Decrease In Lumen Area Research Articles

An agent-based model of cardiac allograft vasculopathy: toward a better understanding of chronic rejection dynamics.

Cardiac allograft vasculopathy (CAV) is a coronary artery disease affecting 50% of heart transplant (HTx) recipients, and it is the major cause of graft loss. CAV is driven by the interplay of immunological and non-immunological factors, setting off a cascade of events promoting endothelial damage and vascular dysfunction. The etiology and evolution of tissue pathology are largely unknown, making disease management challenging. So far, in vivo models, mostly mouse-based, have been widely used to study CAV, but they are resource-consuming, pose many ethical issues, and allow limited investigation of time points and important biomechanical measurements. Recently, agent-based models (ABMs) proved to be valid computational tools for deciphering mechanobiological mechanisms driving vascular adaptation processes at the cell/tissue level, augmenting cost-effective in vivo lab-based experiments, at the same time guaranteeing richness in observation time points and low consumption of resources. We hypothesize that integrating ABMs with lab-based experiments can aid in vivo research by overcoming those limitations. Accordingly, this work proposes a bidimensional ABM of CAV in a mouse coronary artery cross-section, simulating the arterial wall response to two distinct stimuli: inflammation and hemodynamic disturbances, the latter considered in terms of low wall shear stress (WSS). These stimuli trigger i) inflammatory cell activation and ii) exacerbated vascular cell activities. Moreover, an extensive analysis was performed to investigate the ABM sensitivity to the driving parameters and inputs and gain insights into the ABM working mechanisms. The ABM was able to effectively replicate a 4-week CAV initiation and progression, characterized by lumen area decrease due to progressive intimal thickening in regions exposed to high inflammation and low WSS. Moreover, the parameter and input sensitivity analysis highlighted that the inflammatory-related events rather than the WSS predominantly drive CAV, corroborating the inflammatory nature of the vasculopathy. The proof-of-concept model proposed herein demonstrated its potential in deepening the pathology knowledge and supporting the in vivo analysis of CAV.

Claudin-3 regulates luminal fluid accumulation in the developing chick lung

Claudins are a family of tight junction proteins expressed in epithelial tissues during development and in postnatal life. We hypothesized that claudins are required for branching morphogenesis in the developing chick lung. To test this hypothesis, we exposed cultured chick lung explants at embryonic day 5 to a truncated non-toxic form of the Clostridium perfringens enterotoxin known as C-CPE that removes C-CPE-sensitive claudins from tight junctions. Using in situ hybridization and immunofluorescence studies, we established that only one C-CPE-sensitive claudin, Claudin-3, was expressed in the chick lung at this stage. C-CPE treated lung explants did not exhibit any defect in lung branching compared to controls. However, they did exhibit a significantly smaller lumen area, suggesting that paracellular permeability was perturbed. The decrease in lumen area was associated with a loss of Claudin-3 expression within tight junctions of the respiratory epithelium and an increase in permeability of the respiratory epithelium. When C-CPE-treated lung explants were treated with forskolin, lumen area was restored. In summary, removal of a sealing claudin, Claudin-3, from tight junctions in embryonic lung epithelium results in a decrease in lumen area and in hydrostatic pressure needed for lung development.

Prediction of atherosclerotic disease progression combining computational modelling with machine learning.

Non-invasive serial computed tomography coronary angiography (CTCA) was acquired from 32 patients and 3D reconstruction of 58 coronary arteries was achieved. The arterial geometries were utilized for blood flow and LDL transport modelling. Navier-Stokes and convection-diffusion equations were employed for simulation of blood flow and LDL transport, respectively. Disease progression was assessed comparing the follow-up and baseline arterial models after co-registration using side branches as anatomical landmarks. A machine learning model for predicting disease progression was built using the Gradient Boosted Trees (GBT) algorithm. The Accuracy, Sensitivity, Specificity and AUC of the developed methodology for predicting lumen area decrease equal was 0.68, 0.56, 0.34 and 0.59, respectively. The best results were found for the prediction of plaque area increase by 20%, with 0.73, 0.67, 0.86, and 0.76 accuracy, sensitivity, specificity andAUC, respectively. This approach outperforms significantly the predictive capability of models based on binary logistic regression.

