kg-1·d-1), arotinolol (30 mg·kg-1·d-1) for 8 weeks. Central arterial pressure (CAP) and pulse wave velocity (PWV) were evaluated via catheter pressure transducers. Collagen was assessed by immunohistochemistry and biochemistry assay, while endothelial nitric oxide synthase (eNOS) and eNOS phosphorylation (p-eNOS) of HAECs or aortas were analyzed by western blotting. Results Arotinolol relaxed vascular rings and the relaxations were attenuated by Nω-nitro-L-arginine methyl ester (L-NAME, NO synthase inhibitor) and the absence of endothelium. Furthermore, arotinolol-induced relaxations were attenuated by 4-aminopyridine (4-AP, Kv channels blocker). Arotinolol produced more nitric oxide compared to metoprolol and increased the expression of p-eNOS in HAECs. These results indicated that arotinolol-induced vasodilation involves endothelium-derived NO and Kv channels. The treatement with arotinolol in 8 weeks, but not metoprolol, markedly decreased CAP and PWV. Biochemistry assay and immunohistochemistry showed that aortic collagen depositions in the arotinolol groups were reduced compared with SHRs with metoprolol. Moreover, eNOS phosphorylation was significantly increased in aortinolol-treated SHR compared with SHRs with metoprolol. Conclusions Arotinolol improves arterial stiffness in SHR, which involved in increasing NO and decreasing collagen contents in large arteries. PMID:24533142

Activation of muscarinic receptors by a hydroalcoholic extract of Dicksonia sellowiana Presl. HooK (Dicksoniaceae) induces vascular relaxation and hypotension in rats.

PubMed

Rattmann, Yanna D; Crestani, Sandra; Lapa, Fernanda R; Miguel, Obdúlio G; Marques, Maria C A; da Silva-Santos, J Eduardo; Santos, Adair R S

2009-01-01

Dicksonia sellowiana (Presl.) Hook is a native plant from the Central and South Americas that contain high levels of polyphenols, antioxidant compounds involved in protection against inflammation, cancer and cardiovascular risk. A phytomedicinal preparation obtained from aerial parts of D. sellowiana is currently under clinical evaluation in Brazil against asthma, and has been associated with several other beneficial effects. This study demonstrates that a hydroalcoholic extract obtained from D. sellowiana leaves (HEDS) fully relax, in a concentration-dependent manner, rat aortic rings precontracted with phenylephrine. Moreover, administration of HEDS (10, 20 and 40 mg/kg, i.v.) in anaesthetized rats resulted in a strong but reversible hypotension. Aortic relaxation induced by HEDS was abolished by endothelium removal, by incubation of the nitric oxide synthase inhibitor L-NAME, or the soluble guanylate cyclase inhibitor ODQ. In addition, this effect was partially inhibited by indomethacin (a cyclooxygenase inhibitor) and KT 5730 (a PKA inhibitor). The potassium channels blockade by either tetraethylammonium or charybdotoxin also resulted in a potent inhibition of HEDS-induced aortic relaxation, whereas apamine only slightly reduced it. In addition HEDS-induced relaxation was unchanged by 4-amynopiridine and glibenclamide. The selective muscarinic receptor antagonist atropine counteracted both aortic relaxation and blood pressure reduction generated by HEDS. Experiments using HPLC revealed the presence of high amounts of phenolic compounds in this extract. Taken together, our results reveal that the D. sellowiana possess substances with both in vivo and in vitro activities and that the vascular effect of HEDS involves activation of muscarinic receptors, stimulation of the nitric oxide pathway and opening of calcium-activated potassium channels.

The Potential of Computational Fluid Dynamics Simulation on Serial Monitoring of Hemodynamic Change in Type B Aortic Dissection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Simon C. H., E-mail: simonyu@cuhk.edu.hk; Liu, Wen; Wong, Randolph H. L.

PurposeWe aimed to assess the potential of computational fluid dynamics simulation (CFD) in detecting changes in pressure and flow velocity in response to morphological changes in type B aortic dissection.Materials and MethodsPressure and velocity in four morphological models of type B aortic dissection before and after closure of the entry tear were calculated with CFD and analyzed for changes among the different scenarios. The control model (Model 1) was patient specific and built from the DICOM data of CTA, which bore one entry tear and three re-entry tears. Models 2–4 were modifications of Model 1, with two re-entry tears lessmore » in Model 2, one re-entry tear more in Model 3, and a larger entry tear in Model 4.ResultsThe pressure and velocity pertaining to each of the morphological models were unique. Changes in pressure and velocity findings were accountable by the changes in morphological features of the different models. There was no blood flow in the false lumen across the entry tear after its closure, the blood flow direction across the re-entry tears was reversed after closure of the entry tear.ConclusionCFD simulation is probably useful to detect hemodynamic changes in the true and false lumens of type B aortic dissection in response to morphological changes, it may potentially be developed into a non-invasive and patient-specific tool for serial monitoring of hemodynamic changes of type B aortic dissection before and after treatment.« less

Withaferin A protects against palmitic acid-induced endothelial insulin resistance and dysfunction through suppression of oxidative stress and inflammation

PubMed Central

Batumalaie, Kalaivani; Amin, Muhammad Arif; Murugan, Dharmani Devi; Sattar, Munavvar Zubaid Abdul; Abdullah, Nor Azizan

2016-01-01

Activation of inflammatory pathways via reactive oxygen species (ROS) by free fatty acids (FFA) in obesity gives rise to insulin resistance and endothelial dysfunction. Withaferin A (WA), possesses both antioxidant and anti-inflammatory properties and therefore would be a good strategy to suppress palmitic acid (PA)-induced oxidative stress and inflammation and hence, insulin resistance and dysfunction in the endothelium. Effect of WA on PA-induced insulin resistance in human umbilical vein endothelial cells (HUVECs) was determined by evaluating insulin signaling mechanisms whilst effect of this drug on PA-induced endothelial dysfunction was determined in acetylcholine-mediated relaxation in isolated rat aortic preparations. WA significantly inhibited ROS production and inflammation induced by PA. Furthermore, WA significantly decreased TNF-α and IL-6 production in endothelial cells by specifically suppressing IKKβ/NF-κβ phosphorylation. WA inhibited inflammation-stimulated IRS-1 serine phosphorylation and improved the impaired insulin PI3-K signaling, and restored the decreased nitric oxide (NO) production triggered by PA. WA also decreased endothelin-1 and plasminogen activator inhibitor type-1 levels, and restored the impaired endothelium-mediated vasodilation in isolated aortic preparations. These findings suggest that WA inhibited both ROS production and inflammation to restore impaired insulin resistance in cultured endothelial cells and improve endothelial dysfunction in rat aortic rings. PMID:27250532

Nebivolol prevents vascular oxidative stress and hypertension in rats chronically treated with ethanol.

PubMed

do Vale, Gabriel T; Simplicio, Janaina A; Gonzaga, Natália A; Yokota, Rodrigo; Ribeiro, Amanda A; Casarini, Dulce E; de Martinis, Bruno S; Tirapelli, Carlos R

2018-04-30

Chronic ethanol consumption is associated with hypertension and atherosclerosis. Vascular oxidative stress is described as an important mechanism whereby ethanol predisposes to atherosclerosis. We hypothesized that nebivolol would prevent ethanol-induced hypertension and vascular oxidative stress. Male Wistar rats were treated with ethanol 20% (vol./vol.) or nebivolol (10 mg/kg/day, p. o., gavage), a selective β 1 -adrenergic receptor antagonist. Ethanol-induced increase in blood pressure and in the circulating levels of adrenaline and noradrenaline was prevented by nebivolol. Similarly, nebivolol prevented ethanol-induced increase in plasma levels of renin, angiotensin I and II. Chronic ethanol consumption increased the aortic levels of superoxide anion (O 2 - ), thiobarbituric acid reactive species (TBARS) as well as the expression of Nox1 and nitrotyrosine immunostaining in the rat aorta. Treatment with nebivolol prevented these responses. The decrease in aortic levels of nitrate/nitrite (NOx) induced by ethanol was prevented by the treatment with nebivolol. Finally, nebivolol attenuated ethanol-induced increase in phenylephrine- and noradrenaline-induced contraction of endothelium-intact and endothelium-denuded aortic rings. The novelty of our study is that nebivolol prevented ethanol-induced hypertension and vascular oxidative stress. Additionally, we showed that the sympathetic nervous system (SNS) and the renin-angiotensin system (RAS) are important endogenous mediators of the cardiovascular effects of ethanol. Copyright © 2018 Elsevier B.V. All rights reserved.

Hyperphosphatemia induces cellular senescence in human aorta smooth muscle cells through integrin linked kinase (ILK) up-regulation.

PubMed

Troyano, Nuria; Nogal, María Del; Mora, Inés; Diaz-Naves, Manuel; Lopez-Carrillo, Natalia; Sosa, Patricia; Rodriguez-Puyol, Diego; Olmos, Gemma; Ruiz-Torres, María P

2015-12-01

Aging is conditioned by genetic and environmental factors. Hyperphosphatemia is related to some pathologies, affecting to vascular cells behavior. This work analyze whether high concentration of extracellular phosphate induces vascular smooth muscle cells senescence, exploring the intracellular mechanisms and highlighting the in vivo relevance of this phenomenon. Human aortic smooth muscle cells treated with β-Glycerophosphate (BGP, 10mM) suffered cellular senescence by increasing p53, p21 and p16 expression and the senescence associated β-galactosidase activity. In parallel, BGP induced ILK overexpression, dependent on the IGF-1 receptor activation, and oxidative stress. Down-regulating ILK expression prevented BGP-induced senescence and oxidative stress. Aortic rings from young rats treated with 10mM BGP for 48h, showed increased p53, p16 and ILK expression and SA-β-gal activity. Seven/eight nephrectomized rats feeding a hyperphosphatemic diet and fifteenth- month old mice showed hyperphosphatemia and aortic ILK, p53 and p16 expression. In conclusion, we demonstrated that high extracellular concentration of phosphate induced senescence in cultured smooth muscle through the activation of IGF-1 receptor and ILK overexpression and provided solid evidences for the in vivo relevance of these results since aged animals showed high levels of serum phosphate linked to increased expression of ILK and senescence genes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Endothelial CaMKII as a regulator of eNOS activity and NO-mediated vasoreactivity

PubMed Central

Murthy, Shubha; Koval, Olha M.; Ramiro Diaz, Juan M.; Kumar, Santosh; Nuno, Daniel; Scott, Jason A.; Allamargot, Chantal; Zhu, Linda J.; Broadhurst, Kim; Santhana, Velarchana; Kutschke, William J.; Irani, Kaikobad; Lamping, Kathryn G.; Grumbach, Isabella M.

2017-01-01

The multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a serine/threonine kinase important in transducing intracellular Ca2+ signals. While in vitro data regarding the role of CaMKII in the regulation of endothelial nitric oxide synthase (eNOS) are contradictory, its role in endothelial function in vivo remains unknown. Using two novel transgenic models to express CaMKII inhibitor peptides selectively in endothelium, we examined the effect of CaMKII on eNOS activation, NO production, vasomotor tone and blood pressure. Under baseline conditions, CaMKII activation was low in the aortic wall. Consistently, systolic and diastolic blood pressure, heart rate and plasma NO levels were unaltered by endothelial CaMKII inhibition. Moreover, endothelial CaMKII inhibition had no significant effect on NO-dependent vasodilation. These results were confirmed in studies of aortic rings transduced with adenovirus expressing a CaMKII inhibitor peptide. In cultured endothelial cells, bradykinin treatment produced the anticipated rapid influx of Ca2+ and transient CaMKII and eNOS activation, whereas CaMKII inhibition blocked eNOS phosphorylation on Ser-1179 and dephosphorylation at Thr-497. Ca2+/CaM binding to eNOS and resultant NO production in vitro were decreased under CaMKII inhibition. Our results demonstrate that CaMKII plays an important role in transient bradykinin-driven eNOS activation in vitro, but does not regulate NO production, vasorelaxation or blood pressure in vivo under baseline conditions. PMID:29059213

Endoplasmic reticulum stress in perivascular adipose tissue promotes destabilization of atherosclerotic plaque by regulating GM-CSF paracrine.

PubMed

Ying, Ru; Li, Sheng-Wei; Chen, Jia-Yuan; Zhang, Hai-Feng; Yang, Ying; Gu, Zhen-Jie; Chen, Yang-Xin; Wang, Jing-Feng

2018-04-18

Perivascular adipose tissue (PVAT) accelerates plaque progression and increases cardiovascular risk. We tested the hypothesis that PVAT contributed to plaque vulnerability and investigated whether endoplasmic reticulum stress (ER stress) in PVAT played an important role in vulnerable plaque. We transplanted thoracic aortic PVAT or subcutaneous adipose tissue as a control, from donor mice to carotid arteries of recipient apolipoprotein E deficient (apoE -/- ) mice after removing carotid artery collar placed for 6 weeks. Two weeks after transplantation, ER stress inhibitor 4-phenyl butyric acid (4-PBA) was locally administrated to the transplanted PVAT and then animals were euthanized after 4 weeks. Immunohistochemistry was performed to quantify plaque composition and neovascularization. Mouse angiogenesis antibody array kit was used to test the angiogenic factors produced by transplanted adipose tissue. In vitro tube formation assay, scratch wound migration assay and mouse aortic ring assay were used to assess the angiogenic capacity of supernatant of transplanted PVAT. Ultrastructural detection by transmission electron microscopy showed transplanted PVAT was a mixed population of white and brown adipocytes with abundant mitochondria. Transplanted PVAT increased the intraplaque macrophage infiltration, lipid core, intimal and vasa vasorum neovascularization and MMP2/9 expression in plaque while decreased smooth muscle cells and collagen in atherosclerotic plaque, which were restored by local 4-PBA-treatment. Antibody array analysis showed that 4-PBA reduced several angiogenic factors [Granulocyte Macrophage Colony Stimulating Factor (GM-CSF), MCP-1, IL-6] secreted by PVAT. Besides, conditioned medium from 4-PBA treated-PVAT inhibited tube formation and migration capacity of endothelial cells and ex vivo mouse aortic ring angiogenesis compared to conditioned medium from transplanted PVAT. mRNA expression and protein levels of GM-CSF were markedly elevated in adipocytes under ER stress which would be suppressed by 4-PBA. In addition, ER stress enhanced NF-κB binding to the promoter of the mouse GM-CSF gene in adipocytes confirmed by Chromatin immunoprecipitation analyses. Our findings demonstrate that ER stress in PVAT destabilizes atherosclerotic plaque, in part through increasing GM-CSF paracrine via transcription factor NF-κB.

Identification of EGFLAM, SPATC1L and RNASE13 as novel susceptibility loci for aortic aneurysm in Japanese individuals by exome-wide association studies

PubMed Central

Yamada, Yoshiji; Sakuma, Jun; Takeuchi, Ichiro; Yasukochi, Yoshiki; Kato, Kimihiko; Oguri, Mitsutoshi; Fujimaki, Tetsuo; Horibe, Hideki; Muramatsu, Masaaki; Sawabe, Motoji; Fujiwara, Yoshinori; Taniguchi, Yu; Obuchi, Shuichi; Kawai, Hisashi; Shinkai, Shoji; Mori, Seijiro; Arai, Tomio; Tanaka, Masashi

2017-01-01

We performed an exome-wide association study (EWAS) to identify genetic variants - in particular, low-frequency or rare variants with a moderate to large effect size - that confer susceptibility to aortic aneurysm with 8,782 Japanese subjects (456 patients with aortic aneurysm, 8,326 control individuals) and with the use of Illumina HumanExome-12 DNA Analysis BeadChip or Infinium Exome-24 BeadChip arrays. The correlation of allele frequencies for 41,432 single nucleotide polymorphisms (SNPs) that passed quality control to aortic aneurysm was examined with Fisher's exact test. Based on Bonferroni's correction, a P-value of <1.21×10−6 was considered statistically significant. The EWAS revealed 59 SNPs that were significantly associated with aortic aneurysm. None of these SNPs was significantly (P<2.12×10−4) associated with aortic aneurysm by multivariable logistic regression analysis with adjustment for age, gender and hypertension, although 8 SNPs were related (P<0.05) to this condition. Examination of the correlation of these latter 8 SNPs to true or dissecting aortic aneurysm separately showed that rs1465567 [T/C (W229R)] of the EGF-like, fibronectin type III, and laminin G domains gene (EGFLAM) (dominant model; P=0.0014; odds ratio, 1.63) was significantly (P<0.0016) associated with true aortic aneurysm. We next performed EWASs for true or dissecting aortic aneurysm separately and found that 45 and 19 SNPs were significantly associated with these conditions, respectively. Multivariable logistic regression analysis with adjustment for covariates revealed that rs113710653 [C/T (E231K)] of the spermatogenesis- and centriole associated 1-like gene (SPATC1L) (dominant model; P=0.0002; odds ratio, 5.32) and rs143881017 [C/T (R140H)] of the ribonuclease A family member 13 gene (RNASE13) (dominant model; P=0.0006; odds ratio, 5.77) were significantly (P<2.78×10−4 or P<6.58×10−4, respectively) associated with true or dissecting aortic aneurysm, respectively. EGFLAM and SPATC1L may thus be susceptibility loci for true aortic aneurysm and RNASE13 may be such a locus for dissecting aneurysm in Japanese individuals. PMID:28339009

Acyl Chain-Dependent Effect of Lysophosphatidylcholine on Endothelium-Dependent Vasorelaxation

PubMed Central

Rao, Shailaja P.; Riederer, Monika; Lechleitner, Margarete; Hermansson, Martin; Desoye, Gernot; Hallström, Seth; Graier, Wolfgang F.; Frank, Saša

2013-01-01

Previously we identified palmitoyl-, oleoyl-, linoleoyl-, and arachidonoyl-lysophosphatidylcholine (LPC 16:0, 18:1, 18:2 and 20:4) as the most prominent LPC species generated by endothelial lipase (EL). In the present study, we examined the impact of those LPC on acetylcholine (ACh)- induced vascular relaxation. All tested LPC attenuated ACh-induced relaxation, measured ex vivo, using mouse aortic rings and wire myography. The rank order of potency was as follows: 18:2>20:4>16:0>18:1. The attenuating effect of LPC 16:0 on relaxation was augmented by indomethacin-mediated cyclooxygenase (COX)-inhibition and CAY10441, a prostacyclin (PGI2)- receptor (IP) antagonist. Relaxation attenuated by LPC 20:4 and 18:2 was improved by indomethacin and SQ29548, a thromboxane A2 (TXA2)- receptor antagonist. The effect of LPC 20:4 could also be improved by TXA2- and PGI2-synthase inhibitors. As determined by EIA assays, the tested LPC promoted secretion of PGI2, TXA2, PGF2α, and PGE2, however, with markedly different potencies. LPC 16:0 was the most potent inducer of superoxide anion production by mouse aortic rings, followed by LPC 18:2, 20:4 and 18:1, respectively. The strong antioxidant tempol recovered relaxation impairment caused by LPC 18:2, 18:1 and 20:4, but not by LPC 16:0. The tested LPC attenuate ACh-induced relaxation through induction of proconstricting prostanoids and superoxide anions. The potency of attenuating relaxation and the relative contribution of underlying mechanisms are strongly related to LPC acyl-chain length and degree of saturation. PMID:23741477

Dimethylarginine dimethylaminohydrolase 1 modulates endothelial cell growth through nitric oxide and Akt.

PubMed

Zhang, Ping; Hu, Xinli; Xu, Xin; Chen, Yingjie; Bache, Robert J

2011-04-01

Dimethylarginine dimethylaminohydrolase 1 (DDAH1) modulates NO production by degrading the endogenous nitric oxide (NO) synthase (NOS) inhibitors asymmetrical dimethylarginine (ADMA) and L-NG-monomethyl arginine (L-NMMA). This study examined whether, in addition to degrading ADMA, DDAH1 exerts ADMA-independent effects that influence endothelial function. Using selective gene silencing of DDAH1 with small interfering RNA and overexpression of DDAH1 in human umbilical vein endothelial cells, we found that DDAH1 acts to promote endothelial cell proliferation, migration, and tube formation by Akt phosphorylation, as well as through the traditional role of degrading ADMA. Incubation of human umbilical vein endothelial cells with the NOS inhibitors l-NG-nitro-arginine methyl ester (L-NAME) or ADMA, the soluble guanylyl cyclase inhibitor 1H-(1,2,4)oxadiazolo-(4,3-2)quinoxalin-1-one, or the cGMP analog 8-(4-Chlorophenylthio)-cGMP had no effect on phosphorylated (p)-Akt(Ser473), indicating that the increase in p-Akt(Ser473) produced by DDAH1 was independent of the NO-cGMP signaling pathway. DDAH1 formed a protein complex with Ras, and DDAH1 overexpression increased Ras activity. The Ras inhibitor manumycin-A or dominant-negative Ras significantly attenuated the DDAH1-induced increase in p-Akt(Ser473). Furthermore, DDAH1 knockout impaired endothelial sprouting from cultured aortic rings, and overexpression of constitutively active Akt or DDAH1 rescued endothelial sprouting in the aortic rings from these mice. DDAH1 exerts a unique role in activating Akt that affects endothelial function independently of degrading endogenous NOS inhibitors.

Ramipril retards development of aortic valve stenosis in a rabbit model: mechanistic considerations.

PubMed

Ngo, Doan Tm; Stafford, Irene; Sverdlov, Aaron L; Qi, Weier; Wuttke, Ronald D; Zhang, Yuan; Kelly, Darren J; Weedon, Helen; Smith, Malcolm D; Kennedy, Jennifer A; Horowitz, John D

2011-02-01

Aortic valve stenosis (AVS) is associated with significant cardiovascular morbidity and mortality. To date, no therapeutic modality has been shown to be effective in retarding AVS progression. We evaluated the effect of angiotensin-converting enzyme inhibition with ramipril on disease progression in a recently developed rabbit model of AVS. The effects of 8 weeks of treatment with either vitamin D₂ at 25,000 IU for 4 days a week alone or in combination with ramipril (0.5 mg·kg⁻¹) on aortic valve structure and function were examined in New Zealand white rabbits. Echocardiographic aortic valve backscatter (AV(BS)) and aortic valve:outflow tract flow velocity ratio were utilized to quantify changes in valve structure and function. Treatment with ramipril significantly reduced AV(BS) and improved aortic valve :outflow tract flow velocity ratio. The intravalvular content of the pro-oxidant thioredoxin-interacting protein was decreased significantly with ramipril treatment. Endothelial function, as measured by asymmetric dimethylarginine concentrations and vascular responses to ACh, was improved significantly with ramipril treatment. Ramipril retards the development of AVS, reduces valvular thioredoxin-interacting protein accumulation and limits endothelial dysfunction in this animal model. These findings provide important insights into the mechanisms of AVS development and an impetus for future human studies of AVS retardation using an angiotensin-converting enzyme inhibitor. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

A meta-analysis of aortic root size in elite athletes.

PubMed

Iskandar, Aline; Thompson, Paul D

2013-02-19

The aorta is exposed to hemodynamic stress during exercise, but whether or not the aorta is larger in athletes is not clear. We performed a systematic literature review and meta-analysis to examine whethere athletes demonstrate increased aortic root dimensions compared with nonathlete controls. We searched MEDLINE and Scopus from inception through August 12, 2012, for English-language studies reporting the aortic root size in elite athletes. Two investigators independently extracted athlete and study characteristics. A multivariate linear mixed model was used to conduct meta-regression analyses. We identified 71 studies reporting aortic root dimensions in 8564 unique athletes, but only 23 of these studies met our criteria by reporting aortic root dimensions at the aortic valve annulus or sinus of Valsalva in elite athletes (n=5580). Athletes were compared directly with controls (n=727) in 13 studies. On meta-regression, the weighted mean aortic root diameter measured at the sinuses of Valsalva was 3.2 mm (P=0.02) larger in athletes than in the nonathletic controls, whereas aortic root size at the aortic valve annulus was 1.6 mm (P=0.04) greater in athletes than in controls. Elite athletes have a small but significantly larger aortic root diameter at the sinuses of Valsalva and aortic valve annulus, but this difference is minor and clinically insignificant. Clinicians evaluating athletes should know that marked aortic root dilatation likely represents a pathological process and not a physiological adaptation to exercise.

Computational Modeling of Aortic Valvular Stenosis to Asses the Range of Validity of Gorlin Equation

NASA Astrophysics Data System (ADS)

Okpara, Emanuel; Agarwal, Ramesh; Rifkin, Robert; Wendl, Mike

2003-11-01

It is well known from clinical observations that the underestimation errors occur with the use of Gorlin formula (1) for the calculation of valve area of the stenotic aortic valve in patients with low cardiac output, that is in low flow states. Since 1951, empirical modifications to Gorlin formula have been proposed in the literaure by many researchers. In this paper, we study the mild to severe aortic valve stenosis for low to high flow rates by employing a simplified model of aortic valve. The aortic valve stenosis is modeled by a circular orifice in a flat plate embedded in the cross-section of a rigid tube (aorta). Experimental results are available for this configuration for the validation of a CFD solver "FLUENT". The numerical data base generated for this model for various degrees of stenoses and flow rates is employed to asses the range of validity of Gorlin's equation. Modifications to Gorlin formula are suggested to make it valid for all flow rates to determine the valve area for clinical use. (1) R. Gorlin and S. Gorlin," Hydraulic Formula for Calculation of the Area of Stenotic Mitral Valve, Other Cardiac Valves and Central Circulatory Shunts," Am. Heart Journal, Vol. 41, 1951, pp. 1-29.

Effects of hawthorn on the progression of heart failure in a rat model of aortic constriction.

PubMed

Hwang, Hyun Seok; Boluyt, Marvin O; Converso, Kimber; Russell, Mark W; Bleske, Barry E

2009-06-01

To determine the effects of hawthorn (Crataegus oxycantha) on left ventricular remodeling and function in pressure overload-induced heart failure in an animal model. Randomized, parallel, dose-ranging animal study. University research facility. Seventy-four male Sprague-Dawley rats; 44 were included in the final analysis. Rats underwent a sham operation or aortic constriction. Rats subjected to the sham operation were treated with vehicle (10% agar-agar), and those subjected to aortic constriction were treated with vehicle or hawthorn (C. oxycantha special extract WS 1442) 1.3, 13, or 130 mg/kg for 5 months. Rats and their hearts were weighed, and echocardiographic measurements were performed at baseline and at 2, 3, 4, and 5 months after aortic constriction. Protein expression for markers of fibrosis and for atrial natriuretic factor was also measured. Aortic constriction increased the left ventricular:body weight ratio by 53% in vehicle-treated rats; Hawthorn treatment did not significantly affect the aortic constriction-induced increase in this ratio. Left ventricular volumes and dimensions at systole and diastole significantly increased 5 months after aortic constriction compared with baseline in rats given vehicle (> 20% increase, p<0.05) but not in those given hawthorn 130 mg/kg (< 10% increase). After aortic constriction, the velocity of circumferential shortening significantly decreased in the vehicle group but not in the medium- or high-dose groups. In the aortic constriction-vehicle group, the induced increases in messenger RNA expression for atrial natriuretic factor (approximately 1000%) and fibronectin (approximately 80%) were significantly attenuated by high-dose hawthorn treatment by approximately 80% and 50%, respectively. Hawthorn treatment exhibited modest beneficial effects on cardiac remodeling and function during long-term, pressure overload-induced heart failure in rats.

Induction of Macrophage Chemotaxis by Aortic Extracts from Patients with Marfan Syndrome Is Related to Elastin Binding Protein

PubMed Central

Guo, Gao; Gehle, Petra; Doelken, Sandra; Martin-Ventura, José Luis; von Kodolitsch, Yskert; Hetzer, Roland; Robinson, Peter N.

2011-01-01

Marfan syndrome is an autosomal dominantly inherited disorder of connective tissue with prominent skeletal, ocular, and cardiovascular manifestations. Aortic aneurysm and dissection are the major determinants of premature death in untreated patients. In previous work, we showed that extracts of aortic tissues from the mgR mouse model of Marfan syndrome showed increased chemotactic stimulatory activity related to the elastin-binding protein. Aortic samples were collected from 6 patients with Marfan syndrome and 8 with isolated aneurysms of the ascending aorta. Control samples were obtained from 11 organ donors without known vascular or connective tissue diseases. Soluble proteins extracted from the aortic samples of the two patient groups were compared against buffer controls and against the aortic samples from controls with respect to the ability to induce macrophage chemotaxis as measured using a modified Boyden chamber, as well as the reactivity to a monoclonal antibody BA4 against bioactive elastin peptides using ELISA. Samples from Marfan patients displayed a statistically significant increase in chemotactic inductive activity compared to control samples. Additionally, reactivity to BA4 was significantly increased. Similar statistically significant increases were identified for the samples from patients with idiopathic thoracic aortic aneurysm. There was a significant correlation between the chemotactic index and BA4 reactivity, and the increases in chemotactic activity of extracts from Marfan patients could be inhibited by pretreatment with lactose, VGVAPG peptides, or BA4, which indicates the involvement of EBP in mediating the effects. Our results demonstrate that aortic extracts of patients with Marfan syndrome can elicit macrophage chemotaxis, similar to our previous study on aortic extracts of the mgR mouse model of Marfan syndrome (Guo et al., Circulation 2006; 114:1855-62). PMID:21647416

Estimation of aortic valve leaflets from 3D CT images using local shape dictionaries and linear coding

NASA Astrophysics Data System (ADS)

Liang, Liang; Martin, Caitlin; Wang, Qian; Sun, Wei; Duncan, James

2016-03-01

Aortic valve (AV) disease is a significant cause of morbidity and mortality. The preferred treatment modality for severe AV disease is surgical resection and replacement of the native valve with either a mechanical or tissue prosthetic. In order to develop effective and long-lasting treatment methods, computational analyses, e.g., structural finite element (FE) and computational fluid dynamic simulations, are very effective for studying valve biomechanics. These computational analyses are based on mesh models of the aortic valve, which are usually constructed from 3D CT images though many hours of manual annotation, and therefore an automatic valve shape reconstruction method is desired. In this paper, we present a method for estimating the aortic valve shape from 3D cardiac CT images, which is represented by triangle meshes. We propose a pipeline for aortic valve shape estimation which includes novel algorithms for building local shape dictionaries and for building landmark detectors and curve detectors using local shape dictionaries. The method is evaluated on real patient image dataset using a leave-one-out approach and achieves an average accuracy of 0.69 mm. The work will facilitate automatic patient-specific computational modeling of the aortic valve.

Computational comparison of aortic root stresses in presence of stentless and stented aortic valve bio-prostheses.

PubMed

Nestola, M G C; Faggiano, E; Vergara, C; Lancellotti, R M; Ippolito, S; Antona, C; Filippi, S; Quarteroni, A; Scrofani, R

2017-02-01

We provide a computational comparison of the performance of stentless and stented aortic prostheses, in terms of aortic root displacements and internal stresses. To this aim, we consider three real patients; for each of them, we draw the two prostheses configurations, which are characterized by different mechanical properties and we also consider the native configuration. For each of these scenarios, we solve the fluid-structure interaction problem arising between blood and aortic root, through Finite Elements. In particular, the Arbitrary Lagrangian-Eulerian formulation is used for the numerical solution of the fluid-dynamic equations and a hyperelastic material model is adopted to predict the mechanical response of the aortic wall and the two prostheses. The computational results are analyzed in terms of aortic flow, internal wall stresses and aortic wall/prosthesis displacements; a quantitative comparison of the mechanical behavior of the three scenarios is reported. The numerical results highlight a good agreement between stentless and native displacements and internal wall stresses, whereas higher/non-physiological stresses are found for the stented case.

Immersed smoothed finite element method for fluid-structure interaction simulation of aortic valves

NASA Astrophysics Data System (ADS)

Yao, Jianyao; Liu, G. R.; Narmoneva, Daria A.; Hinton, Robert B.; Zhang, Zhi-Qian

2012-12-01

This paper presents a novel numerical method for simulating the fluid-structure interaction (FSI) problems when blood flows over aortic valves. The method uses the immersed boundary/element method and the smoothed finite element method and hence it is termed as IS-FEM. The IS-FEM is a partitioned approach and does not need a body-fitted mesh for FSI simulations. It consists of three main modules: the fluid solver, the solid solver and the FSI force solver. In this work, the blood is modeled as incompressible viscous flow and solved using the characteristic-based-split scheme with FEM for spacial discretization. The leaflets of the aortic valve are modeled as Mooney-Rivlin hyperelastic materials and solved using smoothed finite element method (or S-FEM). The FSI force is calculated on the Lagrangian fictitious fluid mesh that is identical to the moving solid mesh. The octree search and neighbor-to-neighbor schemes are used to detect efficiently the FSI pairs of fluid and solid cells. As an example, a 3D idealized model of aortic valve is modeled, and the opening process of the valve is simulated using the proposed IS-FEM. Numerical results indicate that the IS-FEM can serve as an efficient tool in the study of aortic valve dynamics to reveal the details of stresses in the aortic valves, the flow velocities in the blood, and the shear forces on the interfaces. This tool can also be applied to animal models studying disease processes and may ultimately translate to a new adaptive methods working with magnetic resonance images, leading to improvements on diagnostic and prognostic paradigms, as well as surgical planning, in the care of patients.

The Influence of Blood Pressure on Fetal Aortic Distensibility: An Animal Validation Study.

PubMed

Wohlmuth, Christoph; Moise, Kenneth J; Papanna, Ramesha; Gheorghe, Ciprian; Johnson, Anthony; Morales, Yisel; Gardiner, Helena M

2018-01-01

Aortic distension waveforms describe the change in diameter or cross-sectional area over the cardiac cycle. We aimed to validate the association of aortic fractional area change (AFAC) with blood pressure (BP) in a fetal lamb model. Four pregnant ewes underwent open fetal surgery under general anesthesia at 107-120 gestational days. A 4-Fr catheter was introduced into the fetal femoral artery and vein, or the carotid artery and jugular vein. The thoracic aorta was imaged using real-time ultrasound; AFAC was calculated using offline speckle tracking software. Measurements of invasive BP and AFAC were obtained simultaneously and averaged over 10 cardiac cycles. BP was increased by norepinephrine infusion and the association of aortic distensibility with BP was assessed. Baseline measurements were obtained from 4 lambs, and changes in aortic distensibility with increasing BP were recorded from 3 of them. A positive correlation was found between AFAC and systolic BP (r = 0.692, p = 0.001), diastolic BP (r = 0.647, p = 0.004), mean BP (r = 0.692, p = 0.001), and BP amplitude (r = 0.558, p = 0.016) controlled for heart rate. No association was found between BP and maximum or minimum aortic area. AFAC provides a quantifiable measure of aortic distensibility and correlates with systolic BP, diastolic BP, mean BP, and BP amplitude in a fetal lamb model. © 2017 S. Karger AG, Basel.

Strain measurement of abdominal aortic aneurysm with real-time 3D ultrasound speckle tracking.

PubMed

Bihari, P; Shelke, A; Nwe, T H; Mularczyk, M; Nelson, K; Schmandra, T; Knez, P; Schmitz-Rixen, T

2013-04-01

Abdominal aortic aneurysm rupture is caused by mechanical vascular tissue failure. Although mechanical properties within the aneurysm vary, currently available ultrasound methods assess only one cross-sectional segment of the aorta. This study aims to establish real-time 3-dimensional (3D) speckle tracking ultrasound to explore local displacement and strain parameters of the whole abdominal aortic aneurysm. Validation was performed on a silicone aneurysm model, perfused in a pulsatile artificial circulatory system. Wall motion of the silicone model was measured simultaneously with a commercial real-time 3D speckle tracking ultrasound system and either with laser-scan micrometry or with video photogrammetry. After validation, 3D ultrasound data were collected from abdominal aortic aneurysms of five patients and displacement and strain parameters were analysed. Displacement parameters measured in vitro by 3D ultrasound and laser scan micrometer or video analysis were significantly correlated at pulse pressures between 40 and 80 mmHg. Strong local differences in displacement and strain were identified within the aortic aneurysms of patients. Local wall strain of the whole abdominal aortic aneurysm can be analysed in vivo with real-time 3D ultrasound speckle tracking imaging, offering the prospect of individual non-invasive rupture risk analysis of abdominal aortic aneurysms. Copyright © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Effect of the Antioxidant Lipoic Acid in Aortic Phenotype in a Marfan Syndrome Mouse Model

PubMed Central

Debbas, Victor; Salemi, Vera M.; Tavares, Elaine R.; Meirelles, Thayna; Ferreira-Filho, Julio C. A.; Takimura, Celso K.; Pereira, Lygia V.; Laurindo, Francisco R.

2018-01-01

Marfan syndrome (MFS) cardiovascular manifestations such as aortic aneurysms and cardiomyopathy carry substantial morbidity/mortality. We investigated the effects of lipoic acid, an antioxidant, on ROS production and aortic remodeling in a MFS mgΔloxPneo mouse model. MFS and WT (wild-type) 1-month-old mice were allocated to 3 groups: untreated, treated with losartan, and treated with lipoic acid. At 6 months old, echocardiography, ROS production, and morphological analysis of aortas were performed. Aortic ROS generation in 6-month-old MFS animals was higher at advanced stages of disease in MFS. An unprecedented finding in MFS mice analyzed by OCT was the occurrence of focal inhomogeneous regions in the aortic arch, either collagen-rich extremely thickened or collagen-poor hypotrophic regions. MFS animals treated with lipoic acid showed markedly reduced ROS production and lower ERK1/2 phosphorylation; meanwhile, aortic dilation and elastic fiber breakdown were unaltered. Of note, lipoic acid treatment associated with the absence of focal inhomogeneous regions in MFS animals. Losartan reduced aortic dilation and elastic fiber breakdown despite no change in ROS generation. In conclusion, oxidant generation by itself seems neutral with respect to aneurysm progression in MFS; however, lipoic acid-mediated reduction of inhomogeneous regions may potentially associate with less anisotropy and reduced chance of dissection/rupture. PMID:29765495

Oral administration of the antioxidant, N-acetylcysteine, abrogates diabetes-induced endothelial dysfunction.

PubMed

Pieper, G M; Siebeneich, W

1998-07-01

Oxidative stress is believed to play an important role in the development of vascular complications associated with diabetes mellitus. In this study, we examined the efficacy of long-term treatment with the antioxidant, N-acetylcysteine, in preventing the development of defective endothelium-dependent relaxation in streptozotocin-induced, Sprague-Dawley diabetic rats. At 48 h after injection of streptozotocin, a portion of diabetic rats received 250 mg/L N-acetylcysteine in drinking water for a total duration of 8 weeks. Oral administration did not alter the increase in blood glucose or the reduction in serum insulin but did modestly reduce total glycosylated hemoglobin. In precontracted thoracic aortic rings suspended in isolated tissue baths, endothelium-dependent relaxation to acetylcholine was impaired in diabetic rings compared with control rings. Endothelium-independent relaxation to nitroglycerin was unaltered. Long-term oral administration of N-acetylcysteine did not alter responses to nitroglycerin but completely prevented the defective relaxation to acetylcholine. These studies indicate a dissociation between glycemic control and correction of endothelial dysfunction and suggest that long-term exposure to reactive oxygen subsequent to diabetes rather than hyperglycemia per se is responsible for the development of endothelial dysfunction in diabetes mellitus.

Finite element analysis of TAVI: Impact of native aortic root computational modeling strategies on simulation outcomes.

PubMed

Finotello, Alice; Morganti, Simone; Auricchio, Ferdinando

2017-09-01

In the last few years, several studies, each with different aim and modeling detail, have been proposed to investigate transcatheter aortic valve implantation (TAVI) with finite elements. The present work focuses on the patient-specific finite element modeling of the aortic valve complex. In particular, we aim at investigating how different modeling strategies in terms of material models/properties and discretization procedures can impact analysis results. Four different choices both for the mesh size (from  20 k elements to  200 k elements) and for the material model (from rigid to hyperelastic anisotropic) are considered. Different approaches for modeling calcifications are also taken into account. Post-operative CT data of the real implant are used as reference solution with the aim of outlining a trade-off between computational model complexity and reliability of the results. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

Effects of intra-aortic balloon counterpulsation in a model of septic shock.

PubMed

Solomon, Steven B; Minneci, Peter C; Deans, Katherine J; Feng, Jing; Eichacker, Peter Q; Banks, Steven M; Danner, Robert L; Natanson, Charles; Solomon, Michael A

2009-01-01

Fluid refractory septic shock can develop into a hypodynamic cardiovascular state in both children and adults. Despite management of these patients with empirical inotropic therapy (with or without a vasodilator), mortality remains high. The effect of cardiovascular support using intra-aortic balloon counterpulsation was investigated in a hypodynamic, mechanically ventilated canine sepsis model in which cardiovascular and pulmonary support were titrated based on treatment protocols. Each week, three animals (n = 33, 10-12 kg) were administered intrabronchial Staphylococcus aureus challenge and then randomized to receive intra-aortic balloon counterpulsation for 68 hrs or no intra-aortic balloon counterpulsation (control). Bacterial doses were increased over the study (4-8 x 10(9) cfu/kg) to assess the effects of intra-aortic balloon counterpulsation during sepsis with increasing risk of death. Compared with lower bacterial doses (4-7 x 10(9) colony-forming units/kg), control animals challenged with the highest dose (8 x 10(9) colony-forming units/kg) had a greater risk of death (mortality rate 86% vs. 17%), with worse lung injury ([A - a]O2), and renal dysfunction (creatinine). These sicker animals required higher norepinephrine infusion rates to maintain blood pressure (and higher FIO2) and positive end-expiratory pressure levels to maintain oxygenation (p < or = 0.04 for all). In animals receiving the highest bacterial dose, intra-aortic balloon counterpulsation improved survival time (23.4 +/- 10 hrs longer; p = 0.003) and lowered norepinephrine requirements (0.43 +/- 0.17 microg/kg/min; p = 0.002) and systemic vascular resistance index (1.44 +/- 0.57 dynes/s/cm5/kg; p = 0.0001) compared with controls. Despite these beneficial effects, intra-aortic balloon counterpulsation was associated with an increase in blood urea nitrogen (p = 0.002) and creatinine (p = 0.12). In animals receiving lower doses of bacteria, intra-aortic balloon counterpulsation had no significant effects on survival or renal function. In a canine model of severe septic shock with a low cardiac index, intra-aortic balloon counterpulsation prolongs survival time and lowers vasopressor requirements.

Aortic Root Biomechanics After Sleeve and David Sparing Techniques: A Finite Element Analysis.

PubMed

Tasca, Giordano; Selmi, Matteo; Votta, Emiliano; Redaelli, Paola; Sturla, Francesco; Redaelli, Alberto; Gamba, Amando

2017-05-01

Aortic root aneurysm can be treated with valve-sparing procedures. The David and Yacoub techniques have shown excellent long-term results but are technically demanding. Recently, a new and simpler procedure, the Sleeve technique, was proposed with encouraging results. We aimed to quantify the biomechanics of the initially aneurysmal aortic root (AR) after the Sleeve procedure to assess whether it induces abnormal stresses, potentially undermining its durability. Two finite element (FE) models of the physiologic and aneurysmal AR were built, accounting for the anatomical asymmetry and the nonlinear and anisotropic mechanical properties of human AR tissues. On the aneurysmal model, the Sleeve and David techniques were simulated based on the corresponding published technical features. Aortic root biomechanics throughout 2 consecutive cardiac cycles were computed in each simulated configuration. Both sparing techniques restored physiologic-like kinematics of aortic valve (AV) leaflets but induced different leaflets stresses. The time course averaged over the leaflets' bellies was 35% higher in the David model than in the Sleeve model. Commissural stresses, which were equal to 153 and 318 kPa in the physiologic and aneurysmal models, respectively, became 369 and 208 kPa in the David and Sleeve models, respectively. No intrinsic structural problems were detected in the Sleeve model that might jeopardize the durability of the procedure. If corroborated by long-term clinical outcomes, the results obtained suggest that using this new technique could successfully simplify the surgical repair of AR aneurysms and reduce intraoperative complications. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Regional aortic distensibility and its relationship with age and aortic stenosis: a computed tomography study.

PubMed

Wong, Dennis T L; Narayan, Om; Leong, Darryl P; Bertaso, Angela G; Maia, Murilo G; Ko, Brian S H; Baillie, Timothy; Seneviratne, Sujith K; Worthley, Matthew I; Meredith, Ian T; Cameron, James D

2015-06-01

Aortic distensibility (AD) decreases with age and increased aortic stiffness is independently associated with adverse cardiovascular outcomes. The association of severe aortic stenosis (AS) with AD in different aortic regions has not been evaluated. Elderly subjects with severe AS and a cohort of patients without AS of similar age were studied. Proximal aortic cross-sectional-area changes during the cardiac cycle were determined using retrospective-ECG-gating on 128-detector row computed-tomography. Using oscillometric-brachial-blood-pressure measurements, the AD at the ascending-aorta (AA), proximal-descending-aorta (PDA) and distal-descending-aorta (DDA) was determined. Linear mixed effects modelling was used to determine the association of age and aortic stenosis on regional AD. 102 patients were evaluated: 36 AS patients (70-85 years), 24 AS patients (>85 years) and 42 patients without AS (9 patients <50 years, 20 patients between 51-70 years and 13 patients 70-85 years). When comparing patients 70-85 years, AA distensibility was significantly lower in those with AS compared to those without AS (0.9 ± 0.9 vs. 1.4 ± 1.1, P = 0.03) while there was no difference in the PDA (1.0 ± 1.1 vs. 1.0 ± 1.2, P = 0.26) and DDA (1.1 ± 1.2 vs. 1.2 ± 0.8, P = 0.97). In patients without AS, AD decreased with age in all aortic regions (P < 0.001). The AA in patients <50 years were the most distensible compared to other aortic regions. There is regional variation in aortic distensibility with aging. Patients with aortic stenosis demonstrated regional differences in aortic distensibility with lower distensibility demonstrated in the proximal ascending aorta compared to an age-matched cohort.

