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Biomedical subjects

Jean Raymond

Publications and source records attributed to Jean Raymond.

At least 19 recordsLinked to original sources
PubMed2006

Effect of radioactivity on stent-graft incorporation after endovascular treatment of aneurysms: An animal study.

Poor stent-graft (SG) incorporation into the vessel wall, following endovascular repair of abdominal aortic aneurysms (EVAR), can lead to endoleaks and SG migration. Low-dose radiation can prevent aneurysm recurrence after coil embolization, and has been associated with a "paradoxical" increase in neointima formation after stenting in a few studies. It was hypothesized that in situ beta radiation emitted from SG could improve its incorporation by preventing the persistence of circulating channels between the implant and the vessel wall and increasing neointima formation around the SG. Phosphorus 32 ((32)P, 200 or 400 kBq per SG (n = 6 each)) was ion implanted on the external surface of balloon-expandable SGs. Twelve radioactive and six non-radioactive SGs were deployed in iliac arteries of nine Mongrel dogs. Neointima formation inside the graft and the persistence of circulating flow through an artificial groove created during the endovascular procedure were assessed by follow-up imaging and by blinded, computerized histomorphometric analysis after animal sacrifice at 3 months. Occlusion occurred in four radioactive SGs. A lesser number of patent grooves was observed along high-activity SGs than along control SGs (1/3 versus 4/4). No difference in neointima formation was observed in radioactive and non-radioactive SGs. Alteration of external graft surface was observed after ion implantation. Ion implantation of (32)P on SGs does not seem to be a viable strategy to improve incorporation and prevent type-I endoleak after EVAR.

Aneurysm↗
PubMed2006

Safety and effectiveness of radioactive coil embolization of aneurysms: effects of radiation on recanalization, clot organization, neointima formation, and surrounding nerves in experimental models.

BACKGROUND AND PURPOSE: Recanalization after coil embolization can be prevented by radiation emitted from 32P coils. We wanted to determine the upper limits of 32P activities that could be implanted onto coils with respect to the potential injury to nearby nerves, delay in organization of the clot, and effects on neointima formation and recanalization. METHODS: We studied the effects of various 32P activities on recanalization and organization of thrombus after coil occlusion of canine arteries and on neointima formation at the neck of canine carotid bifurcation aneurysms. We also tested potential injury to nerves in the vicinity of radioactive or nonradioactive coils in 3 models: the brachial plexus (near proximal vertebral arteries) and the lingual nerve in a lingual artery bifurcation aneurysm model, both models being treated by radioactive or standard coil occlusion. Finally, we wrapped lingual nerves with nonradioactive or high-activity coils and studied their effects on lingual nerves and tongues. Results were assessed with a pathological scoring system and compared with Mann-Whitney and Kruskal-Wallis tests. RESULTS: No deleterious effect of radiation on nerves could be detected. Neointima formation was not hampered, scores of aneurysms treated with 32P-coils being significantly better when compared with treatments with standard coils (P=0.002). Arteries treated with high-activity coils (>3.39 microCi) showed absent recanalization but delayed organization of the clot at 3 months compared with low-activity or nonradioactive coils (P<0.05). CONCLUSIONS: beta-Radiation can prevent recanalization after coil occlusion. We could not demonstrate any deleterious effects of radioactivity on nervous structure or on neointima formation. Delayed organization of thrombus provides a rational basis to establish an upper limit for 32P activities to be implanted onto coils.

Animals↗
PubMed2006

Follow-up of treated aneurysms: the challenge of recurrences and potential solutions.

Angiographic recurrences after endovascular treatment of aneurysms with platinum coils are frequent, but hemorrhages are unusual. Recurrences are more frequent in patients with large wide-necked aneurysms, when the initial occlusion is incomplete, and when patients are treated after subarachnoid hemorrhage. Although many occur early on, they can appear years after treatment. None of the recent devices has been proven effective in improving long-term results. A rigorous scientific approach, including randomized trials, is imperative to forward progress in this field.

Angioplasty↗
PubMed2006

Endoluminal cryotherapy to prevent recanalization after endovascular occlusion with platinum coils.

