Rabbit Aorta Research Articles

Contrast Ultrasound Imaging Does Not Affect Heat Shock Protein 70 Expression in Cholesterol-Fed Rabbit Aorta.

Diagnostic ultrasound imaging is enhanced by the use of circulating microbubble contrast agents (UCAs), but the interactions between ultrasound, UCAs, and vascular tissue are not fully understood. We hypothesized that ultrasound with a UCA would stress the vascular tissue and increase levels of heat shock protein 70 (Hsp70), a cellular stress protein. Male New Zealand White rabbits (n = 32) were fed a standard chow diet (n = 4) or a 1% cholesterol, 10% fat, and 0.11% magnesium diet (n = 28). At 21 days, 24 rabbits on the cholesterol diet were either exposed to ultrasound (3.2-MHz f/3 transducer; 2.1 MPa; mechanical index, 1.17; 10 Hz pulse repetition frequency; 1.6 microseconds pulse duration; 2 minutes exposure duration at 4 sites along the aorta) with the UCA Definity (1× concentration, 1 mL/min; Lantheus Medical Imaging, North Billerica, MA) or sham exposed with a saline vehicle injection (n = 12 per group). Four rabbits on the cholesterol diet and 4 on the chow diet served as cage controls and were not exposed to ultrasound or restrained for blood sample collection. Animals were euthanized 24 hours after exposure, and aortas were quickly isolated and frozen in liquid nitrogen. Aorta lysates from the area of ultrasound exposure were analyzed for Hsp70 level by Western blot. Blood plasma was analyzed for cholesterol, Hsp70, and von Willebrand factor, a marker of endothelial function. Plasma total cholesterol levels increased to an average of 705 mg/dL. Ultrasound did not affect plasma von Willebrand factor, plasma Hsp70, or aorta Hsp70. Restraint increased Hsp70 (P < .001, analysis of variance). Restraint, but not ultrasound with the UCA or cholesterol feeding, significantly increased Hsp70.

Validation of ethnopharmacological uses of Heliotropium strigosum Willd. as spasmolytic, bronchodilator and vasorelaxant remedy.

BackgroundHeliotropium strigosum is used in traditional medicine to manage gastrointestinal pain, respiratory distress and vascular disorders. The present study was undertaken to provide scientific evidences for these folkloric uses by in vitro experimental settings.MethodsA crude methanol extract of the Heliotropium strigosum (Hs.Cr) was tested in vitro on isolated rabbit jejunum preparations to detect the possible presence of spasmolytic activity. Moreover, isolated rabbit tracheal and aorta preparations were used to ascertain the relaxant effects of the extract.ResultsThe Hs.Cr exhibited relaxant effects in rabbit jejunum in a concentration dependent manner (0.01-3.0 mg/ml). The Hs.Cr also relaxed K+ (80 mM)-induced spastic contractions in rabbit jejunum and shifted the Ca2+ concentration response curves towards right. The extract relaxed carbachol (1 μM)- as well as K+ (80 mM)-induced contractions in rabbit trachea at concentrations ranging from 0.01 to 10 mg/ml. Moreover, Hs.Cr. also relaxed (0.01-3.0 mg/ml) the phenylephrine (1 μM)- and K+ (80 mM)-induced contractions in isolated rabbit aorta.ConclusionsThe Hs.Cr was found to exhibit spasmolytic, bronchodilator and vasorelaxant activities on isolated rabbit jejunum, trachea and aorta preparations, likely mediated through Ca2+ channel blockade. This finding may provide a scientific basis for the folkloric uses of the plant.