Peri-strut low intensity areas and in-scaffold neointima growth after bioresorbable scaffold implantation in STEMI. A serial optical coherence tomography study

BackgroundPeri-strut low intensity areas (PLIA) visualized by optical coherence tomography (OCT) have been related to neointimal proliferation and increased incidence of target lesion revascularization in stable coronary artery disease. The aim of this study was to determine the association between PLIA by OCT and the long-term vascular healing response after bioresorbable scaffold (BRS) implantation in the setting of ST-segment elevation myocardial infarction (STEMI). MethodsThis is a single-centre, longitudinal, cohort study with a serial: baseline, 1, 2 and 5 years OCT evaluation of neointimal response (lumen area and neoatherosclerosis) after percutaneous coronary intervention (PCI) with BRS Absorb™ 1.0 implantation in patients presenting with STEMI. PLIA was analyzed in every cross section and scored: 0–no PLIA; 1-PLIA < 1 quadrant; 2-PLIA ≥ 1 and <2 quadrants; 3-PLIA ≥ 2 and <3 quadrants; 4-PLIA in ≥3 quadrants. ResultsOf the 23 patients implanted BRS, 18 completed 2-year follow-up, whereas complete OCT data up to 5 years were available in 12 patients. Presence of PLIA was identified in 100% patients at 1 and 2 years, whereas at 5 years neither PLIA nor scaffold struts were visualized by OCT. Neoatherosclerosis was identified in 73,68% patients after 1 year and in all patients at 2 and 5 years. The mean PLIA score > 1 at 2 years was associated with greater percentage of minimum lumen area decrease after 2 years from index procedure. ConclusionsThe extent of PLIA by OCT at 2 years after primary PCI with BRS was associated with lumen area decrease. Neoatherosclerosis formation was detected in all patients at 2 and 5 years. PLIA assessment could serve as an additive means to predict neointimal healing pattern after next generation BRS implantation.

Utility of Multimodality Intravascular Imaging and the Local Hemodynamic Forces to Predict Atherosclerotic Disease Progression

ObjectivesThis study sought to examine the utility of multimodality intravascular imaging and of the endothelial shear stress (ESS) distribution to predict atherosclerotic evolution. BackgroundThere is robust evidence that intravascular ultrasound (IVUS)-derived plaque characteristics and ESS distribution can predict, with however limited accuracy, atherosclerotic evolution; nevertheless, it is yet unclear whether multimodality imaging and ESS mapping enable more accurate prediction of coronary plaque progression. MethodsA total of 44 patients admitted with a myocardial infarction that had successful revascularization and 3-vessel IVUS and optical coherence tomography (OCT) imaging at baseline and 13-month follow-up were included in the study. The IVUS data acquired at baseline in the nonculprit vessels were fused with x-ray angiography to reconstruct coronary anatomy and in the obtained models blood flow simulation was performed and the ESS was estimated. The baseline plaque characteristics and ESS distribution were used to identify predictors of disease progression: defined as a lumen reduction and an increase in plaque burden at follow-up. ResultsSeventy-three vessels were included in the final analysis. Baseline ESS and the IVUS-derived but not the OCT-derived plaque characteristics were independently associated with a decrease in lumen area and an increase in plaque burden. Low ESS (odds ratio: 0.45; 95% confidence interval: 0.28 to 0.71; p < 0.001) and plaque burden (odds ratio: 0.73; 95% confidence interval: 0.54 to 0.97; p = 0.030) were the only independent predictors of disease progression at follow-up. The accuracy of the IVUS-derived plaque characteristics in predicting disease progression did not improve when ESS (AUC: 0.824 vs. 0.847; p = 0.127) or when OCT variables and ESS (AUC: 0.842; p = 0.611) were added into the model. ConclusionsESS and OCT-derived variables did not improve the efficacy of IVUS in predicting disease progression. Further research is required to investigate whether multimodality imaging combined with ESS mapping will allow more reliable vulnerable plaque detection. (Comparison of Biomatrix Versus Gazelle in ST-Elevation Myocardial Infarction [STEMI] [COMFORTABLE]; NCT00962416)

Drought-induced oak decline in the western Mediterranean region: an overview on current evidences, mechanisms and management options to improve forest resilience

