Long-term observation of polycaprolactone small-diameter vascular grafts with thickened outer layer and heparinized inner layer in rabbit carotid arteries.

In our previous study, the pristine bilayer small-diameterin situtissue engineered vascular grafts (pTEVGs) were electrospun from a heparinized polycaprolactone (PCL45k) as an inner layer and a non-heparinized PCL80k as an outer layer in the thickness of about 131 µm and 202 µm, respectively. However, the hydrophilic enhancement of inner layer stemmed from the heparinization accelerated the degradation of grafts leading to the early formation of arterial aneurysms in a period of 3 months, severely hindering the perennial observation of the neo-tissue regeneration, host cell infiltration and graft remodeling in those implanted pTEVGs. Herein to address this drawback, the thickness of the outer layers was increased with PCL80k to around 268 µm, while the inner layer remained unchangeable. The thickened TEVGs named as tTEVGs were evaluated in six rabbits via a carotid artery interpositional model for a period of 9 months. All the animals kept alive and the grafts remained patent until explantation except for one whose one side of arterial blood vessels was occluded after an aneurysm occurred at 6 months. Although a significant degradation was observed in the implanted grafts at 9 month, the occurrence of aneurysms was obviously delayed compared to pTEVGs. The tissue stainings indicated that the endothelial cell remodeling was substantially completed by 3 months, while the regeneration of elastin and collagen remained smaller and unevenly distributed in comparison to autologous vessels. Additionally, the proliferation of macrophages and smooth muscle cells reached the maximum by 3 months. These tTEVGs possessing a heparinized inner layer and a thickened outer layer exhibited good patency and significantly delayed onset time of aneurysms.

Developing and evaluating a chronic ischemic cardiomyopathy in swine model by rest and stress CMR.

A large animal model of chronic coronary artery disease (CAD) is crucial for the understanding the underlying pathophysiological processes of chronic CAD and consequences for cardiac structure and function. The goal of this study was to develop a chronic model of CAD in a swine model and to evaluate the changes of myocardial structure, myocardial motility, and myocardial viability during coronary stenosis. A total of 30 swine (including 24 experimental animals and 6 controls) were enrolled. The chronic ischemia model was constructed by using Ameroid constrictor in experimental group. The 24 experimental animals were further divided into 4 groups (6 animals in each group) and were sacrificed at 1, 2, 3 and 4 weeks after operation for pathological examination, respectively. Cardiac magnetic resonance (CMR) was performed preoperatively and weekly postoperatively until sacrificed both in experimental and control group. CMR cine images, rest/adenosine triphosphate (ATP) stress myocardial contrast perfusion and LGE were performed and analyzed. The rest wall thickening (WT) score was calculated from rest cine images. The MPRI (myocardial perfusion reserve index) and MPR (myocardial perfusion reserve) were calculated based on rest and stress perfusion images. Pathology staining including triphenyltetrazolium chloride, HE and picrosirus red staining were performed after swine were sacrificed and collagen volume fraction (CVF) was calculated. The time to formation of ischemic, hibernating, and infarcted myocardium was recorded. In experimental group, from 1w to 4w after surgery, the rest WT score decreased gradually from 35.2 ± 2.0%, 32.0 ± 2.9% to 30.5 ± 3.0% and finally 29.06 ± 1.78%, p < 0.001. Left ventricular ejection fraction was gradually impaired after modeling (58.9 ± 12.6%, 56.3 ± 10.1%, 55.3 ± 9.0%, 53.8 ± 9.9%, respectively). And the MPR and MPRI also decreased stepwise with extent of surgery time (MPRI dropped from 2.1 ± 0.4, 2.0 ± 0.2 to 1.8 ± 0.3 and finally 1.7 ± 0.1, p = 0.004; MPR dropped from 2.3 ± 0.4, 2.1 ± 0.2 to 1.9 ± 0.4 and finally 1.8 ± 0.1, p < 0.001). Stronger associations between MPR, MPRI and CVF were paralleled lower wall thickening scores in fibrosis-affected areas. The ischemic myocardium was first appeared in the first week after surgery (involving ten segments), hibernated myocardium was first appeared in the second week after surgery (involving seventeen segments). LGE was first appeared in eight swine in the third weeks after surgery (16 segments). At 4w after surgery, average 9.6 g scar tissue was found among 6 swine. At the same time, histological analysis established the presence of fibrosis and ongoing apoptosis in the infarcted area. In conclusion, our study provided valuable insights into the pathophysiological processes of chronic CAD and its consequences for cardiac structure and function in a large animal model through combining myocardial motion and stress perfusion.