Abstract 210: Biosynthesis of D-series Resolvin by Isolated Vascular Cells and Tissues

Introduction: Resolvin-D1 (RvD1) and other specialized pro-resolving lipid mediators (SPM) are synthesized in-vivo from docosahexaenoic acid (DHA) through transcellular pathways involving leukocytes. We investigated if vascular tissues, in the absence of inflammatory cells, can contribute to the local production of SPM. Methods: Primary cultures of human saphenous vein endothelial (EC) and smooth muscle (SMC) cells were supplemented with DHA in cell culture media (10% serum) for 4h-24h. Freshly harvested rabbit aorta was incubated intact or following gentle EC denudation in medium with or without DHA for 48h. RvD1 levels were quantified by ELISA, and lipoxygenase (LO) expression by western blotting. Results: In the absence of DHA supplementation, EC and SMC produced undetectable levels of RvD1. DHA treatment produced a dose and time-dependent increase in RvD1 production by EC and SMC (10.1 ±1.0 pg, 7.4 ±0.2 pg respectively; 1000nM DHA; 24h; Fig A, B). 5-LO expression was demonstrated in both cell types, however DHA induced increased 5-LO expression in EC (Fig C) but not in SMC. DHA-treated intact rabbit aorta segments produced 0.24±0.05 pg RvD1/mg tissue versus 0.13±0.01 pg RvD1/mg tissue in media alone. Moreover, EC-denuded aortas produced significantly less RvD1 (Fig D). Conclusions: Human vascular cells and rabbit vascular tissue can biosynthesize RvD1 de novo from its precursor DHA, signifying a potentially important local source of SPM in the vasculature.

Abstract 132: CETP Deficiency in Rabbits Protects High Fat High Cholesterol Diet Induced Atherosclerosis

CETP has been suggested as an effective and promising target for further reducing cardiovascular events through elevation of the HDL-C levels. The failure of Pfizer’s torcetrapib and Roche’s dalcetrapib raised the question whether increased HDL from pharmacological inhibition of CETP are cardioprotective. Because mice lack CETP naturally, we generated CETP knockout (KO) rabbits by Zinc-finger nucleases (ZFN) to gain insights onto CETP and HDL biology in CVD. The ZFN pairs target on exon 3 of rabbit CETP gene. By microinjection of ZFN mRNA into rabbit embryos, we generated 5 CETP knockout (CETPko) founder rabbits. The founder used for this study contained 4 nucleotides deletion in exon 3 that results in a premature stop codon. Western blot confirms that there is no detectable CETP protein in the homozygous CETPko rabbit plasma and liver. No CETP activity was detected in the CETPko rabbit plasma, consistent with their genotype. At the normal chow fed conditions, there is no significant difference between wild type and CETPko male rabbits in plasma HDLc and total cholesterol (TC) level; whereas female CETPko rabbits show 40 to 100% increase in both HDLc and TC levels compared to wild type ones. By sequential ultracentrifugation method to separate plasma lipoproteins, we found that there is much higher HDL3 component in female CETPko rabbits, but not in male CETPko ones, comparing to their WT age matched control. At the HFHC (3% soy bean oil and 0.3% cholesterol) diet fed conditions, both male and female CETPko rabbits show significantly lower level of TC and LDLc compared to wild type rabbits. At the same time, the HDLc levels are significantly higher in the CETPko rabbits. In addition, apoB depleted plasma from CETPko rabbit showed 2-fold increase in cholesterol efflux tested in human THP1 cells. Furthermore, we measured the atherosclerotic plaque in the rabbit aorta after 16 weeks HFHC diet treatment. The total gross lesion areas in CETPko rabbits were only one-third of those in the wild type rabbits. In conclusion, our study shows that genetic deficiency of CETP in rabbits has beneficial effects on enhancing HDL function and reducing atherosclerosis. Our work sheds light on CETP and HDL biology, and provides valuable information to the development of CETP drugs.

Abstract 300: A Biodegradable Wrap for Peri-vascular Delivery of Pro-resolving Lipid Mediators