Abstract: Increased forest vulnerability is being reflected as more widespread and severe drought-induced decline episodes. In particular, the Mediterranean area is revealing a high susceptibility to phenomena of loss in tree vitality across species. Within tree species, oaks (Quercus spp.) are experiencing extensive decline in many countries. However, in the wake of the so-called “oak decline phenomenon”, the attention on these species has generally been limited. In this paper, we review the current available literature on oak-decline cases reported within the Mediterranean Basin, with particular remark for those occurred in Italy and Spain. More specifically our main aims were to: (i) provide an update on the patterns and mechanisms of decline by focusing on tree-ring and wood-anatomical variables; (ii) provide some hints for improving the resistance and resilience of oak stands experiencing decline. Our review reveals that drought is reported as the main driver triggering oak decline within the Mediterranean Basin, although other causes (i.e., increasing temperature, pathogens attack or excessive stand density) could exacerbate decline. In most reported cases, drought induced a substantial reduction of growth and changes in some wood anatomical properties. Indeed, growth decline prior death is also indicated as an early-warning signal of impending death. In ring-porous oak species, declining trees were often characterized by a very low production of latewood and a decrease in lumen area of the widest earlywood vessels, suggesting a potential reduction of hydraulic conductivity. Moreover, hydraulic dysfunction is reported as the main cause of decline. Finally, regarding management actions that should be considered for improving the resilience of declining stands and preserve the species-specific stand composition, it could be useful to shorten the rotation period of coppice stands or promoting their gradual conversion towards high forests, and favoring more drought-resistant species should also be considered. In addition, regeneration prior to regeneration cuts should be improved by anticipating seed dispersal or by planting oak seedlings obtained from local germoplasm.

Serial 3-Vessel Optical Coherence Tomography and Intravascular Ultrasound Analysis of Changing Morphologies Associated With Lesion Progression in Patients With Stable Angina Pectoris.

Optical coherence tomographic (OCT) morphologies associated with lesion progression are not well studied. The aim of this study was to determine the morphological change for untreated lesion progression using both OCT and intravascular ultrasound (IVUS). We used baseline and 8-month follow-up 3-vessel OCT and IVUS to assess 127 nonculprit lesions (IVUS plaque burden ≥40%) in 45 patients with stable angina after target lesion treatment. Lesion progression was defined as an IVUS lumen area decrease >0.5 mm2. A layered pattern was identified as a superficial layer that had a different optical intensity and a clear demarcation from underlying plaque. Lesion progression was observed in 19% (24/127) lesions, and its pattern was characterized into 3 types: type I, new superficial layered pattern at follow-up that was not present at baseline (n=9); type II, a layered pattern at baseline whose layer thickness increased at follow-up (n=7); or type III, no layered pattern at baseline or follow-up (n=8). The increase of IVUS plaque+media area was largest in type I and least in type III (1.9 mm2 [1.6-2.1], 1.1 mm2 [0.9-1.4], and 0.3 mm2 [-0.2 to 0.8], respectively; P=0.002). Type III, but not types I or II, showed negative remodeling during follow-up (IVUS vessel area; from 14.3 mm2 [11.4-17.2] to 13.5 mm2 [10.4-16.7]; P=0.02). OCT lipidic plaque was associated with lesion progression (odds ratio, 13.6; 95% confidence interval, 3.7-50.6; P<0.001). Lesion progression was categorized to distinct OCT morphologies that were related to changes in plaque mass or vessel remodeling.