Red blood cell membrane-functionalized Nanofibrous tubes for small-diameter vascular grafts.

The off-the-shelf small-diameter vascular grafts (SDVGs) have inferior clinical efficacy. Red blood cell membrane (Rm) has easy availability and multiple bioactive components (such as phospholipids, proteins, and glycoproteins), which can improve the clinic's availability and patency of SDVGs. Here we developed a facile approach to preparing an Rm-functionalized poly-ε-caprolactone/poly-d-lysine (Rm@PCL/PDL) tube by co-incubation and single-step rolling. The integrity, stability, and bioactivity of Rm on Rm@PCL/PDL were evaluated. The revascularization of Rm@PCL/PDL tubes was studied by implantation in the carotid artery of rabbits. Rm@PCL/PDL can be quickly prepared and showed excellent bioactivity with good hemocompatibility and great anti-inflammatory. Rm@PCL/PDL tubes as the substitute for the carotid artery of rabbits had good patency and quick remodeling within 21 days. Rm, as a "self" biomaterial with high biosafety, provides a new and facile approach to developing personalized or universal SDVGs for the clinic, which is of great significance in cardiovascular regenerative medicine and organ chip.

Fabrication of heparinized small diameter TPU/PCL bi-layered artificial blood vessels and in vivo assessment in a rabbit carotid artery replacement model.

Increasingly growing problems in vascular access for long-term hemodialysis lead to a considerable demand for synthetic small diameter vascular prostheses, which usually suffer from some drawbacks and are associated to high failure rates. Incorporating the concept of in situ tissue engineering (TE) into synthetic small diameter blood vessels, for example, thermoplastic poly(ether urethane) (TPU) ones, could provide an alternative approach for vascular access that profits from the advantages of excellent mechanical properties of synthetic polymer materials (early cannulation) and unique biointegration regeneration of autologous neovascular tissues (long-term fistulae). In this study, a kind of heparinized small diameter (d = 2.5 mm) TPU/poly(ε-caprolactone) (TPU/PCL-Hep) bi-layered blood vessels was electrospun with an inner layer of PCL and an outer layer of TPU. Afterward, the inner surface heparinization was conducted by coupling H2N-PEG-NH2 to the corroded PCL layer and then heparin to the attached H2N-PEG-NH2 via the EDCI/NHS chemistry. Herein a heparinized PCL inner layer could not only inhibit thrombosis, but also provide sufficient space for the neotissue regeneration via biodegradation with time. Meanwhile, a TPU outer layer could confer the vascular access the good mechanical properties, such as flexibility, viability and fitness of elasticity between the grafts and host blood vessels as evidenced by the adequate mechanical properties, such as compliance (4.43 ± 0.07%/ 100 mmHg), burst pressure (1447 ± 127 mmHg) and suture retention strength (1.26 ± 0.07 N) without blood seepage after implantation. Furthermore, a rabbit carotid aortic replacement model for 5 months was demonstrated 100% animal survival and 86% graft patency. Puncture assay also revealed the puncture resistance and self-sealing (hemostatic time < 2 min). Histological analysis highlighted neotissue regeneration, host cell infiltration and graft remodeling in terms of extracellular matrix turnover. Altogether, these results showed promising aspects of small diameter TPU/PCL-Hep bi-layered grafts for hemodialytic vascular access applications.

