Metabolic alterations of uterine grafts after extended cold ischemic storage: experimental study in ewes.

Uterine transplantation from a deceased donor could become an available option for widely treating uterine infertility. However, this procedure requires more precise knowledge about the graft's tolerance to extended cold ischemia. Here, we sought to assess the uterine metabolic alterations after extended cold ischemic storage in a model of auto-transplantation in ewe. A total of 14 uterine auto-transplantations were performed, divided into 2 groups: 7 after 3 h of cold ischemia time (CIT) and 7 after 24 h. Venous uterine blood was collected before uterus retrieval and during reperfusion (30, 60 and 90 min); thereafter, blood gases, lactate, glucose and amino acids (AAs) were analyzed. Apoptosis analyses were performed before uterus retrieval and following reperfusion in uterus biopsies. A total of 12 uterine auto-transplantations were successfully performed and 7 ewes were alive ≥8 days after transplantation. After reperfusion, a decrease in pH, a rise of lactate and lactate/glucose ratio and a delayed decrease of pO2 were found in the 3 h CIT group. No significant variation of these parameters was observed in the 24 h CIT group. Significant decreases of AAs were observed during reperfusion and these decreases were more pronounced and concerned a larger number of compounds in the 24 h CIT group than in the 3 h CIT group. There was no significant uterine apoptotic signal in either group. Overall, these results suggest that extended CIT storage delayed restoration of aerobic glycolysis and induced an increase in AA requirements of the uterus after reperfusion. However, this biochemical alteration did not reduce success rate for uterine transplantation.

Uterus tolerance to extended cold ischemic storage after auto-transplantation in ewes.

OBJECTIVE: To assess how the uterus tolerates extended cold ischemic storage before auto-transplantation in ewes. STUDY DESIGN: Fourteen uterine auto-transplantations were performed in ewes from November 2014 to June 2015 at the Analysis and Research Laboratory of Limoges, France. The animals were divided into 2 groups: 7 after 3h of cold ischemia timeand 7 after 24h. Transplant was assessed ≥8days after transplantation. Histology and apoptosis analyses (TUNEL method and indirect immunohistochemistry of cleaved Caspase 3) were performed before uterus retrieval (control), after 90min following reperfusion and ≥8days after transplantation. RESULTS: Twelve uterine auto-transplantations were successfully performed. The histological analysis at 90min following reperfusion revealed a moderate inflammation of the endometrium and serosa in the 3-h group and severe inflammation in the 24-h group, but no significant apoptotic signal was found in either group. Seven ewes were alive at ≥8days after transplantation: the macroscopic and histological analyses revealed two viable uteri in the 3-h group and three in the 24-h group. In each group one uterus was necrotic. CONCLUSION: These first results in ewes suggest that the uterus is an organ with a good tolerance to extended cold ischemic storage before transplantation.

Development of an angiogenesis animal model featuring brain arteriovenous malformation histological characteristics.

BACKGROUND: Angiogenesis has a key role in the formation and evolution of brain arteriovenous malformations (AVMs). Numerous models have been developed aiming to recreate configuration of brain AVMs. OBJECTIVE: To develop an animal model sharing the same pathological characteristics as human brain AVMs. MATERIALS AND METHODS: Ten pigs were divided into two groups. Five animals underwent endovascular left common carotid artery (CCA) and external carotid artery (ECA) occlusion and five animals served as controls. DSA, associated with 3D-rotational angiography, was performed at day 0 and at 3 months in both groups. The volume of the retia was calculated. Vascular endothelial growth factor (VEGF)-A serum levels were measured in both groups at the same time intervals. Finally, the animals were sacrificed at 3 months and the retia were harvested for pathological and immunohistochemistry examinations. RESULTS: At 3 months, a significantly higher rete volume was seen in group A than in group B (2.92±0.33 mL vs 1.87±0.69 mL, respectively; p=0.016). There was a trend for increased VEGF-A levels in group A at 3 months. In the occlusion group, histological findings showed significant reduction of media thickness and disrupted internal elastic lamina; immunohistochemistry findings showed strong reactivity for VEGF receptors and interleukin 6. CONCLUSIONS: Unilateral endovascular occlusion of the CCA-ECA results in angiogenesis triggering of the rete mirabile with both significant augmentation of the rete volume and histological evidence of pro-angiogenic stimulation.