Prospective study on microangiopathy in type 2 diabetic foot ulcer

We investigated the significance of microangiopathy in the development of foot ulcer, which is still disputed. We assessed microangiopathy by histological analysis of the capillary ultrastructure using transmission electron microscopy and capillary density and arteriolar morphology in paraffin-embedded sections from the skin of type 2 diabetic patients: 30 neuroischaemic patients (Isc) revascularised with peripheral angioplasty and 30 neuropathic patients (Neu) with foot ulcer, compared with ten non-diabetic volunteers. In the diabetic patients, capillaries in the dermal papillary layer were fewer (-22.2%, 159 ± 43 vs 205 ± 52mm(2) in non-diabetic volunteers, p < 0.01). They also showed detrimental remodelling, with a 2.2-fold increase in capillary basement membrane thickness (3.44 ± 1.19 vs 1.53 ± 0.34μm in non-diabetic volunteers, p < 0.001) and a 57.7% decrease in lumen area (14.6 ± 11.1 vs 34.7 ± 27.5μm(2), p < 0.001). No differences were observed between the diabetic Isc or Neu patients. Isc were more prone to develop arteriolar occlusion than Neu (16.8 ± 6.9% vs 6.7 ± 3.7%, respectively, p < 0.001). No patient had been amputated at 30days and healing time was significantly longer in Isc (180 ± 120 vs 64 ± 50days in Neu, p < 0.001). Capillary microangiopathy is present in equal measure in neuroischaemic and neuropathic diabetic foot skin. The predominance of arteriolar occlusions with neuroischaemia indicated the existence of an additional 'small vessel disease' that did not affect an effective revascularisation and did not worsen the prognosis of major amputations but slowed the healing process of the neuroischaemic foot ulcer. ClinicalTrials.gov NCT02610036.

In vitro effect of multiple hydrogen peroxide gas plasma sterilizations on the rate of closure of ameroid constrictors.

To evaluate the effect of multiple hydrogen peroxide gas plasma (HPGP) sterilizations on the rate of closure of ameroid constrictors. Thirty-six 5.0-mm ameroid constrictors. Ameroid constrictors were randomly allocated to 6 groups. Each group underwent 1, 2, 3, 4, 5, or 6 HPGP sterilizations. Ameroid constrictors were then incubated for 35 days in canine plasma and digitally imaged at predetermined times during incubation. One individual, who was unaware of the group to which each ameroid constrictor was assigned, measured the lumen area of the constrictor on each digital image. Mean lumen area was compared among groups. No ameroid constrictors were completely closed after 35 days of incubation in canine plasma. Mean lumen area after incubation did not differ among constrictors that underwent 1, 2, and 3 sterilizations. Constrictors that underwent 4 sterilizations were closed significantly more than were those that underwent 1, 2, or 3 sterilizations. Mean lumen area after incubation did not differ significantly between constrictors that underwent 5 and 6 sterilizations, although the final lumen areas for those constrictors were significantly smaller than those for constrictors that underwent 1, 2, 3, and 4 sterilizations. Ameroid constrictors that underwent 5 and 6 HPGP sterilizations had a 9% to 12% decrease in lumen area, compared with that of constrictors that underwent ≤ 4 plasma sterilizations, and the use of such constrictors could increase the risk of portal hypertension and secondary acquired shunting or decrease the risk of persistent shunting.

EFFECT OF DELETION OF CARTILAGE OLIGOMERIC MATRIX PROTEIN (COMP) ON COLLAGEN METABOLISM IN MURINE BRACHIOCEPHALIC ARTERY ATHEROSCLEROTIC LESIONS

Cartilage oligomeric matrix protein (COMP) is commonly found in bone and cartilage, but has also been detected in the extracellular matrix of atherosclerotic plaques. COMP is thought to act as...

Prediction of Progression of Coronary Artery Disease and Clinical Outcomes Using Vascular Profiling of Endothelial Shear Stress and Arterial Plaque Characteristics

Background— Atherosclerotic plaques progress in a highly individual manner. The purposes of the Prediction of Progression of Coronary Artery Disease and Clinical Outcome Using Vascular Profiling of Shear Stress and Wall Morphology (PREDICTION) Study were to determine the role of local hemodynamic and vascular characteristics in coronary plaque progression and to relate plaque changes to clinical events. Methods and Results— Vascular profiling, using coronary angiography and intravascular ultrasound, was used to reconstruct each artery and calculate endothelial shear stress and plaque/remodeling characteristics in vivo. Three-vessel vascular profiling (2.7 arteries per patient) was performed at baseline in 506 patients with an acute coronary syndrome treated with a percutaneous coronary intervention and in a subset of 374 (74%) consecutive patients 6 to 10 months later to assess plaque natural history. Each reconstructed artery was divided into sequential 3-mm segments for serial analysis. One-year clinical follow-up was completed in 99.2%. Symptomatic clinical events were infrequent: only 1 (0.2%) cardiac death; 4 (0.8%) patients with new acute coronary syndrome in nonstented segments; and 15 (3.0%) patients hospitalized for stable angina. Increase in plaque area (primary end point) was predicted by baseline large plaque burden; decrease in lumen area (secondary end point) was independently predicted by baseline large plaque burden and low endothelial shear stress. Large plaque size and low endothelial shear stress independently predicted the exploratory end points of increased plaque burden and worsening of clinically relevant luminal obstructions treated with a percutaneous coronary intervention at follow-up. The combination of independent baseline predictors had a 41% positive and 92% negative predictive value to predict progression of an obstruction treated with a percutaneous coronary intervention. Conclusions— Large plaque burden and low local endothelial shear stress provide independent and additive prediction to identify plaques that develop progressive enlargement and lumen narrowing. Clinical Trial Registration— URL: http:www.//clinicaltrials.gov . Unique Identifier: NCT01316159.