Development of an Experimental Model to Study the Relationship Between Day-to-Day Variability in Blood Pressure and Aortic Stiffness

PubMed Central

Bouissou-Schurtz, Camille; Lindesay, Georges; Regnault, Véronique; Renet, Sophie; Safar, Michel E.; Molinie, Vincent; Dabire, Hubert; Bezie, Yvonnick

2015-01-01

We aimed to develop an animal model of long-term blood pressure variability (BPV) and to investigate its consequences on aortic damage. We hypothesized that day-to-day BPV produced by discontinuous treatment of spontaneously hypertensive rats (SHR) by valsartan may increase arterial stiffness. For that purpose, rats were discontinuously treated, 2 days a week, or continuously treated by valsartan (30 mg/kg/d in chow) or placebo. Telemetered BP was recorded during 2 min every 15 min, 3 days a week during 8 weeks to cover the full BP variations in response to the treatment schedule. Pulse wave velocity (PWV) and aortic structure evaluated by immunohistochemistry were investigated in a second set of rats treated under the same conditions. Continuous treatment with valsartan reduced systolic BP (SBP) and reversed the aortic structural alterations observed in placebo treated SHR (decrease of medial cross-sectional area). Discontinuous treatment with valsartan decreased SBP to a similar extent but increased the day-to-day BPV, short term BPV, diastolic blood pressure (DBP), and PWV as compared with continuous treatment. Despite no modifications in the elastin/collagen ratio and aortic thickness, an increase in PWV was observed following discontinuous treatment and was associated with a specific accumulation of fibronectin and its αv-integrin receptor compared with both groups of rats. Taken together the present results indicate that a discontinuous treatment with valsartan is able to induce a significant increase in day-to-day BPV coupled to an aortic phenotype close to that observed in hypertension. This experimental model should pave the way for future experimental and clinical studies aimed at assessing how long-term BPV increases aortic stiffness. PMID:26696902

Cardiovascular Benefits of Moderate Exercise Training in Marfan Syndrome: Insights From an Animal Model.

PubMed

Mas-Stachurska, Aleksandra; Siegert, Anna-Maria; Batlle, Monsterrat; Gorbenko Del Blanco, Darya; Meirelles, Thayna; Rubies, Cira; Bonorino, Fabio; Serra-Peinado, Carla; Bijnens, Bart; Baudin, Julio; Sitges, Marta; Mont, Lluís; Guasch, Eduard; Egea, Gustavo

2017-09-25

Marfan syndrome (MF) leads to aortic root dilatation and a predisposition to aortic dissection, mitral valve prolapse, and primary and secondary cardiomyopathy. Overall, regular physical exercise is recommended for a healthy lifestyle, but dynamic sports are strongly discouraged in MF patients. Nonetheless, evidence supporting this recommendation is lacking. Therefore, we studied the role of long-term dynamic exercise of moderate intensity on the MF cardiovascular phenotype. In a transgenic mouse model of MF ( Fbn1 C1039G/+ ), 4-month-old wild-type and MF mice were subjected to training on a treadmill for 5 months; sedentary littermates served as controls for each group. Aortic and cardiac remodeling was assessed by echocardiography and histology. The 4-month-old MF mice showed aortic root dilatation, elastic lamina rupture, and tunica media fibrosis, as well as cardiac hypertrophy, left ventricular fibrosis, and intramyocardial vessel remodeling. Over the 5-month experimental period, aortic root dilation rate was significantly greater in the sedentary MF group, compared with the wild-type group (∆mm, 0.27±0.07 versus 0.13±0.02, respectively). Exercise significantly blunted the aortic root dilation rate in MF mice compared with sedentary MF littermates (∆mm, 0.10±0.04 versus 0.27±0.07, respectively). However, these 2 groups were indistinguishable by aortic root stiffness, tunica media fibrosis, and elastic lamina ruptures. In MF mice, exercise also produced cardiac hypertrophy regression without changes in left ventricular fibrosis. Our results in a transgenic mouse model of MF indicate that moderate dynamic exercise mitigates the progression of the MF cardiovascular phenotype. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Computed Tomography Imaging Features in Acute Uncomplicated Stanford Type-B Aortic Dissection Predict Late Adverse Events.

PubMed

Sailer, Anna M; van Kuijk, Sander M J; Nelemans, Patricia J; Chin, Anne S; Kino, Aya; Huininga, Mark; Schmidt, Johanna; Mistelbauer, Gabriel; Bäumler, Kathrin; Chiu, Peter; Fischbein, Michael P; Dake, Michael D; Miller, D Craig; Schurink, Geert Willem H; Fleischmann, Dominik

2017-04-01

Medical treatment of initially uncomplicated acute Stanford type-B aortic dissection is associated with a high rate of late adverse events. Identification of individuals who potentially benefit from preventive endografting is highly desirable. The association of computed tomography imaging features with late adverse events was retrospectively assessed in 83 patients with acute uncomplicated Stanford type-B aortic dissection, followed over a median of 850 (interquartile range 247-1824) days. Adverse events were defined as fatal or nonfatal aortic rupture, rapid aortic growth (>10 mm/y), aneurysm formation (≥6 cm), organ or limb ischemia, or new uncontrollable hypertension or pain. Five significant predictors were identified using multivariable Cox regression analysis: connective tissue disease (hazard ratio [HR] 2.94, 95% confidence interval [CI]: 1.29-6.72; P =0.01), circumferential extent of false lumen in angular degrees (HR 1.03 per degree, 95% CI: 1.01-1.04, P =0.003), maximum aortic diameter (HR 1.10 per mm, 95% CI: 1.02-1.18, P =0.015), false lumen outflow (HR 0.999 per mL/min, 95% CI: 0.998-1.000; P =0.055), and number of intercostal arteries (HR 0.89 per n, 95% CI: 0.80-0.98; P =0.024). A prediction model was constructed to calculate patient specific risk at 1, 2, and 5 years and to stratify patients into high-, intermediate-, and low-risk groups. The model was internally validated by bootstrapping and showed good discriminatory ability with an optimism-corrected C statistic of 70.1%. Computed tomography imaging-based morphological features combined into a prediction model may be able to identify patients at high risk for late adverse events after an initially uncomplicated type-B aortic dissection. © 2017 American Heart Association, Inc.

Uric acid in aortic dissection: A meta-analysis.

PubMed

Li, Xiaodong; Jiang, Shanshan; He, Jiaan; Li, Nan; Fan, Yichuan; Zhao, Xingzhi; Hu, Xinhua

2018-06-04

Studies on the serum uric acid levels in patients with aortic dissection have yielded conflicting results. To compare the difference in serum uric acid (SUA) levels between aortic dissection patients and controls by meta-analysis. Electronic literature search was conducted in PubMed, Embase, CKNI, CBM, Wanfang, and VIP databases until January 31, 2018. All observational studies that investigated SUA levels in aortic dissection patients and controls were included. Weighted mean difference (WMD) with 95% confidence intervals (CI) was used to summarize the difference in SUA levels between aortic dissection and control group. A total of seven case-control studies involving 1197 patients and 1193 controls were included. Pooled analysis showed that SUA levels were significantly higher in aortic dissection patients compared with those in the controls (WMD 58.22 μmol/L; 95% CI 26.71-89.73) in a random effect model. No significant difference (WMD 9.94 μmol/L; 95% CI -17.89-37.76) was observed in SUA levels between Stanford type A and Stanford type B aortic dissection. This meta-analysis provides evidence that SUA levels are significantly higher among patients with aortic dissection than those in controls. Elevated SUA levels may contribute to the pathogenesis of aortic dissection. Further large clinical studies to investigate whether SUA levels are an independently risk factor for aortic dissection are warranted. Copyright © 2018 Elsevier B.V. All rights reserved.

A cost-utility analysis of transcatheter versus surgical aortic valve replacement for the treatment of aortic stenosis in the population with intermediate surgical risk.

PubMed

Tam, Derrick Y; Hughes, Avery; Fremes, Stephen E; Youn, Saerom; Hancock-Howard, Rebecca L; Coyte, Peter C; Wijeysundera, Harindra C

2018-05-01

Although transcatheter aortic valve implantation has been shown to be noninferior to surgical aortic valve replacement in patients with severe aortic stenosis at intermediate surgical risk, the cost-effectiveness of this strategy in this population is unknown. Our objective was to conduct a cost-utility analysis comparing transcatheter aortic valve implantation with surgical aortic valve replacement in the population with intermediate risk severe aortic stenosis. A fully probabilistic Markov model with 30-day cycles was constructed from the Canadian third-party payer's perspective to estimate the difference in cost and effectiveness (measured as quality-adjusted life years) of transcatheter aortic valve implantation versus surgical aortic valve replacement for intermediate-risk patients over a lifetime time horizon, discounted at 1.5% per annum. Clinical trial data from The Placement of Aortic Transcatheter Valve 2 informed the efficacy inputs. Costs (adjusted to 2016 Canadian dollars) were obtained from the Canadian Institute of Health Information and the Ontario Schedule of Benefits. Incremental cost-effectiveness ratios were calculated. In the base-case analysis, total lifetime costs for transcatheter aortic valve implantation were $10,548 higher than surgical aortic valve replacement but added 0.23 quality-adjusted life years, for an incremental cost-effectiveness ratio of $46,083/quality-adjusted life-years gained. Deterministic 1-way analyses showed that the incremental cost-effectiveness ratio was sensitive to rates of complications and cost of the transcatheter aortic valve implantation prosthesis. There was moderate-to-high parameter uncertainty; transcatheter aortic valve implantation was the preferred option in only 52.7% and 55.4% of the simulations at a $50,000 and $100,000 per quality-adjusted life years willingness-to-pay thresholds, respectively. On the basis of current evidence, transcatheter aortic valve implantation may be cost-effective for the treatment of severe aortic stenosis in patients with intermediate surgical risk. There remains moderate-to-high uncertainty surrounding the base-case incremental cost-effectiveness ratio. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

A Web-based nomogram predicting para-aortic nodal metastasis in incompletely staged patients with endometrial cancer: a Korean Multicenter Study.

PubMed

Kang, Sokbom; Lee, Jong-Min; Lee, Jae-Kwan; Kim, Jae-Weon; Cho, Chi-Heum; Kim, Seok-Mo; Park, Sang-Yoon; Park, Chan-Yong; Kim, Ki-Tae

2014-03-01

The purpose of this study is to develop a Web-based nomogram for predicting the individualized risk of para-aortic nodal metastasis in incompletely staged patients with endometrial cancer. From 8 institutions, the medical records of 397 patients who underwent pelvic and para-aortic lymphadenectomy as a surgical staging procedure were retrospectively reviewed. A multivariate logistic regression model was created and internally validated by rigorous bootstrap resampling methods. Finally, the model was transformed into a user-friendly Web-based nomogram (http://http://www.kgog.org/nomogram/empa001.html). The rate of para-aortic nodal metastasis was 14.4% (57/397 patients). Using a stepwise variable selection, 4 variables including deep myometrial invasion, non-endometrioid subtype, lymphovascular space invasion, and log-transformed CA-125 levels were finally adopted. After 1000 repetitions of bootstrapping, all of these 4 variables retained a significant association with para-aortic nodal metastasis in the multivariate analysis-deep myometrial invasion (P = 0.001), non-endometrioid histologic subtype (P = 0.034), lymphovascular space invasion (P = 0.003), and log-transformed serum CA-125 levels (P = 0.004). The model showed good discrimination (C statistics = 0.87; 95% confidence interval, 0.82-0.92) and accurate calibration (Hosmer-Lemeshow P = 0.74). This nomogram showed good performance in predicting para-aortic metastasis in patients with endometrial cancer. The tool may be useful in determining the extent of lymphadenectomy after incomplete surgery.

Tissue expander stimulated lengthening of arteries (TESLA) induces early endothelial cell proliferation in a novel rodent model.

PubMed

Potanos, Kristina; Fullington, Nora; Cauley, Ryan; Purcell, Patricia; Zurakowski, David; Fishman, Steven; Vakili, Khashayar; Kim, Heung Bae

2016-04-01

We examine the mechanism of aortic lengthening in a novel rodent model of tissue expander stimulated lengthening of arteries (TESLA). A rat model of TESLA was examined with a single stretch stimulus applied at the time of tissue expander insertion with evaluation of the aorta at 2, 4 and 7day time points. Measurements as well as histology and proliferation assays were performed and compared to sham controls. The aortic length was increased at all time points without histologic signs of tissue injury. Nuclear density remained unchanged despite the increase in length suggesting cellular hyperplasia. Cellular proliferation was confirmed in endothelial cell layer by Ki-67 stain. Aortic lengthening may be achieved using TESLA. The increase in aortic length can be achieved without tissue injury and results at least partially from cellular hyperplasia. Further studies are required to define the mechanisms involved in the growth of arteries under increased longitudinal stress. Copyright © 2015 Elsevier Inc. All rights reserved.

On the prediction of monocyte deposition in abdominal aortic aneurysms using computational fluid dynamics.

PubMed

Hardman, David; Doyle, Barry J; Semple, Scott I K; Richards, Jennifer M J; Newby, David E; Easson, William J; Hoskins, Peter R

2013-10-01

In abdominal aortic aneurysm disease, the aortic wall is exposed to intense biological activity involving inflammation and matrix metalloproteinase-mediated degradation of the extracellular matrix. These processes are orchestrated by monocytes and rather than affecting the aorta uniformly, damage and weaken focal areas of the wall leaving it vulnerable to rupture. This study attempts to model numerically the deposition of monocytes using large eddy simulation, discrete phase modelling and near-wall particle residence time. The model was first applied to idealised aneurysms and then to three patient-specific lumen geometries using three-component inlet velocities derived from phase-contrast magnetic resonance imaging. The use of a novel, variable wall shear stress-limiter based on previous experimental data significantly improved the results. Simulations identified a critical diameter (1.8 times the inlet diameter) beyond which significant monocyte deposition is expected to occur. Monocyte adhesion occurred proximally in smaller abdominal aortic aneurysms and distally as the sac expands. The near-wall particle residence time observed in each of the patient-specific models was markedly different. Discrete hotspots of monocyte residence time were detected, suggesting that the monocyte infiltration responsible for the breakdown of the abdominal aortic aneurysm wall occurs heterogeneously. Peak monocyte residence time was found to increase with aneurysm sac size. Further work addressing certain limitations is needed in a larger cohort to determine clinical significance.

Establishment of a rat and guinea pig aortic interposition graft model reveals model-specific patterns of intimal hyperplasia.

PubMed

Gregory, Elaine K; Vercammen, Janet M; Flynn, Megan E; Kibbe, Melina R

2016-12-01

Although the aortic interposition bypass model has been widely used to evaluate biomaterials for bypass grafting, there is no comprehensive description of the procedure or of the distribution of intimal hyperplasia that results. The objectives of this study were to (1) review and summarize approaches of aortic interposition grafting in animal models, (2) determine the pertinent anatomy for this procedure, (3) validate this model in the rat and guinea pig, and (4) compare the distribution of intimal hyperplasia that develops in each species. A literature search was performed in PubMed from 1980 to the present to analyze the use of anesthesia, anticoagulation, antiplatelet agents, graft material, suture, and anastomotic techniques. Using 10-week-old male Sprague-Dawley rats and Hartley guinea pigs, we established pertinent aortic anatomy, developed comparable models, and assessed complications for each model. At 30 days, the graft and associated aorta were explanted, intimal formation was assessed morphometrically, and cellularity was assessed via nuclear counting. We reviewed 30 articles and summarized the pertinent procedural findings. Upon establishing both animal models, key anatomic differences between the species that affect this model were noted. Guinea pigs have a much larger cecum, increased retroperitoneal fat, and lack the iliolumbar vessels compared with the rat. Surgical outcomes for the rat model included a 53% technical success rate and a 32% technical error rate. Surgical outcomes for the guinea pig model included a 69% technical success rate and a 31% technical error rate. These two species demonstrated unique distribution of intimal hyperplasia at 30 days. Intimal hyperplasia in the rat model was greatest at two areas, the proximal graft (5400 μm 2 ; P < .001) and distal graft (2800 μm 2 ; P < .04), whereas the guinea pig model developed similar intimal hyperplasia throughout the graft (4500-5100 μm 2 ; P < .01). In this report, we summarize the literature on the aortic interposition graft model, present a detailed description of the anatomy and aortic interposition graft procedure in the rat and guinea pig, and describe a unique distribution of intimal formation that results in both species. This information will be helpful when designing studies to evaluate novel graft materials in the future. Published by Elsevier Inc.

Far Forward Battlefield Telemedicine: Ultrasonic Guidance in Diagnosis and Emergency Therapeutics

DTIC Science & Technology

2006-08-01

bicuspid aortic stenosis . J Am Soc Echocardiogr. 2005 Dec;18(12):1392-8. 44. Eto Y, Yamada H, Shin JH, Agler DA, Tsujino H, Qin JX, Saracino G, Greenberg...nitroprusside in aortic stenosis associated with severe heart failure: pressure- volume loop analysis using a numerical model. Am J Physiol Heart Circ...3D echocardiography, including exercise and intraoperative (epicardial) examinations, with quantitative validation in aneurysmal ventricles,3 aortic

INCLUDING AORTIC VALVE MORPHOLOGY IN COMPUTATIONAL FLUID DYNAMICS SIMULATIONS: INITIAL FINDINGS AND APPLICATION TO AORTIC COARCTATION

PubMed Central

Wendell, David C.; Samyn, Margaret M.; Cava, Joseph R.; Ellwein, Laura M.; Krolikowski, Mary M.; Gandy, Kimberly L.; Pelech, Andrew N.; Shadden, Shawn C.; LaDisa, John F.

2012-01-01

Computational fluid dynamics (CFD) simulations quantifying thoracic aortic flow patterns have not included disturbances from the aortic valve (AoV). 80% of patients with aortic coarctation (CoA) have a bicuspid aortic valve (BAV) which may cause adverse flow patterns contributing to morbidity. Our objectives were to develop a method to account for the AoV in CFD simulations, and quantify its impact on local hemodynamics. The method developed facilitates segmentation of the AoV, spatiotemporal interpolation of segments, and anatomic positioning of segments at the CFD model inlet. The AoV was included in CFD model examples of a normal (tricuspid AoV) and a post-surgical CoA patient (BAV). Velocity, turbulent kinetic energy (TKE), time-averaged wall shear stress (TAWSS), and oscillatory shear index (OSI) results were compared to equivalent simulations using a plug inlet profile. The plug inlet greatly underestimated TKE for both examples. TAWSS differences extended throughout the thoracic aorta for the CoA BAV, but were limited to the arch for the normal example. OSI differences existed mainly in the ascending aorta for both cases. The impact of AoV can now be included with CFD simulations to identify regions of deleterious hemodynamics thereby advancing simulations of the thoracic aorta one step closer to reality. PMID:22917990

Further insights into normal aortic valve function: role of a compliant aortic root on leaflet opening and valve orifice area.

PubMed

Sripathi, Vangipuram Canchi; Kumar, Ramarathnam Krishna; Balakrishnan, Komarakshi R

2004-03-01

This study aims to find the fundamental differences in the mechanism of opening and closing of a normal aortic valve and a valve with a stiff root, using a dynamic finite element model. A dynamic, finite element model with time varying pressure was used in this study. Shell elements with linear elastic properties for the leaflet and root were used. Two different cases were analyzed: (1) normal leaflets inside a compliant root, and (2) normal leaflets inside a stiff root. A compliant aortic root contributes substantially to the smooth and symmetrical leaflet opening with minimal gradients. In contrast, the leaflet opening inside a stiff root is delayed, asymmetric, and wrinkled. However, this wrinkling is not associated with increased leaflet stresses. In compliant roots, the effective valve orifice area can substantially increase because of increased root pressure and transvalvular gradients. In stiff roots this effect is strikingly absent. A compliant aortic root contributes substantially to smooth and symmetrical leaflet opening with minimal gradients. The compliance also contributes much to the ability of the normal aortic valve to increase its effective valve orifice in response to physiologic demands of exercise. This effect is strikingly absent in stiff roots.

Comparison and usefulness of cardiac magnetic resonance versus computed tomography in infants six months of age or younger with aortic arch anomalies without deep sedation or anesthesia.

PubMed

Fogel, Mark A; Pawlowski, Thomas W; Harris, Matthew A; Whitehead, Kevin K; Keller, Marc S; Wilson, Justine; Tipton, Deanna; Harris, Christine

2011-07-01

The present project investigated whether cardiac magnetic resonance (CMR) of aortic arch anomalies can be performed successfully in infants <6 months of age without the use of cardiac anesthesia or deep sedation. We performed a retrospective review of infants ≤6 months old from 2005 to 2009 who underwent either CMR or computed tomography angiography to investigate aortic arch abnormalities. The CMR procedure used a "feed and swaddle" protocol without deep sedation or cardiac anesthesia. Of the 52 infants referred for CMR, 24 underwent the feed and swaddle protocol (aged 2.6 ± 1.4 months). One patient awoke during the study, and examination of the remaining 23 yielded a definitive diagnosis (success rate 96%). The scanning time was 6.2 ± 3.1 minutes, with the large airways evaluation accounting for 1/2 the time. Single-shot axial steady-state free precession, in which the definitive diagnosis was made, accounted for 0.59 ± 0.3 minutes. Fifteen infants were diagnosed with a vascular ring. Of the 8 infants who underwent surgery, the diagnostic accuracy was 100%. During the same period, 19 patients, who had undergone computed tomography angiography (aged 1.67 ± 1.20 months), were referred for aortic arch evaluation. Of these 19 patients, 6 (32%) underwent sedation or anesthesia. The imaging time was 0.08 ± 0.06 minutes, significantly different from the CMR times (p <0.01). However, the overall room times (31.3 ± 22.3 and 35.8 ± 3.86 minutes, respectively) were not different between the CMR and angiographic groups. The radiation dose was 1.41 ± 1.03 mSv. In conclusion, CMR evaluation of aortic arch anomalies in children <6 months old can be successfully completed quickly using a feed and swaddle approach with high diagnostic accuracy. This protocol avoids the risks of sedation, as well as the radiation associated with computed tomography angiography. Copyright © 2011 Elsevier Inc. All rights reserved.

A Structural Finite Element Model for Lamellar Unit of Aortic Media Indicates Heterogeneous Stress Field After Collagen Recruitment

PubMed Central

Thunes, James R.; Pal, Siladitya; Fortunato, Ronald N.; Phillippi, Julie A.; Gleason, Thomas G.; Vorp, David A.; Maiti, Spandan

2016-01-01

Incorporation of collagen structural information into the study of biomechanical behavior of ascending thoracic aortic (ATA) wall tissue should provide better insight into the pathophysiology of ATA. Structurally motivated constitutive models that include fiber dispersion and recruitment can successfully capture overall mechanical response of the arterial wall tissue. However, these models cannot examine local microarchitectural features of the collagen network, such as the effect of fiber disruptions and interaction between fibrous and non-fibrous components, which may influence emergent biomechanical properties of the tissue. Motivated by this need, we developed a finite element based three-dimensional structural model of the lamellar units of the ATA media that directly incorporates the collagen fiber microarchitecture. The fiber architecture was computer generated utilizing network features, namely fiber orientation distribution, intersection density and areal concentration, obtained from image analysis of multiphoton microscopy images taken from human aneurysmal ascending thoracic aortic media specimens with bicuspid aortic valve (BAV) phenotype. Our model reproduces the typical J-shaped constitutive response of the aortic wall tissue. We found that the stress state in the non-fibrous matrix was homogeneous until the collagen fibers were recruited, but became highly heterogeneous after that event. The degree of heterogeneity was dependent upon local network architecture with high stresses observed near disrupted fibers. The magnitude of non-fibrous matrix stress at higher stretch levels was negatively correlated with local fiber density. The localized stress concentrations, elucidated by this model, may be a factor in the degenerative changes in aneurysmal ATA tissue. PMID:27113538

The influence of prototype testing in three-dimensional aortic models on fenestrated endograft design.

PubMed

Taher, Fadi; Falkensammer, Juergen; McCarte, Jamie; Strassegger, Johann; Uhlmann, Miriam; Schuch, Philipp; Assadian, Afshin

2017-06-01

The fenestrated Anaconda endograft (Vascutek/Terumo, Inchinnan, UK) is intended for the treatment of abdominal aortic aneurysms with an insufficient infrarenal landing zone. The endografts are custom-made with use of high-resolution, 1-mm-slice computed tomography angiography images. For every case, a nonsterile prototype and a three-dimensional (3D) model of the patient's aorta are constructed to allow the engineers as well as the physician to test-implant the device and to review the fit of the graft. The aim of this investigation was to assess the impact of 3D model construction and prototype testing on the design of the final sterile endograft. A prospectively held database on fenestrated endovascular aortic repair patients treated at a single institution was completed with data from the Vascutek engineers' prototype test results as well as the product request forms. Changes to endograft design based on prototype testing were assessed and are reported for all procedures. Between April 1, 2013, and August 18, 2015, 60 fenestrated Anaconda devices were implanted. Through prototype testing, engineers were able to identify and report potential risks to technical success related to use of the custom device for the respective patient. Theoretical concerns about endograft fit in the rigid model were expressed in 51 cases (85.0%), and the engineers suggested potential changes to the design of 21 grafts (35.0%). Thirteen cases (21.7%) were eventually modified after the surgeon's testing of the prototype. A second prototype was ordered in three cases (5.0%) because of extensive changes to endograft design, such as inclusion of an additional fenestration. Technical success rates were comparable for grafts that showed a perfect fit from the beginning and cases in which prototype testing resulted in a modification of graft design. Planning and construction of fenestrated endografts for complex aortic anatomies where exact fit and positioning of the graft are paramount to allow cannulation of the aortic branches are challenging. In the current series, approximately one in five endografts was modified after prototype testing in an aortic model. Eventually, success rates were comparable between the groups of patients with a good primary prototype fit and those in which the endograft design was altered. Prototype testing in 3D aortic models is a valuable tool to test the fit of a custom-made endograft before implantation. This may help avoid potentially debilitating adverse events associated with misaligned fenestrations and unconnected aortic branches. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Antioxidant Vitamin C attenuates experimental abdominal aortic aneurysm development in an elastase-induced rat model.

PubMed

Shang, Tao; Liu, Zhao; Liu, Chang-jian

2014-05-01

We investigated the hypothesis that an antioxidant, Vitamin C, could attenuate abdominal aortic aneurysm (AAA) development in a rat model. An AAA model induced by intraluminal infusion was created in 36 male Sprague Dawley rats, which were randomly distributed into three groups: Sham (saline infused, placebo treated), Control (elastase infused, placebo treated), and Vitamin C (elastase infused, vitamin C treated). Vitamin C and placebo were intraperitoneally injected, initiating 1 wk before the infusion and continuing throughout the study. The aortic dilatation ratio was measured, and aortic tissues were further examined using biochemical and histologic techniques. Vitamin C attenuated the development of AAA, decreasing maximal aortic diameter by 25.8% (P < 0.05) and preserving elastin lamellae (P < 0.05). Vitamin C also decreased 8-hydroxyguanine (a marker of oxidative damage to DNA) and 8-isoprostane content (a marker of oxidative stress) in aortic tissues (P < 0.05, respectively). The proteins of matrix metalloproteinase (MMP)-2, MMP-9, and interleukin 6 were markedly downregulated (P < 0.05, respectively), accompanied with notably reduced messenger RNA expression of tumor necrosis factor-α, MMP-2/9, and interleukin 1β (P < 0.05, respectively). However, messenger RNA of tissue inhibitors of metalloproteinase-1 and tissue inhibitors of metalloproteinase-2 were both significantly upregulated in Vitamin C group. Vitamin C treatment had no significant effect on systolic blood pressure (P > 0.05). Vitamin C attenuated AAA development in an elastase-induced rat model via crucial protective effect, which was mediated by an increased level of antioxidant in cooperation with preserving elastin lamellae, inhibiting matrix-degrading proteinases and suppressing inflammatory responses. Copyright © 2014. Published by Elsevier Inc.

Antioxidant and Vasodilator Activity of Ugni molinae Turcz. (Murtilla) and Its Modulatory Mechanism in Hypotensive Response

PubMed Central

Jofré, Ignacio; Pezoa, Cesar; Scheuermann, Erick; Rosalen, Pedro Luiz; Romero, Fernando

2016-01-01

Hypertension is a systemic condition with high morbidity and mortality rates worldwide, which poses an increased risk for cardiovascular diseases. In this study, we demonstrated the antioxidant and vasodilator activity of Ugni molinae Turcz. (Murtilla) fruit, a berry native to Chile and proposed models to explain its modulatory mechanism in hypotensive response. Murtilla fruits were cultivated in a germplasm bank and submitted to chemical and biological analyses. The phenolic compounds gallic acid, Catechin, Quercetin-3-β-D-glucoside, Myricetin, Quercetin, and Kaempferol were identified. Murtilla extract did not generate toxic effects on human endothelial cells and had significant antioxidant activity against ROS production, lipid peroxidation, and superoxide anion production. Furthermore, it showed dose-dependent vasodilator activity in aortic rings in the presence of endothelium, whose hypotensive mechanism is partially mediated by nitric oxide synthase/guanylate cyclase and large-conductance calcium-dependent potassium channels. Murtilla fruits might potentially have beneficial effects on the management of cardiovascular diseases. PMID:27688827

Effect of personalized external aortic root support on aortic root motion and distension in Marfan syndrome patients.

PubMed

Izgi, Cemil; Nyktari, Evangelia; Alpendurada, Francisco; Bruengger, Annina Studer; Pepper, John; Treasure, Tom; Mohiaddin, Raad

2015-10-15

Personalized external aortic root support (PEARS) is a novel surgical approach with the aim of stabilizing the aortic root size and decreasing risk of dissection in Marfan syndrome patients. A bespoke polymer mesh tailored to each patient's individual aorta shape is produced by modeling and then surgically implanted. The aim of this study is to assess the mechanical effects of PEARS on the aortic root systolic downward motion (an important determinant of aortic wall stress), aortic root distension and on the left ventricle (LV). A cohort of 27 Marfan patients had a prophylactic PEARS surgery between 2004 and 2012 with 24 having preoperative and follow-up cardiovascular magnetic resonance imaging studies. Systolic downward aortic root motion, aortic root distension, LV volumes/mass and mitral annular systolic excursion before the operation and in the latest follow-up were measured randomly and blinded. After a median follow-up of 50.5 (IQR 25.5-72) months following implantation of PEARS, systolic downward motion of aortic root was significantly decreased (12.6±3.6mm pre-operation vs 7.9±2.9mm latest follow-up, p<0.00001). There was a tendency for a decrease in systolic aortic root distension but this was not significant (median 4.5% vs 2%, p=0.35). There was no significant change in LV volumes, ejection fraction, mass and mitral annular systolic excursion in follow-up. PEARS surgery decreases systolic downward aortic root motion which is an important determinant of longitudinal aortic wall stress. Aortic wall distension and Windkessel function are not significantly impaired in the follow-up after implantation of the mesh which is also supported by the lack of deterioration of LV volumes or mass. Crown Copyright © 2015. Published by Elsevier Ireland Ltd. All rights reserved.

Effect of soluble guanylyl cyclase activator and stimulator therapy on nitroglycerin-induced nitrate tolerance in rats.

PubMed

Jabs, A; Oelze, M; Mikhed, Y; Stamm, P; Kröller-Schön, S; Welschof, P; Jansen, T; Hausding, M; Kopp, M; Steven, S; Schulz, E; Stasch, J-P; Münzel, T; Daiber, A

2015-08-01

Chronic nitroglycerin (GTN) anti-ischemic therapy induces side effects such as nitrate tolerance and endothelial dysfunction. Both phenomena could be based on a desensitization/oxidation of the soluble guanylyl cyclase (sGC). Therefore, the present study aims at investigating the effects of the therapy with the sGC activator BAY 60-2770 and the sGC stimulator BAY 41-8543 on side effects induced by chronic nitroglycerin treatment. Male Wistar rats were treated with nitroglycerin (100mg/kg/d for 3.5days, s.c. in ethanol) and BAY 60-2770 (0.5 or 2.5mg/kg/d) or BAY 41-8543 (1 and 5mg/kg/d) for 6days. Therapy with BAY 60-2770 but not with BAY 41-8543 improved nitroglycerin-triggered endothelial dysfunction and nitrate tolerance, corrected the decrease in aortic nitric oxide levels, improved the cGMP dependent activation of protein kinase I in aortic tissue and reduced vascular, cardiac and whole blood oxidative stress (fluorescence and chemiluminescence assays; 3-nitrotyrosine staining). In contrast to BAY 41-8543, the vasodilator potency of BAY 60-2770 was not impaired in isolated aortic ring segments from nitrate tolerant rats. sGC activator therapy improves partially the adverse effects of nitroglycerin therapy whereas sGC stimulation has only minor beneficial effects pointing to a nitroglycerin-dependent sGC oxidation/inactivation mechanism contributing to nitrate tolerance. Copyright © 2015 Elsevier Inc. All rights reserved.

Influence of antihypertensive drugs on aortic and coronary effects of Ang-(1-7) in pressure-overloaded rats

PubMed Central

Nunes, A.D.C.; Souza, A.P.S.; Macedo, L.M.; Alves, P.H.; Pedrino, G.R.; Colugnati, D.B.; Mendes, E.P.; Santos, R.A.S.; Castro, C.H.

2017-01-01

This study investigated the influence of antihypertensive drugs, such as angiotensin-converting enzyme inhibitors (ACEIs), AT1 receptor blockers (ARBs), voltage-gated L-type calcium channel blockers, and mineralocorticoid receptor antagonists (MRAs), on the effects of angiotensin-(1-7) [Ang-(1-7)] on aorta and coronary arteries from pressure-overloaded rats. Pressure overload was induced by abdominal aortic banding (AB). To evaluate the role of antihypertensive drugs on the effect of Ang-(1-7), AB male Wistar rats weighing 250–300 g were treated with vehicle or low doses (5 mg·kg-1·day-1, gavage) of losartan, captopril, amlodipine, or spironolactone. Isolated aortic rings and isolated perfused hearts under constant flow were used to evaluate the effect of Ang-(1-7) in thoracic aorta and coronary arteries, respectively. Ang-(1-7) induced a significant relaxation in the aorta of sham animals, but this effect was reduced in the aortas of AB rats. Chronic treatments with losartan, captopril or amlodipine, but not with spironolactone, restored the Ang-(1-7)-induced aorta relaxation in AB rats. The coronary vasodilatation evoked by Ang-(1-7) in sham rats was blunted in hypertrophic rats. Only the treatment with losartan restored the coronary vasodilatory effect of Ang-(1-7) in AB rat hearts. These data support a beneficial vascular effect of an association of Ang-(1-7) and some antihypertensive drugs. Thus, this association may have potential as a new therapeutic strategy for cardiovascular diseases. PMID:28355350

Influence of antihypertensive drugs on aortic and coronary effects of Ang-(1-7) in pressure-overloaded rats.

PubMed

Nunes, A D C; Souza, A P S; Macedo, L M; Alves, P H; Pedrino, G R; Colugnati, D B; Mendes, E P; Santos, R A S; Castro, C H

2017-03-23

This study investigated the influence of antihypertensive drugs, such as angiotensin-converting enzyme inhibitors (ACEIs), AT1 receptor blockers (ARBs), voltage-gated L-type calcium channel blockers, and mineralocorticoid receptor antagonists (MRAs), on the effects of angiotensin-(1-7) [Ang-(1-7)] on aorta and coronary arteries from pressure-overloaded rats. Pressure overload was induced by abdominal aortic banding (AB). To evaluate the role of antihypertensive drugs on the effect of Ang-(1-7), AB male Wistar rats weighing 250-300 g were treated with vehicle or low doses (5 mg·kg-1·day-1, gavage) of losartan, captopril, amlodipine, or spironolactone. Isolated aortic rings and isolated perfused hearts under constant flow were used to evaluate the effect of Ang-(1-7) in thoracic aorta and coronary arteries, respectively. Ang-(1-7) induced a significant relaxation in the aorta of sham animals, but this effect was reduced in the aortas of AB rats. Chronic treatments with losartan, captopril or amlodipine, but not with spironolactone, restored the Ang-(1-7)-induced aorta relaxation in AB rats. The coronary vasodilatation evoked by Ang-(1-7) in sham rats was blunted in hypertrophic rats. Only the treatment with losartan restored the coronary vasodilatory effect of Ang-(1-7) in AB rat hearts. These data support a beneficial vascular effect of an association of Ang-(1-7) and some antihypertensive drugs. Thus, this association may have potential as a new therapeutic strategy for cardiovascular diseases.

Estimated aortic stiffness is independently associated with cardiac baroreflex sensitivity in humans: role of ageing and habitual endurance exercise.

PubMed

Pierce, G L; Harris, S A; Seals, D R; Casey, D P; Barlow, P B; Stauss, H M

2016-09-01

We hypothesised that differences in cardiac baroreflex sensitivity (BRS) would be independently associated with aortic stiffness and augmentation index (AI), clinical biomarkers of cardiovascular disease risk, among young sedentary and middle-aged/older sedentary and endurance-trained adults. A total of 36 healthy middle-aged/older (age 55-76 years, n=22 sedentary and n=14 endurance-trained) and 5 young sedentary (age 18-31 years) adults were included in a cross-sectional study. A subset of the middle-aged/older sedentary adults (n=12) completed an 8-week-aerobic exercise intervention. Invasive brachial artery blood pressure waveforms were used to compute spontaneous cardiac BRS (via sequence technique), estimated aortic pulse wave velocity (PWV) and AI (AI, via brachial-aortic transfer function and wave separation analysis). In the cross-sectional study, cardiac BRS was 71% lower in older compared with young sedentary adults (P<0.05), but only 40% lower in older adults who performed habitual endurance exercise (P=0.03). In a regression model that included age, sex, resting heart rate, mean arterial pressure (MAP), body mass index and maximal exercise oxygen uptake, estimated aortic PWV (β±s.e.=-5.76±2.01, P=0.01) was the strongest predictor of BRS (model R(2)=0.59, P<0.001). The 8-week-exercise intervention improved BRS by 38% (P=0.04) and this change in BRS was associated with improved aortic PWV (r=-0.65, P=0.044, adjusted for changes in MAP). Age- and endurance-exercise-related differences in cardiac BRS are independently associated with corresponding alterations in aortic PWV among healthy adults, consistent with a mechanistic link between variations in the sensitivity of the baroreflex and aortic stiffness with age and exercise.

Estimated Aortic Stiffness is Independently Associated with Cardiac Baroreflex Sensitivity in Humans: Role of Aging and Habitual Endurance Exercise

PubMed Central

Pierce, Gary L.; Harris, Stephen A.; Seals, Douglas R.; Casey, Darren P.; Barlow, Patrick B.; Stauss, Harald M.

2016-01-01

We hypothesized that differences in cardiac baroreflex sensitivity (BRS) would be independently associated with aortic stiffness and augmentation index (AI), clinical biomarkers of cardiovascular disease (CVD) risk, among young sedentary and middle-aged/older sedentary and endurance-trained adults. A total of 36 healthy middle-aged/older (age 55-76 years, n=22 sedentary; n=14 endurance-trained) and 5 young sedentary (age 18-31 years) adults were included in a cross-sectional study. A subset of the middle-aged/older sedentary adults (n=12) completed an 8-week aerobic exercise intervention. Invasive brachial artery blood pressure waveforms were used to compute spontaneous cardiac BRS (via sequence technique) and estimated aortic pulse wave velocity (PWV) and AI (AI, via brachial-aortic transfer function and wave separation analysis). In the cross-sectional study, cardiac BRS was 71% lower in older compared with young sedentary adults (P<0.05), but only 40% lower in older adults who performed habitual endurance exercise (P=0.03). In a regression model that included age, sex, resting heart rate, mean arterial pressure (MAP), body mass index and maximal exercise oxygen uptake, estimated aortic PWV (β±SE = −5.76 ± 2.01, P=0.01) was the strongest predictor of BRS (Model R2=0.59, P<0.001). The 8 week exercise intervention improved BRS by 38% (P=0.04) and this change in BRS was associated with improved aortic PWV (r=−0.65, P=0.044, adjusted for changes in MAP). Age- and endurance exercise-related differences in cardiac BRS are independently associated with corresponding alterations in aortic PWV among healthy adults, consistent with a mechanistic link between variations in the sensitivity of the baroreflex and aortic stiffness with age and exercise. PMID:26911535

Study of the effect of thiols on the vasodilatory potency of S-nitrosothiols by using a modified aortic ring assay

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giustarini, Daniela, E-mail: giustarini@unisi.it; Tsikas, Dimitrios, E-mail: tsikas.dimitros@mh-hannover.de; Rossi, Ranieri, E-mail: ranieri@unisi.it

2011-10-15

Both low-molecular-mass thiols (LMM-SH) and protein thiols (P-SH) can modulate the biological activity of S-nitrosothiols (RSNO) via S-transnitrosation reactions. It has been difficult to evaluate the entity of this effect in blood circulation by in vitro assays with isolated aorta rings so far, because media rich in proteins cannot be used due to the foaming as a consequence of the needed gas bubbling. We have modified the original apparatus for organ bioassay in order to minimize foaming and to increase analytical performance. By using this modified bioassay we investigated the vasodilatory potency of various endogenous RSNOs in the presence ofmore » physiologically relevant concentrations of albumin and LMM-SH. Our results show that the sulfhydryl group of the cysteine moiety of albumin and LMM-SH has a dramatic effect on the vasodilatory potency of RSNO. Considering the equilibrium constants for S-transnitrosation reactions and the concentration of P-SH and LMM-SH we measured in healthy humans (aged 18-85 years), we infer that the age-dependency of hematic levels of LMM-SH may have a considerable impact in RSNO-mediated vasodilation. S-Nitrosoproteins such as S-nitrosoalbumin may constitute a relatively silent and constant amount of circulating RSNO. On the other hand, LMM-SH may mediate and control the biological actions of S-nitrosoproteins via S-transnitrosation reactions, by forming more potent nitric oxide-releasing LMM-S-nitrosothiols. Lifestyle habits, status of health and individual age are proven factors that, in turn, may influence the concentration of these compounds. These aspects should be taken into consideration when testing the vasodilatory effects of RSNO in pre-clinical studies. - Highlights: > A modification of the organ chamber apparatus for aortic ring bioassays is proposed. > The new apparatus can work in the presence of albumin at physiological concentrations. > Potency of RSNOs was studied in the presence of albumin and low molecular mass -SH. > Plasma thiol levels decrease with age. > Potency of RSNOs varies in dependence of age and more in general of plasma thiol status.« less

Vitamin E Inhibits Abdominal Aortic Aneurysm Formation in Angiotensin II–Infused Apolipoprotein E–Deficient Mice

PubMed Central

Gavrila, Dan; Li, Wei Gen; McCormick, Michael L.; Thomas, Manesh; Daugherty, Alan; Cassis, Lisa A.; Miller, Francis J.; Oberley, Larry W.; Dellsperger, Kevin C.; Weintraub, Neal L.

2014-01-01

Background Abdominal aortic aneurysms (AAAs) in humans are associated with locally increased oxidative stress and activity of NADPH oxidase. We investigated the hypothesis that vitamin E, an antioxidant with documented efficacy in mice, can attenuate AAA formation during angiotensin II (Ang II) infusion in apolipoprotein E–deficient mice. Methods and Results Six-month-old male apolipoprotein E–deficient mice were infused with Ang II at 1000 ng/kg per minute for 4 weeks via osmotic minipumps while consuming either a regular diet or a diet enriched with vitamin E (2 IU/g of diet). After 4 weeks, abdominal aortic weight and maximal diameter were determined, and aortic tissues were sectioned and examined using biochemical and histological techniques. Vitamin E attenuated formation of AAA, decreasing maximal aortic diameter by 24% and abdominal aortic weight by 34% (P<0.05, respectively). Importantly, animals treated with vitamin E showed a 44% reduction in the combined end point of fatal+nonfatal aortic rupture (P<0.05). Vitamin E also decreased aortic 8-isoprostane content (a marker of oxidative stress) and reduced both aortic macrophage infiltration and osteopontin expression (P<0.05, respectively). Vitamin E treatment had no significant effect on the extent of aortic root atherosclerosis, activation of matrix metalloproteinases 2 or 9, serum lipid profile, or systolic blood pressure. Conclusions Vitamin E ameliorates AAAs and reduces the combined end point of fatal+nonfatal aortic rupture in this animal model. These findings are consistent with the concept that oxidative stress plays a pivotal role in Ang II–driven AAA formation in hyperlipidemic mice. PMID:15933246

TGFβ (Transforming Growth Factor-β) Blockade Induces a Human-Like Disease in a Nondissecting Mouse Model of Abdominal Aortic Aneurysm.

PubMed

Lareyre, Fabien; Clément, Marc; Raffort, Juliette; Pohlod, Stefanie; Patel, Meghana; Esposito, Bruno; Master, Leanne; Finigan, Alison; Vandestienne, Marie; Stergiopulos, Nikolaos; Taleb, Soraya; Trachet, Bram; Mallat, Ziad

2017-11-01

Current experimental models of abdominal aortic aneurysm (AAA) do not accurately reproduce the major features of human AAA. We hypothesized that blockade of TGFβ (transforming growth factor-β) activity-a guardian of vascular integrity and immune homeostasis-would impair vascular healing in models of nondissecting AAA and would lead to sustained aneurysmal growth until rupture. Here, we test this hypothesis in the elastase-induced AAA model in mice. We analyze AAA development and progression using ultrasound in vivo, synchrotron-based ultrahigh resolution imaging ex vivo, and a combination of biological, histological, and flow cytometry-based cellular and molecular approaches in vitro. Systemic blockade of TGFβ using a monoclonal antibody induces a transition from a self-contained aortic dilatation to a model of sustained aneurysmal growth, associated with the formation of an intraluminal thrombus. AAA growth is associated with wall disruption but no medial dissection and culminates in fatal transmural aortic wall rupture. TGFβ blockade enhances leukocyte infiltration both in the aortic wall and the intraluminal thrombus and aggravates extracellular matrix degradation. Early blockade of IL-1β or monocyte-dependent responses substantially limits AAA severity. However, blockade of IL-1β after disease initiation has no effect on AAA progression to rupture. Endogenous TGFβ activity is required for the healing of AAA. TGFβ blockade may be harnessed to generate new models of AAA with better relevance to the human disease. We expect that the new models will improve our understanding of the pathophysiology of AAA and will be useful in the identification of new therapeutic targets. © 2017 American Heart Association, Inc.

Normal limits in relation to age, body size and gender of two-dimensional echocardiographic aortic root dimensions in persons ≥15 years of age.