Introduction: Persistent inflammation following vascular injury leads to excessive scarring, limiting the success of vascular interventions. Recent work has identified that endogenous specialized proresolving lipid mediators (SPM) such as resolvin D1 (RvD1) actively orchestrate the process of resolution, exerting vasculo-protective effects without associated toxicity. We propose local vascular delivery of SPM through a biodegradable wrap. Methods: RvD1 (200 ng) was heat-sealed between thin layers of polycaprolactone (PCL) or poly-lactic-co-glycolic acid (PLGA). PLGA membranes differed in their composition of lactic versus glycolic acid (%-lactide). Directional drug release was measured via EIA in a cell-free system in vitro and into rabbit aortas exposed to pulsatile flow ex vivo. Bioactivity was confirmed on human vascular smooth muscle cells (VSMC) using migration and proliferation assays. Results: Of the constructs tested, a 3-layered PLGA wrap consisting of 85%/75%/50%-lactide provided the most favorable drug elution (Fig1a), with sustained release of &gt;800 pg/day for at least 14 days and nearly all elution occurring from the 50%-lactide side (Fig1b). Perivascular application of this wrap ex vivo with the 50%-lactide side facing “in” demonstrated uptake into rabbit aortic walls at 8 hours (0.4 ± 0.1 pg/mg). VSMC cultures exposed to drug-loaded wraps showed inhibition of migration (40%) and proliferation (25%). Conclusion: We demonstrate sustained and directional elution of therapeutically relevant amounts of biologically-active RvD1 through a biodegradable perivascular wrap, providing opportunity for translational studies of SPM in vascular injury.

Pharmacological justification of use of Solena heterophylla Lour. in gastrointestinal, respiratory and vascular disorders.

BackgroundSolena heterophylla Lour. has traditionally been used in the management of diseases pertaining to gastrointestinal, respiratory and vascular system and present study was undertaken to validate its traditional uses.MethodsThe aqueous ethanolic extract of Solena heterophylla Lour (Sh.Cr) was tested in-vitro on isolated rabbit jejunum, tracheal and aorta preparations. The responses of tissues were recorded using isotonic transducers coupled with PowerLab data acquisition system.ResultsThe aqueous ethanolic extract of Solena heterophylla Lour (Sh.Cr) (0.03-1.0 mg/ml) on application to spontaneous contractions in isolated rabbit jejunum preparation exerted relaxant effect through decrease in magnitude and frequency of contractions, caused relaxation of K+(80 mM)-induced contractions and shifted the Ca2+ concentration response curves toward right in isolated rabbit jejunum preparations in a manner similar to verapamil (a standard Ca2+ channel blocker), thus confirming its Ca2+ channel blocking activity. The Sh.Cr also caused relaxation of carbachol (1 μM)- and K+(80 mM)-induced contractions in isolated rabbit tracheal preparations in a manner comparable to dicyclomine.ConclusionsThe observed relaxant effect may be outcome of anti-muscarinic and Ca2+ channel blocking activities. The Sh.Cr (0.03-1.0 mg/ml) against phenyephrine (1 μM)- and K+(80 mM)-induced contractions in isolated rabbit aortic preparations exerted a relaxant effect, possibly through Ca2+ channel blocking activity. These findings provide a rationale for the folkloric uses of the plant in the management of ailments pertaining to gastrointestinal, respiratory and vascular system.

(100)-Textured KNN-based thick film with enhanced piezoelectric property for intravascular ultrasound imaging.

Using tape-casting technology, 35 μm free-standing (100)-textured Li doped KNN (KNLN) thick film was prepared by employing NaNbO3 (NN) as template. It exhibited similar piezoelectric behavior to lead containing materials: a longitudinal piezoelectric coefficient (d33) of ∼150 pm/V and an electromechanical coupling coefficient (kt ) of 0.44. Based on this thick film, a 52 MHz side-looking miniature transducer with a bandwidth of 61.5% at -6 dB was built for Intravascular ultrasound (IVUS) imaging. In comparison with 40 MHz PMN-PT single crystal transducer, the rabbit aorta image had better resolution and higher noise-to-signal ratio, indicating that lead-free (100)-textured KNLN thick film may be suitable for IVUS (>50 MHz) imaging.