Circulation: Clinical Summaries

<i>Circulation:</i> Clinical Summaries

Transfusion of autologous late-outgrowth endothelial cells reduces arterial neointima formation after injury

Late-outgrowth endothelial cells (OECs) exist in blood and other organs. We aimed to explore whether and how OECs participate in re-endothelialization and prevent vascular neointima formation after injury. Rabbit bone marrow OECs were cultured for 4 weeks to increase their numbers. Transfusion of autologous OECs (2 × 10⁶-1 × 10⁷/kg) soon after rabbit ear central artery injury reduced the increase in intima area and the decrease in lumen area observed at days 14 and 28. Transfusion of autologous OECs (1 × 10⁷/kg) ameliorated some early (days 2 and 7) inflammatory and angiogenic responses (local and systemic) to the injury. Red fluorescence was seen within 7 days after transfusion of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine-labelled acetylated low-density lipoprotein (Dil-acLDL)-incorporated OECs, and 1 h after perfusion of the isolated rabbit ear with Ringer-Locke solution containing Dil-acLDL-incorporated OECs, in the injured rabbit ear central artery. After transfusion of 5-bromo-2'-deoxyuridine (BrdU) incorporated autologous OECs, BrdU-positive cells appeared in the injured artery intima at day 3 and were present in the rescued artery endothelium at day 28. The OECs, ranging from 5%-15% of vascular smooth muscle cells (VSMCs), and the OEC-conditioned medium (5-15%) both inhibited VSMC proliferation and migration in vitro and regulated the arrangement of VSMCs. The VSMCs were helpful for OECs to form tubes in vitro. Circulating OECs participate in re-endothelialization directly and inhibit VSMC migration and proliferation by a paracrine pathway; transfusion of large numbers of autologous OECs soon after vascular injury may prevent neointima formation.

Fire-related features of wood anatomy in a sweet chestnut (Castanea sativa) coppice in southern Switzerland

Explorative wood anatomical analysis was conducted on a Castanea sativa stand in southern Switzerland, where a moderate-intensity surface fire burned in April 1997. Cross-sections were sampled at multiple heights from 20 scarred shoots, 20 apparently intact shoots, along with cores taken from 20 reference trees outside the fire area. Thin sections were prepared from uphill and downhill locations on the circumference for up to 5 years preceding and following the event year. The thin sections were visually observed in order to identify a response to the known fire event preserved in the wood anatomical structure. Anatomical features were observed at the uphill and downhill locations on both scarred and intact (unscarred) cross-sections, and they occurred in a subset of the observed samples. The features observed in both scarred and intact cross-sections were an apparent increase in vessel density and a decrease in lumen area of the second row of earlywood vessels, along with tyloses formation in the first row of earlywood vessels. Furthermore, the scarred region exhibited a zone of delayed cambial death following the fire, and the onset of woundwood was often initiated later in the season or the following year. Using the type of features and their location around the circumference, we inferred that the observed features may have formed in response to local heating of the cambium, and likely formed in response to canopy damage.