PubMed

Devereux, Richard B; de Simone, Giovanni; Arnett, Donna K; Best, Lyle G; Boerwinkle, Eric; Howard, Barbara V; Kitzman, Dalane; Lee, Elisa T; Mosley, Thomas H; Weder, Alan; Roman, Mary J

2012-10-15

Nomograms to predict normal aortic root diameter for body surface area (BSA) in broad ranges of age have been widely used but are limited by lack of consideration of gender effects, jumps in upper limits of aortic diameter among age strata, and data from older teenagers. Sinus of Valsalva diameter was measured by American Society of Echocardiography convention in normal-weight, nonhypertensive, nondiabetic subjects ≥15 years old without aortic valve disease from clinical or population-based samples. Analyses of covariance and linear regression with assessment of residuals identified determinants and developed predictive models for normal aortic root diameter. In 1,207 apparently normal subjects ≥15 years old (54% women), aortic root diameter was 2.1 to 4.3 cm. Aortic root diameter was strongly related to BSA and height (r = 0.48 for the 2 comparisons), age (r = 0.36), and male gender (+2.7 mm adjusted for BSA and age, p <0.001 for all comparisons). Multivariable equations using age, gender, and BSA or height predicted aortic diameter strongly (R = 0.674 for the 2 comparisons, p <0.001) with minimal relation of residuals to age or body size: for BSA 2.423 + (age [years] × 0.009) + (BSA [square meters] × 0.461) - (gender [1 = man, 2 = woman] × 0.267), SEE 0.261 cm; for height 1.519 + (age [years] × 0.010) + (height [centimeters] × 0.010) - (gender [1 = man, 2 = woman] × 0.247), SEE 0.215 cm. In conclusion, aortic root diameter is larger in men and increases with body size and age. Regression models incorporating body size, age, and gender are applicable to adolescents and adults without limitations of previous nomograms. Copyright © 2012 Elsevier Inc. All rights reserved.

The relative risk of aortic aneurysm in patients with giant cell arteritis compared with the general population of the UK.

PubMed

Robson, Joanna C; Kiran, Amit; Maskell, Joe; Hutchings, Andrew; Arden, Nigel; Dasgupta, Bhaskar; Hamilton, William; Emin, Akan; Culliford, David; Luqmani, Raashid A

2015-01-01

To evaluate the risk of aortic aneurysm in patients with giant cell arteritis (GCA) compared with age-, gender- and location-matched controls. A UK General Practice Research Database (GPRD) parallel cohort study of 6999 patients with GCA and 41 994 controls, matched on location, age and gender, was carried out. A competing risk model using aortic aneurysm as the primary outcome and non-aortic-aneurysm-related death as the competing risk was used to determine the relative risk (subhazard ratio) between non-GCA and GCA subjects, after adjustment for cardiovascular risk factors. Comparing the GCA cohort with the non-GCA cohort, the adjusted subhazard ratio (95% CI) for aortic aneurysm was 1.92 (1.52 to 2.41). Significant predictors of aortic aneurysm were being an ex-smoker (2.64 (2.03 to 3.43)) or a current smoker (3.37 (2.61 to 4.37)), previously taking antihypertensive drugs (1.57 (1.23 to 2.01)) and a history of diabetes (0.32 (0.19 to 0.56)) or cardiovascular disease (1.98 (1.50 to 2.63)). In a multivariate model of the GCA cohort, male gender (2.10 (1.38 to 3.19)), ex-smoker (2.20 (1.22 to 3.98)), current smoker (3.79 (2.20 to 6.53)), previous antihypertensive drugs (1.62 (1.00 to 2.61)) and diabetes (0.19 (0.05 to 0.77)) were significant predictors of aortic aneurysm. Patients with GCA have a twofold increased risk of aortic aneurysm, and this should be considered within the range of other risk factors including male gender, age and smoking. A separate screening programme is not indicated. The protective effect of diabetes in the development of aortic aneurysms in patients with GCA is also demonstrated. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Dietary quercetin attenuates oxidant-induced endothelial dysfunction and atherosclerosis in apolipoprotein E knockout mice fed a high-fat diet: a critical role for heme oxygenase-1.

PubMed

Shen, Yu; Ward, Natalie C; Hodgson, Jonathan M; Puddey, Ian B; Wang, Yutang; Zhang, Di; Maghzal, Ghassan J; Stocker, Roland; Croft, Kevin D

2013-12-01

Several lines of evidence indicate that quercetin, a polyphenol derived in the diet from fruit and vegetables, contributes to cardiovascular health. We aimed to investigate the effects of dietary quercetin on endothelial function and atherosclerosis in mice fed a high-fat diet. Wild-type C57BL/6 (WT) and apolipoprotein E gene knockout (ApoE(-/-)) mice were fed: (i) a high-fat diet (HFD) or (ii) a HFD supplemented with 0.05% w/w quercetin (HFD+Q), for 14 weeks. Compared with animals fed HFD, HFD+Q attenuated atherosclerosis in ApoE(-/-) mice. Treatment with the HFD+Q significantly improved endothelium-dependent relaxation of aortic rings isolated from WT but not ApoE(-/-) mice and attenuated hypochlorous acid-induced endothelial dysfunction in aortic rings of both WT and ApoE(-/-) mice. Mechanistic studies revealed that HFD+Q significantly improved plasma F2-isoprostanes, 24h urinary nitrite, and endothelial nitric oxide synthase activity, and increased heme oxygenase-1 (HO-1) protein expression in the aortas of both WT and ApoE(-/-) mice (P<0.05). HFD+Q also resulted in small changes in plasma cholesterol (P<0.05 in WT) and plasma triacylglycerols (P<0.05 in ApoE (-/-)mice). In a separate experiment, quercetin did not protect against hypochlorite-induced endothelial dysfunction in arteries obtained from heterozygous HO-1 gene knockout mice with low expression of HO-1 protein. Quercetin protects mice fed a HFD against oxidant-induced endothelial dysfunction and ApoE(-/-) mice against atherosclerosis. These effects are associated with improvements in nitric oxide bioavailability and are critically related to arterial induction of HO-1. © 2013 Elsevier Inc. All rights reserved.

Low-dose chronic lead exposure increases systolic arterial pressure and vascular reactivity of rat aortas.

PubMed

Silveira, Edna Aparecida; Siman, Fabiana Dayse Magalhães; de Oliveira Faria, Thaís; Vescovi, Marcos Vinícius Altoé; Furieri, Lorena Barros; Lizardo, Juliana Hott Fúcio; Stefanon, Ivanita; Padilha, Alessandra Simão; Vassallo, Dalton Valentim

2014-02-01

Chronic lead exposure induces hypertension affecting endothelial function. We investigated whether low-concentration lead exposure alters blood pressure and vascular reactivity, focusing on the roles of NO, oxidative stress, cyclooxygenase-derived vasoconstrictor prostanoids, and the local angiotensin-renin system. Aortic rings from 3-month-old Wistar rats were treated daily with lead acetate (first dose 4mg/100g, subsequent doses 0.05mg/100g, im) or vehicle for 30 days. Treatment increased lead blood levels (12μg/dl), blood pressure, and aortic ring contractile response to phenylephrine (1nM-100mM). Contractile response after L-NAME administration increased in both groups but was higher after lead treatment. Lead effects on Rmax decreased more after apocynin and superoxide dismutase administration compared to control. Indomethacin reduced phenylephrine response more after lead treatment than in controls. The selective COX-2 inhibitor NS398, thromboxane A2/prostaglandin H2 receptor antagonist SQ 29,548, TXA2 synthase inhibitor furegrelate, EP1 receptor antagonist SC 19220, and ACE inhibitor and AT1 receptor antagonist losartan reduced phenylephrine responses only in vessels from lead-treated rats. Basal and stimulated NO release was reduced and local O2(-) liberation increased in the lead-treated group compared to controls. eNOS, iNOS, and AT1 receptor protein expression increased with lead exposure, but COX-2 protein expression decreased. This is the first demonstration that blood Pb(2+) (12µg/dl) concentrations below the WHO-established values increased systolic blood pressure and vascular phenylephrine reactivity. This effect was associated with reduced NO bioavailability, increased reactive oxygen species production, increased participation of COX-derived contractile prostanoids, and increased renin-angiotensin system activity. © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

The secretome of endothelial progenitor cells promotes brain endothelial cell activity through PI3-kinase and MAP-kinase.

PubMed

Di Santo, Stefano; Seiler, Stefanie; Fuchs, Anna-Lena; Staudigl, Jennifer; Widmer, Hans Rudolf

2014-01-01

Angiogenesis and vascular remodelling are crucial events in tissue repair mechanisms promoted by cell transplantation. Current evidence underscores the importance of the soluble factors secreted by stem cells in tissue regeneration. In the present study we investigated the effects of paracrine factors derived from cultured endothelial progenitor cells (EPC) on rat brain endothelial cell properties and addressed the signaling pathways involved. Endothelial cells derived from rat brain (rBCEC4) were incubated with EPC-derived conditioned medium (EPC-CM). The angiogenic response of rBCEC4 to EPC-CM was assessed as effect on cell number, migration and tubular network formation. In addition, we have compared the outcome of the in vitro experiments with the effects on capillary sprouting from rat aortic rings. The specific PI3K/AKT inhibitor LY294002 and the MEK/ERK inhibitor PD98059 were used to study the involvement of these two signaling pathways in the transduction of the angiogenic effects of EPC-CM. Viable cell number, migration and tubule network formation were significantly augmented upon incubation with EPC-CM. Similar findings were observed for aortic ring outgrowth with significantly longer sprouts. The EPC-CM-induced activities were significantly reduced by the blockage of the PI3K/AKT and MEK/ERK signaling pathways. Similarly to the outcome of the rBCEC4 experiments, inhibition of the PI3K/AKT and MEK/ERK pathways significantly interfered with capillary sprouting induced by EPC-CM. The present study demonstrates that EPC-derived paracrine factors substantially promote the angiogenic response of brain microvascular endothelial cells. In addition, our findings identified the PI3K/AKT and MEK/ERK pathways to play a central role in mediating these effects.

Evaluation of the in vitro and in vivo angiogenic effects of exendin-4

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kang, Hye-Min; Kang, Yujung; Chun, Hyung J.

2013-04-26

Highlights: •We investigated the effects of exendin-4 on the angiogenic process. •Exendin-4 increased migration, sprouting, and tube formation by HUVECs in in vitro. •Exendin-4 increased sprouts in aortic rings and induced new vessels in Matrigel in in vivo. •Exendin-4 may be of potential use for the treatment of vascular complications of diabetes. -- Abstract: Exendin-4, an analog of glucagon-like peptide (GLP)-1, has beneficial effects on cardiovascular disease induced by diabetes mellitus (DM). Recently, exendin-4 was reported to induce the proliferation of endothelial cells. However, its angiogenic effect on endothelial cells has not been clearly evaluated. Therefore, we investigated the effectsmore » of exendin-4 on the angiogenic process with respect to migration, sprouting, and neovascularization using in vitro and in vivo assays. Treatment with exendin-4 increased the migration of human umbilical vein endothelial cells (HUVECs) in in vitro scratch wound assays, as well as the number of lumenized vessels sprouting from HUVECs in in vitro 3D bead assays. These responses were abolished by co-treatment with exendin (9–39), a GLP-1 receptor antagonist, which suggests that exendin-4 regulates endothelial cell migration and tube formation in a GLP-1 receptor-dependent manner. In an ex vivo assay, treatment of aortic rings with exendin-4 increased the sprouting of endothelial cells. Exendin-4 also significantly increased the number of new vessels and induced blood flow in Matrigel plugs in in vivo assays. Our results provide clear evidence for the angiogenic effect of exendin-4 in in vitro and in vivo assays and provide a mechanism underlying the cardioprotective effects of exendin-4.« less

Glutathione-S-transferase P protects against endothelial dysfunction induced by exposure to tobacco smoke.

PubMed

Conklin, Daniel J; Haberzettl, Petra; Prough, Russell A; Bhatnagar, Aruni

2009-05-01

Exposure to tobacco smoke impairs endothelium-dependent arterial dilation. Reactive constituents of cigarette smoke are metabolized and detoxified by glutathione-S-transferases (GSTs). Although polymorphisms in GST genes are associated with the risk of cancer in smokers, the role of these enzymes in regulating the cardiovascular effects of smoking has not been studied. The P isoform of GST (GSTP), which catalyzes the conjugation of electrophilic molecules in cigarette smoke such as acrolein, was expressed in high abundance in the mouse lung and aorta. Exposure to tobacco smoke for 3 days (5 h/day) decreased total plasma protein. These changes were exaggerated in GSTP(-/-) mice. Aortic rings isolated from tobacco smoke-exposed GSTP(-/-) mice showed greater attenuation of ACh-evoked relaxation than those from GSTP(+/+) mice. The lung, plasma, and aorta of mice exposed to tobacco smoke or acrolein (for 5 h) accumulated more acrolein-adducted proteins than those tissues of mice exposed to air, indicating that exposure to tobacco smoke results in the systemic delivery of acrolein. Relative to GSTP(+/+) mice, modification of some proteins by acrolein was increased in the aorta of GSTP(-/-) mice. Aortic rings prepared from GSTP(-/-) mice that inhaled acrolein (1 ppm, 5 h/day for 3 days) or those exposed to acrolein in an organ bath showed diminished ACh-induced arterial relaxation more strongly than GSTP(+/+) mice. Acrolein-induced endothelial dysfunction was prevented by pretreatment of the aorta with N-acetylcysteine. These results indicate that GSTP protects against the endothelial dysfunction induced by tobacco smoke exposure and that this protection may be related to the detoxification of acrolein or other related cigarette smoke constituents.

The effects of the putative potassium channel activator WAY-120,491 on 86Rb efflux from the rabbit aorta

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lodge, N.J.; Cohen, R.B.; Havens, C.N.

1991-02-01

WAY-120,491 ((-)-(3S-trans)-2-(3,4-dihydro-3-hydroxy-2,2-dimethyl-6-(trifluoromet hox y)- 2H-1-benzopyran-4-yl)-2,3-dihydro-1H-isoindol-1-one) is a novel antihypertensive agent. We have investigated the effects of this compound on contractile force and 86Rb efflux, using the rabbit aorta, in order to assess its K channel activator properties. K channel blockers and ionic conditions thought to modulate specific K channel types have been used to provide insight into the K channel(s) affected by this compound. WAY-120,491 evoked relaxation of precontracted rabbit aortic rings and increased the rate of 86Rb efflux from strips of rabbit aorta; both effects occurring in a concentration-dependent manner. The WAY-120,491 (1 microM)-induced 86Rb efflux was inhibited bymore » tetraethylammonium (IC50 = 0.38 mM), indicating that the increased efflux was mediated by K channels. Glyburide completely blocked the WAY-120,491 (1 microM)-evoked 86Rb efflux with 50% block occurring at a concentration of 0.48 microM. Glyburide also antagonized the WAY-120,491-induced relaxation of aortic rings. Omission of Ca from the solution bathing the aorta did not inhibit the WAY-120,491 induced 86Rb efflux but rather caused an augmentation of the response. It is concluded that WAY-120,491 may be classified as a K channel opener. Furthermore, the K channel upon which WAY-120,491 acts exhibits some characteristics normally associated with the ATP regulated K channel although the involvement of other K channel types has not been ruled out.« less

[Protective mechanism on the vascular pathological process in diabetes mellitus rats by Rheum officeinale].

PubMed

Tian, Feng-Sheng; Li, Zhen-Bin; Wang, Yuan-Song; Su, Xiu-Hai; Li, Wen-Dong; Wang, Xiao-Yun

2008-03-01

To explore the protective mechanism of officeihale on the vascular pathological process in diabetes mellitus (DM) rats. After the DM rat model was established, 24 DM rats were randomly divided into model group (12 DM rats) and Rheum officeinale group (12 DM rats). Rheum officeinale was orally given in 10 g kg(-1) per day, and the other two groups were given equal pure water. 8 weeks later, blood samples were collected to determine the level of nitric oxide (NO) and endothelin-1 (ET-1). Thoracic aortic rings was prepared to observe the inhibiting effect of Ach with different concentration on contraction caused by NE. Another part of aorta was made to observe the expression of ICAM-1 and VCAM-1 by method of SP immunohistochemistry staining, Rheum officeinale group obviously decreased the level of ET-1 and increased the NO compared with model group (P <0.05). The expression of ICAM-1 and VCAM-1 could be obviously inhibited in Rheum officeinale group compared with model group. (P <0.05). Rheum officeinale could decrease the level of ET-1 with increased the NO in diabetes rats, and inhibit the expression of ICAM-1 and VCAM-1, which may be mechanisms of protecting the endothelium of vessel in diabetes rats.

Mathematical, numerical and experimental study in the human aorta with coexisting models of bicuspid aortic stenosis and coarctation of the aorta.

PubMed

Keshavarz-Motamed, Z; Garcia, J; Kadem, L

2011-01-01

Coarctation of the aorta is an obstruction of the aorta and is usually associated with other concomitant cardiovascular abnormalities especially with bicuspid aortic valve stenosis. The objectives of this study are, (1) to investigate the effects of coarctation on the hemodynamics in the aorta to gain a better understanding of the cause of certain post-surgical coarctation problems, (2) to develop and introduce a new lumped parameter model, mainly based on non-invasive data, allowing the description of the interaction between left ventricle, coarctation of the aorta, aortic valve stenosis, and the arterial system.

Modeling of the aorta artery aneurysms and renal artery stenosis using cardiovascular electronic system

PubMed Central

Hassani, Kamran; Navidbakhsh, Mahdi; Rostami, Mostafa

2007-01-01

Background The aortic aneurysm is a dilatation of the aortic wall which occurs in the saccular and fusiform types. The aortic aneurysms can rupture, if left untreated. The renal stenosis occurs when the flow of blood from the arteries leading to the kidneys is constricted by atherosclerotic plaque. This narrowing may lead to the renal failure. Previous works have shown that, modelling is a useful tool for understanding of cardiovascular system functioning and pathophysiology of the system. The present study is concerned with the modelling of aortic aneurysms and renal artery stenosis using the cardiovascular electronic system. Methods The geometrical models of the aortic aneurysms and renal artery stenosis, with different rates, were constructed based on the original anatomical data. The pressure drop of each section due to the aneurysms or stenosis was computed by means of computational fluid dynamics method. The compliance of each section with the aneurysms or stenosis is also calculated using the mathematical method. An electrical system representing the cardiovascular circulation was used to study the effects of these pressure drops and the compliance variations on this system. Results The results showed the decreasing of pressure along the aorta and renal arteries lengths, due to the aneurysms and stenosis, at the peak systole. The mathematical method demonstrated that compliances of the aorta sections and renal increased with the expansion rate of the aneurysms and stenosis. The results of the modelling, such as electrical pressure graphs, exhibited the features of the pathologies such as hypertension and were compared with the relevant experimental data. Conclusion We conclude from the study that the aortic aneurysms as well as renal artery stenosis may be the most important determinant of the arteries rupture and failure. Furthermore, these pathologies play important rules in increase of the cardiovascular pulse pressure which leads to the hypertension. PMID:17559685

A laboratory model of the aortic root flow including the coronary arteries

NASA Astrophysics Data System (ADS)

Querzoli, Giorgio; Fortini, Stefania; Espa, Stefania; Melchionna, Simone

2016-08-01

Cardiovascular flows have been extensively investigated by means of in vitro models to assess the prosthetic valve performances and to provide insight into the fluid dynamics of the heart and proximal aorta. In particular, the models for the study of the flow past the aortic valve have been continuously improved by including, among other things, the compliance of the vessel and more realistic geometries. The flow within the sinuses of Valsalva is known to play a fundamental role in the dynamics of the aortic valve since they host a recirculation region that interacts with the leaflets. The coronary arteries originate from the ostia located within two of the three sinuses, and their presence may significantly affect the fluid dynamics of the aortic root. In spite of their importance, to the extent of the authors' knowledge, coronary arteries were not included so far when modeling in vitro the transvalvular aortic flow. We present a pulse duplicator consisting of a passively pulsing ventricle, a compliant proximal aorta, and coronary arteries connected to the sinuses of Valsalva. The coronary flow is modulated by a self-regulating device mimicking the physiological mechanism, which is based on the contraction and relaxation of the heart muscle during the cardiac cycle. Results show that the model reproduces satisfyingly the coronary flow. The analysis of the time evolution of the velocity and vorticity fields within the aortic root reveals the main characteristics of the backflow generated through the aorta in order to feed the coronaries during the diastole. Experiments without coronary flow have been run for comparison. Interestingly, the lifetime of the vortex forming in the sinus of Valsalva during the systole is reduced by the presence of the coronaries. As a matter of fact, at the end of the systole, that vortex is washed out because of the suction generated by the coronary flow. Correspondingly, the valve closure is delayed and faster compared to the case with no coronary flow.

Myeloid mineralocorticoid receptor deficiency inhibits aortic constriction-induced cardiac hypertrophy in mice.

PubMed

Li, Chao; Zhang, Yu Yao; Frieler, Ryan A; Zheng, Xiao Jun; Zhang, Wu Chang; Sun, Xue Nan; Yang, Qing Zhen; Ma, Shu Min; Huang, Baozhuan; Berger, Stefan; Wang, Wang; Wu, Yong; Yu, Ying; Duan, Sheng Zhong; Mortensen, Richard M

2014-01-01

Mineralocorticoid receptor (MR) blockade has been shown to suppress cardiac hypertrophy and remodeling in animal models of pressure overload (POL). This study aims to determine whether MR deficiency in myeloid cells modulates aortic constriction-induced cardiovascular injuries. Myeloid MR knockout (MMRKO) mice and littermate control mice were subjected to abdominal aortic constriction (AAC) or sham operation. We found that AAC-induced cardiac hypertrophy and fibrosis were significantly attenuated in MMRKO mice. Expression of genes important in generating reactive oxygen species was decreased in MMRKO mice, while that of manganese superoxide dismutase increased. Furthermore, expression of genes important in cardiac metabolism was increased in MMRKO hearts. Macrophage infiltration in the heart was inhibited and expression of inflammatory genes was decreased in MMRKO mice. In addition, aortic fibrosis and inflammation were attenuated in MMRKO mice. Taken together, our data indicated that MR deficiency in myeloid cells effectively attenuated aortic constriction-induced cardiac hypertrophy and fibrosis, as well as aortic fibrosis and inflammation.

Fourier transform infrared spectroscopy to quantify collagen and elastin in an in vitro model of extracellular matrix degradation in aorta.

PubMed

Cheheltani, Rabee; McGoverin, Cushla M; Rao, Jayashree; Vorp, David A; Kiani, Mohammad F; Pleshko, Nancy

2014-06-21

Extracellular matrix (ECM) is a key component and regulator of many biological tissues including aorta. Several aortic pathologies are associated with significant changes in the composition of the matrix, especially in the content, quality and type of aortic structural proteins, collagen and elastin. The purpose of this study was to develop an infrared spectroscopic methodology that is comparable to biochemical assays to quantify collagen and elastin in aorta. Enzymatically degraded porcine aorta samples were used as a model of ECM degradation in abdominal aortic aneurysm (AAA). After enzymatic treatment, Fourier transform infrared (FTIR) spectra of the aortic tissue were acquired by an infrared fiber optic probe (IFOP) and FTIR imaging spectroscopy (FT-IRIS). Collagen and elastin content were quantified biochemically and partial least squares (PLS) models were developed to predict collagen and elastin content in aorta based on FTIR spectra. PLS models developed from FT-IRIS spectra were able to predict elastin and collagen content of the samples with strong correlations (RMSE of validation = 8.4% and 11.1% of the range respectively), and IFOP spectra were successfully used to predict elastin content (RMSE = 11.3% of the range). The PLS regression coefficients from the FT-IRIS models were used to map collagen and elastin in tissue sections of degraded porcine aortic tissue as well as a human AAA biopsy tissue, creating a similar map of each component compared to histology. These results support further application of FTIR spectroscopic techniques for evaluation of AAA tissues.

Fourier Transform Infrared Spectroscopy to Quantify Collagen and Elastin in an In Vitro Model of Extracellular Matrix Degradation in Aorta

PubMed Central

Cheheltani, Rabee; McGoverin, Cushla M.; Rao, Jayashree; Vorp, David A.; Kiani, Mohammad F.; Pleshko, N.

2014-01-01

Extracellular matrix (ECM) is a key component and regulator of many biological tissues including aorta. Several aortic pathologies are associated with significant changes in the composition of the matrix, especially in the content, quality and type of aortic structural proteins, collagen and elastin. The purpose of this study was to develop an infrared spectroscopic methodology that is comparable to biochemical assays to quantify collagen and elastin in aorta. Enzymatically degraded porcine aorta samples were used as a model of ECM degradation in abdominal aortic aneurysm (AAA). After enzymatic treatment, Fourier transform infrared (FTIR) spectra of the aortic tissue were acquired by an infrared fiber optic probe (IFOP) and FTIR imaging spectroscopy (FT-IRIS). Collagen and elastin content were quantified biochemically and partial least squares (PLS) models were developed to predict collagen and elastin content in aorta based on FTIR spectra. PLS models developed from FT-IRIS spectra were able to predict elastin and collagen content of the samples with strong correlations (RMSE of validation = 8.4% and 11.1% of the range respectively), and IFOP spectra were successfully used to predict elastin content (RMSE = 11.3% of the range). The PLS regression coefficients from the FT-IRIS models were used to map collagen and elastin in tissue sections of degraded porcine aortic tissue as well as a human AAA biopsy tissue, creating a similar map of each component compared to histology. These results support further application of FTIR spectroscopic techniques for evaluation of AAA tissues. PMID:24761431

Bicuspid aortic valves are associated with increased wall and turbulence shear stress levels compared to trileaflet aortic valves.

PubMed

Saikrishnan, Neelakantan; Mirabella, Lucia; Yoganathan, Ajit P

2015-06-01

Congenital bicuspid aortic valves (BAVs) are associated with accelerated disease progression, such as leaflet calcification and ascending aorta dilatation. Although common underlying genetic factors have been implicated in accelerated disease in BAV patients, several studies have suggested that altered hemodynamics also play a role in this disease process. The present study compares turbulence and wall shear stress (WSS) measurements between various BAV and trileaflet aortic valve (TAV) models to provide information for mechanobiological models of BAV disease. BAV and TAV models were constructed from excised porcine aortic valves to simulate parametric variations in BAV stenosis, hemodynamics and geometry. Particle image velocimetry experiments were conducted at physiological pressure conditions to characterize velocity fields in the ascending aorta. The velocity fields were post-processed to calculate turbulence, viscous and wall shear stresses in the ascending aorta. Stenosed BAV models showed the presence of eccentric systolic jets, causing increased WSS. Lower cardiac output resulted in a narrower jet, lower turbulence and lower viscous shear stress (VSS). The specific severe stenosis BAV model studied here showed reduced WSS due to reduction in non-fused leaflet mobility. Dilation of the aorta did not affect any turbulence or VSS, but reduced the WSS. In comparison with BAVs, TAVs have similar VSS values, but much smaller WSS and turbulence levels. These increased turbulence  and WSS levels in BAVs may play a key role in amplifying the biological responses of the ascending aorta wall and valvular leaflets, and support the hemodynamic underpinnings of BAV disease processes.

Longitudinal Changes in Segmental Aortic Stiffness Determined by Cardiac Magnetic Resonance in Children and Young Adults With Connective Tissue Disorders (the Marfan, Loeys-Dietz, and Ehlers-Danlos Syndromes, and Nonspecific Connective Tissue Disorders).

PubMed

Merlocco, Anthony; Lacro, Ronald V; Gauvreau, Kimberlee; Rabideau, Nicole; Singh, Michael N; Prakash, Ashwin

2017-10-01

Aortic stiffness measured by cardiac magnetic resonance (CMR) in connective tissue disorder (CTD) patients has been previously shown to be abnormal and to be associated with adverse aortic outcomes. The rate of increase in aortic stiffness with normal aging has been previously described. However, longitudinal changes in aortic stiffness have not been characterized in CTD patients. We examined longitudinal changes in CMR-derived aortic stiffness in children and young adults with CTDs. A retrospective analysis of 50 children and young adults (median age, 20 years; range, 0.2 to 49; 40% < 18 years old) with a CTD, and with at least 2 CMR examinations (total 152 examinations) over a median duration of 3.9 (1 to 13.2) years was performed. Aortic stiffness measures (strain, distensibility, and β stiffness index) were calculated on each examination at the aortic root (AoR), ascending aorta, and descending aorta. Longitudinal changes in parameters were analyzed using linear mixed-effects models. Aortic strain and distensibility decreased with age, whereas the β stiffness index increased at all aortic segments. The average rates of decline in distensibility (x10 -3  mm Hg -1 per 10-year increase in age) were 0.7, 1.3, and 1 at the AoR, ascending aorta, and descending aorta, respectively. The rates of decline in distensibility were not associated with the rates of AoR dilation or surgical AoR replacement. In conclusion, on serial CMR measurements in children and young adults with CTDs, aortic stiffness progressively increased with age, with rates of change only slightly higher than those previously reported in healthy adults. Copyright © 2017 Elsevier Inc. All rights reserved.

Improved aortic enhancement in CT angiography using slope-based triggering with table speed optimization: a pilot study.

PubMed

Bashir, Mustafa R; Weber, Paul W; Husarik, Daniela B; Howle, Laurens E; Nelson, Rendon C

2012-08-01

To assess whether a scan triggering technique based on the slope of the time-attenuation curve combined with table speed optimization may improve arterial enhancement in aortic CT angiography compared to conventional threshold-based triggering techniques. Measurements of arterial enhancement were performed in a physiologic flow phantom over a range of simulated cardiac outputs (2.2-8.1 L/min) using contrast media boluses of 80 and 150 mL injected at 4 mL/s. These measurements were used to construct computer models of aortic attenuation in CT angiography, using cardiac output, aortic diameter, and CT table speed as input parameters. In-plane enhancement was calculated for normal and aneurysmal aortic diameters. Calculated arterial enhancement was poor (<150 HU) along most of the scan length using the threshold-based triggering technique for low cardiac outputs and the aneurysmal aorta model. Implementation of the slope-based triggering technique with table speed optimization improved enhancement in all scenarios and yielded good- (>200 HU; 13/16 scenarios) to excellent-quality (>300 HU; 3/16 scenarios) enhancement in all cases. Slope-based triggering with table speed optimization may improve the technical quality of aortic CT angiography over conventional threshold-based techniques, and may reduce technical failures related to low cardiac output and slow flow through an aneurysmal aorta.

Fluid-structure interaction analysis of the flow through a stenotic aortic valve

NASA Astrophysics Data System (ADS)

Maleki, Hoda; Labrosse, Michel R.; Durand, Louis-Gilles; Kadem, Lyes

2009-11-01

In Europe and North America, aortic stenosis (AS) is the most frequent valvular heart disease and cardiovascular disease after systemic hypertension and coronary artery disease. Understanding blood flow through an aortic stenosis and developing new accurate non-invasive diagnostic parameters is, therefore, of primarily importance. However, simulating such flows is highly challenging. In this study, we considered the interaction between blood flow and the valve leaflets and compared the results obtained in healthy valves with stenotic ones. One effective method to model the interaction between the fluid and the structure is to use Arbitrary Lagrangian-Eulerian (ALE) approach. Our two-dimensional model includes appropriate nonlinear and anisotropic materials. It is loaded during the systolic phase by applying pressure curves to the fluid domain at the inflow. For modeling the calcified stenotic valve, calcium will be added on the aortic side of valve leaflets. Such simulations allow us to determine the effective orifice area of the valve, one of the main parameters used clinically to evaluate the severity of an AS, and to correlate it with changes in the structure of the leaflets.

Three-dimensional finite volume modelling of blood flow in simulated angular neck abdominal aortic aneurysm

NASA Astrophysics Data System (ADS)

Algabri, Y. A.; Rookkapan, S.; Chatpun, S.

2017-09-01

An abdominal aortic aneurysm (AAA) is considered a deadly cardiovascular disease that defined as a focal dilation of blood artery. The healthy aorta size is between 15 and 24 mm based on gender, bodyweight, and age. When the diameter increased to 30 mm or more, the rupture can occur if it is kept growing or untreated. Moreover, the proximal angular neck of aneurysm is categorized as a significant morphological feature with prime harmful effects on endovascular aneurysm repair (EVAR). Flow pattern in pathological vessel can influence the vascular intervention. The aim of this study is to investigate the blood flow behaviours in angular neck abdominal aortic aneurysm with simulated geometry based on patient’s information using computational fluid dynamics (CFD). The 3D angular neck AAA models have been designed by using SolidWorks Software. Consequently, CFD tools are used for simulating these 3D models of angular neck AAA in ANSYS FLUENT Software. Eventually, based on the results, we summarized that the CFD techniques have shown high performance in explaining and investigating the flow patterns for angular neck abdominal aortic aneurysm.

Feasibility of blind aortic catheter placement in the prehospital environment to guide resuscitation in cardiac arrest.

PubMed

Manning, James E

2013-08-01

Aortic catheter-based resuscitation therapies are emerging with laboratory investigations showing benefit in models of trauma-related noncompressible torso hemorrhage and nontraumatic cardiac arrest. For these investigational aortic catheter-based therapies to reach their greatest potential clinical benefit, the ability to initiate them in the prehospital setting will be important. Feasibility of prehospital aortic catheterization without imaging capability supports this potential and is described in this report. A physician prehospital response system was created in cooperation with the local emergency medical services system to provide invasive hemodynamic monitoring during cardiac arrest. Physicians were dispatched to all known or suspected prehospital cardiac arrests covered by the emergency medical services system. Physicians responded with a specialized vascular catheterization pack and a monitor with invasive pressure monitoring capability. The physicians performed blind thoracic aortic and central venous catheterizations in cardiac arrest patients in the prehospital setting to measure coronary perfusion pressure, to optimize closed-chest cardiopulmonary resuscitation technique, and to administer intra-aortic epinephrine. During a 2-year period, 22 medical cardiac arrest patients underwent prehospital invasive hemodynamic monitoring to guide resuscitation. Most patients had both aortic and central venous catheters inserted. The combination of intra-aortic epinephrine and adjustments in closed-chest cardiopulmonary resuscitation technique resulted in improved coronary perfusion pressure. Return of spontaneous circulation with survival to hospital admission was achieved in 50% (11 of 22) of these patients. This report demonstrates the feasibility of successful blind aortic and central venous catheterizations in the prehospital environment and supports the potential feasibility of other emerging aortic catheter-based resuscitation therapies.

Aortic Cross-Sectional Area/Height Ratio and Outcomes in Patients With a Trileaflet Aortic Valve and a Dilated Aorta.

PubMed

Masri, Ahmad; Kalahasti, Vidyasagar; Svensson, Lars G; Roselli, Eric E; Johnston, Douglas; Hammer, Donald; Schoenhagen, Paul; Griffin, Brian P; Desai, Milind Y

2016-11-29

In patients with a dilated proximal ascending aorta and trileaflet aortic valve, we aimed to assess (1) factors independently associated with increased long-term mortality and (2) the incremental prognostic utility of indexing aortic root to patient height. We studied consecutive patients with a dilated aortic root (≥4 cm) that underwent echocardiography and gated contrast-enhanced thoracic aortic computed tomography or magnetic resonance angiography between 2003 and 2007. A ratio of aortic root area over height was calculated (cm 2 /m) on tomography, and a cutoff of 10 cm 2 /m was chosen as abnormal, on the basis of previous reports. All-cause death was recorded. The cohort comprised 771 patients (63 years [interquartile range, 53-71], 87% men, 85% hypertension, 51% hyperlipidemia, 56% smokers). Inherited aortopathies, moderate to severe aortic regurgitation, and severe aortic stenosis were seen in 7%, 18%, and 2%, whereas 91% and 54% were on β-blockers and angiotensin-converting enzyme inhibitors, respectively. Aortic root area/height ratio was ≥10 cm 2 /m in 24%. The Society of Thoracic Surgeons score and right ventricular systolic pressure were 3.3±3 and 31±7 mm Hg, respectively. At 7.8 years (interquartile range, 6.6-8.9), 280 (36%) patients underwent aortic surgery (76% within 1 year) and 130 (17%) died (1% in-hospital postoperative mortality). A lower proportion of patients in the surgical (versus nonsurgical) group died (13% versus 19%, P<0.01). On multivariable Cox proportional hazard analysis, aortic root area/height ratio (hazard ratio, 4.04; 95% confidence interval [CI], 2.69-6.231) was associated with death, whereas aortic surgery (hazard ratio, 0.47; 95% CI, 0.27-0.81) was associated with improved survival (both P<0.01). For longer-term mortality, the addition of aortic root area/height ratio ≥10 cm 2 /m to a clinical model (Society of Thoracic Surgeons score, inherited aortopathies, hypertension, hyperlipidemia, medications, aortic regurgitation, and right ventricular systolic pressure), increased the c-statistic from 0.57 (95% CI, 0.35-0.77) to 0.65 (95% CI, 0.52-0.73) and net reclassification index from 0.17 (95% CI, 0.02-0.31) to 0.23 (95% CI, 0.04-0.34), both P<0.01. Of the 327 patients with aortic root diameter between 4.5 and 5.5 cm, 44% had an abnormal aortic root area/height ratio, of which 78% died. In patients with dilated aortic root and trileaflet aortic valve, a ratio of aortic root area to height provides independent and improved stratification for prediction of death. © 2016 American Heart Association, Inc.

Redox stress in Marfan syndrome: Dissecting the role of the NADPH oxidase NOX4 in aortic aneurysm.

PubMed

Jiménez-Altayó, Francesc; Meirelles, Thayna; Crosas-Molist, Eva; Sorolla, M Alba; Del Blanco, Darya Gorbenko; López-Luque, Judit; Mas-Stachurska, Aleksandra; Siegert, Ana-Maria; Bonorino, Fabio; Barberà, Laura; García, Carolina; Condom, Enric; Sitges, Marta; Rodríguez-Pascual, Fernando; Laurindo, Francisco; Schröder, Katrin; Ros, Joaquim; Fabregat, Isabel; Egea, Gustavo

2018-04-01

Marfan syndrome (MFS) is characterized by the formation of ascending aortic aneurysms resulting from altered assembly of extracellular matrix fibrillin-containing microfibrils and dysfunction of TGF-β signaling. Here we identify the molecular targets of redox stress in aortic aneurysms from MFS patients, and investigate the role of NOX4, whose expression is strongly induced by TGF-β, in aneurysm formation and progression in a murine model of MFS. Working models included aortae and cultured vascular smooth muscle cells (VSMC) from MFS patients, and a NOX4-deficient Marfan mouse model (Fbn1 C1039G/+ -Nox4 -/- ). Increased tyrosine nitration and reactive oxygen species levels were found in the tunica media of human aortic aneurysms and in cultured VSMC. Proteomic analysis identified nitrated and carbonylated proteins, which included smooth muscle α-actin (αSMA) and annexin A2. NOX4 immunostaining increased in the tunica media of human Marfan aorta and was transcriptionally overexpressed in VSMC. Fbn1 C1039G/+ -Nox4 -/- mice aortas showed a reduction of fragmented elastic fibers, which was accompanied by an amelioration in the Marfan-associated enlargement of the aortic root. Increase in the contractile phenotype marker calponin in the tunica media of MFS mice aortas was abrogated in Fbn1 C1039G/+ -Nox4 -/- mice. Endothelial dysfunction evaluated by myography in the Marfan ascending aorta was prevented by the absence of Nox4 or catalase-induced H 2 O 2 decomposition. We conclude that redox stress occurs in MFS, whose targets are actin-based cytoskeleton members and regulators of extracellular matrix homeostasis. Likewise, NOX4 have an impact in the progression of the aortic dilation in MFS and in the structural organization of the aortic tunica media, the VSMC phenotypic modulation, and endothelial function. Copyright © 2018 Elsevier Inc. All rights reserved.

Involvement of nitric oxide in the mediation of the hypotensive action of the essential oil of Mentha x villosa in normotensive conscious rats.

PubMed

Lahlou, Saad; Magalhães, Pedro Jorge Caldas; Carneiro-Leão, Ricardo Ferreira Lima; Leal-Cardoso, José Henrique

2002-08-01

Recently, we showed that intravenous (i.v.) treatment with the essential oil of Mentha x villosa (EOMV) in pentobarbitone-anaesthetised rats decreased blood pressure; the effect occurred independently of the presence of an operational central autonomic drive to the cardiovascular system. This finding suggested that the hypotensive activity of EOMV may result from its vasodilatory effects directly upon vascular smooth muscle. The present study examines this possibility and whether EOMV-induced hypotension is mediated, at least in part, by an endothelial L-arginine/nitric oxide pathway. In conscious rats, i.v. injections of bolus doses (1 to 20 mg/kg) of EOMV elicited immediate and dose-dependent decreases in mean aortic pressure (MAP) and heart rate (HR). Pretreatment with i.v. hexamethonium (30 mg/kg) reduced the EOMV-induced bradycardia without affecting the hypotension. However, i.v. pretreatment with the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl (L-NAME, 20 mg/kg), reduced partially, but significantly, the maximal percent decreases in MAP elicited by EOMV without affecting the bradycardia. In rat isolated thoracic aorta preparations, EOMV (1 - 130 microg/ml) induced a concentration-dependent reduction of potassium (60 mM)-induced contraction. This smooth muscle-relaxant activity of EOMV was significantly reduced by the incubation of endothelium-intact rings with L-NAME (20 microM), as evidenced by the significant enhancement in the IC50 for EOMV-induced reduction of potassium-induced contraction (133.8 +/- 26.5 vs. 65.2 +/- 8.2 microg/ml in the absence of L-NAME). Furthermore, the vasorelaxant effects of EOMV in endothelium-denuded aortic rings were also significantly reduced (IC50 = 109 +/- 10 microg/ml), compared to those observed in segments with intact endothelium (IC50 = 61 +/- 13 microg/ml). These results show that i.v. treatment with EOMV dose-dependently decreases blood pressure in conscious rats, and that this action is due to an active vascular relaxation rather than withdrawal of sympathetic tone. Released nitric oxide from vascular endothelial cells appears partially involved in the aortic relaxation induced by EOMV and in turn in the mediation of EOMV-induced hypotension. They further support the concept that EOMV-induced hypotension and bradycardia occurred independently.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Midulla, Marco, E-mail: marco.midulla@chru-lille.fr; Moreno, Ramiro, E-mail: ramoroa@gmail.com; Negre-Salvayre, Anne, E-mail: anne.negre-salvayre@inserm.fr

PurposeAlthough the widespread acceptance of thoracic endovascular aortic repair (TEVAR) as a first-line treatment option for a multitude of thoracic aortic diseases, little is known about the consequences of the device implantation on the native aortic anatomy. We propose a comparative analysis of the pre- and postoperative geometry on a clinical series of patients and discuss the potential clinical implicationsMethodsCT pre- and postoperative acquisitions of 30 consecutive patients treated by TEVAR for different pathologies (20 thoracic aortic aneurysms, 6 false aneurysms, 3 penetrating ulcers, 1 traumatic rupture) were used to model the vascular geometry. Pre- and postoperative geometries were comparedmore » for each patient by pairing and matching the 3D models. An implantation site was identified, and focal differences were detected and described.ResultsSegmentation of the data sets was successfully performed for all 30 subjects. Geometry differences between the pre- and postoperative meshes were depicted in 23 patients (76 %). Modifications at the upper implantation site were detected in 14 patients (47 %), and among them, the implantation site involved the arch (Z0–3) in 11 (78 %).ConclusionModeling the vascular geometry on the basis of imaging data offers an effective tool to perform patient-specific analysis of the vascular geometry before and after the treatment. Future studies will evaluate the consequences of these changes on the aortic function.« less

Vortex dynamics in Patient-Specific Stenotic Tricuspid and Bicuspid Aortic Valves pre- and post- Trans-catheter Aortic Valve Replacement

NASA Astrophysics Data System (ADS)

Hatoum, Hoda; Dasi, Lakshmi Prasad

2017-11-01

Understanding blood flow related adverse complications such as leaflet thrombosis post-transcatheter aortic valve implantation (TAVI) requires a deeper understanding of how patient-specific anatomic and hemodynamic factors, and relative valve positioning dictate sinus vortex flow and stasis regions. High resolution time-resolved particle image velocimetry measurements were conducted in compliant and transparent 3D printed patient-specific models of stenotic bicuspid and tricuspid aortic valve roots from patients who underwent TAVI. Using Lagrangian particle tracking analysis of sinus vortex flows and probability distributions of residence time and blood damage indices we show that (a) patient specific modeling provides a more realistic assessment of TAVI flows, (b) TAVI deployment alters sinus flow patterns by significantly decreasing sinus velocity and vorticity, and (c) relative valve positioning can control critical vortex structures that may explain preferential leaflet thrombosis corresponding to separated flow recirculation, secondary to valve jet vectoring relative to the aorta axis. This work provides new methods and understanding of the spatio-temporal aortic sinus vortex dynamics in post TAVI pathology. This study was supported by the Ohio State University DHLRI Trifit Challenge award.

Nitric oxide mediates aortic disease in mice deficient in the metalloprotease Adamts1 and in a mouse model of Marfan syndrome.

PubMed

Oller, Jorge; Méndez-Barbero, Nerea; Ruiz, E Josue; Villahoz, Silvia; Renard, Marjolijn; Canelas, Lizet I; Briones, Ana M; Alberca, Rut; Lozano-Vidal, Noelia; Hurlé, María A; Milewicz, Dianna; Evangelista, Arturo; Salaices, Mercedes; Nistal, J Francisco; Jiménez-Borreguero, Luis Jesús; De Backer, Julie; Campanero, Miguel R; Redondo, Juan Miguel

2017-02-01

Heritable thoracic aortic aneurysms and dissections (TAAD), including Marfan syndrome (MFS), currently lack a cure, and causative mutations have been identified for only a fraction of affected families. Here we identify the metalloproteinase ADAMTS1 and inducible nitric oxide synthase (NOS2) as therapeutic targets in individuals with TAAD. We show that Adamts1 is a major mediator of vascular homeostasis, given that genetic haploinsufficiency of Adamts1 in mice causes TAAD similar to MFS. Aortic nitric oxide and Nos2 levels were higher in Adamts1-deficient mice and in a mouse model of MFS (hereafter referred to as MFS mice), and Nos2 inactivation protected both types of mice from aortic pathology. Pharmacological inhibition of Nos2 rapidly reversed aortic dilation and medial degeneration in young Adamts1-deficient mice and in young or old MFS mice. Patients with MFS showed elevated NOS2 and decreased ADAMTS1 protein levels in the aorta. These findings uncover a possible causative role for the ADAMTS1-NOS2 axis in human TAAD and warrant evaluation of NOS2 inhibitors for therapy.