Catheter-Based Intramural Delivery of Red Blood Cells in an Animal Model of Atherosclerosis

This report demonstrates intramural red blood cell (RBC) delivery in an atherosclerotic rabbit aorta model and validates the ability of fluoroscopy and computed tomography to verify RBC deposition. A microinfusion catheter with a 35-gauge needle delivered RBCs mixed with iodinated contrast agent to the aorta wall. Six rabbits were sacrificed after injection to confirm RBC delivery. Iron deposition was examined in four additional rabbits 3–7 weeks after injection. Imaging demonstrated 86% sensitivity and 100% specificity for the detection of RBC deposition (n = 25 injection attempts). Iron deposits were found in all intraplaque injection sites 3–7 weeks after injection.

Effect of cystatin C on adventitia in restenosis after rabbit aorta angioplasty

Objective To investigate the effect of cystatin C (Cys C) on adventitia in rabbit abdominal aorta restenosis after angioplasty and its mechanism. Methods 48 New Zealand white rabbits were randomly divided into injury group (receiving balloon dilation of abdominal aorta), the treatment group (taking Cys C monoclonal antibody therapy) and the control group (receiving femoral artery puncture and catheter sheath without balloon dilation and intervention of Cys C monoclonal antibody injection), and each group had 16 rabbits.Peripheral vein blood was drawn to measure the serum level of cystatin C before and 8 h, 1 day, 1 week, 3 weeks, 6 weeks after the operation in all rabbits.After 6 weeks of operation, the abdominal aorta were taken and stained with HE.Vascular morphometry analysis and adventitial cell count were conducted.Smooth muscle actin (SM-actin) and proliferating cell nuclear antigen (PCNA) expressions in the adventitia were observed by immunohistochemical staining.The number of PCNA positive cell in the adventitia was counted and the PCNA proliferation index was calculated.The vascular remodeling index, vascular external elastic lamina area (EELA), internal elastic lamina area (IEIA) were used to evaluate the vascular remodeling and the residual stenosis and vascular cavity area was used to measure the vascular stenosis. Results Plasma Cys C level began to rise at 8h after operation and reached the peak at 1 week after operation, and continuously increased for 5 weeks in injury group, and reached to respectively at 3 weeks and 6 weeks after operation.The Cys C levels were significantly higher in injury group than in the treatment and control groups at different time points (all P<0.05). There were no significant differences in Cys C levels at different time points between the treatment group and the control group.The injury group showed that the number of PCNA positive cells was higher in injury group than in treatment and control groups, both P<0.05). Compared with the control group, the vascular luminal area, EELA and IELA were significantly increased (all P<0.05). After treated with the monoclonal antibody Cys C intervention, the treatment group showed that lumen area, vascular EELA, IELA was significantly decreased (P<0.05), and the vascular remodeling index and residual stenosis rate were decreased as compared with the injury group (0.871 vs.0.784, 33.1% vs.19.7%, both P<0.05). Correlation analysis showed that Cystatin C level was positively correlated with the vascular lumen area, neointimal area, internal elastic lamina area, external elastic lamina area and the number of PCNA positive cells (r=0.812, 0.797, 0.876, 0.932 and 0.822 respectively, all P<0.01). Conclusions Plasma Cys C level is increased in rabbit after abdominal aorta balloon injury and has a positive correlation with the severity of arterial stenosis.High Cys C level can induce adventitial fibroblast activation, proliferation, phenotype transformation and migration, and accelerate the processes of atherosclerosis and stenosis.Cys C level is the independent risk factor for abdominal aortic stenosis. Key words: Cyalones; Aorta, abdominal; Angioplasty

Dual-element needle transducer for intravascular ultrasound imaging.

A dual-element needle transducer for intravascular ultrasound imaging has been developed. A low-frequency element and a high-frequency element were integrated into one device to obtain images which conveyed both low- and high-frequency information from a single scan. The low-frequency element with a center frequency of 48MHz was fabricated from the single crystal form of lead magnesium niobate-lead titanate solid solution with two matching layers (MLs) and the high frequency element with a center frequency of 152MHz was fabricated from lithium niobate with one ML. The measured axial and lateral resolutions were 27 and [Formula: see text], respectively, for the low-frequency element, and 14 and [Formula: see text], respectively, for the high-frequency element. The performance of the dual-element needle transducer was validated by imaging a tissue-mimicking phantom with lesion-mimicking area, and ex vivo rabbit aortas in water and rabbit whole blood. The results suggest that a low-frequency element effectively provides depth resolved images of the whole vessel and its adjacent tissue, and a high-frequency element visualizes detailed structure near the surface of the lumen wall in the presence of blood within the lumen. The advantages of a dual-element approach for intravascular imaging are also discussed.