Vessel Shrinkage as a Sign of Atherosclerosis Progression in Type 2 Diabetes

OBJECTIVE—The aim of this study was to determine the natural history of vascular remodeling of atherosclerotic plaques in patients with type 2 diabetes and the predictors of vessel shrinkage.RESEARCH DESIGN AND METHODS—In this serial intracoronary ultrasound (IVUS) study, 237 coronary segments from 45 patients enrolled in the DIABETES I, II, and III trials were included. Quantitative volumetric IVUS analyses (motorized pullbacks at 0.5 mm/s) were performed in the same coronary segment after the index procedure and at the 9-month follow-up. Nontreated mild lesions (angiographic stenosis <25%) with ≥0.5 mm plaque thickening and length of ≥5 mm assessed by IVUS were included. Vessel shrinkage was defined as a Δexternal elastic membrane area/Δplaque area < 0. Statistical adjustment by multiple segments and multiple lesions per patient was performed.RESULTS—Vessel shrinkage was identified in 37.1% of segments and was associated with a significant decrease in lumen area at 9 months (vessel shrinkage, 10 ± 4 mm2 vs. non–vessel shrinkage, 11 ± 4 mm2; P = 0.04). Independent predictors of vessel shrinkage were insulin requirements (odds ratio 4.6 [95% CI 1.40–15.10]; P = 0.01), glycated hemoglobin (1.5 [1.05–2.10]; P = 0.02), apolipoprotein B (0.96 [0.94–0.98]; P < 0.001), hypertension (3.7 [1.40–10.30]; P = 0.009), number of diseased vessels (5.6 [2.50–12.50]; P < 0.001), and prior revascularization (17.5 [6.50–46.90]; P < 0.001).CONCLUSIONS—This serial IVUS study suggests that progression of coronary artery disease in patients with type 2 diabetes may be mainly attributed to vessel shrinkage. Besides, vessel shrinkage is influenced by insulin requirements and metabolic control and is associated with more advanced coronary atherosclerosis.

Wood anatomical changes in roots of European ash ( Fraxinus excelsior L.) after exposure

Global changes have distinct influence on fluvial processes in torrents causing erosion on slopes and riverbanks even in forested areas. Continuous as well as discontinuous erosion of riverbanks covered by trees frequently results in destabilisation and finally cause the trees affected to tip over. These uprooted trees may lead to a blockage of the river and, in the case of a collapse of the resulting dam, resulting in severe flooding or even debris-flow surges. Dating the time of root exposure along riverbanks allows the reconstruction of erosion dynamics. In the previous studies, roots of coniferous trees have shown anatomical changes (cell size reduction in earlywood) after exposure. This anatomical feature in the xylem of exposed roots has helped to determine the time of exposure at an annual resolution. In the current study, this methodology is now applied for the first time to European ash ( Fraxinus excelsior L.) to determine its specific reactions to root exposure. First results show different reactions in vessel and fibre dimensions. Fibres show a distinct decrease in lumen area due to exposure, whereas vessel lumen area displays more variability ranging from 50% size reduction to no changes. It is discussed that vessel size characteristics are also related to ecophysiological and climatic patterns.

Partial reversal of experimental pulmonary hypertension by phosphodiesterase-3/4 inhibition

Phosphodiesterase (PDE) inhibitors are currently under investigation for the therapy of pulmonary hypertension. The present study was designed to investigate chronic effects of oral pumafentrine, a mixed selective PDE-3/4 inhibitor, in monocrotaline (MCT)-induced pulmonary hypertension in rats. Treatment with pumafentrine (10 mg.kg(-1) daily) from week 4 to 6 after a single injection of MCT (60 mg.kg(-1)) partially reversed pulmonary hypertension and right heart hypertrophy in rats. In addition, small pulmonary arterial muscularisation, media hypertrophy and decrease in lumen area were largely reversed. Inhibition of smooth muscle proliferation under pumafentrine was demonstrated in vivo as was a pro-apoptotic effect of pumafentrine on vascular cells. Moreover, pumafentrine dose-dependently increased cyclic adenosine monophosphate levels and inhibited proliferation of cultured pulmonary arterial smooth muscle cells. In conclusion, oral pumafentrine partially reverses monocrotaline-induced pulmonary hypertension, lung vascular remodelling and right heart hypertrophy in rats.