Dose Reduction of Dynamic Computed Tomography Myocardial Perfusion Imaging by Tube Voltage Change: Investigation in a Swine Model.

Background: It is unclear whether tube voltage influences the measurement of perfusion parameters. The present study sought to evaluate the influence of tube voltage change on myocardial blood flow (MBF) measurements in dynamic computed tomography myocardial perfusion imaging (CTP). Methods and Results: Seven swine [mean weight 55.8 kg ± 1.6 (standard deviation)] underwent rest and stress dynamic CTP with tube voltages of 100 and 70 kV. The image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), radiation dose and MBF value were compared. The 70 kV images had higher CT attenuation and higher image noise (27.9 ± 2.4 vs. 21.5 ± 1.9, P < 0.001) than the 100 kV images, resulting in a higher SNR (20.5 ± 1.6 vs. 15.6 ± 1.8, P < 0.001) and CNR (17.6 ± 1.5 vs. 12.4 ± 1.7, P < 0.001). Compared to the use of conventional 100 kV, 70 kV yielded an approximately 64.6% radiation dose reduction while generating comparable MBF values, both at rest (88.3 ± 14.9 ml/100 g/min vs. 85.6 ± 17.4 ml/100 g/min, P = 0.21) and stress (101.4 ± 21.5 ml/100 g/min vs. 99.6 ± 21.4 ml/100 g/min, P = 0.58) states. Conclusion: Dynamic CTP using 70 kV instead of 100 kV does not substantially influence the MBF value but significantly reduces the radiation dose. Additional research is required to investigate the clinical significance of this change.

18F-ASEM Imaging for Evaluating Atherosclerotic Plaques Linked to α7-Nicotinic Acetylcholine Receptor.

BACKGROUND: Atherosclerosis is a chronic vascular inflammatory procedure alongside with lipid efflux disorder and foam cell formation. α7-Nicotinic acetylcholine receptor (α7nAChR) is a gated-calcium transmembrane channel widely expressed in neuron and non-neuron cells, such as monocytes and macrophages, activated T cells, dendritic cells, and mast cells. 18F-ASEM is an inhibitor targeted to α7nAChR that had been successfully applied in nervous system diseases. Previous studies had highlighted that α7nAChR was related to the emergency of vulnerable atherosclerotic plaques with excess inflammation cells. Thus, 18F-ASEM could be a complementary diagnostic approach to atherosclerotic plaques. MATERIALS AND METHODS: The synthesis of ASEM precursor and 18F-labeling had been performed successfully. We had established the ApoE-/- mice atherosclerotic plaques model (fed with western diet) and New Zealand rabbits atherosclerotic models (balloon-sprained experiment and western diet). After damage of endothelial cells and primary plaque formation, 18F-ASEM imaging of atherosclerotic plaques linked to α7nAChR had been conducted. In vivo micro-PET/CT imaging of ApoE-/- mice and the control group was performed 1 h after injection of 18F-ASEM (100-150 µCi); PET/CT imaging for rabbits with atherosclerotic plaques and control ones was also performed. Meanwhile, we also conducted CT scan on the abdominal aorta of these rabbits. After that, the animals were sacrificed, and the carotid and abdominal aorta were separately taken out for circular sections. The paraffin-embedded specimens were sectioned with 5 µm thickness and stained with hematoxylin-eosin (H&E) and oil red. RESULTS: In vivo vessel binding of 18F-ASEM and α7nAChR expression in the model group with atherosclerosis plaques was significantly higher than that in the control group. PET/CT imaging successfully identified the atherosclerotic plaques in ApoE-/- mice and model rabbits, whereas no obvious signals were detected in normal mice or rabbits. Compared with 18F-FDG, 18F-ASEM had more significant effect on the early monitoring of inflammation in carotid atherosclerotic plaques of ApoE-/- mice and model rabbits. 18F-ASEM had relatively more palpable effect on the imaging of abdominal aorta with atherosclerosis in rabbits. H&E and oil red staining identified the formation of atherosclerotic plaques in model animals, which provided pathological basis for the evaluation of imaging effects. CONCLUSION: We first confirmed 18F-ASEM as radiotracer with good imaging properties for precise identification of atherosclerotic diseases.