Ranolazine enhances nicardipine-induced relaxation of alpha1-adrenoceptor-mediated contraction on isolated rabbit aorta

Ranolazine (RAN) and nicardipine (NIC) have been studied for their vasorelaxing eff ects but the combination of these agents against adrenergic vasoconstriction has not been tested. The present study aimed at investigating the vasorelaxing eff ect by the combination of the two agents on alpha1-adrenoceptor-mediated contraction on isolated rabbit aorta. Aortic rings were mounted for isometric tension recording in organ baths containingKrebs-Henseleit solution. Concentration-response curves of RAN (10–9 to 10–4 M), NIC (10–9 to 10–5 M), and RAN + NIC (3 × 10–6 M) were obtained in a cumulative manner using phenylephrine (PE, 2 × 10–6 M) as constrictor agent. The eff ective concentration (EC)50 values for RAN and NIC were 6.5 × 10–6 M and 1.4 × 10–5 M, respectively. The treatment of PE-precontracted aortic rings with either RAN or NIC up to 65 min revealed that both agents displayed a biphasic pattern of initial rising and late sustained phases of relaxation. At 35 min of incubation, RAN and NIC induced relaxation by 23 ) 3% and 14 ) 4%, respectively (N = 7, P= NS, RAN vs NIC); their combination resulted in a 34 ) 4% relaxation (N = 7; P< 0.01, RAN + NIC vs NIC). At 65 min the eff ect of NIC prevailed and tended to be closer to the values of the combination treatment (P < 0.01, RAN + NIC vs RAN). The results indicate that RAN at therapeutic concentrations exerts a signifi cant additive vasorelaxing eff ect when combined with NIC in rabbit aorta.

The Effect of the Rho–kinase Inhibitor (Y‐27632) on the Relaxation of Thromboxane A2 mimetic (U‐46619) Induced Contraction in the Presence and Absence of the Endothelium

Previous work from this laboratory has shown that contraction of aortic vessels treated with the thromboxane mimetic (U‐46619) persists for a much longer time compared to contractions evoked by other agonists. The slow relaxation in response to the TxA2 mimetic is dependent on activation of Rho kinase since an inhibitor of Rho kinase (Y‐27632) evokes a faster relaxation. The current experiments are designed to determine if production of nitric oxide (NO) contributes to the relaxation of blood vessels treated with the Rho kinase inhibitor. In order to eliminate production of NO, vessels were either denuded with forceps to remove the endothelium or treated with L‐NAME (specific inhibitor of NO). Isolated segments (n=75) of aorta from white New Zealand rabbits (n=21) were divided into two groups; in the first group the endothelium was denuded using forceps while in the second group the NO synthesis was inhibited by using L‐NAME (100µM). Acetylcholine relaxation was significantly different between rings with endothelium and rings without endothelium (P&lt;0.001). Isolated segments of rabbit aorta were treated with U4 (0.5 µM) followed by addition of the Y2 (1.0 µM). Following treatment with Y2, there was no significant difference between the E+ and E‐ vessels both in forceps denuded vessels (P=0.57) and L‐NAME treated vessels (P=0.68). We therefore concluded that, even though Y2 significantly reduced the sustained contraction induced by U4, it does not require the release of nitric oxide from the endothelium for its action.