Effects of Percutaneous Transluminal Angioplasty and Endovascular Brachytherapy on Vascular Remodeling of Human Femoropopliteal Artery: 2 Years Follow-up by Noninvasive Magnetic Resonance Imaging

We aimed to assess in vivo the long-term effects of percutaneous transluminal angioplasty (PTA) and endovascular brachytherapy (EVBT) on vessel wall by serial MRI. Twenty patients with symptomatic stenosis of the femoropopliteal artery were randomly assigned to PTA (n=10) or PTA+EVBT (n=10, 14Gy by gamma-source). High-resolution MRI was performed prior, at 24-hours, 3-months, and 24-months after intervention. MRI data were analyzed by an independent, blinded observer. The effects of both procedures on vessel wall at 24-hours and 3-months have been reported. Despite similar percent decrease in lumen area between 3- and 24-months in both groups (-8% for PTA and -11% for PTA+EVBT), at 24-months lumen area gain compared to baseline was +30% in PTA versus +82% in PTA+EVBT (p<0.05). Total vessel area, which was increased at 24-hours and 3-months, returned to pre-treatment value in both groups. We demonstrated non-invasively that restenosis and inward remodeling after PTA are delayed by EVBT. At 24-months, patients treated with brachytherapy have larger lumen than those treated with PTA alone. The decrease in luminal and total vessel area between 3- and 24-months after EVBT indicates that the restenotic and remodeling process is not abolished but delayed with this therapy.

A novel model of portal vein transplantation in mice using two‐cuff technique

Allogeneic portal vein (PV) grafts have been widely used for vascular reconstruction in the aggressive biliary-pancreatic surgery and partial liver transplantation. We developed a novel PV transplantation model aimed at studying the pathologic alteration of the grafts and further managements. The PV graft was implanted orthotopically into the recipient using two-cuff technique. A total of 80 PV transplants have been performed, and the overall survival rate for the recipients was 91.3% (73/80). Mice were randomly separated into isografts group, allografts group, and allografts group treated with CTLA4-Ig. PV grafts were harvested on the 1st, 2nd, 4th, and 8th postoperative week. The isografts remained intact vascular structure, and the allografts developed marked rejection with significant increase in wall thickness (95 +/- 19 microm vs. 49 +/- 7 microm; P < 0.01) and decrease in lumen area (1.9 +/- 1.1 x 10(4) microm(2) vs. 7.7 +/- 3.1 x 10(4) microm(2); P < 0.01) on the 4th week. In the CTLA4-Ig treated group, the vascular thickness and lumen area were significantly improved when compared with the untreated allografts (wall-thickness: 53 +/- 3 microm vs. 95 +/- 19 microm, P < 0.01; lumen area: 8.8 +/- 2.4 x 10(4) microm(2) vs. 1.9 +/- 1.1 x 10(4) microm(2), P < 0.01) on the 4th week. In conclusion, the PV transplantation model in mice using two-cuff technique is a feasible procedure with a high survival rate. The PV allografts responded well to the CTLA4-Ig therapy in our preliminary research by the model.

Serial intravascular ultrasound evidence of both plaque stabilization and lesion progression in patients with ruptured coronary plaques: Effects of statin therapy on ruptured coronary plaque

Using serial intravascular ultrasound (IVUS), we evaluated the natural evolution of non-culprit/non-target lesion ruptured coronary plaques and assessed the impact of statin therapy. Twenty-eight patients with non-stenotic ruptured plaques underwent baseline and 12-month follow-up IVUS studies; half were treated with statins. Standard IVUS analyses were performed. Complete healing of ruptured plaques was observed in four (29%) statin-treated patients and no non-statin-treated patients ( p = 0.049). Statin-treated patients had an increase in lumen area of 0.4 ± 0.8 mm 2 (versus a decrease in lumen area of −0.6 ± 1.0 mm 2 in non-statin-treated patients, p = 0.007) and no change in plaque area (versus an increase in plaque area of 0.6 ± 0.9 mm 2, p = 0.051). During 1-year follow-up, target lesion revascularization was performed in three non-statin-treated patients (21%) and no statin-treated patient ( p = 0.11). Compared to lesions that did not require revascularization, lesions requiring revascularization had a decrease in lumen area (−1.7 ± 1.4 mm 2 versus 0.1 ± 0.8 mm 2, p = 0.001) as well as an increase in plaque area (1.6 ± 1.0 mm 2 versus 0.1 ± 0.7 mm 2, p = 0.002). In conclusion, the current observational follow-up IVUS study showed beneficial effects of statin treatment on reduction of revascularization rates and stabilization of non-culprit/non-target lesion plaque ruptures without significant stenosis. Conversely, healing of non-statin-treated non-culprit/non-target lesion plaque ruptures can be responsible for lesion progression requiring revascularization.