Anticoagulant Hydrogel Tubes with Poly(ɛ-Caprolactone) Sheaths for Small-Diameter Vascular Grafts.

Small-diameter vascular grafts (inner diameter < 6 mm) are useful in treating cardiovascular diseases. The off-the-shelf small-diameter vascular grafts for clinical applications remain a great limitation owing to their thrombogenicity or intimal hyperplasia. Herein, bilayer anticoagulant hydrogel tubes with poly(ε-caprolactone) (PCL) sheaths are prepared by freeze-thawing and electrospinning, which contain nanofibrillated cellulose (NFC)/poly(vinyl alcohol) (PVA)-heparin/poly-L-lysine nanoparticles tube as an inner layer and PCL sheath as an outer layer. The structure, anticoagulant property, and biocompatibility of the inner layer are studied. The effects of thickness of the outer layer on perfusion performance and mechanical property of hydrogel tubes with PCL sheaths (PCL-NFC/PVA-NPs tubes) are investigated. The effect of compliance of PCL-NFC/PVA-NPs tubes on their blood flow is studied by numerical simulation. The tissue compatibility and the patency of PCL-NFC/PVA-NPs tubes are evaluated by implantation in subcutaneous tissue of rats and carotid artery of rabbits. PCL-NFC/PVA-NPs tubes have prominent anticoagulation, sufficient burst pressure and good compliance similar to native arteries. PCL-NFC/PVA-NPs tubes facilitate infiltration of host cells and achieve active proliferation of recruited cells, which will be a promising candidate for small-diameter vascular grafts.

A Soft, Conductive External Stent Inhibits Intimal Hyperplasia in Vein Grafts by Electroporation and Mechanical Restriction.

Intimal hyperplasia (IH) in vein grafts (VGs) is a major issue in coronary artery bypass grafting (CABG) surgery. Although external stents can attenuate IH of VGs to some extent, none of the existing external stents have shown satisfactory clinical outcomes. Here we develop a flexible, biodegradable, and conductive external metal-polymer conductor stent (MPCS) that can electroporate the vessel wall and produce a protein that prevents IH. We designed the plasmid DNA encoding the tissue inhibitor of metalloproteinases-3 (TIMP-3) and lyophilized it on the inner surface of the MPCS to deliver into the adventitia and the middle layer of VGs for gene therapy. Coupled with its continuous mechanical support to prevent dilation after implanting, the MPCS can inhibit the IH of VGs significantly in the rabbit model. This proof-of-concept demonstration may aid the development of other implantable bioelectronics for electroporation gene therapy.

Preliminary Outcome of a Novel Edge-to-Edge Closure Device to Manage Mitral Regurgitation in Dogs.

Background: Veterinary management of mitral valve regurgitation due to mxyomatous valve disease in dogs is limited to medical treatments, which only postpones the onset of congestive heart failure or alleviates clinical symptoms. Most surgical procedures to manage this condition in humans require cardiopulmonary bypass and have a high risk of complications. Animals: Eight dogs with naturally occurring mitral valve regurgitation. Methods: Prospective observational study. All dogs were treated with a novel edge-to-edge transcatheter device named ValveClamp. The total surgical procedural time and total catheterization time were recorded. Echocardiographic variables measured pre- and post-procedure were compared using Wilcoxin-signed rank test with a P < 0.05 considered significant. Data were expressed as median and interquartile range and absolute numbers and percentages. Results: The procedural success rate was 100% and all the dogs survived without complications. The median (interquartile range) total surgical procedural time was 86.5 (76-96.2) minutes and catheterization time was 23.5 (22-33.8) minutes. Echocardiography revealed a significant reduction in mitral regurgitation severity in all dogs following the procedure based on both a reduced mitral regurgitant maximum jet area (P = 0.012) and a reduced mitral regurgitant maximum jet area to left atrial area (P = 0.018). Conclusion: The ValveClamp device is effective at reducing the severity of mitral regurgitation in dogs with naturally occurring myxomatous valve disease.