Pharmacological basis for the folkloric uses of &lt;i&gt;Buxus wallichiana&lt;/i&gt; in gastrointestinal, respiratory and vascular disorders

&lt;p&gt;&lt;em&gt;In vitro&lt;/em&gt; study was carried out to explore the pharmacological basis of crude extract of &lt;em&gt;Buxus wallichiana &lt;/em&gt;for its folkloric uses in gastrointestinal, respiratory and vascular disorders. In jejunum preparations, crude extract (0.03 ± 1.0 mg/mL) caused a transient spasmogenic effect followed by the spasmolytic effect at higher doses (3.0–10 mg/mL). In atropinized jejunum preparation, crude extract inhibited the spontaneous and K&lt;sup&gt;+ &lt;/sup&gt;(80 mM)-induced contraction, suggesting that spasmolytic effect is mediated through the Ca&lt;sup&gt;+2&lt;/sup&gt;-channel blockade. The Ca&lt;sup&gt;+2&lt;/sup&gt;-channel blockade effect was confirmed when pretreatment of tissue with extract produced a dose-dependent shift in Ca&lt;sup&gt;+2 &lt;/sup&gt;concentration-response curves to the right, similarly as verapamil. Furthermore, crude extract exhibited non-specific relaxant effect on carbachol- (1 µM) and K&lt;sup&gt;+ &lt;/sup&gt;(80 mM)-induced tracheal contractions, suggesting the coexistence of anticholi-nergic and Ca&lt;sup&gt;+2&lt;/sup&gt;-antagonistic properties. Moreover, it relaxed the K&lt;sup&gt;+ &lt;/sup&gt;(80 mM)- and phenylephrine (1 µM)-induced contraction in rabbit aorta, suggesting the Ca&lt;sup&gt;+2&lt;/sup&gt;-channel blockade. These findings may validate the folkloric uses of &lt;em&gt;B. wallichiana&lt;/em&gt; in constipation, bronchitis, asthma and hypertension.&lt;/p&gt;

Scientific basis for use of Pyrus pashia Buch.-Ham. ex D. Don. fruit in gastrointestinal, respiratory and cardiovascular ailments.

Background Pyrus pashia Buch.-Ham. ex D. Don. has been used conventionally by many communities in the Himalayan region for the management of gastrointestinal, respiratory, and vascular complications. Set against this background, this study was carried out to justify the scientific basis to validate folkloric uses of fruits of Pyrus pashia Buch.-Ham. ex D. Don. (Pp.Cr) in traditional systems of medicine.MethodsThe crude ethanol extract of fruits of Pyrus pashia Buch.-Ham. ex D. Don. (Pp.Cr) was tested in vitro on isolated rabbit jejunum, tracheal, and aorta preparations. The responses of tissues were recorded using isotonic transducers coupled with a PowerLab data acquisition system.ResultsThe Pp.Cr on application (0.01–5.0 mg/ml) to isolated rabbit jejunum preparation exhibited relaxation through decrease in magnitude and frequency of spontaneous contractions. The Pp.Cr also exerted a relaxant (0.01–5.0 mg/ml) effect on K+(80 mM) induced contractions in isolated rabbit jejunum preparations and caused shifting of the Ca2+ curves (1.0–3.0 mg/ml) toward right in a manner similar to that of verapamil (3μM), possibly suggesting presence of Ca2+ channel blocking activity. Subsequently, Pp.Cr in a concentration-dependent fashion (0.01–10.0 mg/ml) caused relaxation of CCh (1μM) and K+ (80 mM) induced contractions in isolated rabbit tracheal preparations in a manner comparable to that of dicyclomine, suggesting that the observed relaxant effect is likely to be mediated through antimuscarinic and/or Ca2+ channel blocking activities. Moreover, when evaluated against isolated rabbit aortic preparations, the Pp.Cr in concentrations up to 10 mg/ml exhibited a contractile response that was found to be abolished subsequent to pretreatment of isolated tissue preparation with cyproheptadine (1μM), phentolamine (1μM), and losartan (1μM), suggesting that Pp.Cr may have some α-adrenergic, muscarinic, serotonergic, and angiotensin II activities.ConclusionsThe aqueous ethanolic extract of Pyrus pashia (Pp.Cr) exhibited spasmolytic, bronchodilator, and vaso-constrictive activities possibly through different mechanisms. The spasmolytic and bronchodilator activities are likely to be mediated through blockade of Ca2+ channels, while vasoconstrictive activity may be due to presence of a α-adrenergic, muscarinic, serotonergic, and angiotensin II agonistic component.