Target-controlled inhalation anaesthesia: A cost-benefit analysis based on the cost per minute of anaesthesia by inhalation.

BACKGROUND: End-tidal target-controlled inhalational anaesthesia (TCIA) with halogenated agents (HA) provides a faster and more accurately titrated anaesthesia as compared to manually-controlled anaesthesia. This study aimed to measure the macro-economic cost-benefit ratio of TCIA as compared to manually-controlled anaesthesia. METHODS: This retrospective and descriptive study compared direct drug spending between two hospitals before 2011 and then after the replacement of three of six anaesthesia machines with TCIA mode machines in 2012 (Aisys carestation®, GE). The direct costs were obtained from the pharmacy department and the number and duration of the anaesthesia procedures from the computerized files of the hospital. RESULTS: The cost of halogenated agents was reduced in the hospital equipped with an Aisys carestation® by 13% as was the cost of one minute of anaesthesia by inhalation (€0.138 and €0.121/min between 2011 and 2012). The extra cost of the implementation of the 3 anaesthesia machines could be paid off with the resulting savings over 6 years. DISCUSSION: TCIA appears to have a favourable cost-benefit ratio. Despite a number of factors, which would tend to minimise the saving and increase costs, we still managed to observe a 13% savings. Shorter duration of surgery, type of induction as well as the way HA concentration is targeted may influence the savings results obtained.

Role of terminal and anastomotic circulation in the patency of arteries jailed by flow-diverting stents: from hemodynamic changes to ostia surface modifications.

OBJECTIVE The outcome for jailing arterial branches that emerge near intracranial aneurysms during flow-diverting stent (FDS) deployment remains controversial. In this animal study, the authors aimed to elucidate the role of collateral supply with regard to the hemodynamic changes and neointimal modifications that occur from jailing arteries with FDSs. To serve this purpose, the authors sought to quantify 1) the hemodynamic changes that occur at the jailed arterial branches immediately after stent placement and 2) the ostia surface values at 3 months after stenting; both parameters were investigated in the presence or absence of collateral arterial flow. METHODS After an a priori power analysis, 2 groups (Group A and Group B) were created according to an animal flow model for terminal and anastomotic arterial circulation; each group contained 7 Large White swine. Group A animals possessed an anastomotic-type arterial configuration to supply the territory of the right ascending pharyngeal artery (APhA), while Group B animals possessed a terminal-type arterial configuration to supply the right APhA territory. Subsequently, all animals underwent FDS placement, thereby jailing the right APhAs. Mean flow rates and velocities inside the jailed branches were quantified using time-resolved 3D phase-contrast MR angiography before and after stenting. Three months after stent placement, the jailed ostia surface values were quantified on scanning electron micrographs. The data were analyzed using descriptive statistics and group comparisons with parametric and nonparametric tests. RESULTS The endovascular procedures were feasible, and there were no findings of in situ thrombus formation on postprocedural optical coherence tomography or ischemia on postprocedural diffusion-weighted imaging. In Group A, the mean flow rate values at the jailed right APhAs were reduced immediately following stent placement as compared with values obtained before stent placement (p = 0.02, power: 0.8). In contrast, the mean poststenting flow rates for Group B remained similar to those obtained before stent placement. Three months after stent placement, the mean ostia surface values were significantly higher for Group B (527,911 ± 306,229 µm2) than for Group A (89,329 ± 59,762 µm2; p < 0.01, power: 1.00), even though the initial dimensions of the jailed ostia were similar between groups. A statistically significant correlation was found between groups (A or B), mean flow rates after stent placement, and ostia surface values at 3 months. CONCLUSIONS When an important collateral supply was present, the jailing of side arteries with flow diverters resulted in an immediate and significant reduction in the flow rate inside these arteries as compared with the prestenting values. In contrast, when competitive flow was absent, jailing did not result in significant flow rate reductions inside the jailed arteries. Ostium surface values at 3 months after stent placement were significantly higher in the terminal group of jailed arteries (Group B) than in the anastomotic group (Group A) and strongly correlated with poststenting reductions in the velocity value.