Nanoparticles Effectively Target Rapamycin Delivery to Sites of Experimental Aortic Aneurysm in Rats.

PubMed

Shirasu, Takuro; Koyama, Hiroyuki; Miura, Yutaka; Hoshina, Katsuyuki; Kataoka, Kazunori; Watanabe, Toshiaki

2016-01-01

Several drugs targeting the pathogenesis of aortic aneurysm have shown efficacy in model systems but not in clinical trials, potentially owing to the lack of targeted drug delivery. Here, we designed a novel drug delivery system using nanoparticles to target the disrupted aortic aneurysm micro-structure. We generated poly(ethylene glycol)-shelled nanoparticles incorporating rapamycin that exhibited uniform diameter and long-term stability. When injected intravenously into a rat model in which abdominal aortic aneurysm (AAA) had been induced by infusing elastase, labeled rapamycin nanoparticles specifically accumulated in the AAA. Microscopic analysis revealed that rapamycin nanoparticles were mainly distributed in the media and adventitia where the wall structures were damaged. Co-localization of rapamycin nanoparticles with macrophages was also noted. Rapamycin nanoparticles injected during the process of AAA formation evinced significant suppression of AAA formation and mural inflammation at 7 days after elastase infusion, as compared with rapamycin treatment alone. Correspondingly, the activities of matrix metalloproteinases and the expression of inflammatory cytokines were significantly suppressed by rapamycin nanoparticle treatment. Our findings suggest that the nanoparticle-based delivery system achieves specific delivery of rapamycin to the rat AAA and might contribute to establishing a drug therapy approach targeting aortic aneurysm.

Nanoparticles Effectively Target Rapamycin Delivery to Sites of Experimental Aortic Aneurysm in Rats

PubMed Central

Shirasu, Takuro; Koyama, Hiroyuki; Miura, Yutaka; Hoshina, Katsuyuki; Kataoka, Kazunori; Watanabe, Toshiaki

2016-01-01

Several drugs targeting the pathogenesis of aortic aneurysm have shown efficacy in model systems but not in clinical trials, potentially owing to the lack of targeted drug delivery. Here, we designed a novel drug delivery system using nanoparticles to target the disrupted aortic aneurysm micro-structure. We generated poly(ethylene glycol)-shelled nanoparticles incorporating rapamycin that exhibited uniform diameter and long-term stability. When injected intravenously into a rat model in which abdominal aortic aneurysm (AAA) had been induced by infusing elastase, labeled rapamycin nanoparticles specifically accumulated in the AAA. Microscopic analysis revealed that rapamycin nanoparticles were mainly distributed in the media and adventitia where the wall structures were damaged. Co-localization of rapamycin nanoparticles with macrophages was also noted. Rapamycin nanoparticles injected during the process of AAA formation evinced significant suppression of AAA formation and mural inflammation at 7 days after elastase infusion, as compared with rapamycin treatment alone. Correspondingly, the activities of matrix metalloproteinases and the expression of inflammatory cytokines were significantly suppressed by rapamycin nanoparticle treatment. Our findings suggest that the nanoparticle-based delivery system achieves specific delivery of rapamycin to the rat AAA and might contribute to establishing a drug therapy approach targeting aortic aneurysm. PMID:27336852

NADPH oxidase activation contributes to native low-density lipoprotein-induced proliferation of human aortic smooth muscle cells.

PubMed

Park, Il Hwan; Hwang, Hye Mi; Jeon, Byeong Hwa; Kwon, Hyung-Joo; Hoe, Kwang Lae; Kim, Young Myeong; Ryoo, Sungwoo

2015-06-12

Elevated plasma concentration of native low-density lipoprotein (nLDL) is associated with vascular smooth muscle cell (VSMC) activation and cardiovascular disease. We investigated the mechanisms of superoxide generation and its contribution to pathophysiological cell proliferation in response to nLDL stimulation. Lucigenin-induced chemiluminescence was used to measure nLDL-induced superoxide production in human aortic smooth muscle cells (hAoSMCs). Superoxide production was increased by nicotinamide adenine dinucleotide phosphate (NADPH) and decreased by NADPH oxidase inhibitors in nLDL-stimulated hAoSMC and hAoSMC homogenates, as well as in prepared membrane fractions. Extracellular signal-regulated kinase 1/2 (Erk1/2), protein kinase C-θ (PKCθ) and protein kinase C-β (PKCβ) were phosphorylated and maximally activated within 3 min of nLDL stimulation. Phosphorylated Erk1/2 mitogen-activated protein kinase, PKCθ and PKCβ stimulated interactions between p47phox and p22phox; these interactions were prevented by MEK and PKC inhibitors (PD98059 and calphostin C, respectively). These inhibitors decreased nLDL-dependent superoxide production and blocked translocation of p47phox to the membrane, as shown by epifluorescence imaging and cellular fractionation experiments. Proliferation assays showed that a small interfering RNA against p47phox, as well as superoxide scavenger and NADPH oxidase inhibitors, blocked nLDL-induced hAoSMC proliferation. The nLDL stimulation in deendothelialized aortic rings from C57BL/6J mice increased dihydroethidine fluorescence and induced p47phox translocation that was blocked by PD98059 or calphostin C. Isolated aortic SMCs from p47phox(-/-) mice (mAoSMCs) did not respond to nLDL stimulation. Furthermore, NADPH oxidase 1 (Nox1) was responsible for superoxide generation and cell proliferation in nLDL-stimulated hAoSMCs. These data demonstrated that NADPH oxidase activation contributed to cell proliferation in nLDL-stimulated hAoSMCs.

Ultra-low profile Ovation device: is it the definitive solution for EVAR?

PubMed

de Donato, G; Setacci, F; Sirignano, P; Galzerano, G; Borrelli, M P; di Marzo, L; Setacci, C

2014-02-01

When Juan Parodi implanted an endograft in a human body for the first time on September 7, 1990 in Buenos Aires, Argentina, the delivery system of the handmade device was primitive, extremely rigid, and had a bulky profile of 27 French (F). Since then, stent-graft technology has evolved rapidly, limitations of earlier-generation devices have been overtaken, and endovascular aneurysm repair (EVAR) eligibility has increased enormously. Nevertheless (still) challenging aortoiliac anatomy such as short and complex proximal aortic neck seal zones and narrow access vessels are responsible for EVAR ineligibility in up to 50% of cases. The Ovation Prime abdominal stent-graft system (TriVascular, Inc., Santa Rosa, CA, USA) is a trimodular device designed with the aortic body delivered via a flexible, hydrophilic-coated, ultra-low profile catheter (14-F outer diameter - OD). The aortic body is provided with a suprarenal nitinol stent with anchors that provide active fixation, while a network of rings and channels that are inflated with a low-viscosity radiopaque polymer during stent-graft deployment, provides effective sealing. The previous EVAR technology aimed to both anchor and seal using stents combined with fabric, with neither optimized for their roles and each forced to compete for the same space within their delivery catheters, which inevitably led to larger profile of the delivery system. The technical revolution of the Ovation endograft includes the idea to truly uncouple the stages of stent-graft fixation and seal during the procedure. In the Ovation endograft platform, stent and fabric are not competing the same space within the delivery system and an ultra-low profile delivery can be achieved without compromise. With such a low-profile delivery catheter, approximately 90% of men and 70% of women with abdominal aortic aneurysm have access vessel diameters considered fit for endovascular repair. The aim of this review paper was to analyze the main properties of Ovation endograft, to emphasize the advantage of the ultra-low profile device, and to sum up current literature.

Flow Behavior in the Left Heart Ventricle Following Apico-Aortic Bypass Surgery

NASA Astrophysics Data System (ADS)

Shahriari, Shahrokh; Jeyhani, Morteza; Labrosse, Michel; Kadem, Lyes

2013-11-01

Apico-aortic bypass (AAB) surgery is an alternative for transcatheter aortic valve implantation (TAVI) to reduce left ventricle (LV) overload in patients with severe aortic stenosis (AS). It consists in connecting the apex of the LV to the descending thoracic aorta with a valved conduit. Postoperative flow assessments show that two thirds of the outflow is conducted from the LV apex to the conduit, while only one third crosses the native aortic valve. In this study, we performed high speed particle image velocimetry (PIV) measurements of flow pattern within an in vitro elastic model of LV in the presence of a very severe AS, before and after AAB. Results indicate that AAB effectively relieves the LV outflow obstruction; however, it also leads to abnormal ventricular flow patterns. Normal LV flow dynamics is characterized by an emerging mitral jet flow followed by the development of a vortical flow with velocities directed towards the aortic valve, while measurements in the presence of AAB show systolic flow bifurcating to the apical conduit and to the aortic valve outflow tract. This study provides the first insight into the LV flow structure after AAB including outflow jets and disturbed stagnation regions.

Effect of cannula shape on aortic wall and flow turbulence: hydrodynamic study during extracorporeal circulation in mock thoracic aorta.

PubMed

Minakawa, Masahito; Fukuda, Ikuo; Yamazaki, Junichi; Fukui, Kozo; Yanaoka, Hideki; Inamura, Takao

2007-12-01

This study was designed to analyze flow pattern, velocity, and strain on the aortic wall of a glass aortic model during extracorporeal circulation, and to elucidate the characteristics of flow pattern in four aortic cannulas. Different patterns of large vortices and helical flow were made by each cannula. The high-velocity flow (0.6 m/s) was observed in end-hole cannula, causing high strain rate tensor (0.3~0.4 without unit) on the aortic arch. In dispersion cannula, a decreased strain rate tensor (less than 0.1) was found on the outer curvature of the aortic arch. In Soft-flow cannula (3M Cardiovascular, Ann Arbor, MI, USA), further decreased flow velocity (0.2 m/s) and strain (less than 0.2) were observed. In Select 3D cannula (Medtronic, Inc., Minneapolis, MN, USA), a high strain (0.4~0.5) was observed along the inner curvature of the aortic arch. In conclusion, end-hole cannula should not be used in atherosclerotic aorta. Particular attention should be paid both for selection of cannulas and cannulation site based on this result.

Secreted Klotho Attenuates Inflammation-Associated Aortic Valve Fibrosis in Senescence-Accelerated Mice P1.

PubMed

Chen, Jianglei; Fan, Jun; Wang, Shirley; Sun, Zhongjie

2018-05-01

Senescence-accelerated mice P1 (SAMP1) is an aging model characterized by shortened lifespan and early signs of senescence. Klotho is an aging-suppressor gene. The purpose of this study is to investigate whether in vivo expression of secreted klotho ( Skl ) gene attenuates aortic valve fibrosis in SAMP1 mice. SAMP1 mice and age-matched (AKR/J) control mice were used. SAMP1 mice developed obvious fibrosis in aortic valves, namely fibrotic aortic valve disease. Serum level of Skl was decreased drastically in SAMP1 mice. Expression of MCP-1 (monocyte chemoattractant protein 1), ICAM-1 (intercellular adhesion molecule 1), F4/80, and CD68 was increased in aortic valves of SAMP1 mice, indicating inflammation. An increase in expression of α-smooth muscle actin (myofibroblast marker), transforming growth factorβ-1, and scleraxis (a transcription factor of collagen synthesis) was also found in aortic valves of SAMP1 mice, suggesting that accelerated aging is associated with myofibroblast transition and collagen gene activation. We constructed adeno-associated virus 2 carrying mouse Skl cDNA for in vivo expression of Skl. Skl gene delivery effectively increased serum Skl of SAMP1 mice to the control level. Skl gene delivery inhibited inflammation and myofibroblastic transition in aortic valves and attenuated fibrotic aortic valve disease in SAMP1 mice. It is concluded that senescence-related fibrotic aortic valve disease in SAMP1 mice is associated with a decrease in serum klotho leading to inflammation, including macrophage infiltration and transforming growth factorβ-1/scleraxis-driven myofibroblast differentiation in aortic valves. Restoration of serum Skl levels by adeno-associated virus 2 carrying mouse Skl cDNA effectively suppresses inflammation and myofibroblastic transition and attenuates aortic valve fibrosis. Skl may be a potential therapeutic target for fibrotic aortic valve disease. © 2018 American Heart Association, Inc.

Impact of wait times on the effectiveness of transcatheter aortic valve replacement in severe aortic valve disease: a discrete event simulation model.

PubMed

Wijeysundera, Harindra C; Wong, William W L; Bennell, Maria C; Fremes, Stephen E; Radhakrishnan, Sam; Peterson, Mark; Ko, Dennis T

2014-10-01

There is increasing demand for transcatheter aortic valve replacement (TAVR) as the primary treatment option for patients with severe aortic stenosis who are high-risk surgical candidates or inoperable. We used mathematical simulation models to estimate the hypothetical effectiveness of TAVR with increasing wait times. We applied discrete event modelling, using data from the Placement of Aortic Transcatheter Valves (PARTNER) trials. We compared TAVR with medical therapy in the inoperable cohort, and compared TAVR to conventional aortic valve surgery in the high-risk cohort. One-year mortality and wait-time deaths were calculated in different scenarios by varying TAVR wait times from 10 days to 180 days, while maintaining a constant wait time for surgery at a mean of 15.6 days. In the inoperable cohort, the 1-year mortality for medical therapy was 50%. When the TAVR wait time was 10 days, the TAVR wait-time mortality was 1.9% with a 1-year mortality of 31.5%. TAVR wait-time deaths increased to 28.9% with a 180-day wait, with a 1-year mortality of 41.4%. In the high-risk cohort, the wait-time deaths and 1-year mortality for the surgical patients were 2.5% and 27%, respectively. The TAVR wait-time deaths increased from 2.2% with a 10-day wait to 22.4% with a 180-day wait, and a corresponding increase in 1-year mortality from 24.5% to 32.6%. Mortality with TAVR exceeded surgery when TAVR wait times exceeded 60 days. Modest increases in TAVR wait times have a substantial effect on the effectiveness of TAVR in inoperable patients and high-risk surgical candidates. Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Evaluation of hawthorn extract on immunomodulatory biomarkers in a pressure overload model of heart failure.

PubMed

Bleske, Barry E; Zineh, Issam; Hwang, Hyun Seok; Welder, Gregory J; Ghannam, Michael M J; Boluyt, Marvin O

2007-12-01

Hawthorn extract (Crataegeus sp.) a botanical complementary and alternative medicine is often used to treat heart failure. The mechanism(s) by which hawthorn extract may treat heart failure is unknown but may include, theoretically, immunological effects. Therefore, the purpose of this study is to determine the effect of hawthorn extract on the immunomodulatory response in a pressure overload model of heart failure. A total of 62 male Sprague-Dawley rats were randomized to either aortic constriction + vehicle (AC; n=15), aortic constriction + hawthorn 1.3 mg/kg (HL, n=17), aortic constriction + hawthorn 13 mg/kg (HM, n=15), or aortic constriction + hawthorn 130 mg/kg (HH, n=15). Six months after surgical procedure animals were sacrificed and plasma samples obtained for the measurement of the following immunomodulatory markers: interleukin (IL) IL-1ss, IL-2, IL-6, IL-10; and leptin. The mortality rate following 6 months of aortic constriction was 40% in the AC group compared to 41%, 60%, and 53% for the HL, HM, and HH groups respectively (P>0.05 compared to AC). Aortic constriction produced a similar increase in the left ventricle/body weight ratio for all groups. Hawthorn extract had no effect on the immunomodulatory markers measured in this study, although there appeared to be a trend suggesting suppression of IL-2 plasma concentrations. In this animal model of heart failure, hawthorn extract failed to significantly affect the immunomodulatory response characterized after 6 months of pressure overload at a time when approximately 50% mortality was exhibited. Mechanisms other than immunological may better define hawthorn's effect in treating heart failure.

Aortic curvature as a predictor of intraoperative type Ia endoleak.

PubMed

Schuurmann, Richte C L; Ouriel, Kenneth; Muhs, Bart E; Jordan, William D; Ouriel, Richard L; Boersen, Johannes T; de Vries, Jean-Paul P M

2016-03-01

Hostile infrarenal neck characteristics are associated with complications such as type Ia endoleak after endovascular aneurysm repair. Aortic neck angulation has been identified as one such characteristic, but its association with complications has not been uniform between studies. Neck angulation assumes triangular oversimplification of the aortic trajectory, which may explain conflicting findings. By contrast, aortic curvature is a measurement that includes the bending rate and tortuosity and may provide better predictive value for neck complications. Data were retrieved from the Heli-FX (Aptus Endosystems, Inc, Sunnyvale, Calif) Aortic Securement System Global Registry (ANCHOR). One cohort included patients who presented with intraoperative endoleak type Ia at the completion angiogram as the indication for EndoAnchors (Aptus Endosystems), and a second cohort comprised those without intraoperative or late type Ia endoleak (controls). The aortic trajectory was divided into six segments with potentially different influence on the stent graft performance: suprarenal, juxtarenal, and infrarenal aortic neck (-30 to -10 mm, -10 to 10 mm, and 10-30 mm from the lowest renal artery, respectively), the entire aortic neck, aneurysm sac, and terminal aorta (20 mm above the bifurcation to the bifurcation). Maximum and average curvature were automatically calculated over the six segments by proprietary custom software. Aortic curvature was compared with other standard neck characteristics, including neck length, neck diameter, maximum aneurysm sac diameter, neck thrombus and calcium thickness and circumference, suprarenal angulation, infrarenal angulation, and the neck tortuosity index. Independent risk factors for intraoperative type Ia endoleak were identified using backwards stepwise logistic regression. For the variables in the final regression model, suitable cutoff values in relation to the prediction of acute type Ia endoleak were defined with the area under the receiver operating characteristic curve. The analysis included 64 patients with intraoperative type Ia endoleak and 79 controls. Logistic regression identified only aortic neck calcification and aortic curvature, expressed over the juxtarenal aortic neck, the aneurysm sac, and the terminal aorta, as independent predictors of intraoperative type Ia endoleak. Together with aortic neck calcification, aortic curvature appears to be the best predictor of intraoperative type Ia endoleak, as expressed within the juxtarenal aortic neck, the aneurysm sac, and the terminal aorta. Aortic neck angulation was not a predictor for acute failure. Aortic curvature may provide a better anatomic characteristic to define patients at risk for early complications after endovascular aneurysm repair. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Anti-ischemic activity and endothelium-dependent vasorelaxant effect of hydrolysable tannins from the leaves of Rhus coriaria (Sumac) in isolated rabbit heart and thoracic aorta.

PubMed

Beretta, Giangiacomo; Rossoni, Giuseppe; Santagati, Natale Alfredo; Facino, Roberto Maffei

2009-11-01

The aim of this work was to investigate the cardioprotective activity of hydrolysable gallotannins from Rhus coriaria L. leaves extract (RCLE) in isolated rabbit heart preparations, submitted to low-flow ischemia/reperfusion damage. RCLE induces a dose-dependent normalization of coronary perfusion pressure (CPP), reducing left ventricular contracture during ischemia, and improving left ventricular developed pressure and the maximum rate of rise and fall of left ventricular pressure at reperfusion. Creatinine kinase (CK) and lactate dehydrogenase (LDH) outflow were significantly reduced during reperfusion. In parallel there was a rise in the release of the cytoprotective 6-ketoprostaglandin F (1alpha) (6-keto-PGF (1alpha)) and a decrease of tumor necrosis factor-alpha (TNF-alpha), both significant only at the highest RCLE concentrations (150-500 microg/mL). The vasorelaxant activity of RCLE was studied in isolated rabbit aorta rings precontracted with norepinephrine (NE) with and without endothelium. The vasorelaxation induced by RCLE was predominantly endothelium-dependent as demonstrated by the loss of RCLE vasorelaxant ability in i) de-endothelized rings and ii) in intact aortic rings after pretreatment with NG-monomethyl- L-arginine (L-NMMA) and 1 H-[1.2.4]oxadiazolo[4.3- A]quinoxalin-1-one (ODQ). The inhibition of vasorelaxation in intact rings by indomethacin (INDO) demonstrates the ability of RCLE to modulate the coronary endothelium cyclooxygenase (COX) pathway. The K-ATP channel antagonist glibenclamide (GLIB) was ineffective. The antioxidant activity of RCLE, investigated in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) model and in living cell systems (rat erythrocytes), was stronger than that of gallic acid, ascorbic acid and trolox. The structure of its main bioactive constituents, profiled by HPLC-ESI-HR-S, comprised a mixture of polygalloylated D-glucopyranose with different degrees of galloylation and 3- O-methylgallic acid. The cardiovascular protective effect of RCLE seems to be due to an interplay of different factors: COX pathway activation, TNF-alpha inhibition, endothelial nitric oxide synthase (eNOS) activation, and free radical and ROS scavenging. Georg Thieme Verlag KG Stuttgart, New York.

IABP timing and ventricular performance--comparison between a compliant and a stiffer aorta: a hybrid model study including baroreflex.

PubMed

Fresiello, Libera; Khir, Ashraf W; Di Molfetta, Arianna; Kozarski, Maciej; Ferrari, Gianfranco

2013-11-01

The aim of this study was to investigate the effects of the intra aortic balloon pump (IABP) and of aortic compliance on left ventricular performance, including the effects of baroreflex control.
 The study was conducted using a hybrid cardiovascular simulator, including a computational cardiovascular sub-model, a hydraulic sub-model of the descending aorta, and a baroreflex computational sub-model. A 40 cc balloon was inserted into a rubber tube component of the hydraulic sub-model. A comparative analysis was conducted for two aortic compliances (C1 = 2.4 and C2 = 1.43 cm3/mmHg, corresponding to an aortic pulse pressure of 23 mmHg and 35 mmHg, respectively), driving the balloon for different trigger timings.
 Under C1 conditions, the IABP induced higher effects on baroreflex activity (decrement of sympathetic efferent activity: 10% for C1 and 14.7% for C2) and ventricular performance (increment of cardiac output (CO): 3.7% for C1 and 5.2% for C2, increment of endocardial viability ratio (EVR): 24.8% for C1 and 55% for C2). The best balloon timing was different for C1 and C2: inflation trigger timing (from the dicrotic notch) -0.09 s for C1 and -0.04 s for C2, inflation duration 0.25 s for C1 and 0.2 s for C2.
 Early inflation ensures better EVR, CO, and an increment of the afferent nerve activity, hence causing peripheral resistance and heart rate to decrease. The best balloon timing depends on aortic compliance, thus suggesting the need for a therapy tailored to the specific conditions of individual patients.

Four Surgical Modifications to the Classic Elastase Perfusion Aneurysm Model Enable Haemodynamic Alterations and Extended Elastase Perfusion.

PubMed

Busch, Albert; Chernogubova, Ekaterina; Jin, Hong; Meurer, Felix; Eckstein, Hans-Henning; Kim, Mia; Maegdefessel, Lars

2018-04-24

Abdominal aortic aneurysm (AAA) is an individual and socioeconomic burden in today's ageing society. Treatment relies on surgical exclusion of the dilated aorta by open or endovascular repair. For research purposes, animal models are necessary and the elastase induced aneurysm model closely mimics end stage human aneurysm disease. To improve the translational value of this model, four modifications to the classic elastase perfusion procedure (PPE) in relation to human aneurysm morphology were conducted. In ten week old male C57BL/6J wild type mice the PPE procedure was modified in four ways using two different techniques. Flow alteration was simulated by partial ligation of the common iliac artery or the distal aorta. Additionally, careful exploration of the abdominal aortic branches allowed PPE induction at the suprarenal and iliac level. Molecular biology, ultrasound, and immunohistochemistry were used to evaluate these pilot results. Two aortic outflow obstructions simulating distal aortic or iliac stenosis significantly increase murine AAA diameter (p = .046), and affect local vascular wall remodelling. Suprarenal aortic dissection allows a juxtarenal aneurysm to be induced, similar to the angiotensin II induced aneurysm model. A separate investigation for canonical activation of transforming growth factor β in the two embryonically distinct juxtarenal and infrarenal segments showed no distinct difference. Creating an aortoiliac bifurcated aneurysm completes the mimicry of human aneurysm morphology. The alteration of the classic PPE aneurysm by outflow modulation and further elastase perfusion to the juxtarenal and aortoiliac segment modifies morphology and diameter, and thus increases the translational value in future research. Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.

Massive aggrecan and versican accumulation in thoracic aortic aneurysm and dissection

PubMed Central

Cikach, Frank S.; Koch, Christopher D.; Mead, Timothy J.; Galatioto, Josephine; Willard, Belinda B.; Emerton, Kelly B.; Eagleton, Matthew J.; Blackstone, Eugene H.; Ramirez, Francesco; Roselli, Eric E.; Apte, Suneel S.

2018-01-01

Proteoglycan accumulation is a hallmark of medial degeneration in thoracic aortic aneurysm and dissection (TAAD). Here, we defined the aortic proteoglycanome using mass spectrometry, and based on the findings, investigated the large aggregating proteoglycans aggrecan and versican in human ascending TAAD and a mouse model of severe Marfan syndrome. The aortic proteoglycanome comprises 20 proteoglycans including aggrecan and versican. Antibodies against these proteoglycans intensely stained medial degeneration lesions in TAAD, contrasting with modest intralamellar staining in controls. Aggrecan, but not versican, was increased in longitudinal analysis of Fbn1mgR/mgR aortas. TAAD and Fbn1mgR/mgR aortas had increased aggrecan and versican mRNAs, and reduced expression of a key proteoglycanase gene, ADAMTS5, was seen in TAAD. Fbn1mgR/mgR mice with ascending aortic dissection and/or rupture had dramatically increased aggrecan staining compared with mice without these complications. Thus, aggrecan and versican accumulation in ascending TAAD occurs via increased synthesis and/or reduced proteolytic turnover, and correlates with aortic dissection/rupture in Fbn1mgR/mgR mice. Tissue swelling imposed by aggrecan and versican is proposed to be profoundly deleterious to aortic wall mechanics and smooth muscle cell homeostasis, predisposing to type-A dissections. These proteoglycans provide potential biomarkers for refined risk stratification and timing of elective aortic aneurysm repair. PMID:29515038

Massive aggrecan and versican accumulation in thoracic aortic aneurysm and dissection.

PubMed

Cikach, Frank S; Koch, Christopher D; Mead, Timothy J; Galatioto, Josephine; Willard, Belinda B; Emerton, Kelly B; Eagleton, Matthew J; Blackstone, Eugene H; Ramirez, Francesco; Roselli, Eric E; Apte, Suneel S

2018-03-08

Proteoglycan accumulation is a hallmark of medial degeneration in thoracic aortic aneurysm and dissection (TAAD). Here, we defined the aortic proteoglycanome using mass spectrometry, and based on the findings, investigated the large aggregating proteoglycans aggrecan and versican in human ascending TAAD and a mouse model of severe Marfan syndrome. The aortic proteoglycanome comprises 20 proteoglycans including aggrecan and versican. Antibodies against these proteoglycans intensely stained medial degeneration lesions in TAAD, contrasting with modest intralamellar staining in controls. Aggrecan, but not versican, was increased in longitudinal analysis of Fbn1mgR/mgR aortas. TAAD and Fbn1mgR/mgR aortas had increased aggrecan and versican mRNAs, and reduced expression of a key proteoglycanase gene, ADAMTS5, was seen in TAAD. Fbn1mgR/mgR mice with ascending aortic dissection and/or rupture had dramatically increased aggrecan staining compared with mice without these complications. Thus, aggrecan and versican accumulation in ascending TAAD occurs via increased synthesis and/or reduced proteolytic turnover, and correlates with aortic dissection/rupture in Fbn1mgR/mgR mice. Tissue swelling imposed by aggrecan and versican is proposed to be profoundly deleterious to aortic wall mechanics and smooth muscle cell homeostasis, predisposing to type-A dissections. These proteoglycans provide potential biomarkers for refined risk stratification and timing of elective aortic aneurysm repair.

Difference in hemodynamic and wall stress of ascending thoracic aortic aneurysms with bicuspid and tricuspid aortic valve

PubMed Central

Pasta, Salvatore; Rinaudo, Antonino; Luca, Angelo; Pilato, Michele; Scardulla, Cesare; Gleason, Thomas G.; Vorp, David A.

2014-01-01

The aortic dissection (AoD) of an ascending thoracic aortic aneurysm (ATAA) initiates when the hemodynamic loads exerted on the aneurysmal wall overcome the adhesive forces holding the elastic layers together. Parallel coupled, two-way fluid–structure interaction (FSI) analyses were performed on patient-specific ATAAs obtained from patients with either bicuspid aortic valve (BAV) or tricuspid aortic valve (TAV) to evaluate hemodynamic predictors and wall stresses imparting aneurysm enlargement and AoD. Results showed a left-handed circumferential flow with slower-moving helical pattern in the aneurysm's center for BAV ATAAs whereas a slight deviation of the blood flow toward the anterolateral region of the ascending aorta was observed for TAV ATAAs. Blood pressure and wall shear stress were found key hemodynamic predictors of aneurysm dilatation, and their dissimilarities are likely associated to the morphological anatomy of the aortic valve. We also observed discontinues, wall stresses on aneurysmal aorta, which was modeled as a composite with two elastic layers (i.e., inhomogeneity of vessel structural organization). This stress distribution was caused by differences on elastic material properties of aortic layers. Wall stress distribution suggests AoD just above sinotubular junction. Moreover, abnormal flow and lower elastic material properties that are likely intrinsic in BAV individuals render the aneurysm susceptible to the initiation of AoD. PMID:23664314

Impact of aortic root size on left ventricular afterload and stroke volume.

PubMed

Sahlén, Anders; Hamid, Nadira; Amanullah, Mohammed Rizwan; Fam, Jiang Ming; Yeo, Khung Keong; Lau, Yee How; Lam, Carolyn S P; Ding, Zee Pin

2016-07-01

The left ventricle (LV) ejects blood into the proximal aorta. Age and hypertension are associated with stiffening and dilation of the aortic root, typically viewed as indicative of adverse remodeling. Based on analytical considerations, we hypothesized that a larger aortic root should be associated with lower global afterload (effective arterial elastance, EA) and larger stroke volume (SV). Moreover, as antihypertensive drugs differ in their effect on central blood pressure, we examined the role of antihypertensive drugs for the relation between aortic root size and afterload. We studied a large group of patients (n = 1250; 61 ± 12 years; 78 % males; 64 % hypertensives) from a single-center registry with known or suspected coronary artery disease. Aortic root size was measured by echocardiography as the diameter of the tubular portion of the ascending aorta. LV outflow tract Doppler was used to record SV. In the population as a whole, after adjusting for key covariates in separate regression models, aortic root size was an independent determinant of both SV and EA. This association was found to be heterogeneous and stronger in patients taking a calcium channel blocker (CCB; 10.6 % of entire population; aortic root size accounted for 8 % of the explained variance of EA). Larger aortic root size is an independent determinant of EA and SV. This association was heterogeneous and stronger in patients on CCB therapy.

Aortopathy in a Mouse Model of Marfan Syndrome Is Not Mediated by Altered Transforming Growth Factor β Signaling.

PubMed

Wei, Hao; Hu, Jie Hong; Angelov, Stoyan N; Fox, Kate; Yan, James; Enstrom, Rachel; Smith, Alexandra; Dichek, David A

2017-01-24

Marfan syndrome (MFS) is caused by mutations in the gene encoding fibrillin-1 (FBN1); however, the mechanisms through which fibrillin-1 deficiency causes MFS-associated aortopathy are uncertain. Recently, attention was focused on the hypothesis that MFS-associated aortopathy is caused by increased transforming growth factor-β (TGF-β) signaling in aortic medial smooth muscle cells (SMC). However, there are many reasons to doubt that TGF-β signaling drives MFS-associated aortopathy. We used a mouse model to test whether SMC TGF-β signaling is perturbed by a fibrillin-1 variant that causes MFS and whether blockade of SMC TGF-β signaling prevents MFS-associated aortopathy. MFS mice (Fbn1 C1039G/+ genotype) were genetically modified to allow postnatal SMC-specific deletion of the type II TGF-β receptor (TBRII; essential for physiologic TGF-β signaling). In young MFS mice with and without superimposed deletion of SMC-TBRII, we measured aortic dimensions, histopathology, activation of aortic SMC TGF-β signaling pathways, and changes in aortic SMC gene expression. Young Fbn1 C1039G/+ mice had ascending aortic dilation and significant disruption of aortic medial architecture. Both aortic dilation and disrupted medial architecture were exacerbated by superimposed deletion of TBRII. TGF-β signaling was unaltered in aortic SMC of young MFS mice; however, SMC-specific deletion of TBRII in Fbn1 C1039G/+ mice significantly decreased activation of SMC TGF-β signaling pathways. In young Fbn1 C1039G/+ mice, aortopathy develops in the absence of detectable alterations in SMC TGF-β signaling. Loss of physiologic SMC TGF-β signaling exacerbates MFS-associated aortopathy. Our data support a protective role for SMC TGF-β signaling during early development of MFS-associated aortopathy. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

New predictor of aortic enlargement in uncomplicated type B aortic dissection based on elliptic Fourier analysis.

PubMed

Sato, Hiroshi; Ito, Toshiro; Kuroda, Yosuke; Uchiyama, Hiroki; Watanabe, Toshitaka; Yasuda, Naomi; Nakazawa, Junji; Harada, Ryo; Kawaharada, Nobuyoshi

2017-12-01

This study aimed to re-examine the conventional predictive factors for dissected aortic enlargement, such as the aortic and false lumen diameter and to consider whether the morphological elements of the dissected aorta could be predictors by quantifying the 'shape' of the true lumen based on elliptic Fourier analysis. A total of 80 patients with uncomplicated type B aortic dissection were included. The patients were divided into 'Enlargement group' and 'No Change group.' Between the 2 groups, the mean systolic blood pressure during follow-up, aortic and false lumen maximum diameters, and analysed morphological data were compared using each statistical method. The maximum aortic and false lumen diameters were significantly larger in the Enlargement group than in the No Change group (39.3 vs 35.9 mm; P = 0.0058) (23.5 vs 18.2 mm; P = 0.000095). The principal component 1, which is the data calculated by elliptic Fourier analysis, was significantly lower in the Enlargement group than in the No Change group (0.020 vs - 0.072; P = 0.000049). The mean systolic blood pressure ≥130 mmHg, aortic diameter, false lumen diameter and principal component 1 were included in the Cox proportional hazard model as covariates to determine the significant predictive variable. Principal component 1 demonstrated the only significance with aortic enlargement on multivariate analysis (odds ratio = 0.32; P = 0.048). The analysed and calculated morphological data of the shape of the true lumen can be more effective predictive factors of aortic enlargement of type B dissection than the conventional factors. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Aortic blood pressure measured via EIT: investigation of different measurement settings.

PubMed

Braun, Fabian; Proença, Martin; Rapin, Michael; Lemay, Mathieu; Adler, Andy; Grychtol, Bartłomiej; Solà, Josep; Thiran, Jean-Philippe

2015-06-01

Electrical impedance tomography (EIT) allows the measurement of intra-thoracic impedance changes related to cardiovascular activity. As a safe and low-cost imaging modality, EIT is an appealing candidate for non-invasive and continuous haemodynamic monitoring. EIT has recently been shown to allow the assessment of aortic blood pressure via the estimation of the aortic pulse arrival time (PAT). However, finding the aortic signal within EIT image sequences is a challenging task: the signal has a small amplitude and is difficult to locate due to the small size of the aorta and the inherent low spatial resolution of EIT. In order to most reliably detect the aortic signal, our objective was to understand the effect of EIT measurement settings (electrode belt placement, reconstruction algorithm). This paper investigates the influence of three transversal belt placements and two commonly-used difference reconstruction algorithms (Gauss-Newton and GREIT) on the measurement of aortic signals in view of aortic blood pressure estimation via EIT. A magnetic resonance imaging based three-dimensional finite element model of the haemodynamic bio-impedance properties of the human thorax was created. Two simulation experiments were performed with the aim to (1) evaluate the timing error in aortic PAT estimation and (2) quantify the strength of the aortic signal in each pixel of the EIT image sequences. Both experiments reveal better performance for images reconstructed with Gauss-Newton (with a noise figure of 0.5 or above) and a belt placement at the height of the heart or higher. According to the noise-free scenarios simulated, the uncertainty in the analysis of the aortic EIT signal is expected to induce blood pressure errors of at least ± 1.4 mmHg.

Gender discrimination in the influence of hyperglycemia and hyperosmolarity on rat aortic tissue responses to insulin.

PubMed

Wong, Nikki L; Achike, Francis I

2010-08-09

Hyperglycaemia initiates endothelial dysfunction causing diabetic macro- and micro-vasculopathy, the main causes of morbidity and mortality in diabetes mellitus. The vasculopathy exhibits gender peculiarities. We therefore explored gender differences in comparing the effects of hyperglycaemia (50 mM) per se with its hyperosmolar (50 mM) effects on vascular tissue responses to insulin. Endothelium-intact or denuded thoracic aortic rings from age-matched male and female Sprague-Dawley rats were incubated for 10 min or 6 h (acute versus chronic exposure) in normal, hyperglycaemic or hyperosmolar Krebs solution. Relaxant responses to insulin (6.9x10(-7)-6.9x10(-5) M) of the phenylephrine-contracted tissues were recorded. Endothelium denudation in both genders inhibited relaxation to insulin in all conditions, more significantly in female than in male tissues, suggesting the female response to insulin is more endothelium-dependent than the male. Acutely and chronically exposed normoglycemic endothelium-intact or -denuded tissues responded similarly to insulin. Chronic hyperglycemic or hyperosmolar exposure did not alter the endothelium-denuded tissue responses to insulin, whereas the responses of the endothelium-intact male and female hyperosmolar, and male hyperglycemic tissues were enhanced. The results show that insulin exerts an endothelium-dependent and independent relaxation with the female tissue responses more endothelium-dependent than the male. The data also suggest that hyperosmolarity per se enhances aortic tissue relaxant responses to insulin whereas hyperglycemia per se inhibits the same and more so in female than male tissues. These effects are endothelium-dependent. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Modification of Aortic Cannula With an Inlet Chamber to Induce Spiral Flow and Improve Outlet Flow.

PubMed

Darlis, Nofrizalidris; Osman, Kahar; Padzillah, Muhamad Hasbullah; Dillon, Jeswant; Md Khudzari, Ahmad Zahran

2018-05-01

Physiologically, blood ejected from the left ventricle in systole exhibited spiral flow characteristics. This spiral flow has been proven to have several advantages such as lateral reduction of directed forces and thrombus formation, while it also appears to be clinically beneficial in suppressing neurological complications. In order to deliver spiral flow characteristics during cardiopulmonary bypass operation, several modifications have been made on an aortic cannula either at the internal or at the outflow tip; these modifications have proven to yield better hemodynamic performances compared to standard cannula. However, there is no modification done at the inlet part of the aortic cannula for inducing spiral flow so far. This study was carried out by attaching a spiral inducer at the inlet of an aortic cannula. Then, the hemodynamic performances of the new cannula were compared with the standard straight tip end-hole cannula. This is achieved by modeling the cannula and attaching the cannula at a patient-specific aorta model. Numerical approach was utilized to evaluate the hemodynamic performance, and a water jet impact experiment was used to demonstrate the jet force generated by the cannula. The new spiral flow aortic cannula has shown some improvements by reducing approximately 21% of impinging velocity near to the aortic wall, and more than 58% reduction on total force generated as compared to standard cannula. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

In Vivo Validation of Numerical Prediction for Turbulence Intensity in an Aortic Coarctation

PubMed Central

Arzani, Amirhossein; Dyverfeldt, Petter; Ebbers, Tino; Shadden, Shawn C.

2013-01-01

This paper compares numerical predictions of turbulence intensity with in vivo measurement. Magnetic resonance imaging (MRI) was carried out on a 60-year-old female with a restenosed aortic coarctation. Time-resolved three-directional phase-contrast (PC) MRI data was acquired to enable turbulence intensity estimation. A contrast-enhanced MR angiography (MRA) and a time-resolved 2D PCMRI measurement were also performed to acquire data needed to perform subsequent image-based computational fluid dynamics (CFD) modeling. A 3D model of the aortic coarctation and surrounding vasculature was constructed from the MRA data, and physiologic boundary conditions were modeled to match 2D PCMRI and pressure pulse measurements. Blood flow velocity data was subsequently obtained by numerical simulation. Turbulent kinetic energy (TKE) was computed from the resulting CFD data. Results indicate relative agreement (error ≈10%) between the in vivo measurements and the CFD predictions of TKE. The discrepancies in modeled vs. measured TKE values were within expectations due to modeling and measurement errors. PMID:22016327

Biomechanical analysis of wrapping of the moderately dilated ascending aorta.

PubMed

Plonek, Tomasz; Rylski, Bartosz; Dumanski, Andrzej; Siedlaczek, Przemyslaw; Kustrzycki, Wojciech

2015-08-01

External wrapping is a surgical method performed to prevent the dilatation of the aorta and to decrease the risk of its dissection and rupture. However, it is also believed to cause degeneration of the aortic wall. A biomechanical analysis was thus performed to assess the stress of the aortic wall subjected to external wrapping. A stress analysis using the finite elements method was carried out on three models: a non-dilated aorta, a moderately dilated aorta and a wrapped aorta. The models were subjected to a pulsatile flow (120/80 mmHg) and a systolic aortic annulus motion of 11 mm. The finite elements analysis showed that the stress exerted on the outer surface of the ascending aorta in the wrapping model (0.05-0.8 MPa) was similar to that observed in the normal aorta (0.03-0.7 MPa) and was lower than in the model of a moderately dilated aorta (0.06-1.4 MPa). The stress on the inner surface of the ascending aorta ranged from 0.2 MPa to 0.4 MPa in the model of the normal aorta, from 0.3 to 1.3 MPa in the model of the dilated aorta and from 0.05 MPa to 0.4 MPa in the wrapping model. The results of this study suggest that the aortic wall is subjected to similar stress following a wrapping procedure to the one present in the normal aorta.

The urea decomposition product cyanate promotes endothelial dysfunction

PubMed Central

El-Gamal, Dalia; Rao, Shailaja Prabhakar; Holzer, Michael; Hallström, Seth; Haybaeck, Johannes; Gauster, Martin; Wadsack, Christian; Kozina, Andrijana; Frank, Saša; Schicho, Rudolf; Schuligoi, Rufina; Heinemann, Akos; Marsche, Gunther

2014-01-01

The dramatic cardiovascular mortality of chronic kidney disease patients is attributable in a significant proportion to endothelial dysfunction. Cyanate, a reactive species in equilibrium with urea, is formed in excess in chronic kidney disease. Cyanate is thought to have a causal role in promoting cardiovascular disease, but the underlying mechanisms remain unclear. Immunohistochemical analysis performed in the present study revealed that carbamylated epitopes associate mainly with endothelial cells in human atherosclerotic lesions. Cyanate treatment of human coronary artery endothelial cells reduced expression of endothelial nitric oxide synthase and increased tissue factor and plasminogen activator inhibitor-1 expression. In mice, administration of cyanate - promoting protein carbamylation at levels observed in uremic patients - attenuated arterial vasorelaxation of aortic rings in response to acetylcholine, without affecting sodium nitroprusside-induced relaxation. Total endothelial nitric oxide synthase and nitric oxide production were significantly reduced in aortic tissue of cyanate-treated mice. This coincided with a marked increase of tissue factor and plasminogen activator inhibitor-1 protein levels in aortas of cyanate-treated mice. These data provide evidence that cyanate compromises endothelial functionality in vitro and in vivo and may contribute to the dramatic cardiovascular risk of patients suffering from chronic kidney disease. PMID:24940796

Direct vascular control results in less physiologic derangement than proximal aortic clamping in a porcine model of noncompressible extrathoracic torso hemorrhage.

PubMed

White, Joseph M; Cannon, Jeremy W; Stannard, Adam; Burkhardt, Gabriel E; Spencer, Jerry R; Williams, Ken; Oh, John S; Rasmussen, Todd E

2011-11-01

The optimal method of vascular control and resuscitation in patients with life-threatening, extrathoracic torso hemorrhage remains debated. Guidelines recommend emergency department thoracotomy (EDT) with aortic clamping, although transabdominal aortic clamping followed by vascular control and direct vascular control (DVC) without aortic clamping are alternatives. The objective of this study is to compare the effectiveness of three approaches to extrathoracic torso hemorrhage in a large animal model. Adolescent swine (Sus Scrofa) (mean weight = 80.9 kg) were randomized into three groups all of which had class IV shock established by hemorrhage from an iliac artery injury. Group 1: EDT with thoracic aortic clamping (N = 6); group 2: transabdominal supraceliac aortic clamping (SCC; N = 6); and group 3: DVC of bleeding site without aortic clamping (N = 6). After hemorrhage, EDT or SCC was performed in groups 1 and 2, respectively, with subsequent exploration of the bleeding site and placement of a temporary vascular shunt (TVS). Group 3 (DVC) underwent direct exploration of the injury and placement of a TVS. All groups were resuscitated to predefined physiologic endpoints over 6 hours with repeated measures of central and cerebral perfusion and end-organ function at standardized time points. Postmortem tissue analysis was performed to quantify injury to critical tissue beds. There was no difference in mortality among the groups and no TVS failures. Central aortic pressure, carotid flow, and partial pressure brain tissue oximetry, all demonstrated increases in EDT and SCC after application of the aortic clamp relative to DVC (p < 0.05). During resuscitation, serum lactate levels were higher in EDT compared with SCC and DVC (6.85 vs. 3.08 and 2.15, respectively; p < 0.05) and serum pH in EDT reflected greater acidosis than SCC and DVC (7.24 vs. 7.36 and 7.39, respectively; p < 0.05). EDT and SCC required more intravenous fluid than DVC (2,166 mL and 2,166 mL vs. 667 mL, respectively; p < 0.05) and more vasopressors were used in EDT and SCC compared with DVC (52.1 μg and 43.5 μg vs. 12.4 μg, respectively; p < 0.05). Brain and myocardial tissue stains demonstrated the same degree of acute ischemic changes in all groups. Although aortic clamping increases central and cerebral perfusion, DVC results in less physiologic derangement. The optimal method of aortic control would incorporate the benefits of maintained central pressure with less associated morbidity. Clinical studies evaluating DVC are warranted.