Angled-focused 45 MHz PMN-PT single element transducer for intravascular ultrasound imaging

A transducer with an angled and focused aperture for intravascular ultrasound imaging has been developed. The acoustic stack for the angled-focused transducer was made of PMN-PT single crystal with one matching layer, one protective coating layer, and a highly damped backing layer. It was then press-focused to a desired focal length and inserted into a thin needle housing with an angled tip. A transducer with an angled and unfocused aperture was also made, following the same fabrication procedure, to compare the performance of the two transducers. The focused and unfocused transducers were tested to measure their center frequencies, bandwidths, and spatial resolutions. Lateral resolution of the angled-focused transducer (AFT) improved more than two times compared to that of the angled-unfocused transducer (AUT). A tissue-mimicking phantom in water and a rabbit aorta tissue sample in rabbit blood were scanned using AFT and AUT. Imaging with AFT offered improved contrast, over imaging with AUT, of the tissue-mimicking phantom and the rabbit aorta tissue sample by 23dB and 8dB, respectively. The results show that AFT has strong potential to provide morphological and pathological information of coronary arteries with high resolution and high contrast.

Intravascular magnetomotive optical coherence tomography of targeted early-stage atherosclerotic changes in ex vivo hyperlipidemic rabbit aortas.

We report the development of an intravascular magnetomotive optical coherence tomography (IV-MM-OCT) system used with targeted protein microspheres to detect early-stage atherosclerotic fatty streaks/plaques. Magnetic microspheres (MSs) were injected in vivo in rabbits, and after 30 minutes of in vivo circulation, excised ex vivo rabbit aorta samples specimens were then imaged ex vivo with our prototype IV-MM-OCT system. The alternating magnetic field gradient was provided by a unique pair of external custom-built electromagnetic coils that modulated the targeted magnetic MSs. The results showed a statistically significant MM-OCT signal from the aorta samples specimens injected with targeted MSs.

Cholesteryl ester transfer protein inhibition enhances endothelial repair and improves endothelial function in the rabbit.

High-density lipoproteins (HDLs) can potentially protect against atherosclerosis by multiple mechanisms, including enhancement of endothelial repair and improvement of endothelial function. This study asks if increasing HDL levels by inhibiting cholesteryl ester transfer protein activity with the anacetrapib analog, des-fluoro-anacetrapib, enhances endothelial repair and improves endothelial function in New Zealand White rabbits with balloon injury of the abdominal aorta. New Zealand White rabbits received chow or chow supplemented with 0.07% or 0.14% (wt/wt) des-fluoro-anacetrapib for 8 weeks. Endothelial denudation of the abdominal aorta was carried out after 2 weeks. The animals were euthanized 6 weeks postinjury. Treatment with 0.07% and 0.14% des-fluoro-anacetrapib reduced cholesteryl ester transfer protein activity by 81±4.9% and 92±12%, increased plasma apolipoprotein A-I levels by 1.4±0.1-fold and 1.5±0.1-fold, increased plasma HDL-cholesterol levels by 1.8±0.2-fold and 1.9±0.1-fold, reduced intimal hyperplasia by 37±11% and 51±10%, and inhibited vascular cell proliferation by 25±6.1% and 35±6.7%, respectively. Re-endothelialization of the injured aorta increased from 43±6.7% (control) to 69±6.6% and 76±7.7% in the 0.07% and 0.14% des-fluoro-anacetrapib-treated animals, respectively. Aortic ring relaxation and guanosine 3',5'-cyclic monophosphate production in response to acetylcholine were also improved. Incubation of HDLs from the des-fluoro-anacetrapib-treated animals with human coronary artery endothelial cells increased cell proliferation and migration relative to control. These effects were abolished by knockdown of scavenger receptor-B1 and PDZ domain-containing protein 1 and by pharmacological inhibition of phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt. Increasing HDL levels by inhibiting cholesteryl ester transfer protein reduces intimal thickening and regenerates functional endothelium in damaged New Zealand White rabbit aortas in an scavenger receptor-B1-dependent and phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt-dependent manner.