PURPOSE: Endovascular embolization with platinum coils is sometimes followed by recanalization. The present study was undertaken to assess whether cryoablation of the endothelial lining could prevent recanalization after coil occlusion. MATERIALS AND METHODS: Recanalization rates of canine maxillary and vertebral arteries (n = 20) occluded with platinum coils with or without previous cryoablation (with temperatures of -40 degrees C to -45 degrees C for 90 seconds) were analyzed by angiography immediately and at 1 and 3 months in five animals. Pathologic recanalization and fibrosis was assessed at 3 months with use of a qualitative scoring system. Findings were compared with Mann-Whitney tests. RESULTS: Recanalization after coil occlusion occurred in 50% and 60% of cases with cryoablation at 1 and 3 months, respectively, compared with 100% without ablation (P = .012 and P= .029). There was no significant difference in pathologic scores (P = .348). The brachial plexus in the vicinity of vertebral arteries was injured by cryotherapy in three animals in which an ipsilateral neurologic deficit developed. CONCLUSIONS: Cryotherapy was moderately effective in the prevention of recanalization after coil occlusion. Deep nerve injury was excessive with the protocol used in the present study.

Aneurysm↗
PubMed2005

In situ beta-irradiation of a brain arteriovenous malformation model.

BACKGROUND AND PURPOSE: The treatment of large brain arteriovenous malformations (BAVMs) is challenging, and embolization alone is seldom curative. The study goal is to enhance the efficacy of arteriovenous malformation embolization by adding a beta-emitting isotope to the embolic agent. METHODS: The pig rete mirabile was used as a BAVM model. The body distribution of radioactivity was evaluated after selective rete injection of N-butyl,2-cyanoacrylate mixed with (131)I-lipiodol in 8 animals using immediate whole body gamma-scintigraphy. Activities within the whole rete mirabile and selected tissue samples were quantified with a gamma counter immediately after sacrifice. Two pigs were submitted to serial gamma-scintigraphies for 6 weeks to detect delayed isotope leaching. Long-term effects of in situ irradiation were evaluated using a mixture of 188Re/N-butyl,2-cyanoacrylate in 8 pigs. In 1 animal, autoradiography was performed to evaluate local rete mirabile distribution of the radioactivity. Seven pigs were injected with 188Re/glue in 1 rete mirabile and with glue only on the opposite side, and the degree of vascular occlusion of both sides was compared on histology at 2 (n=2) or 6 months (n=5). RESULTS: There was negligible activity outside the target. Radiation caused occlusion of vessels unreached by the glue itself but in the vicinity of the radioactive source in 5 of 7 rete mirabile. CONCLUSIONS: Selective deposition of a beta-emitter inside a BAVM model may be achieved by current embolization techniques. The adjunct use of an isotope may increase the efficacy of embolization.

Animals↗
PubMed2005

Production of radioactive particles for endovascular therapeutic interventions.

Recanalization is a common phenomenon that decreases the efficacy of embolization procedures. It can be inhibited by beta-radiation. Two novel ways of producing radioactive particles are described, by neutron beam irradiation of gold-containing microspheres, or by using the 32P binding capacity of zirconium-containing microspheres. Particles were tested in vivo, to assess their ability to deliver radioactivity locally, using canine renal artery, porcine rete mirabile, and rabbit ear embolization models. Both radioactive microspheres (198Au and 32P) showed no detectable activity outside the target territory. 32P microspheres demonstrated typical radiation changes in a porcine rete mirabile arteriovenous malformation model.

Animals↗
PubMed2005

Endovascular treatment of aneurysms: gene expression of neointimal cells recruited on the embolic agent and evolution with recurrence in an experimental model.