Comparison of in vitro flows past a mechanical heart valve in anatomical and axisymmetric aorta models

NASA Astrophysics Data System (ADS)

Haya, Laura; Tavoularis, Stavros

2017-06-01

Flow characteristics past a bileaflet mechanical heart valve were measured under physiological flow conditions in a straight tube with an axisymmetric expansion, similar to vessels used in previous studies, and in an anatomical model of the aorta. We found that anatomical features, including the three-lobed sinus and the aorta's curvature affected significantly the flow characteristics. The turbulent and viscous stresses were presented and discussed as indicators for potential blood damage and thrombosis. Both types of stresses, averaged over the two axial measurement planes, were significantly lower in the anatomical model than in the axisymmetric one. This difference was attributed to the lower height-to-width ratio and more gradual contraction of the anatomical aortic sinus. The curvature of the aorta caused asymmetries in the velocity and stress distributions during forward flow. Secondary flows resulting from the aorta's curvature are thought to have redistributed the fluid stresses transversely, resulting in a more homogeneous stress distribution in the anatomical aortic root than in the axisymmetric root. The results of this study demonstrate the importance of modelling accurately the aortic geometry in experimental and computational studies of prosthetic devices. Moreover, our findings suggest that grafts used for aortic root replacement should approximate as closely as possible the shape of the natural sinuses.

Simulation of heart rate variability model in a network

NASA Astrophysics Data System (ADS)

Cascaval, Radu C.; D'Apice, Ciro; D'Arienzo, Maria Pia

2017-07-01

We consider a 1-D model for the simulation of the blood flow in the cardiovascular system. As inflow condition we consider a model for the aortic valve. The opening and closing of the valve is dynamically determined by the pressure difference between the left ventricular and aortic pressures. At the outflow we impose a peripheral resistance model. To approximate the solution we use a numerical scheme based on the discontinuous Galerkin method. We also considering a variation in heart rate and terminal reflection coefficient due to monitoring of the pressure in the network.

Novel multi-dimensional modelling for surgical planning of acute aortic dissection type A based on computed tomography scan.

PubMed

Hossien, Abdullrazak; Gelsomino, Sandro; Mochtar, Baheramsjah; Maessen, Jos G; Sardari Nia, Peyman

2015-11-01

Acute type A aortic dissection (TAAD) is a life-threatening emergency and requires immediate surgical intervention. We propose a novel finite element multi-dimensional modelling (FE-MDM) technique to identify aortic tears preoperatively to aid surgical preplanning. Thirty-two patients with TAAD were included in this retrospective study. Computed tomography (CT) scans were imported using the segmentation software and reconstruction resulted in modelling of single TAAD components: aortic wall, false lumen, true lumen, gap in the flap and blood in both lumens. CT scans were processed by interpreters who were blinded to the clinical data and then were compared with operative findings. The models were assessed and compared regarding localization and size of the entry tear with the intraoperative findings. Image set data were retrieved from CT scans. Surgical inspection confirmed the localization of the tear obtained by the model in all patients with a 100% chance prediction (P < 0.0001) in all patients. With the simulation of the guided-cannulation, it was possible to place the cannula in the ascending aorta in 100% of patients (P < 0.0001 vs surgery). Using the virtual volume model, the chance of inserting into the false lumen was 0% (P < 0.0001). There was a strong correlation between the virtual volume model and cannulation in the true lumen (r = 0.88, P < 0.0001). The FE-MDM technique of aortic dissection is helpful in identifying the site of the tear and may be considered as an additional tool in surgical preplanning. It may also enhance the efficiency of deep hypothermic circulatory arrest in patients with single entry sites in the ascending aorta and it may facilitate direct cannulation of the ascending aorta. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Full-length human placental sFlt-1-e15a isoform induces distinct maternal phenotypes of preeclampsia in mice.

PubMed

Szalai, Gabor; Romero, Roberto; Chaiworapongsa, Tinnakorn; Xu, Yi; Wang, Bing; Ahn, Hyunyoung; Xu, Zhonghui; Chiang, Po Jen; Sundell, Birgitta; Wang, Rona; Jiang, Yang; Plazyo, Olesya; Olive, Mary; Tarca, Adi L; Dong, Zhong; Qureshi, Faisal; Papp, Zoltan; Hassan, Sonia S; Hernandez-Andrade, Edgar; Than, Nandor Gabor

2015-01-01

Most anti-angiogenic preeclampsia models in rodents utilized the overexpression of a truncated soluble fms-like tyrosine kinase-1 (sFlt-1) not expressed in any species. Other limitations of mouse preeclampsia models included stressful blood pressure measurements and the lack of postpartum monitoring. We aimed to 1) develop a mouse model of preeclampsia by administering the most abundant human placental sFlt-1 isoform (hsFlt-1-e15a) in preeclampsia; 2) determine blood pressures in non-stressed conditions; and 3) develop a survival surgery that enables the collection of fetuses and placentas and postpartum (PP) monitoring. Pregnancy status of CD-1 mice was evaluated with high-frequency ultrasound on gestational days (GD) 6 and 7. Telemetry catheters were implanted in the carotid artery on GD7, and their positions were verified by ultrasound on GD13. Mice were injected through tail-vein with adenoviruses expressing hsFlt-1-e15a (n = 11) or green fluorescent protein (GFP; n = 9) on GD8/GD11. Placentas and pups were delivered by cesarean section on GD18 allowing PP monitoring. Urine samples were collected with cystocentesis on GD6/GD7, GD13, GD18, and PPD8, and albumin/creatinine ratios were determined. GFP and hsFlt-1-e15a expression profiles were determined by qRT-PCR. Aortic ring assays were performed to assess the effect of hsFlt-1-e15a on endothelia. Ultrasound predicted pregnancy on GD7 in 97% of cases. Cesarean section survival rate was 100%. Mean arterial blood pressure was higher in hsFlt-1-e15a-treated than in GFP-treated mice (∆MAP = 13.2 mmHg, p = 0.00107; GD18). Focal glomerular changes were found in hsFlt-1-e15a -treated mice, which had higher urine albumin/creatinine ratios than controls (109.3 ± 51.7 μg/mg vs. 19.3 ± 5.6 μg/mg, p = 4.4 x 10(-2); GD18). Aortic ring assays showed a 46% lesser microvessel outgrowth in hsFlt-1-e15a-treated than in GFP-treated mice (p = 1.2 x 10(-2)). Placental and fetal weights did not differ between the groups. One mouse with liver disease developed early-onset preeclampsia-like symptoms with intrauterine growth restriction (IUGR). A mouse model of late-onset preeclampsia was developed with the overexpression of hsFlt-1-e15a, verifying the in vivo pathologic effects of this primate-specific, predominant placental sFlt-1 isoform. HsFlt-1-e15a induced early-onset preeclampsia-like symptoms associated with IUGR in a mouse with a liver disease. Our findings support that hsFlt-1-e15a is central to the terminal pathway of preeclampsia, and it can induce the full spectrum of symptoms in this obstetrical syndrome.

Full-Length Human Placental sFlt-1-e15a Isoform Induces Distinct Maternal Phenotypes of Preeclampsia in Mice

PubMed Central

Szalai, Gabor; Romero, Roberto; Chaiworapongsa, Tinnakorn; Xu, Yi; Wang, Bing; Ahn, Hyunyoung; Xu, Zhonghui; Chiang, Po Jen; Sundell, Birgitta; Wang, Rona; Jiang, Yang; Plazyo, Olesya; Olive, Mary; Tarca, Adi L.; Dong, Zhong; Qureshi, Faisal; Papp, Zoltan; Hassan, Sonia S.; Hernandez-Andrade, Edgar; Than, Nandor Gabor

2015-01-01

Objective Most anti-angiogenic preeclampsia models in rodents utilized the overexpression of a truncated soluble fms-like tyrosine kinase-1 (sFlt-1) not expressed in any species. Other limitations of mouse preeclampsia models included stressful blood pressure measurements and the lack of postpartum monitoring. We aimed to 1) develop a mouse model of preeclampsia by administering the most abundant human placental sFlt-1 isoform (hsFlt-1-e15a) in preeclampsia; 2) determine blood pressures in non-stressed conditions; and 3) develop a survival surgery that enables the collection of fetuses and placentas and postpartum (PP) monitoring. Methods Pregnancy status of CD-1 mice was evaluated with high-frequency ultrasound on gestational days (GD) 6 and 7. Telemetry catheters were implanted in the carotid artery on GD7, and their positions were verified by ultrasound on GD13. Mice were injected through tail-vein with adenoviruses expressing hsFlt-1-e15a (n = 11) or green fluorescent protein (GFP; n = 9) on GD8/GD11. Placentas and pups were delivered by cesarean section on GD18 allowing PP monitoring. Urine samples were collected with cystocentesis on GD6/GD7, GD13, GD18, and PPD8, and albumin/creatinine ratios were determined. GFP and hsFlt-1-e15a expression profiles were determined by qRT-PCR. Aortic ring assays were performed to assess the effect of hsFlt-1-e15a on endothelia. Results Ultrasound predicted pregnancy on GD7 in 97% of cases. Cesarean section survival rate was 100%. Mean arterial blood pressure was higher in hsFlt-1-e15a-treated than in GFP-treated mice (∆MAP = 13.2 mmHg, p = 0.00107; GD18). Focal glomerular changes were found in hsFlt-1-e15a -treated mice, which had higher urine albumin/creatinine ratios than controls (109.3±51.7μg/mg vs. 19.3±5.6μg/mg, p = 4.4x10-2; GD18). Aortic ring assays showed a 46% lesser microvessel outgrowth in hsFlt-1-e15a-treated than in GFP-treated mice (p = 1.2x10-2). Placental and fetal weights did not differ between the groups. One mouse with liver disease developed early-onset preeclampsia-like symptoms with intrauterine growth restriction (IUGR). Conclusions A mouse model of late-onset preeclampsia was developed with the overexpression of hsFlt-1-e15a, verifying the in vivo pathologic effects of this primate-specific, predominant placental sFlt-1 isoform. HsFlt-1-e15a induced early-onset preeclampsia-like symptoms associated with IUGR in a mouse with a liver disease. Our findings support that hsFlt-1-e15a is central to the terminal pathway of preeclampsia, and it can induce the full spectrum of symptoms in this obstetrical syndrome. PMID:25860260

Multi-physics 3D computational study of leaflet thrombus formation following surgical and transcatheter aortic valve replacement

NASA Astrophysics Data System (ADS)

Vahidkhah, Koohyar; Abbasi, Mostafa; Barakat, Mohammed; Dvir, Danny; Azadani, Ali

2017-11-01

An increasingly recognized complication following surgical/transcatheter aortic valve replacement is thrombosis or blood clot formation on replacement valve leaflets. A predisposing factor in thrombus formation on biomaterial surfaces of a bioprosthetic heart valve is blood stasis. Longer residence time of blood provides an opportunity for platelets and agonists to accumulate to critical concentrations that leads to platelet activation and then thrombosis. In this study, we have developed a fluid-solid interaction (FSI) modeling approach, to quantify blood stasis on the leaflets of bioprosthetic aortic valves with different design operating in a patient-specific geometry. We have validated our FSI model against experimental measurements of valve opening/closing as well as in-vitro particle image velocimetry. We have also embedded in our method a model for transport of platelets and agonists (ADP, TxA2, and thrombin) and their interactions that result in platelets activation and adhesion to biomaterial bioprosthetic surfaces. We have provided quantitative evidence for the correlation between long residence of blood on bioprosthetic aortic valve leaflets and formation of high thrombogenicity risk regions on the leaflets that are characterized by accumulation of activated platelet.

Kangaroo vs. porcine aortic valves: calcification potential after glutaraldehyde fixation.

PubMed

Narine, K; Chéry, Cyrille C; Goetghebeur, Els; Forsyth, R; Claeys, E; Cornelissen, Maria; Moens, L; Van Nooten, G

2005-01-01

The aim of this study was to evaluate and compare the calcification potential of kangaroo and porcine aortic valves after glutaraldehyde fixation at both low (0.6%) and high (2.0%) concentrations of glutaraldehyde in the rat subcutaneous model. To our knowledge this is the first report comparing the time-related, progressive calcification of these two species in the rat subcutaneous model. Twenty-two Sprague-Dawley rats were each implanted with two aortic valve leaflets (porcine and kangaroo) after fixation in 0.6% glutaraldehyde and two aortic valve leaflets (porcine and kangaroo) after fixation in 2% glutaraldehyde respectively. Animals were sacrificed after 24 h and thereafter weekly for up to 10 weeks after implantation. Calcium content was determined using inductively coupled plasma-mass spectrometry and confirmed histologically. Mean calcium content per milligram of tissue (dry weight) treated with 0.6 and 2% glutaraldehyde was 116.2 and 110.4 microg/mg tissue for kangaroo and 95.0 and 106.8 microg/mg tissue for porcine valves. Calcium content increased significantly over time (8.8 microg/mg tissue per week) and was not significantly different between groups. Regression analysis of calcification over time showed no significant difference in calcification of valves treated with 0.6 or 2% glutaraldehyde within and between the two species. Using the subcutaneous model, we did not detect a difference in calcification potential between kangaroo and porcine aortic valves treated with either high or low concentrations of glutaraldehyde. Copyright 2005 S. Karger AG, Basel.

Beneficial Effects of Galectin-3 Blockade in Vascular and Aortic Valve Alterations in an Experimental Pressure Overload Model

PubMed Central

Ibarrola, Jaime; Martínez-Martínez, Ernesto; Sádaba, J. Rafael; Arrieta, Vanessa; García-Peña, Amaia; Álvarez, Virginia; Fernández-Celis, Amaya; Gainza, Alicia; Rossignol, Patrick; Cachofeiro Ramos, Victoria; López-Andrés, Natalia

2017-01-01

Galectin-3 (Gal-3) is involved in cardiovascular fibrosis and aortic valve (AV) calcification. We hypothesized that Gal-3 pharmacological inhibition with modified citrus pectin (MCP) could reduce aortic and AV remodeling in normotensive rats with pressure overload (PO). Six weeks after aortic constriction, vascular Gal-3 expression was up-regulated in male Wistar rats. Gal-3 overexpression was accompanied by an increase in the aortic media layer thickness, enhanced total collagen, and augmented expression of fibrotic mediators. Further, vascular inflammatory markers as well as inflammatory cells content were greater in aorta from PO rats. MCP treatment (100 mg/kg/day) prevented the increase in Gal-3, media thickness, fibrosis, and inflammation in the aorta of PO rats. Gal-3 levels were higher in AVs from PO rats. This paralleled enhanced AV fibrosis, inflammation, as well as greater expression of calcification markers. MCP treatment prevented the increase in Gal-3 as well as fibrosis, inflammation, and calcification in AVs. Overall, Gal-3 is overexpressed in aorta and AVs from PO rats. Gal-3 pharmacological inhibition blocks aortic and AV remodeling in experimental PO. Gal-3 could be a new therapeutic approach to delay the progression and the development of aortic remodeling and AV calcification in PO. PMID:28758988

Vehicular Causation Factors and Conceptual Design Modifications to Reduce Aortic Strain in Numerically Reconstructed Real World Nearside Lateral Automotive Crashes

PubMed Central

Yang, King H.

2015-01-01

Aortic injury (AI) leading to disruption of the aorta is an uncommon but highly lethal consequence of trauma in modern society. Most recent estimates range from 7,500 to 8,000 cases per year from a variety of causes. It is observed that more than 80% of occupants who suffer an aortic injury die at the scene due to exsanguination into the chest cavity. It is evident that effective means of substantially improving the outcome of motor vehicle crash-induced AIs is by preventing the injury in the first place. In the current study, 16 design of computer experiments (DOCE) were carried out with varying levels of principal direction of force (PDOF), impact velocity, impact height, and impact position of the bullet vehicle combined with occupant seating positions in the case vehicle to determine the effects of these factors on aortic injury. Further, a combination of real world crash data reported in the Crash Injury Research and Engineering Network (CIREN) database, Finite Element (FE) vehicle models, and the Wayne State Human Body Model-II (WSHBM-II) indicates that occupant seating position, impact height, and PDOF, in that order play, a primary role in aortic injury. PMID:26448781

Hydroelastic effects in the aorta bifurcation zone

NASA Technical Reports Server (NTRS)

Volmir, A. S.; Gersheyn, M. S.; Purinya, B. A.

1980-01-01

The mechanical behavior of the vessels and blood is mathematically analyzed at the point of aortic bifurcation using a homogeneous single layer channel as a model of the aorta. Allowance is made for the fact that the aortic intima is considerably less rigid than the other layers. For analysis of blood flow in the major arteries, the blood is treated as a viscous Newtonian fluid whose movements are described by Navier-Stokes equations and a continuity equation. Blood flow dynamics at the aortic bifurcation are discussed on the basis of the results.

Decision analysis in clinical cardiology: When is coronary angiography required in aortic stenosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Georgeson, S.; Meyer, K.B.; Pauker, S.G.

1990-03-15

Decision analysis offers a reproducible, explicit approach to complex clinical decisions. It consists of developing a model, typically a decision tree, that separates choices from chances and that specifies and assigns relative values to outcomes. Sensitivity analysis allows exploration of alternative assumptions. Cost-effectiveness analysis shows the relation between dollars spent and improved health outcomes achieved. In a tutorial format, this approach is applied to the decision whether to perform coronary angiography in a patient who requires aortic valve replacement for critical aortic stenosis.

Systematic Design of a Magnetically Levitated Brushless DC Motor for a Reversible Rotary Intra-Aortic Blood Pump.

PubMed

Wang, Yaxin; Logan, Thomas G; Smith, P Alex; Hsu, Po-Lin; Cohn, William E; Xu, Liping; McMahon, Richard A

2017-10-01

The IntraVAD is a miniature intra-aortic ventricular assist device (VAD) designed to work in series with the compromised left ventricle. A reverse-rotation control (RRc) mode has been developed to increase myocardial perfusion and reduce ventricular volume. The RRc mode includes forward rotation in systole and reverse rotation in diastole, which requires the IntraVAD to periodically reverse its rotational direction in synchrony with the cardiac cycle. This periodic reversal leads to changes in pressure force over the impeller, which makes the entire system less stable. To eliminate the mechanical wear of a contact bearing and provide active control over the axial position of the rotor, a miniature magnetically levitated bearing (i.e., the PM-Coil module) composed of two concentric permanent magnetic (PM) rings and a pair of coils-one on each side-was proposed to provide passive radial and active axial rotor stabilization. In the early design stage, the numerical finite element method (FEM) was used to optimize the geometry of the brushless DC (BLDC) motor and the maglev module, but constructing a new model each time certain design parameters were adjusted required substantial computation time. Because the design criteria for the module had to be modified to account for the magnetic force produced by the motor and for the hemodynamic changes associated with pump operation, a simplified analytic expression was derived for the expected magnetic forces. Suitable bearings could then be designed capable of overcoming these forces without repeating the complicated FEM simulation for the motor. Using this method at the initial design stage can inform the design of the miniature maglev BLDC motor for the proposed pulsatile axial-flow VAD. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Early changes in vascular reactivity in response to 56Fe irradiation in ApoE-/- mice

NASA Astrophysics Data System (ADS)

White, C. Roger; Yu, Tao; Gupta, Kiran; Babitz, Stephen K.; Black, Leland L.; Kabarowski, Janusz H.; Kucik, Dennis F.

2015-03-01

Epidemiological studies have established that radiation from a number of terrestrial sources increases the risk of atherosclerosis. The accelerated heavy ions in the galacto-cosmic radiation (GCR) that astronauts will encounter on in space, however, interact very differently with tissues than most types of terrestrial radiation, so the health consequences of exposure on deep-space missions are not clear. We demonstrated earlier that 56Fe, an important component of cosmic radiation, accelerates atherosclerotic plaque development. In the present study, we examined an earlier, pro-atherogenic event that might be predictive of later atherosclerotic disease. Decreased endothelium-dependent vasodilation is a prominent manifestation of vascular dysfunction that is thought to predispose humans to the development of structural vascular changes that precede the development of atherosclerotic plaques. To test the effect of heavy-ion radiation on endothelium-dependent vasodilation, we used the same ApoE-/- mouse model in which we previously demonstrated the pro-atherogenic effect of 56Fe on plaque development. Ten week old male ApoE mice (an age at which there is little atherosclerotic plaque in the descending aorta) were exposed to 2.6 Gy 56Fe. The mice were then fed a normal diet and housed under standard conditions. At 4-5 weeks post-irradiation, aortic rings were isolated and endothelial-dependent relaxation was measured. Relaxation in response to acetylcholine was significantly impaired in irradiated mice compared to age-matched, un-irradiated mice. This decrease in vascular reactivity following 56Fe irradiation occurred eight weeks prior to the development of statistically significant exacerbation of aortic plaque formation and may contribute to the formation of later atherosclerotic lesions.

Percutaneous Transcatheter One-Step Mechanical Aortic Disc Valve Prosthesis Implantation: A Preliminary Feasibility Study in Swine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sochman, Jan; Peregrin, Jan H.; Rocek, Miloslav

Purpose. To evaluate the feasibility of one-step implantation of a new type of stent-based mechanical aortic disc valve prosthesis (MADVP) above and across the native aortic valve and its short-term function in swine with both functional and dysfunctional native valves. Methods. The MADVP consisted of a folding disc valve made of silicone elastomer attached to either a nitinol Z-stent (Z model) or a nitinol cross-braided stent (SX model). Implantation of 10 MADVPs (6 Z and 4 SX models) was attempted in 10 swine: 4 (2 Z and 2 SX models) with a functional native valve and 6 (4 Z andmore » 2 SX models) with aortic regurgitation induced either by intentional valve injury or by MADVP placement across the native valve. MADVP function was observed for up to 3 hr after implantation. Results. MADVP implantation was successful in 9 swine. One animal died of induced massive regurgitation prior to implantation. Four MADVPs implanted above functioning native valves exhibited good function. In 5 swine with regurgitation, MADVP implantation corrected the induced native valve dysfunction and the device's continuous good function was observed in 4 animals. One MADVP (SX model) placed across native valve gradually migrated into the left ventricle. Conclusion. The tested MADVP can be implanted above and across the native valve in a one-step procedure and can replace the function of the regurgitating native valve. Further technical development and testing are warranted, preferably with a manufactured MADVP.« less

Advanced transcatheter aortic valve implantation (TAVI) planning from CT with ShapeForest.

PubMed

Swee, Joshua K Y; Grbić, Saša

2014-01-01

Transcatheter aortic valve implantation (TAVI) is becoming a standard treatment for non-operable and high-risk patients with symptomatic severe aortic valve stenosis. As there is no direct view or access to the affected anatomy, comprehensive preoperative planning is crucial for a successful outcome, with the most important decisions made during planning being the selection of the proper implant size, and determining the correct C-arm angulations. While geometric models extracted from 3D images are often used to derive these measurements, the complex shape variation of the AV anatomy found in these patients causes many of the shape representations used to estimate such geometric models to fail in capturing morphological characteristics in sufficient detail. In addition, most current approaches only model the aortic valve (AV), omitting modeling the left ventricle outflow tract (LVOT) entirely despite its high correlation with severe complications such as annulus ruptures, paravalvular leaks and myocardial infarction. We propose a fully automated method to extract patient specific models of the AV and the LVOT, and derive comprehensive biomarkers for accurate TAVI planning. We utilize a novel shape representation--the ShapeForest--which is able to model complex shape variation, preserves local shape information, and incorporates prior knowledge during shape space inference. Extensive quantitative and qualitative experiments performed on 630 volumetric data sets demonstrate an accuracy of 0.69 mm for the AV and 0.83 mm for the LVOT, an improvement of over 16% and 18% respectively when compared against state of the art methods.

Three-dimensional flow structures past a bio-prosthetic valve in an in-vitro model of the aortic root.

PubMed

Hasler, David; Obrist, Dominik

2018-01-01

The flow field past a prosthetic aortic valve comprises many details that indicate whether the prosthesis is functioning well or not. It is, however, not yet fully understood how an optimal flow scenario would look, i.e. which subtleties of the fluid dynamics in place are essential regarding the durability and compatibility of a prosthetic valve. In this study, we measured and analyzed the 3D flow field in the vicinity of a bio-prosthetic heart valve in function of the aortic root size. The measurements were conducted within aortic root phantoms of different size, mounted in a custom-built hydraulic setup, which mimicked physiological flow conditions in the aorta. Tomographic particle image velocimetry was used to measure the 3D instantaneous velocity field at various instances. Several 3D fields (e.g. instantaneous and mean velocity, 3D shear rate) were analyzed and compared focusing on the impact of the aortic root size, but also in order to gain general insight in the 3D flow structure past the bio-prosthetic valve. We found that the diameter of the aortic jet relative to the diameter of the ascending aorta is the most important parameter in determining the characteristics of the flow. A large aortic cross-section, relative to the cross-section of the aortic jet, was associated with higher levels of turbulence intensity and higher retrograde flow in the ascending aorta.

Medical Treatment of Aortic Aneurysms in Marfan Syndrome and other Heritable Conditions

PubMed Central

Jost, Christine H. Attenhofer; Greutmann, Matthias; Connolly, Heidi M.; Weber, Roland; Rohrbach, Marianne; Oxenius, Angela; Kretschmar, Oliver; Luscher, Thomas F.; Matyas, Gabor

2014-01-01

Thoracic aortic aneurysms can be triggered by genetic disorders such as Marfan syndrome (MFS) and related aortic diseases as well as by inflammatory disorders such as giant cell arteritis or atherosclerosis. In all these conditions, cardiovascular risk factors, such as systemic arterial hypertension, may contribute to faster rate of aneurysm progression. Optimal medical management to prevent progressive aortic dilatation and aortic dissection is unknown. β-blockers have been the mainstay of medical treatment for many years despite limited evidence of beneficial effects. Recently, losartan, an angiotensin II type I receptor antagonist (ARB), has shown promising results in a mouse model of MFS and subsequently in humans with MFS and hence is increasingly used. Several ongoing trials comparing losartan to β-blockers and/or placebo will better define the role of ARBs in the near future. In addition, other medications, such as statins and tetracyclines have demonstrated potential benefit in experimental aortic aneurysm studies. Given the advances in our understanding of molecular mechanisms triggering aortic dilatation and dissection, individualized management tailored to the underlying genetic defect may be on the horizon of individualized medicine. We anticipate that ongoing research will address the question whether such genotype/pathogenesis-driven treatments can replace current phenotype/syndrome-driven strategies and whether other forms of aortopathies should be treated similarly. In this work, we review currently used and promising medical treatment options for patients with heritable aortic aneurysmal disorders. PMID:24527681

``Smart'' baroreception along the aortic arch, with reference to essential hypertension

NASA Astrophysics Data System (ADS)

Kember, G. C.; Zamir, M.; Armour, J. A.

2004-11-01

Beat-to-beat regulation of heart rate is dependent upon sensing of local stretching or local “disortion” by aortic baroreceptors. Distortions of the aortic wall are due mainly to left ventricular output and to reflected waves arising from the arterial tree. Distortions are generally believed to be useful in cardiac control since stretch receptors or aortic baroreceptors embedded in the adventitia of the aortic wall, transduce the distortions to cardiovascular neural reflex pathways responsible for beat-to-beat regulation of heart rate. Aortic neuroanatomy studies have also found a continuous strip of mechanosensory neurites spread along the aortic inner arch. Although their purpose is now unknown, such a combined sensing capacity would allow measurement of the space and time dependence of inner arch wall distortions due, among other things, to traveling waves associated with pulsatile flow in an elastic tube. We call this sensing capability-“smart baroreception.” In this paper we use an arterial tree model to show that the cumulative effects of wave reflections, from many sites far downstream, have a surprisingly pronounced effect on the pressure distribution in the root segment of the tree. By this mechanism global hemodynamics can be focused by wave reflections back to the aortic arch, where they can rapidly impact cardiac control via smart baroreception. Such sensing is likely important to maintain efficient heart function. However, alterations in the arterial tree due to aging and other natural processes can lead in such a system to altered cardiac control and essential hypertension.

The vertical structure of the F ring of Saturn from ring-plane crossings

NASA Astrophysics Data System (ADS)

Scharringhausen, Britt R.; Nicholson, Philip D.

2013-11-01

We present a photometric model of the rings of Saturn which includes the main rings and an F ring, inclined to the main rings, with a Gaussian vertical profile of optical depth. This model reproduces the asymmetry in brightness between the east and west ansae of the rings of Saturn that was observed by the Hubble Space Telescope (HST) within a few hours after the Earth ring-plane crossing (RPX) of 10 August 1995. The model shows that during this observation the inclined F ring unevenly blocked the east and west ansae of the main rings. The brightness asymmetry produced by the model is highly sensitive to the vertical thickness and radial optical depth of the F ring. The F-ring model that best matches the observations has a vertical full width at half maximum of 13 ± 7 km and an equivalent depth of 10 ± 4 km. The model also reproduces the shape of the HST profiles of ring brightness vs. distance from Saturn, both before and after the time of ring-plane crossing. Smaller asymmetries observed before the RPX, when the Earth was on the dark side of the rings, cannot be explained by blocking of the main rings by the F ring or vice versa and are probably instead due to the intrinsic longitudinal variation exhibited by the F ring.

Dynamics of the aortic arch submitted to a shock loading: Parametric study with fluid-structure models.

PubMed

El Baroudi, A; Razafimahery, F; Rakotomanana, L

2012-01-01

This work aims to present some fluid-structure models for analyzing the dynamics of the aorta during a brusque loading. Indeed, various lesions may appear at the aortic arch during car crash or other accident such as brusque falling. Aortic stresses evolution are simulated during the shock at the cross section and along the aorta. One hot question was that if a brusque deceleration can generate tissue tearing, or a shock is necessary to provoke such a damage. Different constitutive laws of blood are then tested whereas the aorta is assumed linear and elastic. The overall shock model is inspired from an experimental jig. We show that the viscosity has strong influence on the stress and parietal moments and forces. The nonlinear viscosity has no significant additional effects for healthy aorta, but modifies the stress and parietal loadings for the stenotic aorta.

Macroscopic anatomy of the great vessels and structures associated with the heart of the ringed seal (Pusa hispida).

PubMed

Smodlaka, H; Henry, R W; Reed, R B

2009-06-01

The ringed seal [Pusa (Phoca) hispida], as well as other seals, exhibits unique anatomical properties when compared to its terrestrial counterparts. In the ringed seal, the most conspicuous marine adaptation is the aortic bulb. This large dilatation of the ascending aorta is comparable to that found in other seal species and marine mammals. The branches of the ascending aorta (brachiocephalic trunk, left common carotid artery and left subclavian artery) are similar to those of higher primates and man. The peculiarities of the venous system are: three pulmonary veins, a pericardial venous plexus, a caval sphincter, a hepatic sinus with paired caudal vena cavae and a large extradural venous plexus. Generally, three common pulmonary veins (right, left and caudal) empty into the left atrium. The pericardial venous plexus lies deep to the mediastinal pericardial pleura (pleura pericardica) on the auricular (ventral) surface of the heart. The caval sphincter surrounds the caudal vena cava as it passes through the diaphragm. Caudal to the diaphragm, the vena cava is dilated (the hepatic sinus), and near the cranial extremity of the kidneys, it becomes biphid. The azygos vein is formed from the union of the right and left azygos veins at the level of the 5th thoracic vertebra. Cardiovascular physiological studies show some of these anatomical variations, especially of the venous system and the ascending aorta, to be modifications for diving. This investigation documents the large blood vessels associated with the heart and related structures in the ringed seal.

3D Fluid-Structure Interaction Simulation of Aortic Valves Using a Unified Continuum ALE FEM Model.

PubMed

Spühler, Jeannette H; Jansson, Johan; Jansson, Niclas; Hoffman, Johan

2018-01-01

Due to advances in medical imaging, computational fluid dynamics algorithms and high performance computing, computer simulation is developing into an important tool for understanding the relationship between cardiovascular diseases and intraventricular blood flow. The field of cardiac flow simulation is challenging and highly interdisciplinary. We apply a computational framework for automated solutions of partial differential equations using Finite Element Methods where any mathematical description directly can be translated to code. This allows us to develop a cardiac model where specific properties of the heart such as fluid-structure interaction of the aortic valve can be added in a modular way without extensive efforts. In previous work, we simulated the blood flow in the left ventricle of the heart. In this paper, we extend this model by placing prototypes of both a native and a mechanical aortic valve in the outflow region of the left ventricle. Numerical simulation of the blood flow in the vicinity of the valve offers the possibility to improve the treatment of aortic valve diseases as aortic stenosis (narrowing of the valve opening) or regurgitation (leaking) and to optimize the design of prosthetic heart valves in a controlled and specific way. The fluid-structure interaction and contact problem are formulated in a unified continuum model using the conservation laws for mass and momentum and a phase function. The discretization is based on an Arbitrary Lagrangian-Eulerian space-time finite element method with streamline diffusion stabilization, and it is implemented in the open source software Unicorn which shows near optimal scaling up to thousands of cores. Computational results are presented to demonstrate the capability of our framework.

Cost-utility of transcatheter aortic valve implantation for inoperable patients with severe aortic stenosis treated by medical management: a UK cost-utility analysis based on patient-level data from the ADVANCE study

PubMed Central

Brecker, Stephen; Mealing, Stuart; Padhiar, Amie; Eaton, James; Sculpher, Mark; Busca, Rachele; Bosmans, Johan; Gerckens, Ulrich J; Wenaweser, Peter; Tamburino, Corrado; Bleiziffer, Sabine; Piazza, Nicolo; Moat, Neil; Linke, Axel

2014-01-01

Objective To use patient-level data from the ADVANCE study to evaluate the cost-effectiveness of transcatheter aortic valve implantation (TAVI) compared to medical management (MM) in patients with severe aortic stenosis from the perspective of the UK NHS. Methods A published decision-analytic model was adapted to include information on TAVI from the ADVANCE study. Patient-level data informed the choice as well as the form of mathematical functions that were used to model all-cause mortality, health-related quality of life and hospitalisations. TAVI-related resource use protocols were based on the ADVANCE study. MM was modelled on publicly available information from the PARTNER-B study. The outcome measures were incremental cost-effectiveness ratios (ICERs) estimated at a range of time horizons with benefits expressed as quality-adjusted life-years (QALY). Extensive sensitivity/subgroup analyses were undertaken to explore the impact of uncertainty in key clinical areas. Results Using a 5-year time horizon, the ICER for the comparison of all ADVANCE to all PARTNER-B patients was £13 943 per QALY gained. For the subset of ADVANCE patients classified as high risk (Logistic EuroSCORE >20%) the ICER was £17 718 per QALY gained). The ICER was below £30 000 per QALY gained in all sensitivity analyses relating to choice of MM data source and alternative modelling approaches for key parameters. When the time horizon was extended to 10 years, all ICERs generated in all analyses were below £20 000 per QALY gained. Conclusion TAVI is highly likely to be a cost-effective treatment for patients with severe aortic stenosis. PMID:25349700

Cost-utility of transcatheter aortic valve implantation for inoperable patients with severe aortic stenosis treated by medical management: a UK cost-utility analysis based on patient-level data from the ADVANCE study.

PubMed

Brecker, Stephen; Mealing, Stuart; Padhiar, Amie; Eaton, James; Sculpher, Mark; Busca, Rachele; Bosmans, Johan; Gerckens, Ulrich J; Wenaweser, Peter; Tamburino, Corrado; Bleiziffer, Sabine; Piazza, Nicolo; Moat, Neil; Linke, Axel

2014-01-01

To use patient-level data from the ADVANCE study to evaluate the cost-effectiveness of transcatheter aortic valve implantation (TAVI) compared to medical management (MM) in patients with severe aortic stenosis from the perspective of the UK NHS. A published decision-analytic model was adapted to include information on TAVI from the ADVANCE study. Patient-level data informed the choice as well as the form of mathematical functions that were used to model all-cause mortality, health-related quality of life and hospitalisations. TAVI-related resource use protocols were based on the ADVANCE study. MM was modelled on publicly available information from the PARTNER-B study. The outcome measures were incremental cost-effectiveness ratios (ICERs) estimated at a range of time horizons with benefits expressed as quality-adjusted life-years (QALY). Extensive sensitivity/subgroup analyses were undertaken to explore the impact of uncertainty in key clinical areas. Using a 5-year time horizon, the ICER for the comparison of all ADVANCE to all PARTNER-B patients was £13 943 per QALY gained. For the subset of ADVANCE patients classified as high risk (Logistic EuroSCORE >20%) the ICER was £17 718 per QALY gained). The ICER was below £30 000 per QALY gained in all sensitivity analyses relating to choice of MM data source and alternative modelling approaches for key parameters. When the time horizon was extended to 10 years, all ICERs generated in all analyses were below £20 000 per QALY gained. TAVI is highly likely to be a cost-effective treatment for patients with severe aortic stenosis.

3D Fluid-Structure Interaction Simulation of Aortic Valves Using a Unified Continuum ALE FEM Model

PubMed Central

Spühler, Jeannette H.; Jansson, Johan; Jansson, Niclas; Hoffman, Johan

2018-01-01

Due to advances in medical imaging, computational fluid dynamics algorithms and high performance computing, computer simulation is developing into an important tool for understanding the relationship between cardiovascular diseases and intraventricular blood flow. The field of cardiac flow simulation is challenging and highly interdisciplinary. We apply a computational framework for automated solutions of partial differential equations using Finite Element Methods where any mathematical description directly can be translated to code. This allows us to develop a cardiac model where specific properties of the heart such as fluid-structure interaction of the aortic valve can be added in a modular way without extensive efforts. In previous work, we simulated the blood flow in the left ventricle of the heart. In this paper, we extend this model by placing prototypes of both a native and a mechanical aortic valve in the outflow region of the left ventricle. Numerical simulation of the blood flow in the vicinity of the valve offers the possibility to improve the treatment of aortic valve diseases as aortic stenosis (narrowing of the valve opening) or regurgitation (leaking) and to optimize the design of prosthetic heart valves in a controlled and specific way. The fluid-structure interaction and contact problem are formulated in a unified continuum model using the conservation laws for mass and momentum and a phase function. The discretization is based on an Arbitrary Lagrangian-Eulerian space-time finite element method with streamline diffusion stabilization, and it is implemented in the open source software Unicorn which shows near optimal scaling up to thousands of cores. Computational results are presented to demonstrate the capability of our framework. PMID:29713288

The impact of personalized probabilistic wall thickness models on peak wall stress in abdominal aortic aneurysms.

PubMed

Biehler, J; Wall, W A

2018-02-01

If computational models are ever to be used in high-stakes decision making in clinical practice, the use of personalized models and predictive simulation techniques is a must. This entails rigorous quantification of uncertainties as well as harnessing available patient-specific data to the greatest extent possible. Although researchers are beginning to realize that taking uncertainty in model input parameters into account is a necessity, the predominantly used probabilistic description for these uncertain parameters is based on elementary random variable models. In this work, we set out for a comparison of different probabilistic models for uncertain input parameters using the example of an uncertain wall thickness in finite element models of abdominal aortic aneurysms. We provide the first comparison between a random variable and a random field model for the aortic wall and investigate the impact on the probability distribution of the computed peak wall stress. Moreover, we show that the uncertainty about the prevailing peak wall stress can be reduced if noninvasively available, patient-specific data are harnessed for the construction of the probabilistic wall thickness model. Copyright © 2017 John Wiley & Sons, Ltd.

The risk of stanford type-A aortic dissection with different tear size and location: a numerical study.

PubMed

Shi, Yue; Zhu, Minjia; Chang, Yu; Qiao, Huanyu; Liu, Yongmin

2016-12-28

This study is to investigate the influence of hemodynamics on Stanford type-A aortic dissection with different tear size and location, to provide some support for the relationships between the risks (rupture, reverse tearing and further tearing) and tear size and location for clinical treatment. Four numerical models of Stanford type-A aortic dissection were established, with different size and location of the tears. The ratio of the area between the entry and re-entry tears(RA) is various within the model; while, the size and the location of the re-entry in the distal descending aorta are fixed. In model A11 and A21, the entry tears are located near the ascending aorta. The RA in these models are 1 and 2, respectively; In the model B11 and B21, the entry tears are located near the proximal descending aorta and the RA in these models are again assigned to 1 and 2, respectively. Then hemodynamics in these models was solved with numerically and the flow patterns and loading distributions were investigated. The flow velocity of the true lumen in model A21, B21 is lower than that in A11, B11, respectively; the time-averaged wall shear stress (TAWSS) of the false lumen in model A21 and B21 is higher, and for ascending aorta false lumen, A11, A21 are higher than B11, B21, respectively. False lumen intimal wall pressure of A11, A21 are always higher than the true lumen ones. The variation of the RA can significantly affect the dynamics of blood within the aortic dissection. When the entry tear size is larger than the re-entry tear ones, the false lumen, proximal descending aorta and the wall near re-entry tear are prone to cracking. Entry tear location can significantly alter the hemodynamics of aortic dissection as well. When entry tear location is closer to proximal ascending aorta, false lumen continues to expand and compress the true lumen resulting in the true lumen reduction. For proximal ascending aorta, high pressure in false lumen predicts a higher risk of reverse tear.

Design of Bioprosthetic Aortic Valves using biaxial test data.

PubMed

Dabiri, Y; Paulson, K; Tyberg, J; Ronsky, J; Ali, I; Di Martino, E; Narine, K

2015-01-01

Bioprosthetic Aortic Valves (BAVs) do not have the serious limitations of mechanical aortic valves in terms of thrombosis. However, the lifetime of BAVs is too short, often requiring repeated surgeries. The lifetime of BAVs might be improved by using computer simulations of the structural behavior of the leaflets. The goal of this study was to develop a numerical model applicable to the optimization of durability of BAVs. The constitutive equations were derived using biaxial tensile tests. Using a Fung model, stress and strain data were computed from biaxial test data. SolidWorks was used to develop the geometry of the leaflets, and ABAQUS finite element software package was used for finite element calculations. Results showed the model is consistent with experimental observations. Reaction forces computed by the model corresponded with experimental measurements when the biaxial test was simulated. As well, the location of maximum stresses corresponded to the locations of frequent tearing of BAV leaflets. Results suggest that BAV design can be optimized with respect to durability.

Bioprosthetic Valve Fracture During Valve-in-valve TAVR: Bench to Bedside.

PubMed

Saxon, John T; Allen, Keith B; Cohen, David J; Chhatriwalla, Adnan K

2018-01-01

Valve-in-valve (VIV) transcatheter aortic valve replacement (TAVR) has been established as a safe and effective means of treating failed surgical bioprosthetic valves (BPVs) in patients at high risk for complications related to reoperation. Patients who undergo VIV TAVR are at risk of patient-prosthesis mismatch, as the transcatheter heart valve (THV) is implanted within the ring of the existing BPV, limiting full expansion and reducing the maximum achievable effective orifice area of the THV. Importantly, patient-prosthesis mismatch and high residual transvalvular gradients are associated with reduced survival following VIV TAVR. Bioprosthetic valve fracture (BVF) is as a novel technique to address this problem. During BPV, a non-compliant valvuloplasty balloon is positioned within the BPV frame, and a highpressure balloon inflation is performed to fracture the surgical sewing ring of the BPV. This allows for further expansion of the BPV as well as the implanted THV, thus increasing the maximum effective orifice area that can be achieved after VIV TAVR. This review focuses on the current evidence base for BVF to facilitate VIV TAVR, including initial bench testing, procedural technique, clinical experience and future directions.

Recombinant apolipoprotein A-I Milano rapidly reverses aortic valve stenosis and decreases leaflet inflammation in an experimental rabbit model.

PubMed

Speidl, Walter S; Cimmino, Giovanni; Ibanez, Borja; Elmariah, Sammy; Hutter, Randolph; Garcia, Mario J; Fuster, Valentin; Goldman, Martin E; Badimon, Juan J

2010-08-01

Aortic stenosis (AS) is associated with significant morbidity and mortality. Recombinant apolipoprotein A-I Milano (rApoA-I(M)) induces atherosclerotic plaque regression. The aims of this study were to determine the effects of rApoA-I(M) on experimental aortic valve degeneration and its mechanisms of action. New Zealand White rabbits (n = 20) were fed an atherogenic diet for 9 months and then randomized to either placebo or rApoA-I(M). Echocardiography was used to assess the effect of the treatments on AS. Porcine aortic valve myofibroblasts (PAVMF) treated with oxidized low-density lipoprotein served to define the effects of rApoA-I(M) on the expression of monocyte chemoattractant protein-1 (MCP-1), nuclear factor (NF)-kappaB, and alkaline phosphatase (AP). Recombinant apolipoprotein A-I Milano increased aortic valve area (AVA) by 32% (0.25 +/- 0.05 to 0.34 +/- 0.07 cm(2), P < 0.01); whereas AVA remained unchanged in the placebo group (0.24 +/- 0.05 to 0.26 +/- 0.04 cm(2), P = 0.58). Histopathological examination of aortic valves in the rApoA-I(M) animals showed significantly less leaflet thickening, inflammation, and calcification vs. the placebo group. In vitro, rApoA-I(M) significantly inhibited MCP-1, AP, and NF-kappaB and decreased intracellular cholesterol content in PAVMF. Recombinant apolipoprotein A-I Milano treatment reverses AS in this experimental rabbit model. The beneficial effects seem to be mediated by enhanced cholesterol removal and by reduced inflammation and calcification.

Ameliorative role of gemfibrozil against partial abdominal aortic constriction-induced cardiac hypertrophy in rats.