Selective Venous Vasodilator Properties of the Analgesic Metamizole - An Adverse Effect that may Exacerbate venous Pooling after Cardiac Surgery

Objectives: Metamizole is a mainstay of perioperative pain management after cardiac surgery. Metamizole and its metabolites were shown to relax rabbit aortas. Venous pooling may be fostered by vasodilation and lead to increased volume requirements. We investigated the effects of metamizole on preconstricted human vessels in an ex vivo system to assess potential contributions to venous pooling.

Dose-dependent neuroprotection of delta-opioid peptide [D-Ala2, D-Leu5] enkephalin on spinal cord ischemia-reperfusion injury by regional perfusion into the abdominal aorta in rabbits

In our prior study, we showed that delta-opioid peptide [D-Ala(2), D-Leu(5)] enkephalin (DADLE), by regional perfusion into the abdominal aorta, could protect the spinal cord against ischemia-reperfusion (I/R) injury caused by aortic occlusion. However, the relative dose-response effects of DADLE still remain unclear. This study investigated whether DADLE has a dose-dependent efficiency on spinal cord I/R injury. New Zealand White rabbits were randomly divided into one of six groups: normal saline (NS; n= 8), DADLE (D) groups D0.0005 (n= 8), D0.005 (n= 8), D0.05 (n= 8), and D0.5mg/kg (n= 8), and a sham group (n= 6). In the NS and DADLE groups, spinal cord ischemia was induced by infrarenal aortic occlusion for 30minutes. During the occlusion, the same volume of NS or DADLE at the indicated doses was infused continuously through a catheter to the distally clamped abdominal aorta. Heart rate, blood pressure, and core temperature were monitored continuously to evaluate the potential adverse effects of DADLE. Neurologic behavioral function was assessed with the Tarlov scale system at 1, 6, 24, 48, and 72hours after reperfusion. Neuronal injury evaluation in the ventral horn of the gray matter was evaluated by counting the normal motor neurons at 72hours after reperfusion. The therapeutic benefits increased at the doses of DADLE from 0.0005 to 0.05mg/kg and decreased at 0.5mg/kg, whereas the hemodynamic parameter was suppressed temporarily at the dose of 0.5mg/kg. These data revealed that regional administration of DADLE through the abdominal aorta provided dose-dependent protection on spinal cord I/R in rabbits.

Chemical Composition and Vasorelaxant and Antispasmodic Effects of Essential Oil from Rosa indica L. Petals.

Rosa indica L. belongs to the family Rosaceae and is locally known as gulaab. It has different traditional uses in cardiovascular and gastrointestinal disorders but there is no scientific data available in this regard. Therefore, the basic aim of this study was to explore the chemical composition and gastrointestinal and cardiovascular effects of the essential oil obtained from R. indica. The chemical composition of the essential oil was investigated using gas chromatography-mass spectrometry (GC-MS) technique. The cardiovascular and gastrointestinal effects were investigated using electrophysiological measurements. The GC-MS analysis of the essential oil showed various chemical components including acetic acid, mercaptohexyl ester, butanoic acid, 2-methyl-5-oxo-1-cyclopentene-1-yl ester, artemiseole, methyl santonilate, isosteviol, caryophyllene oxide, pentyl phenyl acetate, dihydromyrcene, 1,5-octadecadien, octadecanoic acid, ethyl ester, palmitic acid (2-phenyl-1,3-dioxolan-4-yl methyl ester), santolina epoxide, and 9-farnesene. The electrophysiological measurements revealed that essential oil was more potent against K+ (80 mM) than phenylephrine precontractions using isolated rabbit aorta preparations. In isolated rabbit jejunum preparations, it showed more potency against high K+ induced contractions than spontaneous contractions. Considering these evidences, it can be concluded that R. indica essential oil may work as a complementary and alternative medicine in gastrointestinal and cardiovascular diseases.