Jailed Artery Ostia Modifications After Flow-Diverting Stent Deployment at Arterial Bifurcations: A Scanning Electron Microscopy Translational Study.

BACKGROUND: Even though flow-diverting stents are being increasingly used to treat intracranial aneurysms, the fate of jailed side branches remains controversial, with recent clinical data contradicting finding of earlier animal studies that reported patency. OBJECTIVE: To quantify the surface area of the ostia after 3 months of jailing by flow-diverting stents as a more accurate means of patency evaluation. METHODS: Ten large white swine were stented by flow-diverting stents placed at common carotid-ascending pharyngeal arterial bifurcation sites. A dual antiplatelet regimen was initiated 72 hours before stenting and maintained during follow-up. Optical coherence tomography was used to search for per-procedural thrombus formation. Selective control digital subtraction angiography was performed 12 weeks post-stenting. Subsequently, the stented arterial segments were harvested en bloc and observed under scanning electron microscopy, photographed, and quantified. RESULTS: The absence of per-procedural thrombus formation was confirmed. All ostia were patent at 12 weeks (or 3 months) post stenting, with no angiographic or scanning electron microscopy-evident thrombus formation. The mean initial ostium surface was 2 048 617 ± 731 625 µm. At 3 months, the mean nonendothelialized ostium surface was 229 218 ± 140 172 µm, and mean endothelialized ostium surface was 1 819 399 ± 672 632 µm. A statistically significant difference (reduction) was observed between the initial and 12-week ostium surfaces (P < .001), with an significant statistical power (1.000). CONCLUSION: Jailed side branches remained patent after stenting, but the surface quantifications showed significant endothelial coverage, with a significant reduction of patent ostium surfaces at 12 weeks post-stenting. ABBREVIATIONS: APhA, ascending pharyngeal arteryCI, confidence interval3DRA, 3-dimensional rotational angiographyDSA, digital subtraction angiographyFDS, flow-diverting stentOCT, optical coherence tomographyOS, ostium surfaceSEM, scanning electron microscopy.

Intravascular optical coherence tomography for the evaluation of arterial bifurcations covered by flow diverters.

BACKGROUND AND OBJECTIVE: Due to its high spatial resolution, intravascular optical coherence tomography (OCT) has been used as a valid method for in vivo evaluation of several types of coronary stents at straight lumen and bifurcation sites. We sought to evaluate its effectiveness for flow diverting stents deployed in arterial bifurcation sites involving jailing of a side branch. METHODS: Four large white swine were stented with flow diverting stents covering the right common carotid artery-ascending pharyngeal artery bifurcation. After 12 weeks of follow-up the animals were evaluated by digital subtraction angiography and intravascular OCT and subsequently sacrificed. Neointimal thickness on the parent arteries and the free segments of the stent were measured. The stented arteries were harvested and underwent scanning electron microscopy (SEM) imaging. Ostia surface values were measured with OCT three-dimensional (3D) reconstructions and SEM images. RESULTS: All endovascular procedures and OCT pullback runs were feasible. Stent apposition was satisfactory on the immediate post-stent OCT reconstructions. At 12-week controls, all stents and jailed branches were patent. Mean neointimal thickness was 0.11±0.04 mm on the free segments of the stent. The mean ostia surface at 12 weeks was 319 750±345 533 µm2 with 3D-OCT reconstructions and 351 198±396 355 µm2 with SEM image-derived calculations. Good correlation was found for ostia surface values between the two techniques; the values did not differ significantly in this preliminary study. CONCLUSIONS: Intravascular OCT appears to be a promising technique for immediate and follow-up assessment of the orifice of arterial branches covered by flow diverting stents.