PubMed

Singh, Amrit Pal; Singh, Randhir; Krishan, Pawan

2015-04-01

Fibrates are peroxisome proliferator-activated receptor-α agonists and are clinically used for treatment of dyslipidemia and hypertriglyceridemia. Fenofibrate is reported as a cardioprotective agent in various models of cardiac dysfunction; however, limited literature is available regarding the role of gemfibrozil as a possible cardioprotective agent, especially in a non-obese model of cardiac remodelling. The present study investigated the role of gemfibrozil against partial abdominal aortic constriction-induced cardiac hypertrophy in rats. Cardiac hypertrophy was induced by partial abdominal aortic constriction in rats and they survived for 4 weeks. The cardiac hypertrophy was assessed by measuring left ventricular weight to body weight ratio, left ventricular wall thickness, and protein and collagen content. The oxidative stress in the cardiac tissues was assessed by measuring thiobarbituric acid-reactive substances, superoxide anion generation, and reduced glutathione level. The haematoxylin-eosin and picrosirius red staining was used to observe cardiomyocyte diameter and collagen deposition, respectively. Moreover, serum levels of cholesterol, high-density lipoproteins, triglycerides, and glucose were also measured. Gemfibrozil (30 mg/kg, p.o.) was administered since the first day of partial abdominal aortic constriction and continued for 4 weeks. The partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy are indicated by significant change in various parameters used in the present study that were ameliorated with gemfibrozil treatment in rats. No significant change in serum parameters was observed between various groups used in the present study. It is concluded that gemfibrozil ameliorates partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy and in rats.

Aortic remodeling after transverse aortic constriction in mice is attenuated with AT1 receptor blockade.

PubMed

Kuang, Shao-Qing; Geng, Liang; Prakash, Siddharth K; Cao, Jiu-Mei; Guo, Steven; Villamizar, Carlos; Kwartler, Callie S; Peters, Andrew M; Brasier, Allan R; Milewicz, Dianna M

2013-09-01

Although hypertension is the most common risk factor for thoracic aortic diseases, it is not understood how increased pressures on the ascending aorta lead to aortic aneurysms. We investigated the role of angiotensin II type 1 receptor activation in ascending aortic remodeling in response to increased biomechanical forces using a transverse aortic constriction (TAC) mouse model. Two weeks after TAC, the increased biomechanical pressures led to ascending aortic dilatation and thickening of the medial and adventitial layers of the aorta. There was significant adventitial hyperplasia and inflammatory responses in TAC ascending aortas were accompanied by increased adventitial collagen, elevated inflammatory and proliferative markers, and increased cell density attributable to accumulation of myofibroblasts and macrophages. Treatment with losartan significantly blocked TAC-induced vascular inflammation and macrophage accumulation. However, losartan only partially prevented TAC-induced adventitial hyperplasia, collagen accumulation, and ascending aortic dilatation. Increased Tgfb2 expression and phosphorylated-Smad2 staining in the medial layer of TAC ascending aortas were effectively blocked with losartan. In contrast, the increased Tgfb1 expression and adventitial phospho-Smad2 staining were only partially attenuated by losartan. In addition, losartan significantly blocked extracellular signal-regulated kinase activation and reactive oxygen species production in the TAC ascending aorta. Inhibition of the angiotensin II type 1 receptor using losartan significantly attenuated the vascular remodeling associated with TAC but did not completely block the increased transforming growth factor-β1 expression, adventitial Smad2 signaling, and collagen accumulation. These results help to delineate the aortic transforming growth factor-β signaling that is dependent and independent of the angiotensin II type 1 receptor after TAC.

Human mesenchymal stromal cell-derived extracellular vesicles attenuate aortic aneurysm formation and macrophage activation via microRNA-147.

PubMed

Spinosa, Michael; Lu, Guanyi; Su, Gang; Bontha, Sai Vineela; Gehrau, Ricardo; Salmon, Morgan D; Smith, Joseph R; Weiss, Mark L; Mas, Valeria R; Upchurch, Gilbert R; Sharma, Ashish K

2018-05-29

The formation of an abdominal aortic aneurysm (AAA) is characterized by inflammation, macrophage infiltration, and vascular remodeling. In this study, we tested the hypothesis that mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) immunomodulate aortic inflammation, to mitigate AAA formation via modulation of microRNA-147. An elastase-treatment model of AAA was used in male C57BL/6 wild-type (WT) mice. Administration of EVs in elastase-treated WT mice caused a significant attenuation of aortic diameter and mitigated proinflammatory cytokines, inflammatory cell infiltration, an increase in smooth muscle cell α-actin expression, and a decrease in elastic fiber disruption, compared with untreated mice. A 10-fold up-regulation of microRNA (miR)-147, a key mediator of macrophage inflammatory responses, was observed in murine aortic tissue in elastase-treated mice compared with controls on d 14. EVs derived from MSCs transfected with miR-147 mimic, but not with miR-147 inhibitor, attenuated aortic diameter, inflammation, and leukocyte infiltration in elastase-treated mice. In vitro studies of human aortic tissue explants and murine-derived CD11b + macrophages induced proinflammatory cytokines after elastase treatment, and the expression was attenuated by cocultures with EVs transfected with miR-147 mimic, but not with miR-147 inhibitor. Thus, our findings define a critical role of MSC-derived EVs in attenuation of aortic inflammation and macrophage activation via miR-147 during AAA formation.-Spinosa, M., Lu, G., Su, G., Bontha, S. V., Gehrau, R., Salmon, M. D., Smith, J. R., Weiss, M. L., Mas, V. R., Upchurch, G. R., Sharma, A. K. Human mesenchymal stromal cell-derived extracellular vesicles attenuate aortic aneurysm formation and macrophage activation via microRNA-147.

Effects of a new advanced glycation inhibitor, LR-90, on mitigating arterial stiffening and improving arterial elasticity and compliance in a diabetic rat model: aortic impedance analysis.

PubMed

Satheesan, S; Figarola, J L; Dabbs, T; Rahbar, S; Ermel, R

2014-06-01

We determined the effects of treatment with LR-90, an inhibitor of advanced glycation end products, on the mechanical properties of the arterial system in streptozotocin (STZ)-induced diabetic Sprague Dawley rats, using aortic impedance analysis, and further investigated the effects of LR-90 on the progression of aortic pathology. STZ-induced diabetic rats were treated with or without LR-90 (50 mg L(-1) in drinking water) for 8 weeks and compared with control groups. Arterial BP measurements, various metabolic parameters, aortic histopathology, collagen cross-linking, AGE accumulation, and RAGE protein expression in aortic tissue were determined. Pulsatile parameters were evaluated using a standard Fourier series expansion technique and impulse response function of the filtered aortic input impedance spectra. LR-90 reduced glycated haemoglobin and triglycerides levels, although it had no effect on the glycaemic status. LR-90 did not affect arterial BP, but prevented the diabetes-induced increase in peripheral resistance and variations in aortic distensibility, as it reduced aortic characteristic impedance by 21%. LR-90 also prevented the elevation in wave reflection factor, as indicated by a 22.5% reduction and an associated increase of 23.5% in wave transit time, suggesting it prevents the augmentation of the systolic load of the left ventricle. Moreover, LR-90 inhibited collagen cross-linking and the accumulation of AGE and RAGE in the vasculature of diabetic rats. Treatment with LR-90 may impart significant protection against diabetes-induced aortic stiffening and cardiac hypertrophy and provides an additional therapeutic option for treatment of AGE associated diabetic complications. © 2014 The British Pharmacological Society.

Effects of chronic N-acetylcysteine treatment on the actions of peroxynitrite on aortic vascular reactivity in hypertensive rats.

PubMed

Cabassi, A; Dumont, E C; Girouard, H; Bouchard, J F; Le Jossec, M; Lamontagne, D; Besner, J G; de Champlain, J

2001-07-01

Peroxynitrite (ONOO-), the product of superoxide and nitric oxide, seems to be involved in vascular alterations in hypertension. To evaluate the effects of ONOO- on endothelium-dependent and independent aortic vascular responsiveness, oxidized/reduced glutathione balance (GSSG/GSH), malondialdehyde aortic content, and the formation of 3-nitrotyrosine (3-NT), a stable marker of ONOO-, in N-acetylcysteine (NAC)-treated normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). In SHR only, NAC significantly reduced heart rate and systolic, but not diastolic, blood pressure. It also improved endothelium-dependent aortic relaxation in SHR, but not after exposure to ONOO-. Endothelium-dependent and independent aortic relaxations were markedly impaired by ONOO- in both strains of rat. NAC partially protected SHR against the ONOO- -induced reduction in endothelium-independent relaxation. Aortic GSSG/GSH ratio and malondialdehyde, which were higher in SHR than in WKY rats, showed a greater increase in SHR after exposure to ONOO-. NAC decreased GSSG/GSH and malondialdehyde in both strains of rat before and after exposure to ONOO-. The 3-NT concentration, which was similar in both strains of rat under basal conditions, was greater in SHR than in WKY rats after the addition of ONOO-, with a reduction only in NAC-treated SHR. These findings suggest an increased vulnerability of SHR aortas to the effects of ONOO- as compared with those of WKY rats. The selective improvements produced by NAC, in systolic arterial pressure, heart rate, aortic endothelial function, ONOO- -induced impairment of endothelium-independent relaxation, aortic GSSG/GSH balance, malondialdehyde content and 3-NT formation in SHR suggest that chronic administration of NAC may have a protective effect against aortic vascular dysfunction in the SHR model of hypertension.

Wave energy patterns of counterpulsation: a novel approach with wave intensity analysis.

PubMed

Lu, Pong-Jeu; Yang, Chi-Fu Jeffrey; Wu, Meng-Yu; Hung, Chun-Hao; Chan, Ming-Yao; Hsu, Tzu-Cheng

2011-11-01

In counterpulsation, diastolic augmentation increases coronary blood flow and systolic unloading reduces left ventricular afterload. We present a new approach with wave intensity analysis to revisit and explain counterpulsation principles. In an acute porcine model, a standard intra-aortic balloon pump was placed in descending aorta in 4 pigs. We measured pressure and velocity with probes in left anterior descending artery and aorta during and without intra-aortic balloon pump assistance. Wave intensities of aortic and left coronary waves were derived from pressure and flow measurements with synchronization correction. We identified predominating waves in counterpulsation. In the aorta, during diastolic augmentation, intra-aortic balloon inflation generated a backward compression wave, with a "pushing" effect toward the aortic root that translated to a forward compression wave into coronary circulation. During systolic unloading, intra-aortic balloon pump deflation generated a backward expansion wave that "sucked" blood from left coronary bed into the aorta. While this backward expansion wave translated to reduced left ventricular afterload, the "sucking" effect resulted in left coronary blood steal, as demonstrated by a forward expansion wave in left anterior descending coronary flow. The waves were sensitive to inflation and deflation timing, with just 25 ms delay from standard deflation timing leading to weaker forward expansion wave and less coronary regurgitation. Intra-aortic balloon pumps generate backward-traveling waves that predominantly drive aortic and coronary blood flow during counterpulsation. Wave intensity analysis of arterial circulations may provide a mechanism to explain diastolic augmentation and systolic unloading of intra-aortic balloon pump counterpulsation. Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Heart failure and sudden cardiac death in heritable thoracic aortic disease caused by pathogenic variants in the SMAD3 gene.

PubMed

Backer, Julie De; Braverman, Alan C

2018-05-01

Predominant cardiovascular manifestations in the spectrum of Heritable Thoracic Aortic Disease include by default aortic root aneurysms- and dissections, which may be associated with aortic valve disease. Mitral- and tricuspid valve prolapse are other commonly recognized features. Myocardial disease, characterized by heart failure and/or malignant arrhythmias has been reported in humans and in animal models harboring pathogenic variants in the Fibrillin1 gene. Description of clinical history of three cases from one family in Ghent (Belgium) and one family in St. Louis (US). We report on three cases from two families presenting end-stage heart failure (in two) and lethal arrhythmias associated with moderate left ventricular dilatation (in one). All three cases harbor a pathogenic variant in the SMAD3 gene, known to cause aneurysm osteoarthritis syndrome, Loeys-Dietz syndrome type 3 or isolated Heritable Thoracic Aortic Disease. These unusual presentations warrant awareness for myocardial disease in patients harboring pathogenic variants in genes causing Heritable Thoracic Aortic Disease and indicate the need for prospective studies in larger cohorts. © 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

Improving the Efficiency of Abdominal Aortic Aneurysm Wall Stress Computations

PubMed Central

Zelaya, Jaime E.; Goenezen, Sevan; Dargon, Phong T.; Azarbal, Amir-Farzin; Rugonyi, Sandra

2014-01-01

An abdominal aortic aneurysm is a pathological dilation of the abdominal aorta, which carries a high mortality rate if ruptured. The most commonly used surrogate marker of rupture risk is the maximal transverse diameter of the aneurysm. More recent studies suggest that wall stress from models of patient-specific aneurysm geometries extracted, for instance, from computed tomography images may be a more accurate predictor of rupture risk and an important factor in AAA size progression. However, quantification of wall stress is typically computationally intensive and time-consuming, mainly due to the nonlinear mechanical behavior of the abdominal aortic aneurysm walls. These difficulties have limited the potential of computational models in clinical practice. To facilitate computation of wall stresses, we propose to use a linear approach that ensures equilibrium of wall stresses in the aneurysms. This proposed linear model approach is easy to implement and eliminates the burden of nonlinear computations. To assess the accuracy of our proposed approach to compute wall stresses, results from idealized and patient-specific model simulations were compared to those obtained using conventional approaches and to those of a hypothetical, reference abdominal aortic aneurysm model. For the reference model, wall mechanical properties and the initial unloaded and unstressed configuration were assumed to be known, and the resulting wall stresses were used as reference for comparison. Our proposed linear approach accurately approximates wall stresses for varying model geometries and wall material properties. Our findings suggest that the proposed linear approach could be used as an effective, efficient, easy-to-use clinical tool to estimate patient-specific wall stresses. PMID:25007052

Hemodynamics of physiological blood flow in the aorta with nonlinear anisotropic heart valve

NASA Astrophysics Data System (ADS)

Sotiropoulos, Fotis; Gilmanov, Anvar; Stolarski, Henryk

2016-11-01

The hemodynamic blood flow in cardiovascular system is one of the most important factor, which causing several vascular diseases. We developed a new Curvilinear Immersed Boundary - Finite Element - Fluid Structure Interaction (CURVIB-FE-FSI) method to analyze hemodynamic of pulsatile blood flow in a real aorta with nonlinear anisotropic aortic valve at physiological conditions. Hyperelastic material model, which is more realistic for describing heart valve have been incorporated in the CURVIB-FE-FSI code to simulate interaction of aortic heart valve with pulsatile blood flow. Comparative studies of hemodynamics for linear and nonlinear models of heart valve show drastic differences in blood flow patterns and hence differences of stresses causing impact at leaflets and aortic wall. This work is supported by the Lillehei Heart Institute at the University of Minnesota.

3D-printed aortic stenosis model with fragile and crushable calcifications for off-the-job training and surgical simulation.

PubMed

Shirakawa, Takashi; Yoshitatsu, Masao; Koyama, Yasushi; Mizoguchi, Hiroki; Toda, Koichi; Sawa, Yoshiki

2018-05-14

Surgical simulation devices can be helpful and cost-effective adjuncts to on-the-job training. In this tutorial we present our method for creating an aortic stenosis model with realistically fragile and crushable calcifications, using modern 3D-printing techniques.  The model can be used for training and surgical simulation and is an effective aid to learning for young cardiovascular surgeons. © The Author 2016. Published by MMCTS on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Cardiovascular causes of airway compression.

PubMed

Kussman, Barry D; Geva, Tal; McGowan, Francis X

2004-01-01

Compression of the paediatric airway is a relatively common and often unrecognized complication of congenital cardiac and aortic arch anomalies. Airway obstruction may be the result of an anomalous relationship between the tracheobronchial tree and vascular structures (producing a vascular ring) or the result of extrinsic compression caused by dilated pulmonary arteries, left atrial enlargement, massive cardiomegaly, or intraluminal bronchial obstruction. A high index of suspicion of mechanical airway compression should be maintained in infants and children with recurrent respiratory difficulties, stridor, wheezing, dysphagia, or apnoea unexplained by other causes. Prompt diagnosis is required to avoid death and minimize airway damage. In addition to plain chest radiography and echocardiography, diagnostic investigations may consist of barium oesophagography, magnetic resonance imaging (MRI), computed tomography, cardiac catheterization and bronchoscopy. The most important recent advance is MRI, which can produce high quality three-dimensional reconstruction of all anatomic elements allowing for precise anatomic delineation and improved surgical planning. Anaesthetic technique will depend on the type of vascular ring and the presence of any congenital heart disease or intrinsic lesions of the tracheobronchial tree. Vascular rings may be repaired through a conventional posterolateral thoracotomy, or utilizing video-assisted thoracoscopic surgery (VATS) or robotic endoscopic surgery. Persistent airway obstruction following surgical repair may be due to residual compression, secondary airway wall instability (malacia), or intrinsic lesions of the airway. Simultaneous repair of cardiac defects and vascular tracheobronchial compression carries a higher risk of morbidity and mortality.

Comparison of valvular resistance, stroke work loss, and Gorlin valve area for quantification of aortic stenosis. An in vitro study in a pulsatile aortic flow model.

PubMed

Voelker, W; Reul, H; Nienhaus, G; Stelzer, T; Schmitz, B; Steegers, A; Karsch, K R

1995-02-15

Valvular resistance and stroke work loss have been proposed as alternative measures of stenotic valvular lesions that may be less flow dependent and, thus, superior over valve area calculations for the quantification of aortic stenosis. The present in vitro study was designed to compare the impacts of valvular resistance, stroke work loss, and Gorlin valve area as hemodynamic indexes of aortic stenosis. In a pulsatile aortic flow model, rigid stenotic orifices in varying sizes (0.5, 1.0, 1.5 and 2.0 cm2) and geometry were studied under different hemodynamic conditions. Ventricular and aortic pressures were measured to determine the mean systolic ventricular pressure (LVSPm) and the transstenotic pressure gradient (delta Pm). Transvalvular flow (Fm) was assessed with an electromagnetic flowmeter. Valvular resistance [VR = 1333.(delta Pm/Fm)] and stroke work loss [SWL = 100.(delta Pm/LVSPm)] were calculated and compared with aortic valve area [AVA = Fm/(50 square root of delta Pm)]. The measurements were performed for a large range of transvalvular flows. At low-flow states, flow augmentation (100-->200 mL/s) increased calculated valvular resistance between 21% (2.0 cm2 orifice) and 66% (0.5-cm2 orifice). Stroke work loss demonstrated an increase from 43% (2.0 cm2) to 100% (1.0 cm2). In contrast, Gorlin valve area revealed only a moderate change from 29% (2.0 cm2) to 5% (0.5 cm2). At physiological flow rates, increase in transvalvular flow (200-->300 mL/s) did not alter calculated Gorlin valve area, whereas valvular resistance and stroke work loss demonstrated a continuing increase. Our experimental results were adopted to interpret the results of three clinical studies in aortic stenosis. The flow-dependent increase of Gorlin valve area, which was found in the cited clinical studies, can be elucidated as true further opening of the stenotic valve but not as a calculation error due to the Gorlin formula. Within the physiological range of flow, calculated aortic valve area was less dependent on hemodynamic conditions than were valvular resistance and stroke work loss, which varied as a function of flow. Thus, for the assessment of the severity of aortic stenosis, the Gorlin valve area is superior over valvular resistance and stroke work loss, which must be indexed for flow to adequately quantify the hemodynamic severity of the obstruction.

Transcription Factor Runx2 Promotes Aortic Fibrosis and Stiffness in Type 2 Diabetes Mellitus.

PubMed

Raaz, Uwe; Schellinger, Isabel N; Chernogubova, Ekaterina; Warnecke, Christina; Kayama, Yosuke; Penov, Kiril; Hennigs, Jan K; Salomons, Florian; Eken, Suzanne; Emrich, Fabian C; Zheng, Wei H; Adam, Matti; Jagger, Ann; Nakagami, Futoshi; Toh, Ryuji; Toyama, Kensuke; Deng, Alicia; Buerke, Michael; Maegdefessel, Lars; Hasenfuß, Gerd; Spin, Joshua M; Tsao, Philip S

2015-08-28

Accelerated arterial stiffening is a major complication of diabetes mellitus with no specific therapy available to date. The present study investigates the role of the osteogenic transcription factor runt-related transcription factor 2 (Runx2) as a potential mediator and therapeutic target of aortic fibrosis and aortic stiffening in diabetes mellitus. Using a murine model of type 2 diabetes mellitus (db/db mice), we identify progressive structural aortic stiffening that precedes the onset of arterial hypertension. At the same time, Runx2 is aberrantly upregulated in the medial layer of db/db aortae, as well as in thoracic aortic samples from patients with type 2 diabetes mellitus. Vascular smooth muscle cell-specific overexpression of Runx2 in transgenic mice increases expression of its target genes, Col1a1 and Col1a2, leading to medial fibrosis and aortic stiffening. Interestingly, increased Runx2 expression per se is not sufficient to induce aortic calcification. Using in vivo and in vitro approaches, we further demonstrate that expression of Runx2 in diabetes mellitus is regulated via a redox-sensitive pathway that involves a direct interaction of NF-κB with the Runx2 promoter. In conclusion, this study highlights Runx2 as a previously unrecognized inducer of vascular fibrosis in the setting of diabetes mellitus, promoting arterial stiffness irrespective of calcification. © 2015 American Heart Association, Inc.

Aortic Wall Inflammation Predicts Abdominal Aortic Aneurysm Expansion, Rupture, and Need for Surgical Repair.

PubMed

2017-08-29

Ultrasmall superparamagnetic particles of iron oxide (USPIO) detect cellular inflammation on magnetic resonance imaging (MRI). In patients with abdominal aortic aneurysm, we assessed whether USPIO-enhanced MRI can predict aneurysm growth rates and clinical outcomes. In a prospective multicenter open-label cohort study, 342 patients with abdominal aortic aneurysm (diameter ≥40 mm) were classified by the presence of USPIO enhancement and were monitored with serial ultrasound and clinical follow-up for ≥2 years. The primary end point was the composite of aneurysm rupture or repair. Participants (85% male, 73.1±7.2 years) had a baseline aneurysm diameter of 49.6±7.7 mm, and USPIO enhancement was identified in 146 (42.7%) participants, absent in 191 (55.8%), and indeterminant in 5 (1.5%). During follow-up (1005±280 days), 17 (5.0%) abdominal aortic aneurysm ruptures, 126 (36.8%) abdominal aortic aneurysm repairs, and 48 (14.0%) deaths occurred. Compared with those without uptake, patients with USPIO enhancement have increased rates of aneurysm expansion (3.1±2.5 versus 2.5±2.4 mm/year, P =0.0424), although this was not independent of current smoking habit ( P =0.1993). Patients with USPIO enhancement had higher rates of aneurysm rupture or repair (47.3% versus 35.6%; 95% confidence intervals, 1.1-22.2; P =0.0308). This finding was similar for each component of rupture (6.8% versus 3.7%, P =0.1857) or repair (41.8% versus 32.5%, P =0.0782). USPIO enhancement was associated with reduced event-free survival for aneurysm rupture or repair ( P =0.0275), all-cause mortality ( P =0.0635), and aneurysm-related mortality ( P =0.0590). Baseline abdominal aortic aneurysm diameter ( P <0.0001) and current smoking habit ( P =0.0446) also predicted the primary outcome, and the addition of USPIO enhancement to the multivariate model did not improve event prediction (c-statistic, 0.7935-0.7936). USPIO-enhanced MRI is a novel approach to the identification of aortic wall cellular inflammation in patients with abdominal aortic aneurysms and predicts the rate of aneurysm growth and clinical outcome. However, it does not provide independent prediction of aneurysm expansion or clinical outcomes in a model incorporating known clinical risk factors. URL: http://www.isrctn.com. Unique identifier: ISRCTN76413758. © 2017 The Authors.

Novel experimental model of pressure overload hypertrophy in rats.

PubMed

Molina, Ezequiel J; Gupta, Dipin; Palma, Jon; Torres, Denise; Gaughan, John P; Houser, Steven; Macha, Mahender

2009-05-15

We studied a novel animal model of pressure overload hypertrophy in transition to heart failure following ascending aortic constriction. We sought to assess chronologic changes in hemodynamic parameters, echocardiographic signs of left ventricular (LV) remodeling, exercise tolerance, and profiles of systemic and local inflammation. A cohort of Sprague Dawley rats underwent aortic constriction proximal to the innominate artery and were followed by echocardiography. A group of animals were euthanized 20 wk after aortic constriction, before any detectable decline in fractional shortening (normal fractional shortening (FS) or control group; n = 6). When additional animals reached an absolute 25% decline in fractional shortening, they were randomized to be euthanized on d 0 (25% downward arrow FS group; n = 5), or d 21 (>25% downward arrow FS group; n = 6). Hemodynamic and echocardiographic assessment, swim testing to exhaustion, and measurement of systemic and local inflammatory markers was performed at each time interval. An absolute decline of 25% in FS after aortic constriction was observed between 24 and 28 wk for most animals. The transition from compensated to decompensated hypertrophy was associated with markedly decreased dP/dt(max) and dP/dt(min), increased LV end-systolic diameter and LV end-diastolic diameter, stabilization of LV free wall diameter, decreased exercise performance and up-regulation in expression of interleukin-1, interleukin-6, tumor necrosis factor-alpha, and atrial natriuretic peptide. All animals developed heart failure. This study demonstrates that proximal aortic constriction in young rats represents an excellent experimental model of pressure overload hypertrophy that may be useful for testing the efficacy of novel therapies for the treatment of heart failure.

Blood flow dynamic improvement with aneurysm repair detected by a patient-specific model of multiple aortic aneurysms.

PubMed

Sughimoto, Koichi; Takahara, Yoshiharu; Mogi, Kenji; Yamazaki, Kenji; Tsubota, Ken'ichi; Liang, Fuyou; Liu, Hao

2014-05-01

Aortic aneurysms may cause the turbulence of blood flow and result in the energy loss of the blood flow, while grafting of the dilated aorta may ameliorate these hemodynamic disturbances, contributing to the alleviation of the energy efficiency of blood flow delivery. However, evaluating of the energy efficiency of blood flow in an aortic aneurysm has been technically difficult to estimate and not comprehensively understood yet. We devised a multiscale computational biomechanical model, introducing novel flow indices, to investigate a single male patient with multiple aortic aneurysms. Preoperative levels of wall shear stress and oscillatory shear index (OSI) were elevated but declined after staged grafting procedures: OSI decreased from 0.280 to 0.257 (first operation) and 0.221 (second operation). Graftings may strategically counter the loss of efficient blood delivery to improve hemodynamics of the aorta. The energy efficiency of blood flow also improved postoperatively. Novel indices of pulsatile pressure index (PPI) and pulsatile energy loss index (PELI) were evaluated to characterize and quantify energy loss of pulsatile blood flow. Mean PPI decreased from 0.445 to 0.423 (first operation) and 0.359 (second operation), respectively; while the preoperative PELI of 0.986 dropped to 0.820 and 0.831. Graftings contributed not only to ameliorate wall shear stress or oscillatory shear index but also to improve efficient blood flow. This patient-specific modeling will help in analyzing the mechanism of aortic aneurysm formation and may play an important role in quantifying the energy efficiency or loss in blood delivery.

Transcatheter aortic valve implantation for failing surgical aortic bioprosthetic valve: from concept to clinical application and evaluation (part 2).

PubMed

Piazza, Nicolo; Bleiziffer, Sabine; Brockmann, Gernot; Hendrick, Ruge; Deutsch, Marcus-André; Opitz, Anke; Mazzitelli, Domenico; Tassani-Prell, Peter; Schreiber, Christian; Lange, Rüdiger

2011-07-01

This study sought to review the acute procedural outcomes of patients who underwent transcatheter aortic valve (TAV)-in-surgical aortic valve (SAV) implantation at the German Heart Center, Munich, and to summarize the existing literature on TAV-in-SAV implantation (n = 47). There are several case reports and small case series describing transcatheter aortic valve implantation for a failing surgical aortic valve bioprosthesis (TAV-in-SAV implantation). From January 2007 to March 2011, 20 out of 556 patients underwent a TAV-in-SAV implantation at the German Heart Center Munich. Baseline characteristics and clinical outcome data were prospectively entered into a dedicated database. The mean patient age was 75 ± 13 years, and the mean logistic European System for Cardiac Operative Risk Evaluation and Society of Thoracic Surgeons' Risk Model scores were 27 ± 13% and 7 ± 4%, respectively. Of the 20 patients, 14 had stented and 6 had stentless surgical bioprostheses. Most cases (12 of 20) were performed via the transapical route using a 23-mm Edwards Sapien prosthesis (Edwards Lifesciences, Irvine, California). Successful implantation of a TAV in a SAV with the patient leaving the catheterization laboratory alive was achieved in 18 of 20 patients. The mean transaortic valve gradient was 20.0 ± 7.5 mm Hg. None-to-trivial, mild, and mild-to-moderate paravalvular aortic regurgitation was observed in 10, 6, and 2 patients, respectively. We experienced 1 intraprocedural death following pre-implant balloon aortic valvuloplasty ("stone heart") and 2 further in-hospital deaths due to myocardial infarction. TAV-in-SAV implantation is a safe and feasible treatment for high-risk patients with failing aortic bioprosthetic valves and should be considered as part of the armamentarium in the treatment of aortic bioprosthetic valve failure. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Accuracy and reproducibility of novel echocardiographic three-dimensional automated software for the assessment of the aortic root in candidates for thanscatheter aortic valve replacement.

PubMed

García-Martín, Ana; Lázaro-Rivera, Carla; Fernández-Golfín, Covadonga; Salido-Tahoces, Luisa; Moya-Mur, Jose-Luis; Jiménez-Nacher, Jose-Julio; Casas-Rojo, Eduardo; Aquila, Iolanda; González-Gómez, Ariana; Hernández-Antolín, Rosana; Zamorano, José Luis

2016-07-01

A specialized three-dimensional transoesophageal echocardiography (3D-TOE) reconstruction tool has recently been introduced; the system automatically configures a geometric model of the aortic root from the images obtained by 3D-TOE and performs quantitative analysis of these structures. The aim of this study was to compare the measurements of the aortic annulus (AA) obtained by the new model to that obtained by 3D-TOE and multidetector computed tomography (MDCT) in candidates to transcatheter aortic valve implantation (TAVI) and to assess the reproducibility of this new method. We included 31 patients who underwent TAVI. The AA diameters and area were evaluated by the manual 3D-TOE method and by the automatic software. We showed an excellent correlation between the measurements obtained by both methods: intra-class correlation coefficient (ICC): 0.731 (0.508-0.862), r: 0.742 for AA diameter and ICC: 0.723 (0.662-0.923), r: 0.723 for the AA area, with no significant differences regardless of the method used. The interobserver variability was superior for the automatic measurements than for the manual ones. In a subgroup of 10 patients, we also found an excellent correlation between the automatic measurements and those obtained by MDCT, ICC: 0.941 (0.761-0.985), r: 0.901 for AA diameter and ICC: 0.853 (0.409-0.964), r: 0.744 for the AA area. The new automatic 3D-TOE software allows modelling and quantifying the aortic root from 3D-TOE data with high reproducibility. There is good correlation between the automated measurements and other 3D validated techniques. Our results support its use in clinical practice as an alternative to MDCT previous to TAVI. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Hemodynamics of Aortic Stenosis and Implications for Non-invasive Diagnosis via Auscultation

NASA Astrophysics Data System (ADS)

Zhu, Chi; Seo, Jung-Hee; Mittal, Rajat

2017-11-01

Aortic stenosis refers to the abnormal narrowing of the aortic valve and it is one of the most common valvular diseases. It is also known to generate ejection murmurs, which contain valuable disease-related information. However, an incomplete understanding of the flow mechanism(s) responsible for the murmur generation, as well as the effect of intervening tissue on murmur propagation has limited the diagnostic information can be extracted through cardiac auscultation. In this study, a canonical model of the aorta with stenosis is used, and a multiphysics computational modeling approach is employed to investigate the generation and propagation of the murmurs. First, direct numerical simulation (DNS) is used to explore the hemodynamics of the post-stenotic flow. Then, a high-order, linear viscoelastic wave solver is used to investigate the wave propagation in a modeled thorax. The results show that both the aortic jet and the secondary flow contribute significantly to the murmur generation. The murmur signals on the epidermal surface are measured and analyzed. The break frequencies obtained from the spectra of cases with different degrees of stenosis are found to follow a universal scaling. The implications of these results for cardiac auscultation are discussed. The authors would like to acknowledge support from NSF Grants IIS-1344772, CBET-1511200, and NSF XSEDE Grant TG-CTS100002.

Pre-procedural assessment of aortic annulus dimensions for transcatheter aortic valve replacement: comparison of a non-contrast 3D MRA protocol with contrast-enhanced cardiac dual-source CT angiography.

PubMed

Ruile, Philipp; Blanke, Philipp; Krauss, Tobias; Dorfs, Stephan; Jung, Bernd; Jander, Nikolaus; Leipsic, Jonathon; Langer, Mathias; Neumann, Franz-Josef; Pache, Gregor

2016-04-01

To evaluate the feasibility of a non-contrast three-dimensional (3D)-FLASH magnetic resonance angiography (MRA) protocol for pre-procedural aortic annulus assessment for transcatheter aortic valve replacement (TAVR) in comparison with cardiac dual-source computed tomography angiography (CTA). In this prospective study, 69 of 104 consecutive patients (mean age 81.8 ± 5.4 years, 37.7% arrhythmic) with severe aortic stenosis who had undergone pre-TAVR cardiac CTA received a respiratory and ECG-triggered, non-contrast 3D-FLASH MRA at 3 T. Annular area measurements were obtained at mid-diastole for both modalities whereas maximum systolic area was assessed by CTA only. Systolic MRA dimensions were modelled, by adding the relative difference of systolic and diastolic CTA area dimensions as a corrective factor. Hypothetical prosthesis sizing was performed based on systolic CTA, diastolic, and modelled systolic MRA area measurements. MR image quality and degree of annular calcifications were evaluated using 4-point-grading scales. The mean acquisition time was 14 ± 4.2 min. The mean image quality was 3.1 ± 0.9 with only two examinations rated non-diagnostic. The mean degree of calcifications was equal. As assessed by Bland-Altman analysis, there was no relevant systematic difference between area measurements for modelled systolic MRA and systolic CTA [the mean difference -3.1 mm(2) (limits of agreement -44.4 mm(2); 38.2 mm(2))]. Agreement for hypothetical prosthesis sizing was found in 63 of 67 (94%) patients for systolic CTA and modelled systolic MRA. The employed non-contrast 3D-FLASH MRA protocol allows for reliable assessment of aortic annulus dimensions and calcifications even in the presence of arrhythmias in an all-comers pre-TAVR population. Implementation of this technique appears legitimate in patients at an increased risk for contrast-induced nephropathy. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

A numerical framework for studying the biomechanical behavior of abdominal aortic aneurysm

NASA Astrophysics Data System (ADS)

Jalalahmadi, Golnaz; Linte, Cristian; Helguera, María.

2017-03-01

Abdominal aortic aneurysm (AAA) is known as a leading cause of death in the United States. AAA is an abnormal dilation of the aorta, which usually occurs below the renal arteries and causes an expansion at least 1.5 times its normal diameter. It has been shown that biomechanical parameters of the aortic tissue coupled with a set of specific geometric parameters characterizing the vessel expansion, affect the risk of aneurysm rupture. Here, we developed a numerical framework that incorporates both biomechanical and geometrical factors to study the behavior of abdominal aortic aneurysm. Our workflow enables the extraction of the aneurysm geometry from both clinical quality, as well as low-resolution MR images. We used a two-parameter, hyper-elastic, isotropic, incompressible material to model the vessel tissue. Our numerical model was tested using both synthetic and mouse data and we evaluated the effects of the geometrical and biomechanical properties on the developed peak wall stress. In addition, we performed several parameter sensitivity studies to investigate the effect of different factors affecting the AAA and its behavior and rupture. Lastly, relationships between different geometrical and biomechanical parameters and peak wall stress were determined. These studies help us better understand vessel tissue response to various loading, geometry and biomechanics conditions, and we plan to further correlate these findings with the pathophysiological conditions from a patient population diagnosed with abdominal aortic aneurysms.

Cross-sectional relations of arterial stiffness, pressure pulsatility, wave reflection, and arterial calcification.

PubMed

Tsao, Connie W; Pencina, Karol M; Massaro, Joseph M; Benjamin, Emelia J; Levy, Daniel; Vasan, Ramachandran S; Hoffmann, Udo; O'Donnell, Christopher J; Mitchell, Gary F

2014-11-01

Arterial hemodynamics and vascular calcification are associated with increased risk for cardiovascular disease, but their inter-relations remain unclear. We sought to examine the associations of arterial stiffness, pressure pulsatility, and wave reflection with arterial calcification in individuals free of prevalent cardiovascular disease. Framingham Heart Study Third Generation and Offspring Cohort participants free of cardiovascular disease underwent applanation tonometry to measure arterial stiffness, pressure pulsatility, and wave reflection, including carotid-femoral pulse wave velocity, central pulse pressure, forward wave amplitude, and augmentation index. Participants in each cohort (n=1905, 45±6 years and n=1015, 65±9 years, respectively) underwent multidetector computed tomography to assess the presence and quantity of thoracic aortic calcification, abdominal aortic calcification, and coronary artery calcification. In multivariable-adjusted models, both higher carotid-femoral pulse wave velocity and central pulse pressure were associated with greater thoracic aortic calcification and abdominal aortic calcification, whereas higher augmentation index was associated with abdominal aortic calcification. Among the tonometry measures, carotid-femoral pulse wave velocity was the strongest correlate of all calcification measures in multivariable-adjusted models (odds ratio per SD for thoracic aortic calcification, 2.69 [95% confidence interval, 2.17-3.35]; abdominal aortic calcification, 1.47 [95% confidence interval, 1.26-1.73]; and coronary artery calcification, 1.48 [95% confidence interval, 1.28-1.72]; all P<0.001, respectively). We observed stronger relations of carotid-femoral pulse wave velocity, central pulse pressure, and forward wave amplitude with nearly all continuous calcification measures in the younger Third Generation Cohort as compared with the Offspring Cohort. In community-dwelling individuals without prevalent cardiovascular disease, abnormal central arterial hemodynamics were positively associated with vascular calcification and were observed at younger ages than previously recognized. The mechanisms of these associations may be bidirectional and deserve further study. © 2014 American Heart Association, Inc.

Contributions of aortic pulse wave velocity and backward wave pressure to variations in left ventricular mass are independent of each other.

PubMed

Bello, Hamza; Norton, Gavin R; Ballim, Imraan; Libhaber, Carlos D; Sareli, Pinhas; Woodiwiss, Angela J

2017-05-01

Aortic pulse wave velocity (PWV) and backward waves, as determined from wave separation analysis, predict cardiovascular events beyond brachial blood pressure. However, the extent to which these aortic hemodynamic variables contribute independent of each other is uncertain. In 749 randomly selected participants of African ancestry, we therefore assessed the extent to which relationships between aortic PWV or backward wave pressures (Pb) (and hence central aortic pulse pressure [PPc]) and left ventricular mass index (LVMI) occur independent of each other. Aortic PWV, PPc, forward wave pressure (Pf), and Pb were determined using radial applanation tonometry and SphygmoCor software and LVMI using echocardiography; 44.5% of participants had an increased left ventricular mass indexed to height 1.7 . With adjustments for age, brachial systolic blood pressure or PP, and additional confounders, PPc and Pb, but not Pf, were independently related to LVMI and left ventricular hypertrophy (LVH) in both men and women. However, PWV was independently associated with LVMI in women (partial r = 0.16, P < .001), but not in men (partial r = 0.03), and PWV was independently associated with LVH in women (P < .05), but not in men (P = .07). With PWV and Pb included in the same multivariate regression models, PWV (partial r = 0.14, P < .005) and Pb (partial r = 0.10, P < .05) contributed to a similar extent to variations in LVMI in women. In addition, with PWV and Pb included in the same multivariate regression models, PWV (P < .05) and Pb (P < .02) contributed to LVH in women. In conclusion, aortic PWV and Pb (and hence pulse pressure) although both associated with LVMI and LVH produce effects which are independent of each other. Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Red wine polyphenols increase calcium in bovine aortic endothelial cells: a basis to elucidate signalling pathways leading to nitric oxide production

PubMed Central

Martin, Sophie; Andriambeloson, Emile; Takeda, Ken; Andriantsitohaina, Ramaroson

2002-01-01

The present study investigates the mechanisms by which polyphenolic compounds from red wine elicit Ca2+ mobilization in bovine aortic endothelial cells (BAECs). Two polyphenol-containing red wine extracts, red wine polyphenolic compounds (RWPC) and Provinols™, and delphinidin, an anthocyanin were used. RWPC stimulated a Ca2+-dependent release of nitric oxide (NO) from BAECs accounting for the relaxation of endothelium-denuded rat aortic rings as shown by cascade bioassay. RWPC, Provinols™ and delphinidin increased cytosolic free calcium ([Ca2+]i), by releasing Ca2+ from intracellular stores and by increasing Ca2+ entry. The RWPC-induced increase in [Ca2+]i was decreased by exposure to ryanodine (30 μM), whereas Provinols™ and delphinidin-induced increases in [Ca2+]i were decreased by bradykinin (0.1 μM) and thapsigargin (1 μM) pre-treatment. RWPC, Provinols™ and delphinidin-induced increases in [Ca2+]i were sensitive to inhibitors of phospholipase C (neomycin, 3 mM; U73122, 3 μM) and tyrosine kinase (herbimycin A, 1 μM). RWPC, Provinols™ and delphinidin induced herbimycin A (1 μM)-sensitive tyrosine phosphorylation of several intracellular proteins. Provinols™ released Ca2+ via both a cholera (CTX) and pertussis toxins (PTX)-sensitive pathway, whereas delphinidin released Ca2+ only via a PTX-sensitive mechanism. Our data contribute in defining the mechanisms of endothelial NO production caused by wine polyphenols including the increase in [Ca2+]i and the activation of tyrosine kinases. Furthermore, RWPC, Provinols™ and delphinidin display differences in the process leading to [Ca2+]i increases in endothelial cells illustrating multiple cellular targets of natural dietary polyphenolic compounds. PMID:11906973

Kinetic modeling of the Saturn ring-ionosphere plasma environment

NASA Technical Reports Server (NTRS)

Wilson, G. R.; Waite, J. H., Jr.

1989-01-01

A time-independent kinetic plasma model was developed on the basis of the Li et al. (1988) semikinetic plasma model and was used to study the interaction of the Saturnian ionosphere and ring plasma. The model includes the gravitational magnetic mirror and centripetal and ambipolar electric forces, and the effect of the mixing of two plasma populations. The results obtained indicate that the density, temperature, and composition of plasma near the rings changing in the direction from the inner C ring to the outer A ring, due to the fact that the predominant source of plasma changes from the ionosphere to the rings. The model results also suggest that the outflow of hydrogen from the ionosphere to the rings may be shut off for field lines passing through the outer B and A ring, due to the ambipolar electric field set up by the warm ring plasma trapped near the ring plane by the centipetal force. In these regions, there will be a net flux of O(+) ions from the rings to the ionosphere.

[Significance of endogenous sulfur dioxide in the regulation of cardiovascular system].

PubMed

Jin, Hong Fang; DU, Shu Xu; Zhao, Xia; Zhang, Su Qing; Tian, Yue; Bu, Ding Fang; Tang, Chao Shu; DU, Jun Bao

2007-08-18

Since the 1980's nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H(2)S), the endogenous gas molecules produced from metabolic pathway, have been realized as signal molecules to be involved in the regulation of body homeostasis and to play important roles under physiological and pathophysiological conditions. The researches on these endogenous gas signal molecules opened a new avenue in life science. To explore the new member of gasotransmitter family, other endogenous gas molecules which have been regarded as metabolic waste up to date, and their biological regulatory effects have been paid close attention to in the current fields of life science and medicine. Sulfur dioxide (SO(2)) can be produced endogenously from normal metabolism of sulfur-containing amino acids. L-cysteine is oxidized via cysteine dioxygenase to L-cysteinesulfinate, and the latter can proceed through transamination by glutamate oxaloacetate transaminase (GOT) to beta-sulfinyl pyruvate which decomposes spontaneously to pyruvate and SO(2). In mammals, activated neutrophils by oxidative stress can convert H(2)S to sulfite through a reduced form of nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase-dependent process. The authors detected endogenous production of SO(2) in all cardiovascular tissues, including in heart, aorta, pulmonary artery, mesenteric artery, renal artery, tail artery and the plasma SO(2) content. As the key enzyme producing SO(2), GOT mRNA in cardiovascular system was detected and found to be located enriched in endothelial cells and vascular smooth muscle cells near the endothelial layer. When the normal rats were treated with hydroxamate(HDX), a GOT inhibitor, at a dose of 3.7 mg/kg body weight, the blood pressure (BP) went high markedly, the ratio of wall thickness to lumen radius was increased by 18.34%, and smooth muscle cell proliferation was enhanced. The plasma SO(2) level in the rats injected with 125 micromol/kg body weight SO(2) donor was increased to 721.98+/-30.11 micromol/L at the end of 30 seconds, while the blood pressure was decreased to the lowest point 65.0+/- 4.9 mm Hg at the end of 1 minute. The above results showed that endogenous SO(2) might be involved in the maintenance of blood pressure and normal vascular structure. In spontaneous hypertensive rat (SHR) animal model, exogenous supplement of SO(2) donor decreased the BP, the media cross-sectional area, and pressure of the media and the ratio of wall thickness to lumen radius in the SHR. Moreover, the proliferative index of aortic smooth muscle cells was decreased in the SHR treated with SO(2) donor compared with that in SHR. The above data showed that SO(2) could prevent the aortic structural remodeling by inhibiting the proliferation of aortic smooth muscle cells. The authors observed the direct vasorelaxant effects of SO(2) on the aortic ring pre-treated with norepinephrine (NE). SO(2) donor at a concentration of 25-100 micromol/L relaxed the aortic ring temporarily and slightly, but SO(2) donor at a concentration of 1-12 mmol/L induced relaxation of the ring in a concentration-dependent manner. Administration with nicardipine, an L-type calcium channel blocker other than glibenclamide, an ATP sensitive potassium channel (K(ATP) channel) blocker or removal of vascular endothelium could decrease the SO(2)-induced vasorelaxation. In hypoxic pulmonary hypertension animal model, SO(2) donor decreased the mean pulmonary artery pressure and the systolic pulmonary artery pressure (P<0.01), respectively as compared with hypoxic group, and alleviated obviously the hypoxic pulmonary vascular structural remodeling. The percentage of muscularized arteries of small pulmonary vessels was significantly decreased in hypoxia+SO(2) donor-treated rats compared with that of hypoxic rats (P<0.01), while the percentage of non-muscularized vessels was obviously higher in hypoxia with SO(2) donor-treated rats than that of hypoxic rats (P<0.01). Similarly, SO(2) obviously decreased relative media area and relative media thickness of small muscularized pulmonary arteries in hypoxic rats (P<0.01). The above data showed that SO(2) might play an important role in development of hypoxic pulmonary hypertension. Perfusion with SO(2) donor (10(-6)-10(-3) mol/L) to the isolated rat heart obviously inhibited the left ventricular peak rate of contraction ( + LV dp/ dtmax) , peak rate of relaxation (-LV dp/ dtmax) and difference of left ventricular pressure ( DeltaLVP) in a concentration dependent manner. Nicardipine, an L-type calcium channel blocker, could partly antagonize the inhibitory effect of SO(2) on the heart function. In a word, SO(2) could be endogenously generated in cardiovascular tissues and exert important cardiovascular effects such as vasorelaxant effect and negative inotropic effects. Moreover, SO(2) might play considerable roles in the regulation of systemic circulatory pressure, pulmonary circulatory pressure and vascular structural remodeling in the pathogenesis of hypertension and hypoxic pulmonary hypertension. On the basis of the above findings, we presumed that endogenous SO(2) might be a novel cardiovascular functional regulatory gasotransmitter. More studies on the significance of endogenous SO(2) in cardiovascular system under physiological and pathophysiological conditions need to be investigated.