PURPOSE: The authors attempted to identify genes associated with healing or recurrence after embolization in an aneurysm model in which neointima formation at the neck varies according to flow zones. A better understanding of the relationship between blood flow, molecular events, and healing or recurrence may provide future avenues to improve results of endovascular treatment of aneurysms. METHODS: Bilateral carotid venous pouch aneurysms were constructed in 36 dogs and embolized with gelatin sponges. Angiography and pathological studies were performed at T0 and/or 3 weeks (n=22). Angiographic results and neointima formation were scored using a qualitative index applied to the distal (inflow) and proximal (outflow) zones of the neck. In 14 animals, mRNA expression 1 to 14 days after embolization at the proximal or distal segment of the sponge was analyzed by RT-PCR, attempting to correlate flow zones, gene expression, and neointima formation. RESULTS: Aneurysms recurred at 3 weeks, as shown by significantly worse angiographic scores as compared to T0 (P<.01). Neointimal scores differed at pathology, with a more complete neointima at the proximal as compared to the distal aspect of the sponge at 3 weeks (P=.027). Embolization was followed by migration of CD31+, CD14+, smooth muscle alpha-actin+ (SMA+) cells that progressively expressed metalloproteinases (MMP-9,-12,-14), but stable or lesser, retarded expression of inhibitors (TIMP1-4). Growth factors (PDGF-BB, TGF-beta1, TNF-alpha, MCP-1 and Ang-1) were expressed at increasing levels, maximal at 7 to 14 days. Differences between distal and proximal zones were limited to increased expression of MMP-2 proximally (P<.035). CONCLUSION: Gene expression after embolization is compatible with patterns associated with neointima formation. The authors have not identified key factors involved in recurrence.

Actins↗
PubMed2004

Role of the endothelial lining in recurrences after coil embolization: prevention of recanalization by endothelial denudation.

BACKGROUND AND PURPOSE: Endovascular treatment can improve the outcome of patients treated for ruptured intracranial aneurysms as compared with surgical clipping, but angiographic recurrences are frequent. Endothelial denudation before coil embolization may prevent recanalization and improve results of endovascular treatment. METHODS: We compared angiographic and pathological results 3 months after coil occlusion of paired canine arteries (n=16), with or without previous denudation of the endothelial lining using an endovascular device. The technique was then used to denude the neck of carotid venous pouch bifurcation aneurysms before coil embolization in 8 dogs, and the angiographic evolution at 12 weeks was compared with 7 control aneurysms treated by coiling only. Qualitative scoring systems were used to compare angiographic results with time and neointimal coverage at the neck of aneurysm after necropsy. The evolution of angiographic scores was analyzed using Wilcoxon signed rank tests whereas angiographic and neointimal scores of the 2 groups were compared using the Mann-Whitney test. RESULTS: All arteries embolized with platinum coils recanalized, whereas most arteries (12/16 or 75%) denuded before coil embolization remained occluded at 3 and 12 weeks (P<0.001). Aneurysms treated with coils without previous denudation tended to recur, with angiographic scores significantly worse at 12 weeks as compared with T(0) (P=0.015). Median angiographic and neointimal scores were significantly better at 12 weeks with endothelial denudation (P=0.011 and 0.026, respectively). CONCLUSIONS: Endothelial denudation can prevent recanalization after coil embolization.

Animals↗
PubMed2004

Gene therapy and endovascular treatment of intracranial aneurysms.

BACKGROUND: Endovascular treatment of intracranial aneurysms is safe and effective but too often is followed by recurrences. Gene therapy may improve healing after embolization, and endovascular approaches may offer future in situ delivery systems designed to prevent aneurysm rupture. SUMMARY OF REVIEW: Advances in coil technology have focused on coating strategies designed to modify the biological reaction to the embolic agent. Gene therapy in cardiovascular applications is limited by low efficiency and transient gene expression. Current advances include the potential use of circulating progenitor cells for ex vivo genetic manipulations followed by in vivo delivery. Direct gene transfer may also be enhanced in situ by coils carrying antibody-tethered adenovirus or through the use of cell-specific or radiation-inducible promoters. Candidate genes that may be of value in promoting healing after endovascular treatment include growth factors and metalloproteinase inhibitors. A better understanding of the biology of aneurysm is necessary to conceive strategies designed to control the development of these lesions before their rupture. CONCLUSIONS: Many technical difficulties remain to be solved, but the combination of gene therapy and endovascular techniques offers multiple therapeutic possibilities in the future control of intracranial aneurysms.