Role of terminal and anastomotic circulation in the patency of arteries jailed by flow-diverting stents: animal flow model evaluation and preliminary results.

OBJECTIVE The authors describe herein the creation of an animal model capable of producing quantifiable data regarding blood flow rate and velocity modifications in terminal and anastomotic types of cerebrofacial circulation. They also present the preliminary results of a translational study aimed at investigating the role of terminal and anastomotic types of circulation in arterial branches jailed by flow-diverting stents as factors contributing to arterial patency or occlusion. METHODS Two Large White swine were used to validate a terminal-type arterial model at the level of the right ascending pharyngeal artery (APhA), created exclusively by endovascular means. Subsequently 4 Large White swine, allocated to 2 groups corresponding to the presence (Group B) or absence (Group A) of terminal-type flow modification, underwent placement of flow-diverting stents. Blood flow rates and velocities were quantified using a dedicated time-resolved 3D phase-contrast MRA sequence before and after stenting. Three months after stent placement, the stented arteries were evaluated with digital subtraction angiography (DSA) and scanning electron microscopy (SEM). Patent (circulating) ostia quantification was performed on the SEM images. RESULTS Terminal-type flow modification was feasible; an increase of 75.8% in mean blood velocities was observed in the right APhAs. The mean blood flow rate for Group A was 0.31 ± 0.19 ml/sec (95% CI -1.39 to 2.01) before stenting and 0.21 ± 0.07 ml/sec (95% CI -0.45 to 0.87) after stenting. The mean blood flow rate for Group B was 0.87 ± 0.32 ml/sec (95% CI -1.98 to 3.73) before stenting and 0.76 ± 0.13 ml/sec (95% CI -0.41 to 1.93) after stenting. Mean flow rates after stenting showed a statistically significant difference between Groups A and B (Welch test). Mean and maximal blood velocities were reduced in Group A cases and did not decrease in Group B cases. Control DSA and SEM findings showed near occlusion of the jailed APhAs in both cases of anastomotic circulation (mean patent ostium surface 32,776 µm2) and patency in both cases of terminal-type circulation (mean patent ostium surface 422,334 µm2). CONCLUSIONS Terminal-type arterial modification in swine APhAs is feasible. Sufficient data were acquired to perform an a priori analysis for further research. Flow diversion at the level of the APhA ostium resulted in significant stenosis in cases of anastomotic circulation, while sufficient patency was observed in terminal-type circulation.

Endothelialization of over- and undersized flow-diverter stents at covered vessel side branches: An in vivo and in silico study.

Although flow-diverting devices are promising treatment options for intracranial aneurysms, jailed side branches might occlude leading to insufficient blood supply. Especially differences in the local stent strut compression may have a drastic influence on subsequent endothelialization. To investigate the outcome of different treatment scenarios, over- and undersized stent deployments were realized experimentally and computationally. Two Pipeline Embolization Devices were placed in the right common carotid artery of large white swine, crossing the right ascending pharyngeal artery. DSA and PC-MRI measurements were acquired pre- and post-stenting and after three months. To evaluate the stent strut endothelialization and the corresponding ostium patency, the swine were sacrificed and scanning electron microscopy measurements were carried out. A more detailed analysis of the near-stent hemodynamics was enabled by a realistic virtual stenting in combination with highly resolved Computational Fluid Dynamics simulations using case-specific boundary conditions. The oversizing resulted in an elongated stent deployment with more open stent pores, while for the undersized case a shorter deployment with more condensed pores was present. In consequence, the side branch of the first case remained patent after three months and the latter almost fully occluded. The virtual investigation confirmed the experimental findings by identifying differences between the individual velocities as well as stent shear stresses at the distal part of the ostia. The choice of flow-diverting device and the subsequent deployment strategy strongly influences the patency of jailed side branches. Therefore, careful treatment planning is required, to guarantee sufficient blood supply in the brain territories supplied those branches.