The effects of ginsenoside Rb1 on endothelial damage and ghrelin expression induced by hyperhomocysteine.

PubMed

Xu, Zhiwei; Lan, Taohua; Wu, Weikang; Wu, Yiling

2011-01-01

Studies have indicated that ginsenoside Rb1 and ghrelin could both prevent homocysteine (Hcy)-induced endothelial dysfunction through the endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) mechanism. This study investigated whether endogenous ghrelin mediates the endothelial protection of ginsenosidee Rb1 through in vitro and in vivo experiments. Rats were randomized into a control group, a hyperhomocysteine (HHcy) model group with a high methionine diet, a ginsenosides (GS) group, and HHcy plus GS group. Plasma ghrelin was detected by enzyme-linked immunosorbent assay. Aortic rings for control and HHcy groups were treated with ghrelin or not. Endothelium-dependent vasodilatation function was evaluated by the aortic ring assay, and the structural changes were visualized by hematoxylin and eosin staining. Human umbilical vein endothelial cells (HUVECs) were cultured, and the experimental conditions were optimized according to NO production. After treatment, the NO, ghrelin, and von Willebrand factor (vWF) levels in the media were detected and analyzed with linear regression. Ghrelin and eNOS expression were observed by cell immunohistochemical staining. Ghrelin receptor antagonist was used to detect the mechanism of ginsenoside Rb1 on NO production, which was reflected by diacetylated 4,5-diaminofluorescein-2 diacetate fluorescence. In vivo experiments demonstrated that plasma ghrelin levels in the HHcy group were significantly elevated vs controls (P < .05) and were significantly increased in the HHcy plus GS group (P < .01). Compared with control, endothelium-dependent vasodilatation function was greatly reduced in the HHcy group (P < .01), which was significantly increased in HHcy plus ghrelin group compared with HHcy group (P < .01). The arterial walls of HHcy group exhibited characteristic pathologic changes, which were repaired in HHcy plus ghrelin group. In vivo, compared with Hcy (200 μM) group, HUVECs pretreated with ginsenoside Rb1 (10 μM) for 30 minutes showed significant increases in NO and ghrelin levels and evident reduction in vWF levels. Linear regression analysis demonstrated that ghrelin levels were significantly positively correlated with NO levels and significantly negatively correlated with vWF levels. The addition of Rb1 to Hcy also greatly reversed Hcy-induced downregulation of ghrelin and eNOS expression. Ghrelin inhibition significantly abolished the upregulation of NO levels induced by Rb1. Ghrelin can prevent Hcy-induced vascular endothelial dysfunction and structural damage. The compensatory elevation of plasma ghrelin levels in an Hcy-induced endothelial injury model may be a protective response. Ginsenoside Rb1 can significantly stimulate the ghrelin endocrine to inhibit endothelial injury. Ginsenoside also upregulates the NO signaling pathway reduced by Hcy through the ghrelin molecular mechanism. Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Effects of chronic administration of ethanolic extract of kolanut (Cola nitida) and caffeine on vascular function.

PubMed

Salahdeen, H M; Omoaghe, A O; Isehunwa, G O; Murtala, B A; Alada, A R A

2014-03-01

Kolanut (Cola nitida) is consumed in virtually every part of the world. The caffeine content of kolanut is scarce and the number of investigations studying the health benefits of kolanut is negligible compared to coffee. The present study was designed to identify the caffeine content of kolanut and evaluate the effect of its chronic consumption on cardiovascular functions in rats. The caffeine content of kolanut was determined by Gas chromatography-mass spectrometry (GC-MS). Wistar albino rats were divided into four groups (10 Rats/group). Kolanut extract (11.9 mg/kg), caffeine extracted from kolanut (7.5 mg/kg), decaffeinated of kolanut extract (6 mg/kg) and distilled water (control) was administered orally to each group for six-weeks. Effect of treatment on body weight, blood pressure and relaxation response to acetylcholine (ACh) and sodium nitroprusside (SNP) of the aortic rings was assessed. The total caffeine content of kolanut extract was found to be 51% and it was 96% pure from GC-MS analysis. Chronic consumption of kolanut and caffeine significantly (p < 0.05) decreased body weight. Similarly, kolanut extract decaffeinated kolanut and caffeine significantly (p < 0.05) reduced the contractile response to noradrenaline and higher potassium solution. Kolanut extract and caffeine also significantly (p < 0.05) increased the mean arterial blood pressure. Caffeine and kolanut consumption reduced the relaxation response to both acetylcholine and sodium nitroprusside. Atropine and L-NAME considerably inhibit the ACh-induced relaxation of the rat aortic ring suggesting the involvement of cholinergic mechanism. However, indomethacin (10(-4)M) also attenuated the ACh response indicating involvement of protanoids. The results suggest that treatment with both kolanut extract and caffeine had similar characteristics between the two groups with no significant differences in the ACh-induced relaxation of thering suggesting that the action of kolanut extract is due to its caffeine content.

Emerging Role of Angiotensin Type 2 Receptor (AT2R)/Akt/NO Pathway in Vascular Smooth Muscle Cell in the Hyperthyroidism

PubMed Central

Carrillo-Sepúlveda, Maria Alícia; Ceravolo, Graziela S.; Furstenau, Cristina R.; Monteiro, Priscilla de Souza; Bruno-Fortes, Zuleica; Carvalho, Maria Helena; Laurindo, Francisco R.; Tostes, Rita C.; Webb, R. Clinton; Barreto-Chaves, Maria Luiza M.

2013-01-01

Hyperthyroidism is characterized by increased vascular relaxation and decreased vascular contraction and is associated with augmented levels of triiodothyronine (T3) that contribute to the diminished systemic vascular resistance found in this condition. T3 leads to augmented NO production via PI3K/Akt signaling pathway, which in turn causes vascular smooth muscle cell (VSMC) relaxation; however, the underlying mechanisms involved remain largely unknown. Evidence from human and animal studies demonstrates that the renin-angiotensin system (RAS) plays a crucial role in vascular function and also mediates some of cardiovascular effects found during hyperthyroidism. Thus, in this study, we hypothesized that type 2 angiotensin II receptor (AT2R), a key component of RAS vasodilatory actions, mediates T3 induced-decreased vascular contraction. Marked induction of AT2R expression was observed in aortas from T3-induced hyperthyroid rats (Hyper). These vessels showed decreased protein levels of the contractile apparatus: α-actin, calponin and phosphorylated myosin light chain (p-MLC). Vascular reactivity studies showed that denuded aortic rings from Hyper rats exhibited decreased maximal contractile response to angiotensin II (AngII), which was attenuated in aortic rings pre-incubated with an AT2R blocker. Further study showed that cultured VSMC stimulated with T3 (0.1 µmol/L) for 24 hours had increased AT2R gene and protein expression. Augmented NO levels and decreased p-MLC levels were found in VSMC stimulated with T3, both of which were reversed by a PI3K/Akt inhibitor and AT2R blocker. These findings indicate for the first time that the AT2R/Akt/NO pathway contributes to decreased contractile responses in rat aorta, promoted by T3, and this mechanism is independent from the endothelium. PMID:23637941

Effects of agents that inactivate free radical NO (NO•) on nitroxyl anion-mediated relaxations, and on the detection of NO• released from the nitroxyl anion donor Angeli's salt

PubMed Central

Ellis, Anthie; Lu, Hong; Li, Chun Guang; Rand, Michael J

2001-01-01

The effects of agents that inactivate free radical nitric oxide (carboxy-PTIO, hydroxocobalamin and pyrogallol) were tested on relaxations produced by the nitroxyl anion (NO−) donor Angeli's salt in rat aortic rings and anococcygeus muscles. The amount of NO• generated from Angeli's salt in the presence of these agents was measured using a NO•-selective electrode sensor. Carboxy-PTIO (100, 300 μM), hydroxocobalamin (30, 100 μM) and pyrogallol (10, 30 μM) significantly reduced relaxations produced by Angeli's salt (0.3 μM) in aortic rings but not in anococcygeus muscles. NO• generated from Angeli's salt (0.1 – 10 μM), as detected by the sensor electrode, was less than 0.5% of the amount of Angeli's salt added. Carboxy-PTIO (100 μM) and hydroxocobalamin (30 μM), but not pyrogallol significantly increased the amount of NO• detected. In the presence of an oxidizing agent copper [II] (as CuSO4 100 μM), the amount of NO• detected from 0.3 μM of Angeli's salt increased from an undetectable level of 142.7±15.7 nM (equivalent to 47.6% of Angeli's salt added). Under these conditions, carboxy-PTIO, hydroxocobalamin and pyrogallol significantly reduced the amount of NO• detected from Angeli's salt as well as the signal generated by an equivalent amount of authentic NO (0.33 μM). The difference in effects of these agents on relaxations to Angeli's salt in the aorta and the anococcygeus muscle may be explained by the ready conversion of NO− to NO• in the aorta through an unidentified mechanism, which makes NO− susceptible to inactivation by these agents. Furthermore, in addition to inactivating NO•, carboxy-PTIO and hydroxocobalamin may themselves oxidize NO− to NO•, albeit slightly. PMID:11588105

Treatment with sodium nitroprusside improves the endothelial function in aortic rings with endothelial dysfunction.

PubMed

Buzinari, Tereza Cristina; Oishi, Jorge Camargo; De Moraes, Thiago Francisco; Vatanabe, Izabela Pereira; Selistre-de-Araújo, Heloisa Sobreiro; Pestana, Cezar Rangel; Rodrigues, Gerson Jhonatan

2017-07-15

Verify if sodium nitroprusside (SNP) is able to improve endothelial function and if this effect is independent of nitric oxide (NO) release of the compound. Normotensive (2K) and hypertensive (2K-1C) wistar rats were used. Intact endothelium aortas were placed in a myograph and incubated with SNP: 0.1nM; 1nM or 10nM during 30min. Cumulative concentration-effect curves for acetylcholine (Ach) were realized to measure the relaxing capacity. Intracellular NO were measured (by DAF-2DA probe) in HUVEC treated with SNP 0.1nM or DETA/NO 0.1μM. The detection of intracellular superoxide radical (O 2 •- ) was obtained by using DHE probe. Treatment of 2K-1C aortic rings with SNP (0.1; 1.0 and 10nM) improved endothelium dependent relaxation induced by acetylcholine. This improvement induced by SNP was verified at the concentration of 0.1nM, which does not release NO, suggesting that this effect was not induced due to NO release by SNP compound. Besides, we show that the cell treatment with 0.1nM of SNP decreased the fluorescence intensity to DHE in cells stimulated with angiotensin II. These results indicate that SNP decreases the concentration of O 2 •- in HUVEC cells. The SNP at a concentration that does not release NO inside the cells is able to attenuate endothelial dysfunction. Acetylcholine (Ach) (PubChem CID:6060); angiotensin II human (Ang II) (PubChem CID: 16211177); diethylenetriamine/nitric oxide (DETA-NO) (PubChem CID 4518); dihydroethidium (DHE) (PubChem CID: 128682); phenylephrine (Phe) (PubChem CID: 5284443); sodium nitroprusside (SNP) (PubChem CID: 11963579); Thiazolyl Blue Tetrazolium Bromide (MTT) (PubChem CID: 64965); 4,5-diaminofluorescein diacetate (DAF-2DA); 4-hidroxy-Tempo (Tempol) (PubChem CID: 137994), were purchased from Sigma-Aldrich (St. Louis, MO, USA). Copyright © 2017 Elsevier B.V. All rights reserved.

In vitro vascular effects produced by crude aqueous extract of green marine algae, Cladophora patentiramea (Mont.) Kützing, in aorta from normotensive rats.

PubMed

Lim, Yee-Ling; Mok, Shiueh-Lian

2010-01-01

To investigate the antihypertensive activity of aqueous extracts obtained from Malaysian coastal seaweeds and to determine the pharmacological mechanisms of the extracts on rat aorta in vitro. The antihypertensive activity of 11 species of seaweeds (5 brown, 1 red and 5 green algae) were tested by cumulative addition of the extracts to phenylephrine (PE)-precontracted Wistar-Kyoto (WKY) aortic rings in in vitro isometric contraction studies. Mechanisms for vasorelaxant effect were investigated in the presence of various antagonists. Of the 11 species tested, 2 showed a vasorelaxant effect. Further investigation of the mechanisms of action of the aqueous extract of green alga, Cladophora patentiramea (AECP),showed that the vascular relaxant effect was endothelium- and concentration-dependent. A maximum relaxation of 45.8 +/- 4.6% (n = 8, p < 0.001) was obtained at 0.1 mg/ml of extract, after which the response was found to reduce in a concentration-dependent manner to 15.7 +/- 4.9% (n = 8, p < 0.001) at the highest extract concentration tested. Pretreatment of endothelium-intact aortic rings with Nomega-nitro-L-arginine methyl ester (L-NAME, 30 microM), (1)H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 microM) and methylene blue (100 microM) resulted in a complete blockade of AECP-induced vasorelaxation. However, the relaxant effects of the extract were not blocked by atropine (1 microM), indomethacin (10 microM) and glibenclamide (10 microM), although the maximum relaxant responses were enhanced in the presence of glibenclamide. Our data showed that the in vitro vascular relaxant effect of AECPwas mediated through endothelium-dependent nitric oxide-cGMP pathway, and was not associated with the release of vasodilator prostaglandins, activation of muscarinic receptors, or ATP-sensitive potassium channels opening. Copyright 2010 S. Karger AG, Basel.

GPER-1 agonist G1 induces vasorelaxation through activation of epidermal growth factor receptor-dependent signalling pathway.

PubMed

Jang, Eun Jin; Seok, Young Mi; Arterburn, Jeffrey B; Olatunji, Lawrence A; Kim, In Kyeom

2013-10-01

The G protein-coupled oestrogen receptor-1 (GPER-1) agonist G1 induces endothelium-dependent relaxation. Activation of the epidermal growth factor (EGF) receptor leads to transduction of signals from the plasma membrane for the release of nitric oxide. We tested the hypothesis that G1 induces endothelium-dependent vasorelaxation through activation of the EGF receptor. Rat aortic rings were mounted in organ baths. After pretreatment with various inhibitors, aortic rings contracted with 11,9-epoxymethano-prostaglandin F2α or KCl were subjected to relaxation by G1. G1 induced endothelium-dependent vasorelaxation, which was attenuated by pretreatment with either L -N(ω) -nitroarginine methyl ester (L -NAME), an inhibitor of nitric oxide synthase, or (3aS,4R,9bR)-4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline HB-EGF, heparin-binding EGF-like growth factor, a GPER-1 antagonist. Neither a general oestrogen receptor antagonist, ICI 182 780, nor a selective oestrogen receptor-α antagonist, methyl-piperidino-pyrazole dihydrochloride (MPP), had an effect on G1-induced vasorelaxation. However, pretreatment with EGF receptor blockers, AG1478 or DAPH, resulted in attenuated G1-induced vasorelaxation. In addition, pretreatment with Src inhibitor 4-amino-3-(4-chlorophenyl)-1-(t-butyl)-1H-pyrazolo[3,4-d]pyrimidine, 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine or Akt inhibitor VIII also resulted in attenuated vascular relaxation induced by the cumulative addition of G1. However, neither phosphatidylinositol-3 kinase inhibitors LY294002 and wortmannin nor an extracellular signal-regulated kinase inhibitor 1,4-diamino-2,3-dicyano-1,4-bis(o-aminophenylmercapto) butadiene monoethanolate had effect on vascular relaxation induced by the cumulative addition of G1. G1 induces endothelium-dependent vasorelaxation through Src-mediated activation of the EGF receptor and the Akt pathway in rat aorta. © 2013 Royal Pharmaceutical Society.

Scutellarin protects against vascular endothelial dysfunction and prevents atherosclerosis via antioxidation.

PubMed

Mo, Jiao; Yang, Renhua; Li, Fan; Zhang, Xiaochao; He, Bo; Zhang, Yue; Chen, Peng; Shen, Zhiqiang

2018-03-15

Scutellarin is the major constituent responsible for the clinical benefits of Erigeron breviscapus (Vant.) Hand.-Mazz which finds a long history of ethnopharmacological use in Traditional Chinese Medicine. Scutellarin as a pure compound is now under investigation for its protections against various tissue injuries. This study aims to examine the effects of scutellarin on oxidative stress-induced vascular endothelial dysfunction and endothelial cell damage, and then to evaluate the therapeutic efficacy of scutellarin in preventing atherosclerosis in rats. Radical scavenging ability of scutellarin was determined in vitro. Impact of scutellarin on endothelium-dependent relaxation (EDR) of rabbit thoracic aortic rings upon 1, 1-diphenyl-2-picrylhydrazyl (DPPH) challenge was measured. Influences of scutellarin pre-treatment on the levels of reactive oxygen species (ROS), activities of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase and catalase, and the expression of SOD1 and NADPH oxidase 4 (Nox4) in human umbilical vein endothelial cells (HUVECs) injured by H 2 O 2 were examined. Anti-atherosclerotic effect of scutellarin was evaluated in rats fed with high fat diet (HFD). Scutellarin showed potent antioxidant activity in vitro. Pretreatment of scutellarin retained the EDR of rabbit thoracic aortic rings damaged by DPPH. In H 2 O 2 injured-HUVECs the deleterious alterations in ROS levels and antioxidant enzymes activity were reversed by scutellarin and the mRNA and protein expression of SOD1 and Nox4 were restored also. Oral administration of scutellarin dose-dependently ameliorated hyperlipidemia in HFD-fed rats and alleviated oxidative stress in rat serum, mimicking the effects of reference drug atorvastatin. Scutellarin protects against oxidative stress-induced vascular endothelial dysfunction and endothelial cell damage in vitro and prevents atherosclerosis in vivo through antioxidation. The results rationalize further investigation into the clinical use of scutellarin in cardiovascular diseases. Copyright © 2018 Elsevier GmbH. All rights reserved.

Potential role of follicle-stimulating hormone (FSH) and transforming growth factor (TGFβ1) in the regulation of ovarian angiogenesis.

PubMed

Kuo, Shih-Wei; Ke, Ferng-Chun; Chang, Geen-Dong; Lee, Ming-Ting; Hwang, Jiuan-Jiuan

2011-06-01

Angiogenesis occurs during ovarian follicle development and luteinization. Pituitary secreted FSH was reported to stimulate the expression of endothelial mitogen VEGF in granulosa cells. And, intraovarian cytokine transforming growth factor (TGF)β1 is known to facilitate FSH-induced differentiation of ovarian granulosa cells. This intrigues us to investigate the potential role of FSH and TGFβ1 regulation of granulosa cell function in relation to ovarian angiogenesis. Granulosa cells were isolated from gonadotropin-primed immature rats and treated once with FSH and/or TGFβ1 for 48 h, and the angiogenic potential of conditioned media (granulosa cell culture conditioned media; GCCM) was determined using an in vitro assay with aortic ring embedded in collagen gel and immunoblotting. FSH and TGFβ1 increased the secreted angiogenic activity in granulosa cells (FSH + TGFβ1 > FSH ≈ TGFβ1 >control) that was partly attributed to the increased secretion of pro-angiogenic factors VEGF and PDGF-B. This is further supported by the evidence that pre-treatment with inhibitor of VEGF receptor-2 (Ki8751) or PDGF receptor (AG1296) throughout or only during the first 2-day aortic ring culture period suppressed microvessel growth in GCCM-treated groups, and also inhibited the FSH + TGFβ1-GCCM-stimulated release of matrix remodeling-associated gelatinase activities. Interestingly, pre-treatment of AG1296 at late stage suppressed GCCM-induced microvessel growth and stability with demise of endothelial and mural cells. Together, we provide original findings that both FSH and TGFβ1 increased the secretion of VEGF and PDGF-B, and that in turn up-regulated the angiogenic activity in rat ovarian granulosa cells. This implicates that FSH and TGFβ1 play important roles in regulation of ovarian angiogenesis during follicle development. Copyright © 2010 Wiley-Liss, Inc.

Haemodynamic outcome at four-dimensional flow magnetic resonance imaging following valve-sparing aortic root replacement with tricuspid and bicuspid valve morphology

PubMed Central

Semaan, Edouard; Markl, Michael; Chris Malaisrie, S.; Barker, Alex; Allen, Bradley; McCarthy, Patrick; Carr, James C.; Collins, Jeremy D.

2014-01-01

OBJECTIVE To provide a more complete characterization of aortic blood flow in patients following valve-sparing aortic root replacement (VSARR) compared with presurgical cohorts matched by tricuspid and bicuspid valve morphology, age and presurgical aorta size. METHODS Four-dimensional (4D) flow magnetic resonance imaging (MRI) was performed to analyse three-dimensional (3D) blood flow in the thoracic aorta of n = 13 patients after VSARR with reimplantation of native tricuspid aortic valve (TAV, n = 6) and bicuspid aortic valve (BAV, n = 7). Results were compared with presurgical age and aortic size-matched control cohorts with TAV (n = 10) and BAV (n = 10). Pre- and post-surgical aortic flow was evaluated using time-resolved 3D pathlines using a blinded grading system (0–2, 0 = small, 1 = moderate and 2 = prominent) analysing ascending aortic (AAo) helical flow. Systolic flow profile uniformity in the aortic root, proximal and mid-AAo was evaluated using a four-quadrant model. Further analysis in nine analysis planes distributed along the thoracic aorta quantified peak systolic velocity, retrograde fraction and peak systolic flow acceleration. RESULTS Pronounced AAo helical flow in presurgical control subjects (both BAV and TAV: helix grading = 1.8 ± 0.4) was significantly reduced (0.2 ± 0.4, P < 0.001) in cohorts after VSARR independent of aortic valve morphology. Presurgical AAo flow was highly eccentric for BAV patients but more uniform for TAV. VSARR resulted in less eccentric flow profiles. Systolic peak velocities were significantly (P < 0.05) increased in post-root repair BAV patients throughout the aorta (six of nine analysis planes) and to a lesser extent in TAV patients (three of nine analysis planes). BAV reimplantation resulted in significantly increased peak velocities in the proximal AAo compared with root repair with TAV (2.3 ± 0.6 vs 1.6 ± 0.4 m/s, P = 0.017). Post-surgical patients showed a non-significant trend towards higher systolic flow acceleration as a surrogate measure of reduced aortic compliance. CONCLUSIONS VSARR restored a cohesive flow pattern independent of native valve morphology but resulted in increased peak velocities throughout the aorta. 4D flow MRI methods can assess the clinical implications of altered aortic flow dynamics in patients undergoing VSARR. PMID:24317086

Vitamin K2 regression aortic calcification induced by warfarin via Gas6/Axl survival pathway in rats.

PubMed

Jiang, Xiaoyu; Tao, Huiren; Qiu, Cuiting; Ma, Xiaolei; Li, Shan; Guo, Xian; Lv, Anlin; Li, Huan

2016-09-05

The aim of this study was to investigate the effect of vitamin K2 on aortic calcification induced by warfarin via Gas6/Axl survival pathway in rats. A calcification model was established by administering 3mg/g warfarin to rats. Rats were divided into 9 groups: control group (0W, 4W, 6W and 12W groups), 4W calcification group, 6W calcification group, 12W calcification group, 6W calcification+6W normal group and 6W calcification+6W vitamin K2 group. Alizarin red S staining measured aortic calcium depositions; alkaline phosphatase activity in serum was measured by a kit; apoptosis was evaluated by TUNEL assay; protein expression levels of Gas6, Axl, phosphorylated Akt (p-Akt), and Bcl-2 were determined by western blotting. The calcium content, calcium depositions, ALP activity and apoptosis were significantly higher in the calcification groups than control group. Gas6, Axl, p-Akt and Bcl-2 expression was lower in the calcification group than control group. 100μg/g vitamin K2 treatment decreased calcium depositions, ALP activity and apoptosis significantly, but increased Gas6, Axl, p-Akt and Bcl-2 expression. 100μg/g vitamin K2 reversed 44% calcification. Pearson correlation analysis showed a positive correlation between formation calcification and apoptosis (R(2)=0.8853, P<0.0001). In conclusion, we established a warfarin-induced calcification model and showed vitamin K2 can inhibit warfarin-induced aortic calcification and apoptosis. The regression of aortic calcification by vitamin K2 involved the Gas6/Axl axis. This data may provide a theoretical basis for future clinical treatments for aortic calcification. Copyright © 2016 Elsevier B.V. All rights reserved.

Segmental and age differences in the elastin network, collagen, and smooth muscle phenotype in the tunica media of the porcine aorta.

PubMed

Tonar, Zbyněk; Kubíková, Tereza; Prior, Claudia; Demjén, Erna; Liška, Václav; Králíčková, Milena; Witter, Kirsti

2015-09-01

The porcine aorta is often used in studies on morphology, pathology, transplantation surgery, vascular and endovascular surgery, and biomechanics of the large arteries. Using quantitative histology and stereology, we estimated the area fraction of elastin, collagen, alpha-smooth muscle actin, vimentin, and desmin within the tunica media in 123 tissue samples collected from five segments (thoracic ascending aorta; aortic arch; thoracic descending aorta; suprarenal abdominal aorta; and infrarenal abdominal aorta) of porcine aortae from growing domestic pigs (n=25), ranging in age from 0 to 230 days. The descending thoracic aorta had the greatest elastin fraction, which decreased proximally toward the aortic arch as well as distally toward the abdominal aorta. Abdominal aortic segments had the highest fraction of actin, desmin, and vimentin positivity and all of these vascular smooth muscle markers were lower in the thoracic aortic segments. No quantitative differences were found when comparing the suprarenal abdominal segments with the infrarenal abdominal segments. The area fraction of actin within the media was comparable in all age groups and it was proportional to the postnatal growth. Thicker aortic segments had more elastin and collagen with fewer contractile cells. The collagen fraction decreased from ascending aorta and aortic arch toward the descending aorta. By revealing the variability of the quantitative composition of the porcine aorta, the results are suitable for planning experiments with the porcine aorta as a model, i.e. power test analyses and estimating the number of samples necessary to achieving a desirable level of precision. The complete primary morphometric data, in the form of continuous variables, are made publicly available for biomechanical modeling of site-dependent distensibility and compliance of the porcine aorta. Copyright © 2015 Elsevier GmbH. All rights reserved.

Pathogenetic Basis of Aortopathy and Aortic Valve Disease

ClinicalTrials.gov

2018-02-19

Aortopathies; Thoracic Aortic Aneurysm; Aortic Valve Disease; Thoracic Aortic Disease; Thoracic Aortic Dissection; Thoracic Aortic Rupture; Ascending Aortic Disease; Descending Aortic Disease; Ascending Aortic Aneurysm; Descending Aortic Aneurysm; Marfan Syndrome; Loeys-Dietz Syndrome; Ehlers-Danlos Syndrome; Shprintzen-Goldberg Syndrome; Turner Syndrome; PHACE Syndrome; Autosomal Recessive Cutis Laxa; Congenital Contractural Arachnodactyly; Arterial Tortuosity Syndrome

Preventing local regeneration of glucocorticoids by 11β-hydroxysteroid dehydrogenase type 1 enhances angiogenesis

PubMed Central

Small, Gary R.; Hadoke, Patrick W. F.; Sharif, Isam; Dover, Anna R.; Armour, Danielle; Kenyon, Christopher J.; Gray, Gillian A.; Walker, Brian R.

2005-01-01

Angiogenesis restores blood flow to healing tissues, a process that is inhibited by high doses of glucocorticoids. However, the role of endogenous glucocorticoids and the potential for antiglucocorticoid therapy to enhance angiogenesis is unknown. Using in vitro and in vivo models of angiogenesis in mice, we examined effects of (i) endogenous glucocorticoids, (ii) blocking endogenous glucocorticoid action with the glucocorticoid receptor antagonist RU38486, and (iii) abolishing local regeneration of glucocorticoids by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1). Glucocorticoids, administered at physiological concentrations, inhibited angiogenesis in an in vitro aortic ring model and in vivo in polyurethane sponges implanted s.c. RU38486-enhanced angiogenesis in s.c. sponges, in healing surgical wounds, and in the myocardium of mice 7 days after myocardial infarction induced by coronary artery ligation. 11βHSD1 knockout mice showed enhanced angiogenesis in vitro and in vivo within sponges, wounds, and infarcted myocardium. Endogenous glucocorticoids, including those generated locally by 11βHSD1, exert tonic inhibition of angiogenesis. Inhibition of 11βHSD1 in liver and adipose has been advocated to reduce cardiovascular risk in the metabolic syndrome: these data suggest that 11βHSD1 inhibition offers a previously uncharacterized therapeutic approach to improve healing of ischemic or injured tissue. PMID:16093320

Etiology impacts survival in patients with severe aortic regurgitation: results from a cohort of 756 patients.

PubMed

Varadarajan, Padmini; Patel, Reena; Turk, Rami; Kamath, Ashvin R; Sampath, Unnati; Khandhar, Sumit; Pai, Ramdas G

2013-01-01

Severe aortic regurgitation (AR) is caused by a variety of mechanisms, which include the degenerative process, bicuspid aortic valve (BAV), aortic root dilation, endocarditis or a combination of these. Their frequency in a contemporary clinical series, and their impact on survival, are currently unknown. The authors' echocardiographic database between 1993 and 2007 was screened for patients with severe AR, and yielded 756 patients. Detailed chart reviews were performed to acquire clinical and demographic data. Mortality data were obtained from the social security death index and analyzed as a function of the condition's etiology. The probable etiologies for AR were: degenerative in 29% of patients, BAV in 10%, aortic root pathology in 11%, endocarditis in 10%, and mixed or unclear mechanism in 40%. Survival was a function of the etiology (p < 0.0001), with degenerative mechanism having the worst prognosis and BAV the best. This differential impact on mortality remained significant after adjusting for age, gender, coronary artery disease, diabetes mellitus, renal insufficiency, left ventricular ejection fraction and aortic valve replacement, using the Cox regression model (p < 0.0001). Etiology has a significant independent impact on mortality in patients with severe AR, with the worst survival being seen in degenerative AR.

Influence of surgical implantation angle of left ventricular assist device outflow graft and management of aortic valve opening on the risk of stroke in heart failure patients

NASA Astrophysics Data System (ADS)

Chivukula, V. Keshav; McGah, Patrick; Prisco, Anthony; Beckman, Jennifer; Mokadam, Nanush; Mahr, Claudius; Aliseda, Alberto

2016-11-01

Flow in the aortic vasculature may impact stroke risk in patients with left ventricular assist devices (LVAD) due to severely altered hemodynamics. Patient-specific 3D models of the aortic arch and great vessels were created with an LVAD outflow graft at 45, 60 and 90° from centerline of the ascending aorta, in order to understand the effect of surgical placement on hemodynamics and thrombotic risk. Intermittent aortic valve opening (once every five cardiac cycles) was simulated and the impact of this residual native output investigated for the potential to wash out stagnant flow in the aortic root region. Unsteady CFD simulations with patient-specific boundary conditions were performed. Particle tracking for 10 cardiac cycles was used to determine platelet residence times and shear stress histories. Thrombosis risk was assessed by a combination of Eulerian and Lagrangian metrics and a newly developed thrombogenic potential metric. Results show a strong influence of LVAD outflow graft angle on hemodynamics in the ascending aorta and consequently on stroke risk, with a highly positive impact of aortic valve opening, even at low frequencies. Optimization of LVAD implantation and management strategies based on patient-specific simulations to minimize stroke risk will be presented

Relationship of Aortic Wall Distensibility to Mitral and Aortic Valve Calcification: The Multi-Ethnic Study of Atherosclerosis.

PubMed

Cohoon, Kevin P; Criqui, Michael H; Budoff, Matthew J; Lima, Joao A; Blaha, Michael J; Decker, Paul A; Durazo, Ramon; Liu, Kiang; Kramer, Holly

2018-05-01

Data are limited on whether valvular calcification is associated with aortic wall stiffness. We tested whether aortic valve calcification (AVC) and/or mitral valve calcification (MVC) is inversely associated with aortic distensibility (AD). Cross-sectional study conducted in a subset of the Multi-Ethnic Study of Atherosclerosis (MESA) included 3676 MESA participants aged 44 to 84 years with AD measured with magnetic resonance imaging and with AVC and MVC measured with noncontrast cardiac computed tomography scans. Both AVC and MVC were divided into 3 categories: zero, < median values (low), and ≥ median values (high) for patients with nonzero values. Overall, 88% (n = 3256) and 92% (n = 3365) of participants had zero AVC and MVC, while 6% (n = 211) and 4% (n = 156) had low, and 6% (n = 209) and 4% (n = 155) had high values of AVC and MVC, respectively. The AVC was independently associated with AD after adjusting for age, gender, and ethnicity ( P = .035). No association was noted between AVC groups and AD after adjustment for all covariates or MVC groups and AD in any model.

The intraventricular filling vortex under heightened aortic blood pressure

NASA Astrophysics Data System (ADS)

Nelsen, Nicholas; Gaddam, Manikantam; Santhanakrishnan, Arvind

2017-11-01

Hypertension, or high aortic blood pressure, can induce structural changes in the left ventricle (LV) such as concentric hypertrophy. Previous studies have identified that the intraventricular filling vortex serves as an effective means of blood transport during diastolic filling. However, a fundamental understanding of how hypertension affects this vortex is unavailable. This knowledge can be useful for improving diagnosis and treatment of related heart disease conditions, including hypertensive heart failure. In this experimental study, we hypothesized that the circulation of the filling vortex would diminish with increased aortic pressure. Using a LV physical model within a left heart simulator, we performed hemodynamic measurements to acquire pressure and volumetric inflow profiles and 2D particle image velocimetry to visualize the intraventricular flow fields. Peak aortic pressures of 120 mm Hg, 140 mm Hg, and 160 mm Hg were each tested at heart rates of 70, 100, and 110 beats per minute, under: 1) reduced ejection fraction (EF), and 2) constant EF. Our results indicate that peak vortex circulation is reduced under elevated aortic pressures. Hemodynamics and characteristics of the intraventricular filling vortex in all examined experimental cases will be presented.

[Orientation hypercolumns of the visual cortex: ring model].

PubMed

Smirnova, E Iu; Chizhov, A V

2011-01-01

A hypercolumn of the visual cortex is a functional unit formed of the neighbouring columns whose neurons respond to a stimulus of particular orientation. The function of the hypercolumn is to amplify the orientation tuning of visually evoked responses. According to the conventional simple model of a hypercolumn, neuronal populations with different orientation preferences are distributed on a ring. Every population is described by the frequency (FR) model. To determine the limitations of the FR-ring model, it was compared with a more detailed ring model, which takes into account the distribution of neurons of each population according to their voltage values. In the case of the leaky integrate-and-fire neurons, every neural population is described by the Fokker-Planck (FP) equation. The mapping of parameters was obtained. The simulations revealed differences in the behaviour of the two models. Contrary to the FR model, the model based on the Fokker-Planck equation reacts faster to a change in stimulus orientation. The Fokker-Planck ring model gives a steady-state solution in the form of waves of activity travelling on the ring, whereas the FR ring model presents amplitude instability for the same parameter set. The FR ring model reproduces the characteristic effects of the ring model: the virtual rotation and the symmetry breaking.

Automatic aortic root segmentation in CTA whole-body dataset

NASA Astrophysics Data System (ADS)

Gao, Xinpei; Kitslaar, Pieter H.; Scholte, Arthur J. H. A.; Lelieveldt, Boudewijn P. F.; Dijkstra, Jouke; Reiber, Johan H. C.

2016-03-01

Trans-catheter aortic valve replacement (TAVR) is an evolving technique for patients with serious aortic stenosis disease. Typically, in this application a CTA data set is obtained of the patient's arterial system from the subclavian artery to the femoral arteries, to evaluate the quality of the vascular access route and analyze the aortic root to determine if and which prosthesis should be used. In this paper, we concentrate on the automated segmentation of the aortic root. The purpose of this study was to automatically segment the aortic root in computed tomography angiography (CTA) datasets to support TAVR procedures. The method in this study includes 4 major steps. First, the patient's cardiac CTA image was resampled to reduce the computation time. Next, the cardiac CTA image was segmented using an atlas-based approach. The most similar atlas was selected from a total of 8 atlases based on its image similarity to the input CTA image. Third, the aortic root segmentation from the previous step was transferred to the patient's whole-body CTA image by affine registration and refined in the fourth step using a deformable subdivision surface model fitting procedure based on image intensity. The pipeline was applied to 20 patients. The ground truth was created by an analyst who semi-automatically corrected the contours of the automatic method, where necessary. The average Dice similarity index between the segmentations of the automatic method and the ground truth was found to be 0.965±0.024. In conclusion, the current results are very promising.

AP-1 Oligodeoxynucleotides Reduce Aortic Elastolysis in a Murine Model of Marfan Syndrome.

PubMed

Arif, Rawa; Zaradzki, Marcin; Remes, Anca; Seppelt, Philipp; Kunze, Reiner; Schröder, Hannes; Schwill, Simon; Ensminger, Stephan M; Robinson, Peter N; Karck, Matthias; Müller, Oliver J; Hecker, Markus; Wagner, Andreas H; Kallenbach, Klaus

2017-12-15

Marfan syndrome is characterized by high expression of matrix metalloproteinases (MMPs) in aortic smooth muscle cells (AoSMCs) associated with medial elastolysis and aortic root aneurysm. We aimed to reduce aortic elastolysis through decrease of MMP expression with decoy oligodeoxynucleotides (dODNs) neutralizing the transcription factor activating factor-1 (AP-1). AP-1 abundance in nuclear extracts as well as MMP-2 and MMP-9 expression were significantly increased in isolated mAoSMC of mgR/mgR Marfan mice compared to wild-type cells. Exposure to AP-1 neutralizing dODNs resulted in a significant reduction of basal and interleukin-1β-stimulated MMP expression and activity in mAoSMCs. Moreover, increased migration and formation of superoxide radical anions was substantially decreased in mAoSMCs by AP-1 dODN treatment. Aortic grafts from donor Marfan mice were treated with AP-1- dODN ex vivo and implanted as infrarenal aortic interposition grafts in mgR/mgR mice. Pretreatment of aortic grafts with AP-1 dODN led to reduced elastolysis, macrophage infiltration, and MMP activity. Permeability of the endothelial monolayer was increased for dODN in mgR/mgR aortae with observed loss of tight junction proteins ZO-1 and occludin, enabling dODN to reach the tunica media. Targeting AP-1 activity offers a new potential strategy to treat the vascular phenotype associated with Marfan syndrome. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Vascular mechanisms of cyanidin-3-glucoside response in streptozotocin-diabetic rats.

PubMed

Nasri, Sima; Roghani, Mehrdad; Baluchnejadmojarad, Tourandokht; Rabani, Tahereh; Balvardi, Mahboubeh

2011-09-01

Considering the high incidence of cardiovascular disorders in diabetes mellitus and some evidence on the antioxidant and antidiabetic potential of cyanidin-3-glucoside (C3G), this study was conducted to evaluate the possible beneficial effect of C3G administration on vascular reactivity of isolated thoracic aorta in diabetic rats and some of its underlying mechanisms. Male diabetic rats received C3G (10mg/kg; i.p.) on alternate days for 8 weeks one week after streptozotocin (STZ) diabetes induction. It was found out that treatment of diabetic rats with C3G exerted a hypoglycaemic effect and attenuated the increased malondialdehyde (MDA) content and reduced the activity of superoxide dismutase (SOD) in aortic tissue. Maximum contractile response of endothelium-intact aortic rings to phenylephrine (PE) was significantly lower in C3G-treated diabetic rats relative to untreated diabetics and endothelium removal abolished this difference. Meanwhile, endothelium-dependent relaxation to acetylcholine (ACh) was significantly higher in C3G-treated diabetic rats as compared to diabetic group. Chronic treatment with C3G may prevent some diabetes-related changes in vascular reactivity observed in diabetic rats directly and/or indirectly due to its hypoglycaemic effect and attenuation of lipid peroxidation and through endothelial-derived factors. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

[Sedation and anesthesia in dogs and cats with cardiovascular diseases. III. Ventilation, respiratory monitoring, treatment for postoperative pain].

PubMed

Skarda, R T; Hubbell, J A; Muir, W W; Bednarski, R M; Mason, D E

1996-01-01

The purpose of this study was to review ventilation and postoperative analgesic technics in 137 dogs and 13 cats with congenital or acquired heart disease. The animals were referred to the Department of Veterinary Clinical Sciences at The Ohio State University, U.S.A, for the following surgical interventions: correction of patent ductus arteriosus (PDA-ligation, 28%), cardiac catheterization with angiogram and angioplasty (22%), pacemaker implantation (18%), exploratory lateral thoracotomy (8.7%), correction of right aortic arch ring anomaly (3.3%), correction of subvalvular aortic stenosis (2.7%), correction of PDA with coil in patients with mitral regurgitation and congestive heart failure (2%), pericardectomy and removal of heart base tumor (2%), and palliative surgery for ventricular septal defect (VSD, 0.7%). Controlled ventilation was used in all animals during thoracotomy. Anesthesia was maintained over 2.3 +/- 1.3 hours by using either isoflurane, halothane, propofol, or diazepam-ketamine in 64%, 32%, 2%, and 0.7% of animals, respectively. Postoperative analgesia was necessary in 20% of animals and was provided by using different technics over several hours. The technics and respective percentages of animals in which they were used, were: intravenous buprenorphine (3.3%), intercostal nerve blocks (8.7%), epidural morphine (4%), and interpleural regional analgesia (4%).

Serum-deprived human multipotent mesenchymal stromal cells (MSCs) are highly angiogenic

PubMed Central

Oskowitz, Adam; McFerrin, Harris; Gutschow, Miriam; Carter, Mary Leita; Pochampally, Radhika

2016-01-01

Recent reports have indicated that mesenchymal stromal cells (MSCs) from bone marrow have a potential in vascular remodeling and angiogenesis. Here, we report a unique phenomenon that under serum-deprived conditions MSCs survive and replicate. Secretome analysis of MSCs grown under serum-deprived conditions (SD-MSCs) identified a significant upregulation of prosurvival and angiogenic factors including VEGF-A, ANGPTs, IGF-1, and HGF. An ex vivo rat aortic assay demonstrated longer neovascular sprouts generated from rat aortic rings cultured in SD-MSC-conditioned media compared to neovascular sprouts from aortas grown in MSC-conditioned media. With prolonged serum deprivation, a subpopulation of SD-MSCs began to exhibit an endothelial phenotype. This population expressed endothelial-specific proteins including VEGFR2, Tie2/TEK, PECAM/CD31, and eNOS and also demonstrated the ability to uptake acetylated LDL. SD-MSCs also exhibited enhanced microtubule formation in an in vitro angiogenesis assay. Modified chick chorioallantoic membrane (CAM) angiogenesis assays showed significantly higher angiogenic potential for SD-MSCs compared to MSCs. Analysis of CAMs grown with SD-MSCs identified human-specific CD31-positive cells in vascular structures. We conclude that under the stress of serum deprivation MSCs are highly angiogenic and a population of these cells has the potential to differentiate into endothelial-like cells. PMID:21421339

Outcomes of ring versus suture annuloplasty for tricuspid valve repair in patients undergoing mitral valve surgery.

PubMed

Shinn, Sung Ho; Dayan, Victor; Schaff, Hartzell V; Dearani, Joseph A; Joyce, Lyle D; Lahr, Brian; Greason, Kevin L; Stulak, John M; Daly, Richard C

2016-08-01

There is controversy regarding the comparative effectiveness of methods of tricuspid valve (TV) repair-prosthetic ring versus suture annuloplasty-in patients undergoing operation for primary mitral valve (MV) disease. In this study, we analyzed factors associated with patient survival and recurrent tricuspid regurgitation (TR) following TV repair and focused on results stratified by method of tricuspid valve repair. We reviewed patients who underwent TV repair with suture (De Vega) or flexible ring annuloplasties at the time of MV surgery from 1995 to 2010. Patients with prior cardiac or concomitant aortic valve operations were excluded. Propensity matching was performed to account for potential differences in baseline characteristics between the groups. Primary outcomes were long-term mortality and postoperative TR grade. In the overall study, there were 415 patients with median age 72 years (range, 63-78 years), from which 148 matched pairs were identified by propensity score analysis. In the overall cohort, patients in the ring annuloplasty group more often had preoperative transvenous pacemakers (P = .05), lower ejection fractions (P = .028), and more recent years of operation (P < .001). For patients who had De Vega suture annuloplasty, long-term mortality was not different from that of patients who had ring annuloplasty (hazard ratio, 0.93; 95% confidence interval, 0.67-1.30). Older age, preoperative diabetes, and preoperative right ventricular dysfunction were predictors for long-term mortality. Durability of the annuloplasty methods was similar with no significant difference in trend of recurrent TR grades over follow-up (P = .807). Etiology of mitral regurgitation was not associated with recurrent TR during follow-up (P = .857). Late survival and TV durability following concomitant TV repair during MV surgery did not differ with respect to TV repair technique. In this series of patients with repaired tricuspid valves, etiology of MV disease did not influence postoperative changes in TR. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

A mathematical model of aortic aneurysm formation

PubMed Central

Hao, Wenrui; Gong, Shihua; Wu, Shuonan; Xu, Jinchao; Go, Michael R.; Friedman, Avner; Zhu, Dai

2017-01-01

Abdominal aortic aneurysm (AAA) is a localized enlargement of the abdominal aorta, such that the diameter exceeds 3 cm. The natural history of AAA is progressive growth leading to rupture, an event that carries up to 90% risk of mortality. Hence there is a need to predict the growth of the diameter of the aorta based on the diameter of a patient’s aneurysm at initial screening and aided by non-invasive biomarkers. IL-6 is overexpressed in AAA and was suggested as a prognostic marker for the risk in AAA. The present paper develops a mathematical model which relates the growth of the abdominal aorta to the serum concentration of IL-6. Given the initial diameter of the aorta and the serum concentration of IL-6, the model predicts the growth of the diameter at subsequent times. Such a prediction can provide guidance to how closely the patient’s abdominal aorta should be monitored. The mathematical model is represented by a system of partial differential equations taking place in the aortic wall, where the media is assumed to have the constituency of an hyperelastic material. PMID:28212412

Effect of fatty acids on endothelium-dependent relaxation in the rabbit aorta.