Preparation of Small-Diameter Tissue-Engineered Vascular Grafts Electrospun from Heparin End-Capped PCL and Evaluation in a Rabbit Carotid Artery Replacement Model.

Aiming to construct small diameter (ID <6 mm) off-the-shelf tissue-engineered vascular grafts, the end-group heparinizd poly(ε-caprolactone) (PCL) is synthesized by a three-step process and then electrospun into an inner layer of double-layer vascular scaffolds (DLVSs) showing a hierarchical double distribution of nano- and microfibers. Afterward, PCL without the end-group heparinization is electrospun into an outer layer. A steady release of grafted heparin and the existence of a glycocalyx structure give the grafts anticoagulation activity and the conjugation of heparin also improves hydrophilicity and accelerates degradation of the scaffolds. The DLVSs are evaluated in six rabbits via a carotid artery interpositional model for a period of three months. All the grafts are patent until explantation, and meanwhile smooth endothelialization and fine revascularization are observed in the grafts. The composition of the outer layer of scaffolds exhibits a significant effect on the aneurysm dilation after implantation. Only one aneurysm dilation is detected at two months and no calcification is formed in the follow-up term. How to prevent aneurysms remains a challenging topic.

Structural, functional and histological features of a novel ischemic heart failure model.

There is still no satisfactory large-animal model of ischemic heart failure (IHF) with ideal survival rate and model time. The aim of this study is to explore a novel chronic IHF model in swine. 23 healthy Ba-Ma miniature pigs were included. Pigs in the experimental group underwent multiple strategic ligations on side branches of the left anterior descending (LAD) and circumflex coronary arteries. One week later, sequential intervention occlusion of the distal end of the LAD trunk was performed. In the experimental groups, LV end-diastolic (LVEDV) and end-systolic volume (LVESV) gradually increased starting at 4 weeks post operation. At 12 WPO, LVEDV increased from 45.0 ± 2.9 ml at baseline to 110.0 ± 9.8 ml and LVESV increased from 17.0 ± 1.4 ml at baseline to 42.0 ± 3.6 ml. Meanwhile, left ventricular ejection fraction significantly decreased from 73.8 ± 4.2 % at baseline to 31.0 ± 2.5%. According to histomorphometric assessment, viable cells were observed in infarction lesions, indicating the model has replicated the structural and functional features of chronic IHF.

Chronic median nerve modulation reduces ventricular arrhythmia and improves ventricular function in a postmyocardial infarction rabbit model.

AIM: Median nerve stimulation (MNS) is a novel neuromodulation approach for treatment of ventricular arrhythmia, but little is known about its chronic effects. The aim of this study was to investigate the effects of chronic MNS on ventricular arrhythmia and ventricular dysfunction postmyocardial infarction (MI). METHOD: Two weeks after MI, 12 rabbits were randomly divided into control and MNS groups, and chronic MNS was performed in MNS group for 2 weeks. Ventricular function and arrhythmias; sympathetic innervation and activity; and interleukin-1 ß (IL-1 ß) and norepinephrine (NE) levels were analyzed. RESULTS: Both the total number of premature ventricular complex and episodes of ventricular tachycardia were lower in MNS group than in control group (20 560 ± 10 314 beats vs 70 079 ± 37 184 beats, P = .021, and 115 ± 63 episodes vs 307 ± 164 episodes, P = .034, respectively). Compared with control group, MNS decreased the cardiac sympathetic nerve density and level of circulating NE in MNS group (1798.42 ± 644.07 µm2 /mm2 vs 1003.79 ± 453.00 µm2 /mm2, P = .041, and 20.86 ± 4.54 pg/mL vs 11.07 ± 1.43 pg/mL, P = .002, respectively). MNS also improved the left ventricular ejection fraction (59.07 ± 1.91% vs 49.77 ± 3.47%, P = .003) and inhibited the level of IL-1 ß in serum (69.19 ± 4.71 pg/mL vs 85.93 ± 12.80 pg/mL, P = .013). CONCLUSION: Chronic MNS appears to protect against ventricular arrhythmia and improves ventricular function post-MI, which may be mediated by suppressing cardiac sympathetic activity and anti-inflammatory effects.

