ABSTRACT
BACKGROUND AND PURPOSE: To evaluate the ready-to-use iodine-containing polyvinyl alcohol (I-PVA) dissolved in the low angiotoxic solvent N-methyl pyrrolidone (NMP) for embolization of porcine wide-necked aneurysms. METHODS: Fourteen broad-based carotid sidewall aneurysms were surgically constructed in 7 swine. I-PVA (40%) in NMP was injected under temporary balloon occlusion bridging the aneurysm neck. After 4 weeks, follow-up angiography, multisection CT angiography (MSCTA), and 3T MR imaging including MR angiography (MRA) sequences were performed. Afterward, harvested aneurysms were investigated histopathologically. RESULTS: The liquid embolic was well visible under fluoroscopy and displayed a favorable precipitation pattern, allowing for controlled polymer delivery. Ten aneurysms (71%) were initially completely occluded, whereas in 1 aneurysm, a minimal polymer leakage was observed. The other 4 aneurysms (29%) were almost completely occluded. One animal suffered a lethal rebleeding from the anastomosis after uneventful embolization. Aneurysms embolized with I-PVA could be discriminated well from the parent artery without beam-hardening artifacts on MSCTA, and no susceptibility artifacts were encountered on MR imaging. Histologic examination revealed all aneurysms covered with a membrane of fibroblasts and an endothelial cell layer while a moderate intraaneurysmal inflammatory response to the polymer was observed. CONCLUSION: I-PVA dissolved in NMP has proved its effectiveness for the embolization of experimental wide-necked aneurysms. This precipitating liquid embolic offers several interesting features in that it needs no preparation before use and no radiopaque admixtures, the latter allowing for artifact-free evaluation of treated aneurysms with MSCTA and MRA. Moreover, it uses NMP as a solvent, which has only a low angiotoxicity.
Subject(s)
Carotid Artery Diseases/therapy , Disease Models, Animal , Embolization, Therapeutic/methods , Intracranial Aneurysm/therapy , Polyvinyl Alcohol/analogs & derivatives , Pyrrolidinones , Solvents , Animals , Carotid Arteries/drug effects , Carotid Arteries/pathology , Carotid Artery Diseases/diagnostic imaging , Carotid Artery Diseases/pathology , Cerebral Angiography , Chemical Precipitation , Female , In Vitro Techniques , Injections, Intra-Arterial , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/pathology , Magnetic Resonance Angiography , Polyvinyl Alcohol/administration & dosage , Swine , Tomography, Spiral ComputedABSTRACT
BACKGROUND AND PURPOSE: The organic solvent dimethyl-sulfoxide (DMSO), as a commonly used vehicle for nonadhesive liquid embolics, is not devoid of local angiotoxic effects. We compared microvascular toxicities of superselective infusions of DMSO with potentially more compatible solvents in swine rete mirabile. METHODS: Fourteen swine underwent angiography for superselective catheterization of 28 arteries of the rete while electrocardiography and intra-arterial pressure were continuously monitored. The investigated solvents were DMSO, dimethyl isosorbide (DMI), ethyl lactate, glycofurol 75, N-methyl pyrrolidone (NMP), and solketal. Control infusion of saline ruled out catheter induced vasospasm in all cases. Each artery of the rete was infused only once with 0.8 mL of one of the solvents over 60 seconds. Acute angiographic and hemodynamic consequences were evaluated. Blood samples were assessed for signs of intravascular hemolysis. Brains and retia were harvested for gross and histopathologic investigation. RESULTS: On the basis of the angiographic data, DMSO induced the most pronounced vasospasm with the longest recovery period of all solvents investigated. Ethyl lactate, glycofurol 75, and solketal elicited less severe vasospasms and accordingly resolved much more quickly. DMI and NMP induced only minimal vasospasms with comparably short duration. No solvent caused significant hemodynamic alterations or hemolysis. Gross inspection of brains showed no abnormalities, whereas histopathologic examination revealed mostly nonspecific findings. One rete exposed to solketal displayed possible causal histotoxic changes. CONCLUSION: DMI and NMP produced far less vasospasm than DMSO. No changes in hemodynamic or hemolytic parameters and no histopathologic findings were observed with infusion of these solvents.