PubMed

Edirisinghe, Indika; McCormick Hallam, Kellie; Kappagoda, C Tissa

2006-08-01

The metabolic syndrome, Type II (non-insulin-dependent) diabetes and obesity are associated with endothelial dysfunction and increased plasma concentrations of NEFAs (non-esterified fatty acids; free fatty acids). The present study was undertaken to define the inhibitory effects of saturated NEFAs on EDR (endothelium-dependent relaxation). Experiments were performed in rings of rabbit aorta to establish (i) dose-response relationships, (ii) the effect of chain length, (iii) the effect of the presence of double bonds, (iv) reversibility and time course of inhibition, and (v) the effect on nitric oxide production. Aortic rings were incubated (1 h) with NEFA-albumin complexes derived from lauric (C(12:0)), myristic (C(14:0)), palmitic (C(16:0)), stearic (C(18:0)) and linolenic (C(18:3)) acids. EDR induced by acetylcholine (0.1-10 mumol/l) was measured after pre-contraction with noradrenaline. Inhibition of EDR was dose-dependent (0.5-2 mmol/l NEFA), and the greatest inhibition (51%) was observed with stearic acid (2 mmol/l). Lauric acid had the smallest inhibitory effect. The inhibitory effects were always reversible and were evident after 15 min of incubation. Linolenic acid caused a significantly lower inhibition of EDR than stearic acid. SOD (superoxide dismutase) restored the inhibitory effect caused by NEFAs, suggesting the involvement of ROS (reactive oxygen species) in removing nitric oxide. The nitric oxide concentration measured after exposure of the rings to acetylcholine was lower after incubation with NEFAs than with Krebs buffer alone. This finding is consistent with removal of nitric oxide by ROS. This claim was supported by the demonstration of increased concentrations of nitrated tyrosine in the rings incubated with NEFAs.

Chronic hypertension increases aortic endothelial hydraulic conductivity by upregulating endothelial aquaporin-1 expression.

PubMed

Toussaint, Jimmy; Raval, Chirag Bharavi; Nguyen, Tieuvi; Fadaifard, Hadi; Joshi, Shripad; Wolberg, George; Quarfordt, Steven; Jan, Kung-Ming; Rumschitzki, David S

2017-11-01

Numerous studies have examined the role of aquaporins in osmotic water transport in various systems, but virtually none have focused on the role of aquaporin in hydrostatically driven water transport involving mammalian cells save for our laboratory's recent study of aortic endothelial cells. Here, we investigated aquaporin-1 expression and function in the aortic endothelium in two high-renin rat models of hypertension, the spontaneously hypertensive genetically altered Wistar-Kyoto rat variant and Sprague-Dawley rats made hypertensive by two-kidney, one-clip Goldblatt surgery. We measured aquaporin-1 expression in aortic endothelial cells from whole rat aortas by quantitative immunohistochemistry and function by measuring the pressure-driven hydraulic conductivities of excised rat aortas with both intact and denuded endothelia on the same vessel. We used them to calculate the effective intimal hydraulic conductivity, which is a combination of endothelial and subendothelial components. We observed well-correlated enhancements in aquaporin-1 expression and function in both hypertensive rat models as well as in aortas from normotensive rats whose expression was upregulated by 2 h of forskolin treatment. Upregulated aquaporin-1 expression and function may be a response to hypertension that critically determines conduit artery vessel wall viability and long-term susceptibility to atherosclerosis. NEW & NOTEWORTHY The aortic endothelia of two high-renin hypertensive rat models express greater than two times the aquaporin-1 and, at low pressures, have greater than two times the endothelial hydraulic conductivity of normotensive rats. Data are consistent with theory predicting that higher endothelial aquaporin-1 expression raises the critical pressure for subendothelial intima compression and for artery wall hydraulic conductivity to drop. Copyright © 2017 the American Physiological Society.

Pulsatile flows and wall-shear stresses in models simulating normal and stenosed aortic arches

NASA Astrophysics Data System (ADS)

Huang, Rong Fung; Yang, Ten-Fang; Lan, Y.-K.

2010-03-01

Pulsatile aqueous glycerol solution flows in the models simulating normal and stenosed human aortic arches are measured by means of particle image velocimetry. Three transparent models were used: normal, 25% stenosed, and 50% stenosed aortic arches. The Womersley parameter, Dean number, and time-averaged Reynolds number are 17.31, 725, and 1,081, respectively. The Reynolds numbers based on the peak velocities of the normal, 25% stenosed, and 50% stenosed aortic arches are 2,484, 3,456, and 3,931, respectively. The study presents the temporal/spatial evolution processes of the flow pattern, velocity distribution, and wall-shear stress during the systolic and diastolic phases. It is found that the flow pattern evolving in the central plane of normal and stenosed aortic arches exhibits (1) a separation bubble around the inner arch, (2) a recirculation vortex around the outer arch wall upstream of the junction of the brachiocephalic artery, (3) an accelerated main stream around the outer arch wall near the junctions of the left carotid and the left subclavian arteries, and (4) the vortices around the entrances of the three main branches. The study identifies and discusses the reasons for the flow physics’ contribution to the formation of these features. The oscillating wall-shear stress distributions are closely related to the featured flow structures. On the outer wall of normal and slightly stenosed aortas, large wall-shear stresses appear in the regions upstream of the junction of the brachiocephalic artery as well as the corner near the junctions of the left carotid artery and the left subclavian artery. On the inner wall, the largest wall-shear stress appears in the region where the boundary layer separates.

Dilation of the ascending aorta after balloon valvuloplasty for aortic stenosis during infancy and childhood.

PubMed

McElhinney, Doff B; Lacro, Ronald V; Gauvreau, Kimberlee; O'Brien, Cheryl M; Yaroglu Kazanci, Selcen; Vogel, Melanie; Emani, Sitaram; Brown, David W

2012-09-01

Dilation of the ascending aorta (AA) is common in patients with a bicuspid aortic valve. The natural history of the aortic root and AA and the risk factors for dilation have not been characterized in patients with congenital aortic stenosis (AS) treated with balloon valvuloplasty during childhood. The present study was performed to determine the prevalence of aortic dilation in patients with congenital AS before and up to 20 years after balloon valvuloplasty performed during childhood. In patients who underwent balloon valvuloplasty for AS at age ≤ 18 years from 1984 to 2005, the aortic diameter measurements before intervention and at 5-year intervals afterward were recorded and the Z scores calculated. Among 156 patients (median age 1.5 years at valvuloplasty), the AA Z scores were significantly larger than normal before intervention (median Z score 1.5) and at all follow-up points (all p <0.001). Using mixed modeling, with time as a categorical variable (before intervention, 5-year window, 10-year window, and so forth), the mean AA Z score was greater at all postvalvuloplasty points than before the intervention, with mean Z score increases of 1.20 at 5 years and 2.11 at 20 years (p <0.001). Moderate or greater aortic regurgitation early after valvuloplasty was associated with greater AA Z scores than mild or less aortic regurgitation, with a progressive difference over time. More significant residual AS after valvuloplasty was associated with lower AA Z scores over time. In conclusion, AA dilation is common in children with congenital AS and continues to progress over many years after balloon valvuloplasty. Copyright © 2012 Elsevier Inc. All rights reserved.

Concomitant replacement of the dilated ascending aorta during aortic valve replacement; does it increase the perioperative morbidity and mortality risks?

PubMed

Lim, Ju Y; Jung, Sung H; Kim, Joon B; Kim, Dong K; Chung, Cheol H; Song, Hyun; Lee, Jae W; Choo, Suk J

2013-05-01

Concerns of increased surgical risks with ascending aortic replacement have led surgeons to manage post-stenotic aortic dilatation more conservatively during aortic valve replacement (AVR). The present study aimed to assess the prognostic implications and surgical risks of replacing the dilated aorta during AVR. Between January 1999 and March 2010, 134 patients who received surgery for aortic stenosis and post-stenotic dilatation (aorta size ≥40 mm) were included in the present study. AVR was performed in 92 patients (AVR group) while aortic valve and ascending aorta replacement (AVR + aorta group) were performed in 42 patients. Overall survival was compared between the two groups using Cox proportional hazard model after adjustment with inverse-probability-of-treatment weighting. The mean follow-up duration was 3.5 ± 3 years. There were no significant differences in the operative mortality and morbidity between the two groups. The late cardiac deaths were also not significantly different between the two groups (p = 1.00). In the AVR group, the ascending aortic expansion rate which was 0.18 mm/year over a mean follow-up duration of 2.3 ± 2.2 years by echocardiography showed a positive correlation with time (r = 0.3, p = 0.08). A relatively greater aortic expansion rate was identified as a risk factor for late mortality (p = 0.015, HR 1.08 (CI: 1.02 to 1.15). Concomitant replacement of the dilated ascending aorta during AVR did not increase the immediate postoperative morbidity or mortality risks and tended to exert a long-term beneficial effect on the risk of late mortality. © 2013 Wiley Periodicals, Inc.

Blood Pressure and Arterial Load After Transcatheter Aortic Valve Replacement for Aortic Stenosis.

PubMed

Lindman, Brian R; Otto, Catherine M; Douglas, Pamela S; Hahn, Rebecca T; Elmariah, Sammy; Weissman, Neil J; Stewart, William J; Ayele, Girma M; Zhang, Feifan; Zajarias, Alan; Maniar, Hersh S; Jilaihawi, Hasan; Blackstone, Eugene; Chinnakondepalli, Khaja M; Tuzcu, E Murat; Leon, Martin B; Pibarot, Philippe

2017-07-01

After aortic valve replacement, left ventricular afterload is often characterized by the residual valve obstruction. Our objective was to determine whether higher systemic arterial afterload-as reflected in blood pressure, pulsatile and resistive load-is associated with adverse clinical outcomes after transcatheter aortic valve replacement (TAVR). Total, pulsatile, and resistive arterial load were measured in 2141 patients with severe aortic stenosis treated with TAVR in the PARTNER I trial (Placement of Aortic Transcatheter Valve) who had systolic blood pressure (SBP) and an echocardiogram obtained 30 days after TAVR. The primary end point was 30-day to 1-year all-cause mortality. Lower SBP at 30 days after TAVR was associated with higher mortality (20.0% for SBP 100-129 mm Hg versus 12.0% for SBP 130-170 mm Hg; P <0.001). This association remained significant after adjustment, was consistent across subgroups, and confirmed in sensitivity analyses. In adjusted models that included SBP, higher total and pulsatile arterial load were associated with increased mortality ( P <0.001 for all), but resistive load was not. Patients with low 30-day SBP and high pulsatile load had a 3-fold higher mortality than those with high 30-day SBP and low pulsatile load (26.1% versus 8.1%; hazard ratio, 3.62; 95% confidence interval, 2.36-5.55). Even after relief of valve obstruction in patients with aortic stenosis, there is an independent association between post-TAVR blood pressure, systemic arterial load, and mortality. Blood pressure goals in patients with a history of aortic stenosis may need to be redefined. Increased pulsatile arterial load, rather than blood pressure, may be a target for adjunctive medical therapy to improve outcomes after TAVR. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894. © 2017 American Heart Association, Inc.

Inputs for subject-specific computational fluid dynamics simulation of blood flow in the mouse aorta.

PubMed

Van Doormaal, Mark; Zhou, Yu-Qing; Zhang, Xiaoli; Steinman, David A; Henkelman, R Mark

2014-10-01

Mouse models are an important way for exploring relationships between blood hemodynamics and eventual plaque formation. We have developed a mouse model of aortic regurgitation (AR) that produces large changes in plaque burden with charges in hemodynamics [Zhou et al., 2010, "Aortic Regurgitation Dramatically Alters the Distribution of Atherosclerotic Lesions and Enhances Atherogenesis in Mice," Arterioscler. Thromb. Vasc. Biol., 30(6), pp. 1181-1188]. In this paper, we explore the amount of detail needed for realistic computational fluid dynamics (CFD) calculations in this experimental model. The CFD calculations use inputs based on experimental measurements from ultrasound (US), micro computed tomography (CT), and both anatomical magnetic resonance imaging (MRI) and phase contrast MRI (PC-MRI). The adequacy of five different levels of model complexity (a) subject-specific CT data from a single mouse; (b) subject-specific CT centerlines with radii from US; (c) same as (b) but with MRI derived centerlines; (d) average CT centerlines and averaged vessel radius and branching vessels; and (e) same as (d) but with averaged MRI centerlines) is evaluated by demonstrating their impact on relative residence time (RRT) outputs. The paper concludes by demonstrating the necessity of subject-specific geometry and recommends for inputs the use of CT or anatomical MRI for establishing the aortic centerlines, M-mode US for scaling the aortic diameters, and a combination of PC-MRI and Doppler US for estimating the spatial and temporal characteristics of the input wave forms.

Influence of aortic neck characteristics on successful aortic wall penetration of EndoAnchors in therapeutic use during endovascular aneurysm repair.

PubMed

Goudeketting, Seline R; van Noort, Kim; Ouriel, Kenneth; Jordan, William D; Panneton, Jean M; Slump, Cornelis H; de Vries, Jean-Paul P M

2018-04-21

This study sought to quantify EndoAnchor (Medtronic Vascular, Santa Rosa, Calif) penetration into the aortic wall in patients undergoing endovascular abdominal aortic aneurysm repair and to assess predictors of successful penetration and its relationship to postprocedural type IA endoleak. A subset of patients from the Aneurysm Treatment Using the Heli-FX Aortic Securement System Global Registry (ANCHOR) were included if they met the following criteria: the indication for EndoAnchor use was to treat a type IA endoleak, and postprocedure contrast-enhanced computed tomography (CT) scans of sufficient quality were available for core laboratory review. Patients undergoing implantation of cuffs or stents during the EndoAnchor implantation procedure were excluded. Baseline anatomic characteristics were recorded. The cohort was divided into patients with and without persistent type IA endoleaks at the first postoperative CT scan. Penetration of each EndoAnchor measured on this CT scan was defined as good penetration when the EndoAnchor penetrated ≥2 mm into the aortic wall, borderline penetration when EndoAnchor penetration was <2 mm or a gap remained between the endograft and aortic wall, or no penetration when the EndoAnchor did not penetrate into the aortic wall. Differences between the groups were analyzed with the Mann-Whitney U test or Fisher exact test. Multivariate analyses were performed to identify independent predictors of EndoAnchor penetration, and procedural success was defined by absence of type IA endoleak. Eighty-six patients of the primary (n = 61 [71%]) and revision (n = 25 [29%]) arms of the ANCHOR registry were included. There were 53 (62%) without and 33 (38%) with persistent type IA endoleaks on the first postprocedural CT scan. The median number of EndoAnchors with good penetration was significantly greater in the cohort without endoleaks, 4 (interquartile range, 3-5) vs 3 (interquartile range, 1.5-4), respectively (P = .002). A multivariate model for EndoAnchor penetration identified use of a Medtronic Endurant endograft as a factor associated with good penetration (P = .001), whereas poor penetration was associated with a larger aortic neck diameter 10 mm distal to the lowest renal artery (P < .001) and greater proximal neck calcium thickness (P = .004). EndoAnchor penetration was the only variable that attained significance (P < .001) in the multivariate model for successful treatment of a type IA endoleak. Adequate EndoAnchor penetration into the aortic wall is less likely when the aortic neck diameter is large or when the neck contains significant mural calcium. No penetration of the EndoAnchor was the only factor predictive of postprocedural type IA endoleak. This study stresses the importance of careful selection of patients based on preoperative assessment of the infrarenal neck on CT angiography and emphasizes careful deployment of EndoAnchors into the aortic wall to improve successful treatment of type IA endoleaks. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Analysis of flow patterns in a patient-specific aortic dissection model.

PubMed

Cheng, Z; Tan, F P P; Riga, C V; Bicknell, C D; Hamady, M S; Gibbs, R G J; Wood, N B; Xu, X Y

2010-05-01

Aortic dissection is the most common acute catastrophic event affecting the thoracic aorta. The majority of patients presenting with an uncomplicated type B dissection are treated medically, but 25% of these patients develop subsequent aneurysmal dilatation of the thoracic aorta. This study aimed at gaining more detailed knowledge of the flow phenomena associated with this condition. Morphological features and flow patterns in a dissected aortic segment of a presurgery type B dissection patient were analyzed based on computed tomography images acquired from the patient. Computational simulations of blood flow in the patient-specific model were performed by employing a correlation-based transitional version of Menter's hybrid k-epsilon/k-omega shear stress transport turbulence model implemented in ANSYS CFX 11. Our results show that the dissected aorta is dominated by locally highly disturbed, and possibly turbulent, flow with strong recirculation. A significant proportion (about 80%) of the aortic flow enters the false lumen, which may further increase the dilatation of the aorta. High values of wall shear stress have been found around the tear on the true lumen wall, perhaps increasing the likelihood of expanding the tear. Turbulence intensity in the tear region reaches a maximum of 70% at midsystolic deceleration phase. Incorporating the non-Newtonian behavior of blood into the same transitional flow model has yielded a slightly lower peak wall shear stress and higher maximum turbulence intensity without causing discernible changes to the distribution patterns. Comparisons between the laminar and turbulent flow simulations show a qualitatively similar distribution of wall shear stress but a significantly higher magnitude with the transitional turbulence model.

Dynamic autophagic activity affected the development of thoracic aortic dissection by regulating functional properties of smooth muscle cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Yang; Zhao, Zhi-Min; Zhang, Guan-Xin

The aortic medial degeneration is the key histopathologic feature of Thoracic aortic dissection (TAD). The aim of this study was to identify the change of autophagic activity in the aortic wall during TAD development, and to explore the roles of autophagy on regulating functional properties of smooth muscle cells (SMCs). Firstly, compared with control group (n = 11), the increased expression of autophagic markers Beclin1 and LC3 was detected in the aortic wall from TAD group (n = 23) by immunochemistry and western blot. We found that more autophagic vacuoles were present in the aortic wall of TAD patients using Transmission electron microscopy. Next,more » autophagic activity was examined in AD mice model established by β-aminopropionitrile fumarate (BAPN) and angiotensin II. Immunochemistry proved that autophagic activity was dynamically changed during AD development. Beclin1 and LC3 were detected up-regulated in the aortic wall in the second week after BAPN feeding, earlier than the fragmentation or loss of elastic fibers. When AD occurred in the 4th week, the expression of Beclin1 and LC3 began to decrease, but still higher than the control. Furthermore, autophagy was found to inhibit starvation-induced apoptosis of SMCs. Meanwhile, blockage of autophagy could suppress PDGF-induced phenotypic switch of SMCs. Taken together, autophagic activity was dynamically changed in the aortic wall during TAD development. The abnormal autophagy could regulate the functional properties of aortic SMCs, which might be the potential pathogenesis of TAD. - Highlights: • Autophagy is up-regulated in aorta wall from thoracic aorta dissection (TAD) patient. • Autophagic activity is dynamically changed during TAD development. • Dynamically change of autophagy is associated with pathological process of TAD. • Autophagy participate in the development of TAD by regulating function of SMCs.« less

Nitric oxide donor beta2-agonists: furoxan derivatives containing the fenoterol moiety and related furazans.

PubMed

Buonsanti, M Federica; Bertinaria, Massimo; Stilo, Antonella Di; Cena, Clara; Fruttero, Roberta; Gasco, Alberto

2007-10-04

The structure of fenoterol, a beta2-adrenoceptor agonist used in therapy, has been joined with furoxan NO-donor moieties to give new NO-donor beta2-agonists. The furazan analogues, devoid of the property to release NO, were also synthesized for comparison. All the compounds retained beta2-agonistic activity at micromolar or submicromolar concentration when tested on guinea pig tracheal rings precontracted with carbachol. Among the furoxan derivatives, the NO contribution to trachea relaxation was evident with product 15b at micromolar concentrations. All the new NO-donor hybrids were able to dilate rat aortic strips precontracted with phenylephrine. Both furoxan and furazan derivatives displayed antioxidant activity greater than that of fenoterol.

Inhibitor of prostacyclin production in sporadic haemolytic uraemic syndrome.

PubMed Central

Levin, M; Elkon, K B; Nokes, T J; Buckle, A M; Dillon, M J; Hardisty, R M; Barratt, T M

1983-01-01

Prostacyclin (PGI2) production was diminished when rat aortic rings were incubated with plasma from 5 of 6 patients with the sporadic form of haemolytic uraemic syndrome but was normal in the presence of plasma from 7 patients with the epidemic form of haemolytic uraemic syndrome or from patients with other renal diseases. The reduced PGI2 production was caused by an unstable inhibitor, extractable into polar lipid solvents, in sporadic haemolytic uraemic plasma. These results suggest that there may be at least 2 different pathogenetic mechanisms in epidemic and sporadic haemolytic uraemic syndrome and that the reduced PGI2 production observed in the sporadic type is due to an inhibitor of PGI2 production rather than a deficiency of stimulating factors. PMID:6354101

Simulation of personalised haemodynamics by various mounting positions of a prosthetic valve using computational fluid dynamics.

PubMed

Bongert, Markus; Geller, Marius; Pennekamp, Werner; Nicolas, Volkmar

2018-03-03

Diseases of the cardiovascular system account for nearly 42% of all deaths in the European Union. In Germany, approximately 12,000 patients receive surgical replacement of the aortic valve due to heart valve disease alone each year. A three-dimensional (3D) numerical model based on patient-specific anatomy derived from four-dimensional (4D) magnetic resonance imaging (MRI) data was developed to investigate preoperatively the flow-induced impact of mounting positions of aortic prosthetic valves to select the best orientation for individual patients. Systematic steady-state analysis of blood flow for different rotational mounting positions of the valve is only possible using a virtual patient model. A maximum velocity of 1 m/s was used as an inlet boundary condition, because the opening angle of the valve is at its largest at this velocity. For a comparative serial examination, it is important to define the standardised general requirements to avoid impacts other than the rotated implantation of the prosthetic aortic valve. In this study, a uniform velocity profile at the inlet for the inflow of the aortic valve and the real aortic anatomy were chosen for all simulations. An iterative process, with the weighted parameters flow resistance (1), shear stress (2) and velocity (3), was necessary to determine the best rotated orientation. Blood flow was optimal at a 45° rotation from the standard implantation orientation, which will offer a supply to the coronary arteries.

CXCL8 hyper-signaling in the aortic abdominal aneurysm.

PubMed

Kokje, Vivianne B C; Gäbel, Gabor; Dalman, Ron L; Koole, Dave; Northoff, Bernd H; Holdt, Lesca M; Hamming, Jaap F; Lindeman, Jan H N

2018-08-01

There are indications for elevated CXCL8 levels in abdominal aortic aneurysm disease (AAA). CXCL8 is concurrently involved in neutrophil-mediated inflammation and angiogenesis, two prominent and distinctive characteristics of AAA. As such we considered an evaluation of a role for CXCL8 in AAA progression relevant. ELISA's, real time PCR and array analysis were used to explore CXCL8 signaling in AAA wall samples. A role for CXCL8 in AAA disease was tested through the oral CXCR1/2 antagonist DF2156A in the elastase model of AAA disease. There is an extreme disparity in aortic wall CXCL8 content between AAA and aortic atherosclerotic disease (median [IQR] aortic wall CXCL8 content: 425 [141-1261] (AAA) vs. 23 [2.8-89] (atherosclerotic aorta) µg/g protein (P < 1 · 10 -14 )), and abundant expression of the CXCR1 and 2 receptors in AAA. Array analysis followed by pathway analysis showed that CXCL8 hyper-expression in AAA is followed increased by IL-8 signaling (Z-score for AAA vs. atherosclerotic control: 2.97, p < 0.0001). Interference with CXCL8 signaling through DF2156A fully abrogated AAA formation and prevented matrix degradation in the murine elastase model of AAA disease (p < 0.001). CXCL8-signaling is a prominent and distinctive feature of AAA, interference with the pathway constitutes a promising target for medical stabilization of AAA. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Relation of aortic valve calcium to chronic kidney disease (from the Chronic Renal Insufficiency Cohort Study).

PubMed

Guerraty, Marie A; Chai, Boyang; Hsu, Jesse Y; Ojo, Akinlolu O; Gao, Yanlin; Yang, Wei; Keane, Martin G; Budoff, Matthew J; Mohler, Emile R

2015-05-01

Although subjects with chronic kidney disease (CKD) are at markedly increased risk for cardiovascular mortality, the relation between CKD and aortic valve calcification has not been fully elucidated. Also, few data are available on the relation of aortic valve calcification and earlier stages of CKD. We sought to assess the relation of aortic valve calcium (AVC) with estimated glomerular filtration rate (eGFR), traditional and novel cardiovascular risk factors, and markers of bone metabolism in the Chronic Renal Insufficiency Cohort (CRIC) Study. All patients who underwent aortic valve scanning in the CRIC study were included. The relation between AVC and eGFR, traditional and novel cardiovascular risk factors, and markers of calcium metabolism were analyzed using both unadjusted and adjusted regression models. A total of 1,964 CRIC participants underwent computed tomography for AVC quantification. Decreased renal function was independently associated with increased levels of AVC (eGFR 47.11, 44.17, and 39 ml/min/1.73 m2, respectively, p<0.001). This association persisted after adjusting for traditional, but not novel, AVC risk factors. Adjusted regression models identified several traditional and novel risk factors for AVC in patients with CKD. There was a difference in AVC risk factors between black and nonblack patients. In conclusion, our study shows that eGFR is associated in a dose-dependent manner with AVC in patients with CKD, and this association is independent of traditional cardiovascular risk factors. Copyright © 2015 Elsevier Inc. All rights reserved.

Peptide inhibitor of CXCL4-CCL5 heterodimer formation, MKEY, inhibits experimental aortic aneurysm initiation and progression.

PubMed

Iida, Yasunori; Xu, Baohui; Xuan, Haojun; Glover, Keith J; Tanaka, Hiroki; Hu, Xiaolei; Fujimura, Naoki; Wang, Wei; Schultz, Joshua R; Turner, Court R; Dalman, Ronald L

2013-04-01

Macrophages are critical contributors to abdominal aortic aneurysm (AAA) disease. We examined the ability of MKEY, a peptide inhibitor of CXCL4-CCL5 interaction, to influence AAA progression in murine models. AAAs were created in 10-week-old male C57BL/6J mice by transient infrarenal aortic porcine pancreatic elastase infusion. Mice were treated with MKEY via intravenous injection either (1) before porcine pancreatic elastase infusion or (2) after aneurysm initiation. Immunostaining demonstrated CCL5 and CCR5 expression on aneurysmal aortae and mural monocytes/macrophages, respectively. MKEY treatment partially inhibited migration of adaptively transferred leukocytes into aneurysmal aortae in recipient mice. Although all vehicle-pretreated mice developed AAAs, aneurysms formed in only 60% (3/5) and 14% (1/7) of mice pretreated with MKEY at 10 and 20 mg/kg, respectively. MKEY pretreatment reduced aortic diameter enlargement, preserved medial elastin fibers and smooth muscle cells, and attenuated mural macrophage infiltration, angiogenesis, and aortic metalloproteinase 2 and 9 expression after porcine pancreatic elastase infusion. MKEY initiated after porcine pancreatic elastase infusion also stabilized or reduced enlargement of existing AAAs. Finally, MKEY treatment was effective in limiting AAA formation after angiotensin II infusion in apolipoprotein E-deficient mice. MKEY suppresses AAA formation and progression in 2 complementary experimental models. Peptide inhibition of CXCL4-CCL5 interactions may represent a viable translational strategy to limit progression of human AAA disease.

Aortic Wall Inflammation Predicts Abdominal Aortic Aneurysm Expansion, Rupture, and Need for Surgical Repair

PubMed Central

2017-01-01

Background: Ultrasmall superparamagnetic particles of iron oxide (USPIO) detect cellular inflammation on magnetic resonance imaging (MRI). In patients with abdominal aortic aneurysm, we assessed whether USPIO-enhanced MRI can predict aneurysm growth rates and clinical outcomes. Methods In a prospective multicenter open-label cohort study, 342 patients with abdominal aortic aneurysm (diameter ≥40 mm) were classified by the presence of USPIO enhancement and were monitored with serial ultrasound and clinical follow-up for ≥2 years. The primary end point was the composite of aneurysm rupture or repair. Results Participants (85% male, 73.1±7.2 years) had a baseline aneurysm diameter of 49.6±7.7 mm, and USPIO enhancement was identified in 146 (42.7%) participants, absent in 191 (55.8%), and indeterminant in 5 (1.5%). During follow-up (1005±280 days), 17 (5.0%) abdominal aortic aneurysm ruptures, 126 (36.8%) abdominal aortic aneurysm repairs, and 48 (14.0%) deaths occurred. Compared with those without uptake, patients with USPIO enhancement have increased rates of aneurysm expansion (3.1±2.5 versus 2.5±2.4 mm/year, P=0.0424), although this was not independent of current smoking habit (P=0.1993). Patients with USPIO enhancement had higher rates of aneurysm rupture or repair (47.3% versus 35.6%; 95% confidence intervals, 1.1–22.2; P=0.0308). This finding was similar for each component of rupture (6.8% versus 3.7%, P=0.1857) or repair (41.8% versus 32.5%, P=0.0782). USPIO enhancement was associated with reduced event-free survival for aneurysm rupture or repair (P=0.0275), all-cause mortality (P=0.0635), and aneurysm-related mortality (P=0.0590). Baseline abdominal aortic aneurysm diameter (P<0.0001) and current smoking habit (P=0.0446) also predicted the primary outcome, and the addition of USPIO enhancement to the multivariate model did not improve event prediction (c-statistic, 0.7935–0.7936). Conclusions USPIO-enhanced MRI is a novel approach to the identification of aortic wall cellular inflammation in patients with abdominal aortic aneurysms and predicts the rate of aneurysm growth and clinical outcome. However, it does not provide independent prediction of aneurysm expansion or clinical outcomes in a model incorporating known clinical risk factors. Clinical Trial Registration: URL: http://www.isrctn.com. Unique identifier: ISRCTN76413758. PMID:28720724

Computational assessment of model-based wave separation using a database of virtual subjects.

PubMed

Hametner, Bernhard; Schneider, Magdalena; Parragh, Stephanie; Wassertheurer, Siegfried

2017-11-07

The quantification of arterial wave reflection is an important area of interest in arterial pulse wave analysis. It can be achieved by wave separation analysis (WSA) if both the aortic pressure waveform and the aortic flow waveform are known. For better applicability, several mathematical models have been established to estimate aortic flow solely based on pressure waveforms. The aim of this study is to investigate and verify the model-based wave separation of the ARCSolver method on virtual pulse wave measurements. The study is based on an open access virtual database generated via simulations. Seven cardiac and arterial parameters were varied within physiological healthy ranges, leading to a total of 3325 virtual healthy subjects. For assessing the model-based ARCSolver method computationally, this method was used to perform WSA based on the aortic root pressure waveforms of the virtual patients. Asa reference, the values of WSA using both the pressure and flow waveforms provided by the virtual database were taken. The investigated parameters showed a good overall agreement between the model-based method and the reference. Mean differences and standard deviations were -0.05±0.02AU for characteristic impedance, -3.93±1.79mmHg for forward pressure amplitude, 1.37±1.56mmHg for backward pressure amplitude and 12.42±4.88% for reflection magnitude. The results indicate that the mathematical blood flow model of the ARCSolver method is a feasible surrogate for a measured flow waveform and provides a reasonable way to assess arterial wave reflection non-invasively in healthy subjects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Distant downstream steady-state flow studies of a mechanical heart valve: PIV study of secondary flow in a model aortic arch

NASA Astrophysics Data System (ADS)

Fix, Brandon R.; Popma, Christopher J.; Bulusu, Kartik V.; Plesniak, Michael W.

2013-11-01

Each year, hundreds of thousands of aortic and mitral heart valves are replaced with prosthetic valves. In efforts to develop a valve that does not require lifelong anticoagulation therapy, previous experimental research has been devoted to analyzing the hemodynamics of various heart valve designs, limited to the flow up to only 2 diameters downstream of the valve. Two-component, two-dimensional (2C-2D) particle image velocimetry (PIV) was used in this study to examine secondary flow velocity fields in a curved tube modeling an aorta at five locations (0-, 45-, 90-, 135-, 180-degrees). A bileaflet valve, opened to 30-, 45-, and 59-degrees, and one (no-valve) baseline condition were examined under three steady flow inflows (Re = 218, 429, 634). In particular, variations in the two-dimensional turbulent shear stresses at each cross sectional plane were analyzed. The results suggest that bileaflet valves in the aortic model produce significant turbulence and vorticity up to 5.5 downstream diameters, i.e. up to the 90-degrees location. Expanding this research towards aortic heart valve hemodynamics highlights a need for additional studies extending beyond the typical few diameters downstream to fully characterize valvular function. Supported by the NSF Grant No. CBET- 0828903 and GW Center for Biomimetics and Bioinspired Engineering.

Incremental balloon deflation following complete resuscitative endovascular balloon occlusion of the aorta results in steep inflection of flow and rapid reperfusion in a large animal model of hemorrhagic shock.

PubMed

Davidson, Anders J; Russo, Rachel M; Ferencz, Sarah-Ashley E; Cannon, Jeremy W; Rasmussen, Todd E; Neff, Lucas P; Johnson, M Austin; Williams, Timothy K

2017-07-01

To avoid potential cardiovascular collapse after resuscitative endovascular balloon occlusion of the aorta (REBOA), current guidelines recommend methodically deflating the balloon for 5 minutes to gradually reperfuse distal tissue beds. However, anecdotal evidence suggests that this approach may still result in unpredictable aortic flow rates and hemodynamic instability. We sought to characterize aortic flow dynamics following REBOA as the balloon is deflated in accordance with current practice guidelines. Eight Yorkshire-cross swine were splenectomized, instrumented, and subjected to rapid 25% total blood volume hemorrhage. After 30 minutes of shock, animals received 60 minutes of Zone 1 REBOA with a low-profile REBOA catheter. During subsequent resuscitation with shed blood, the aortic occlusion balloon was gradually deflated in stepwise fashion at the rate of 0.5 mL every 30 seconds until completely deflated. Aortic flow rate and proximal mean arterial pressure (MAP) were measured continuously over the period of balloon deflation. Graded balloon deflation resulted in variable initial return of aortic flow (median, 78 seconds; interquartile range [IQR], 68-105 seconds). A rapid increase in aortic flow during a single-balloon deflation step was observed in all animals (median, 819 mL/min; IQR, 664-1241 mL/min) and corresponded with an immediate decrease in proximal MAP (median, 30 mm Hg; IQR, 14.5-37 mm Hg). Total balloon volume and time to return of flow demonstrated no correlation (r = 0.016). This study is the first to characterize aortic flow during balloon deflation following REBOA. A steep inflection point occurs during balloon deflation that results in an abrupt increase in aortic flow and a concomitant decrease in MAP. Furthermore, the onset of distal aortic flow was inconsistent across study animals and did not correlate with initial balloon volume or relative deflation volume. Future studies to define the factors that affect aortic flow during balloon deflation are needed to facilitate controlled reperfusion following REBOA.

Robot-assisted antegrade in-situ fenestrated stent grafting.

PubMed

Riga, Celia V; Bicknell, Colin D; Wallace, Daniel; Hamady, Mohamad; Cheshire, Nicholas

2009-05-01

To determine the technical feasibility of a novel approach of in-situ fenestration of aortic stent grafts by using a remotely controlled robotic steerable catheter system in the porcine model. A 65-kg pig underwent robot-assisted bilateral antegrade in-situ renal fenestration of an abdominal aortic stent graft with subsequent successful deployment of a bare metal stent into the right renal artery. A 16-mm iliac extension covered stent served as the porcine aortic endograft. Under fluoroscopic guidance, the graft was punctured with a 20-G customized diathermy needle that was introduced and kept in place by the robotic arm. The needle was exchanged for a 4 x 20 mm cutting balloon before successful deployment of the renal stent. Robot-assisted antegrade in-situ fenestration is technically feasible in a large mammalian model. The robotic system enables precise manipulation, stable positioning, and minimum instrumentation of the aorta and its branches while minimizing radiation exposure.

Three-dimensional printed prototypes refine the anatomy of post-modified Norwood-1 complex aortic arch obstruction and allow presurgical simulation of the repair.

PubMed

Kiraly, Laszlo; Tofeig, Magdi; Jha, Neerod Kumar; Talo, Haitham

2016-02-01

Three-dimensional (3D) printed prototypes of malformed hearts have been used for education, communication, presurgical planning and simulation. We present a case of a 5-month old infant with complex obstruction at the neoaortic to transverse arch and descending aortic junction following the neonatal modified Norwood-1 procedure for hypoplastic left heart syndrome. Digital 3D models were created from a routine 64-slice CT dataset; then life-size solid and magnified hollow models were printed with a 3D printer. The solid model provided further insights into details of the anatomy, whereas the surgical approach and steps of the operation were simulated on the hollow model. Intraoperative assessment confirmed the anatomical accuracy of the 3D models. The operation was performed in accordance with preoperative simulation: sliding autologous flaps achieved relief of the obstruction without additional patching. Knowledge gained from the models fundamentally contributed to successful outcome and improved patient safety. This case study presents an effective use of 3D models in exploring complex spatial relationship at the aortic arch and in simulation-based planning of the operative procedure. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Three-dimensional imaging of the aortic vessel wall using an elastin-specific magnetic resonance contrast agent.

PubMed

Makowski, Marcus R; Preissel, Anne; von Bary, Christian; Warley, Alice; Schachoff, Sylvia; Keithan, Alexandra; Cesati, Richard R; Onthank, David C; Schwaiger, Markus; Robinson, Simon P; Botnar, René M

2012-07-01

The aim of this study was to demonstrate the feasibility of high-resolution 3-dimensional aortic vessel wall imaging using a novel elastin-specific magnetic resonance contrast agent (ESMA) in a large animal model. The thoracic aortic vessel wall of 6 Landrace pigs was imaged using a novel ESMA and a nonspecific control agent. On day 1, imaging was performed before and after the administration of a nonspecific control agent, gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA; Bayer Schering AG, Berlin, Germany). On day 3, identical scans were repeated before and after the administration of a novel ESMA (Lantheus Medical Imaging, North Billerica, Massachusetts). Three-dimensional inversion recovery gradient echo delayed-enhancement imaging and magnetic resonance (MR) angiography of the thoracic aortic vessel wall were performed on a 1.5-T MR scanner (Achieva; Philips Medical Systems, the Netherlands). The signal-to-noise ratio and the contrast-to-noise ratio of arterial wall enhancement, including the time course of enhancement, were assessed for ESMA and Gd-DTPA. After the completion of imaging sessions, histology, electron microscopy, and inductively coupled plasma mass spectroscopy were performed to localize and quantify the gadolinium bound to the arterial vessel wall. Administration of ESMA resulted in a strong enhancement of the aortic vessel wall on delayed-enhancement imaging, whereas no significant enhancement could be measured with Gd-DTPA. Ninety to 100 minutes after the administration of ESMA, significantly higher signal-to-noise ratio and contrast-to-noise ratio could be measured compared with the administration of Gd-DTPA (45.7 ± 9.6 vs 13.2 ± 3.5, P < 0.05 and 41.9 ± 9.1 vs 5.2 ± 2.0, P < 0.05). A significant correlation (0.96; P < 0.01) between area measurements derived from ESMA scans and aortic MR angiography scans could be found. Electron microscopy and inductively coupled plasma mass spectroscopy confirmed the colocalization of ESMA with elastic fibers. We demonstrate the feasibility of aortic vessel wall imaging using a novel ESMA in a large animal model under conditions resembling a clinical setting. Such an approach could be useful for the fast 3-dimensional assessment of the arterial vessel wall in the context of atherosclerosis, aortic aneurysms, and hypertension.

Circulating Vascular Basement Membrane Fragments are Associated with the Diameter of the Abdominal Aorta and Their Expression Pattern is Altered in AAA Tissue.

PubMed

Holsti, Mari; Wanhainen, Anders; Lundin, Christina; Björck, Martin; Tegler, Gustaf; Svensson, Johan; Sund, Malin

2018-04-12

Abdominal aortic aneurysm (AAA) is characterised by enhanced proteolytic activity, and extracellular matrix (ECM) remodelling in the vascular wall. Type IV and XVIII collagen/endostatin are structural proteins in vascular basement membrane (VBM), a specialised ECM structure. Here the association between plasma levels of these collagens with the aortic diameter and expansion rate is studied, and their expression in aortic tissue characterised. This was a retrospective population based cohort study. Type IV and XVIII collagen/endostatin were analysed in plasma by ELISA assay in 615 men, divided into three groups based on the aortic diameter: 1) normal aorta ≤ 25 mm, 2) sub-aneurysmal aorta (SAA) 26-29 mm, and 3) AAA ≥ 30 mm. Follow up data were available for 159 men. The association between collagen levels and aortic diameter at baseline, and with the expansion rate at follow up were analysed in ordinal logistic regression and linear regression models, controlling for common confounding factors. Tissue expression of the collagens was analysed in normal aorta (n = 6) and AAA (n = 6) by immunofluorescence. Plasma levels of type XVIII collagen/endostatin (136 ng/mL [SD 29] in individuals with a normal aorta diameter, 154 ng/ml [SD 45] in SAA, and 162 ng/ml [SD 46] in AAA; p = .001) and type IV collagen (105 ng/mL [SD 42] normal aorta, 124 ng/ml [SD 46] SAA, and 127 ng/ml [SD 47] AAA; p = .037) were associated with a larger aortic diameter. A significant association was found between the baseline levels of type XVIII/endostatin and the aortic expansion rate (p = .035), but in the multivariable model, only the initial aortic diameter remained significantly associated with expansion (p = .005). Altered expression patterns of both collagens were observed in AAA tissue. Plasma levels of circulating type IV and XVIII collagen/endostatin increase with AAA diameter. The expression pattern of VBM proteins is altered in the aneurysm wall. Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.

Evaluation of stimulation parameters on aortomyoplasty, using Latissimus Dorsi muscle in a goat model: an acute study.

PubMed

Hakami, A; Santamore, W P; Stremel, R W; Tobin, G; Hjortdal, V E

1999-08-01

Dynamic aortomyoplasty using Latissimus Dorsi muscle (LDM) has been shown to improve myocardial function. However, systematic examination of the effects of stimulation parameters on aortic wrap function has not been done. Thus, the present study measures the direct effect of stimulation voltage, pulse train duration, frequency of the pulses, and the duration of the stimulation delay from R wave on the aortic wrap function. In eight female goats, the left LDM was wrapped around the descending aorta. The muscle was then subjected to electrical stimulation, altering frequency of stimulation pulses (16.6, 20, 25, 33 and 50 Hz), amplitude (2, 4, 6, 8 and 10 V), and number of pulses (2, 4, 6, 8 and 10 pulses) in a train stimulation. Left ventricular, aortic pressure, and pressure generated by LDM on aorta (wrap pressure) was measured. The changes in hemodynamic parameters mentioned above were calculated and compared for different stimulation parameters during unassisted and assisted cardiac cycles. Aortomyoplasty counterpulsation using LDM provided significant improvement in wrap pressure (78 mmHg +/- 2), aortic diastolic pressure, and changes in aortic diastolic pressure from 2 to 4 V (P < 0.05). Further increase in amplitude did not make any significant improvements of the above mentioned parameters. Significant augmentation of wrap pressure (82 mmHg +/- 2), aortic diastolic pressure (79 mmHg +/- 3) and changes in aortic diastolic pressure (12 mmHg +/- 1) occurred at 6 pulses (P < 0.05). Other changes in number of pulses did not show any significant improvements. Significant improvement of wrap pressure (80 mmHg +/- 2), aortic diastolic pressure (73 mmHg +/- 3) and changes in aortic diastolic pressure (12 mmHg +/- 1) was observed with a frequency of 33 Hz. To examine a wide range of delays from the onset of the QRS complex to LDM stimulation, stimulation was delivered randomly. The exact delay was determined from the ECG signal and superimposed LDM stimulation pulses. In this study we present a new measurement, wrap pressure. We also present that in aortomyoplasty using LDM, the most significant improvement in wrap pressure, aortic diastolic pressure and changes in aortic diastolic pressure occurs when the stimulation consists of an amplitude of 4 V, a frequency of 33 Hz and a train stimulation of 6 pulses.

Simulation for transthoracic echocardiography of aortic valve

PubMed Central

Nanda, Navin C.; Kapur, K. K.; Kapoor, Poonam Malhotra

2016-01-01

Simulation allows interactive transthoracic echocardiography (TTE) learning using a virtual three-dimensional model of the heart and may aid in the acquisition of the cognitive and technical skills needed to perform TTE. The ability to link probe manipulation, cardiac anatomy, and echocardiographic images using a simulator has been shown to be an effective model for training anesthesiology residents in transesophageal echocardiography. A proposed alternative to real-time reality patient-based learning is simulation-based training that allows anesthesiologists to learn complex concepts and procedures, especially for specific structures such as aortic valve. PMID:27397455