Detection of Recent Myocardial Infarction Using Native T1 Mapping in a Swine Model: A Validation Study.

Late gadolinium enhancement (LGE) imaging is the currently the gold standard for in-vivo detection of myocardial infarction. However, gadolinium contrast administration is contraindicated in patients with renal insufficiency. We aim to evaluate the diagnostic sensitivity and specificity of this contrast-free MRI technique, native T1 mapping, in detecting recent myocardial infarction versus a reference histological gold standard. Ten pigs underwent CMR at 2 weeks after induced MI. The infarct size and transmural extent of MI was calculated using native T1 maps and LGE images. Histological validation was performed using triphenyl tetrazolium chloride (TTC) staining in the corresponding ex-vivo slices. The infarct size and transmural extent of myocardial infarction assessed by T1 mapping correlated well with that assessed by LGE and TTC images. Using TTC staining as the reference, T1 mapping demonstrated underestimation of infarct size and transmural extent of infarction. Additionally, there was a slight but not significant difference found in the diagnostic performance between the native T1 maps and LGE images for the location of MI. Our study shows that native T1 mapping is feasible alternative method to the LGE technique for the assessment of the size, transmural extent, and location of MI in patients who cannot receive gadolinium contrast.

Transapical implantation of a self-expandable aortic valve prosthesis utilizing a novel designed positioning element.

OBJECTIVES: To evaluate a new transapical system which utilizes a novel designed positioning element and a two-step positioning mechanism for easy and accurate implantation of transcatheter valves. BACKGROUND: Transcatheter aortic valve implantation is an important treatment option for non-surgical patients with severe aortic stenosis. However, accurate placement of the transcatheter valve remains challenging. METHODS: Self-expandable aortic valve prosthesis with a flexibly connected, annulus-like positioning element was implanted through a transapical approach in 12 pigs. The positioning element was separated and can be released independent of the valve prosthesis. During valve implantation, firstly, the positioning element was unsheathed and fixed into the aortic sinus. Then, the prosthetic valve was guided to an anatomically oriented position and deployed. Six animals were followed up to 180 days. RESULTS: With the help of the positioning element, all 12 valves were successfully deployed at the anticipated site. The valve release procedure took an average of 7.3 ± 2.5 min. The mean transvalvular pressure gradient was 2.8 ± 1.1 mm Hg at valve deployment. Of the six chronic animals, the mean transvalvular pressure gradient was 3.0 ± 1.0 mm Hg on day 7, and 2.9 ± 1.6 mm Hg on day 180 (P = 0.91). No migration, embolization, or coronary obstruction was observed during surgery and at necropsy. Pathological examination showed anatomically correct positioning of the prosthetic valve without signs of thrombosis or calcification. CONCLUSIONS: In this study, we confirmed the feasibility of the J-Valve transapical system for transapical implantation through a two-step process. Satisfactory hemodynamic and pathological performance during a follow-up of 180 days was demonstrated. © 2016 Wiley Periodicals, Inc.

Application of sodium alginate microspheres in ischemic stroke modeling in miniature pigs.