Animals↗
PubMed2004

Temporary vascular occlusion with poloxamer 407.

There is a need for safe and reversible occlusions during percutaneous endovascular procedures. Poloxamer 407 is a non-ionic surfactant with rapid reversible sol-gel transition behaviour. The safety and efficacy of this polymer as a temporary embolic agent was investigated. First, dissolution time after gelation of poloxamer was determined in an in vitro model. Then, transient poloxamer occlusion of renal and pulmonary arteries of seven dogs was followed by serial angiograms. Macroscopic and pathological changes were studied 1 week later. This experiment was repeated in similar arteries in one pig, and in auricular arteries of two rabbits. Poloxamer dissolution after in vitro polymerization was completed within 1-20 h, depending on concentrations. In vivo poloxamer 22% injections led to complete occlusion, followed by full recanalization within 10-90 min without complication. The only biochemical effect of poloxamer occlusions was transient elevation of triglyceride levels. There were no pathological abnormalities at 1 week. Poloxamer 407 could be used as an embolic material for temporary occlusions.

Animals↗
PubMed2004

Transcatheter embolization using degradable crosslinked hydrogels.

Therapeutic embolization is the selective transcatheter blockage of blood vessels or diseased vascular structures. The majority of current embolization materials in clinical use are permanent. There are clinical situations however, in which temporary embolization is desired. Degradable hydroxyethyl acrylate (HEA) microspheres have been synthesized. Canine renal arteries and rabbit central auricular arteries were embolized with HEA microspheres, and compared with degradable human serum albumin (HSA) microspheres, and permanent microspheres. HSA and HEA microspheres both achieved temporary occlusions. HSA and HEA microspheres were recanalizated at 1 and 3 weeks, respectively, while arteries occluded with permanent microspheres did not recanalize. All embolic microspheres led to tissue infarction, with the short-term HSA microspheres providing the least damage, and the permanent microspheres leading to extensive damage. Advantages of temporary embolization were not convincingly demonstrated since temporary occlusions still led to tissue infarction.

Absorbable Implants↗
PubMed2004

Recanalization of arterial thrombus, and inhibition with beta-radiation in a new murine carotid occlusion model: MRNA expression of angiopoietins, metalloproteinases, and their inhibitors.

BACKGROUND: Recanalization is an important physiologic phenomenon because it can efficiently reestablish circulation after thrombosis. We attempted to characterize molecular events related to recanalization or organization of arterial thrombus in a new murine model by studying genes reported to be involved in angiogenesis or neointima formation. METHODS: Platinum coils, radioactive phosphorus 32 coils or not, were implanted in the carotid artery in mice to cause thrombotic occlusion. The outcome of the occlusion was followed up with transmyocardial angiography and pathologic analysis at 2, 6, or 15 days. Angiographic results were compared with the Pearson chi2 test. Messenger RNA expression of von Willebrand factor (vWF); smooth muscle alpha-actin (SMA+); platelet endothelial cell adhesion molecule-1 (PECAM-1); vascular endothelium cadherin (VE-Cad); endothelial nitric oxide synthase (eNOS); vascular cell adhesion molecule-1 (VCAM-1); tumor necrosis factor alpha (TNF-alpha); matrix metalloproteinase (MMP-9, MMP-12, and MMP-14), and tissue inhibitors of MMPs (TIMPs: TIMP-1, TIMP-2, TIMP-3, TIMP-4); angiopoietins (Ang-1, Ang-2); and receptors Tie-1 and Tie-2, were analyzed with reverse transcriptase polymerase chain reaction 2, 6, and 15 days after surgery. Levels of mRNA expression were compared with analysis of variance and the Student t test. RESULTS: Carotid arteries implanted with nonradioactive 0.015-caliber coils were occluded in 84% of arteries on day 2, but in only 57% of arteries on day 15, which confirms that recanalization occurred in this model. Arteries implanted with 0.015-caliber 32P coils did not become recanalized, and 100% were occluded on day 15 (n = 13; P = .006). Recanalization was associated with endothelial-like cell-lined channels, whereas persistent occlusion was caused by complete filling of the lumen with conjunctive tissue. Coil occlusion, with or without recanalization, was followed by decreased expression of vWf, VE-Cad, eNOS, VCAM-1, MMP-2, TIMP-1, and TIMP-2; stable expression of PECAM-1, SMA+, and TIMP-3; and overexpression of Ang-1 and Ang-2, MMP-9, MMP-14, and TIMP-4. Statistically significant differences when arteries were implanted with 32P coils included decreased expression of TIMP-4 (P = .011) and increased expression of MMP-9 (P = .02). CONCLUSION: Recanalization and organization of arterial thrombus is associated with expression of genes involved in angiogenesis and neointima formation. Recanalization can be prevented with beta-radiation, but molecular mechanisms remain to be refined. CLINICAL RELEVANCE: A better understanding of molecular mechanisms involved in angiogenesis has permitted its regulation as a new option in treatment of various diseases. Inhibition of angiogenesis may help control diseases such as cancer, arthritis, or diabetes retinopathy. On the other hand, stimulation of angiogenesis may palliate conditions associated with insufficient blood supply, such as ischemic heart disease or critical limb ischemia. Yet little is known regarding recanalization (to be differentiated from thrombolysis), a cellular process that occurs concurrently with thrombus "organization." Recanalization is an important physiologic phenomenon because it can efficiently reestablish antegrade circulation after thrombosis both in veins and in arteries, and could be modulated for therapeutic purposes. Thus our efforts at better understanding of mechanisms involved in recanalization could be used, in addition to its promotion to recover flow after thrombotic occlusions, to prevent its occurrence after endovascular interventions designed to permanently occlude aneurysms.