Subject(s)
Embolization, Therapeutic/methods , Endothelium, Vascular/drug effects , Muscle, Smooth, Vascular/drug effects , Solvents/toxicity , Alkenes/toxicity , Angiography, Digital Subtraction , Animals , Blood Circulation/drug effects , Cerebral Arteries/drug effects , Cerebral Arteries/pathology , Chemical Precipitation , Dimethyl Sulfoxide/toxicity , Drug Combinations , Endothelium, Vascular/diagnostic imaging , Endothelium, Vascular/pathology , Female , Glycerol/toxicity , Hemolysis , Isosorbide/toxicity , Lactates/toxicity , Muscle, Smooth, Vascular/diagnostic imaging , Muscle, Smooth, Vascular/pathology , Polyethylene Glycols/toxicity , Pyrrolidinones/toxicity , SwineABSTRACT
Iodine-containing polyvinyl alcohol polymer (I-PVAL) is a novel precipitating liquid embolic that allows for artifact-free evaluation of CT angiography (CTA). As accurate aneurysm volumetry can be performed with multidetector CTA, we determined volumes of experimental aneurysms before, immediately after, and 4 weeks after embolization of 14 porcine experimental carotid sidewall aneurysms with this liquid embolic. An automated three-dimensional software measurement tool was used for volumetric analysis of volume-rendering CTA data. Furthermore, intra-aneurysmal pressure changes during liquid embolization were measured in four silicone aneurysms and potential polymer volume changes within 4 weeks were assessed in vitro. Liquid embolic injection was performed during temporary balloon occlusion of the aneurysm neck, resulting in a mean occlusion rate of 98.3%. Aneurysms enlarged significantly during embolization by 61.1 +/- 28.9%, whereas a significant shrinkage of 5.6 +/- 2.7% was observed within the follow-up period. Histologic analysis revealed an inflammatory foreign body reaction with partial polymer degradation. In silicone aneurysm models, intra-aneurysmal pressure remained unchanged during liquid embolic injection, whereas balloon inflation resulted in a mean pressure increase of 31.2 +/- 0.7%. No polymer shrinkage was observed in vitro. The aneurysm enlargement noted was presumably due to pressure elevation after balloon inflation, which resulted in dilatation of the weak venous wall of the newly constructed aneurysm--another shortcoming of this experimental aneurysm model. The volume decrease after 4 weeks expressed partial polymer degradation.
Subject(s)
Carotid Artery, Common/diagnostic imaging , Carotid Artery, Common/surgery , Chemoembolization, Therapeutic/adverse effects , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/therapy , Polyvinyl Alcohol/adverse effects , Tomography, Spiral Computed , Angiography, Digital Subtraction , Animals , Artifacts , Balloon Occlusion/adverse effects , Carotid Artery, Common/pathology , Carotid Artery, Common/physiopathology , Cerebrovascular Circulation , Dilatation, Pathologic/diagnostic imaging , Dilatation, Pathologic/etiology , Disease Models, Animal , Female , Follow-Up Studies , Foreign-Body Reaction/diagnostic imaging , Foreign-Body Reaction/etiology , Foreign-Body Reaction/pathology , Foreign-Body Reaction/physiopathology , Image Processing, Computer-Assisted , Intracranial Aneurysm/physiopathology , Intracranial Pressure , Polyvinyl Alcohol/administration & dosage , Polyvinyl Alcohol/metabolism , Swine , Time FactorsABSTRACT
AIMS: Matrix metalloproteinases (MMPs) are a pivotal enzyme system involved in extracellular matrix (ECM) degradation and are considered to be important in the development and invasion of human tumours. Little is known about the regulation of MMPs in meningioma development and prognosis. The transcription factor Ets-1 is the main regulator of several MMPs, including MMP-2 and -9. The aim of this study was to determine the relationship between the expression of Ets-1, MMP-2 and -9 and the malignant potential of meningiomas. METHODS AND RESULTS: Seventy-four meningiomas of different histological grades were investigated immunohistochemically. Up-regulation of Ets-1, MMP-2 and MMP-9 expression was observed in atypical and anaplastic meningiomas. Invasive meningiomas showed increased immunohistochemical expression of these proteins compared with non-invasive meningiomas. We also observed a correlation between the expression of Ets-1 and of its target genes MMP-2 and MMP-9. CONCLUSIONS: Ets-1 may be involved in the transcriptional regulation of MMP-2 and MMP-9 as well as in the invasive process in meningiomas. Evaluation of these expressions might be of prognostic value for meningiomas.