The miniature pig is an optimal animal model for studying nervous system disease because of its physiologic and pathologic features. However, the rete mirabile composed of arteries and veins at the skull base limits their application as a model of ischemic stroke by middle cerebral artery occlusion. The present study investigated the possibility of establishing an ischemic stroke model in the miniature pig by blocking the skull base retia with sodium alginate microspheres. Three Bama miniature pigs were used. Using the monitor of C-arm X-ray machine, sodium alginate microspheres (100-300 µm), a novel embolic material, were injected through the femoral artery, aortic arch, common carotid artery, ascending pharyngeal artery and the retia. Results were evaluated using carotid arteriography, MRI, behavior observation and histology. The unilateral rete mirabile was completely blocked, resulting in disturbance in blood supply to the basal ganglia, astasia of the right hind limb and salivation. MRI and hematoxylin-eosin staining showed an evident infarction focus in the basal ganglia. These findings indicate that sodium alginate microspheres are a suitable embolic material for blocking the skull base retia in miniature pigs to establish an ischemic stroke models.

[Establishment and evaluation of acute pulmonary thromboembolism model in minipig].

OBJECTIVE: To establish and evaluate an acute pulmonary embolism (APTE) model by selective thromboembolism of lower left pulmonary artery in minipig. METHODS: Through intervention technique, a guiding catheter was inserted via femoral vein into pulmonary artery. And quantitative autologous venous thrombus was injected into the selected lower left pulmonary arteries in 8 minipigs. Thus the intended APTE model was established by selective thromboembolism of lower left pulmonary artery. Hemodynamic parameters were monitored. And computed tomography (CT) and macroscopic dissection were performed to evaluate the minipig APTE model. RESULTS: The measurements of mean pulmonary artery pressure (MPAP, mm Hg, 1 mm Hg = 0.133 kPa) and pulmonary capillary wedge pressure (PCWP, mm Hg) immediately increased significantly after thromboembolism versus the baseline values (MPAP: 42.0 ± 3.4 vs 20.2 ± 3.0, PCWP: 8 ± 2 vs 4 ± 3, both P < 0.05) and stayed at a higher level during the following 2 h. No significant difference existed between the value of cardiac output (CO) at 2 h post-thromboembolism and its baseline counterpart. Moreover, systemic arterial pressure (SAP, mm Hg) and heart rate (HR, beats/min) significantly increased after embolism versus the baseline values (SAP: 102 ± 12 vs 80 ± 7, HR: 119 ± 22 vs 86 ± 14, P = 0.008). Pulmonary arteriography, CT scan and gross anatomy all demonstrated that the selected lower left pulmonary arteries was successfully embolized. CONCLUSION: The establishment of APTE model by selective thromboembolism of lower left pulmonary artery is feasible, well-controlled and stable in minipigs.

Effect of monochromatic light on melatonin secretion and arylalkylamine N-acetyltransferase mRNA expression in the retina and pineal gland of broilers.

The goal of this study is to investigate the effects of various monochromatic lights on plasma melatonin (MT) levels and the expression of arylalkylamine N-acetyltransferase (AANAT) mRNA in the pineal gland and retina. A total of 160 newly hatched (posthatching day 1, P1) broilers, including intact, sham-operated, and pinealectomized groups were exposed to blue light (BL), green light (GL), red light (RL), and white light (WL) by light emitting diode (LED) system for short term (24 hr) or long term (2 weeks), separately. For intact and sham-operated birds, the plasma MT level exhibited marked circadian rhythms at P7 and P14 regardless of short-term and long-term exposure to four monochromatic lights. However, WL and BL showed a faint suppression of MT secretion in contrast to GL and RL at either light or dark time points, with the following rank order: GL < RL < WL < BL. Larger circadian amplitude of MT levels was observed in GL group versus BL group (at P14: 87.70 pg/mL vs. 19.85 pg/mL, respectively). Pinealectomy disturbed the MT rhythm under different light colors, especially in RL. Additionally, consistent with the alteration of plasma MT levels, we observed increased AANAT mRNA expression and immunoreactive cell numbers of proliferating cell nuclear antigen (PCNA) and c-Fos in the pineal gland or retina in GL than that of BL, whereas 5-HT immunoreactive cell number was significantly decreased in GL. These data suggested that GL enhanced chick pinealocytes and retinal cells to express AANAT mRNA and to secrete MT, which may be depended on promoting c-Fos expression and cell proliferation.