Angiography↗
PubMed2004

Endovascular aortic aneurysm repair with stent-grafts: experimental models can reproduce endoleaks.

PURPOSE: To develop canine aneurysm models that can reproduce type II endoleaks after endovascular aneurysm repair (EVAR) with stent-grafts. MATERIALS AND METHODS: A fusiform infrarenal abdominal aortic aneurysm model (AAA) was surgically created with a jugular vein patch, while preserving collateral vessels (n = 3). To allow comparative studies within the same animal, a bilateral iliac aneurysm model was also constructed with venous patches and surgical re-implantation of the sacroiliac trunk (n = 3). Stent-grafts were implanted by femoral approach at least 2 months later in both aortic and iliac models. Follow-up imaging was performed by Doppler ultrasound (US) and angiography until animals were killed 3 months after EVAR. RESULTS: Angiography revealed immediate type II leaks in all cases. Leaks were still present at autopsy 3 months after EVAR in all cases, and were revealed at pre-death angiography in all but one case. At autopsy, leaks were characterized by the presence of large endothelialized channels that formed within the thrombus between the stent-graft and the aneurysmal wall. CONCLUSION: As shown in this pilot study, persistent type II leaks after EVAR can be reproduced in aortic and iliac animal models. The iliac model can be created bilaterally in the same animal, thus allowing for comparative evaluation of different therapies. These models could be used to better understand the mechanisms of endoleak, and to assess future developments aimed to improve the outcomes after EVAR.

Aneurysm↗
PubMed2004

Surgical construction of an in vivo carotid siphon model to test neurovascular devices.

OBJECTIVE: We developed an animal model to evaluate vascular trauma induced by endovascular devices that are proposed for the treatment of cerebrovascular diseases. METHODS: The model was constructed in six domestic swine by elongating the common carotid artery using interpositional grafts. Balloon catheters (n = 3), stents (n = 2), and a snare were tested 9 to 13 days after surgery. Device performance was evaluated by angiography, macroscopic photography, and histopathological examination. RESULTS: Animals tolerated the surgical procedure well, and artificial siphons were thought to provide realistic conditions for device testing. Balloon catheters induced minimal trauma, whereas coronary stents caused severe spasm or thrombosis and extensive macroscopic changes. CONCLUSION: Construction of an in vivo siphon model is feasible and potentially useful for testing neurovascular devices.

Anastomosis, Surgical↗