Cardiovascular effects of selected water-miscible solvents for pharmaceutical injections and embolization materials: a comparative hemodynamic study using a sheep model.

Generally, organic water-miscible solvents are used intravascularly (both intravenously and intra-arterially) for preparing two types of formulations, namely, pharmaceutical injections of poorly soluble drugs and precipitating liquid embolic polymeric materials for the minimally invasive treatment of aneurysms, arteriovenous malformations, or tumors, by arterial route. Although several of such solvents have been used in both drug delivery and interventional radiology, their safety profile is a concern. In particular, there is a lack of comparative investigations of their cardiovascular effects when injected intra-arterially. We selected 13 non-aqueous water-miscible solvents based on their capacity to solubilize drugs or embolic polymeric materials, and on their described use, at least diluted with water, in pharmaceutical formulations. Their in vivo hemodynamic toxicity in male adult sheep after infra-renal aorta catheterization has been estimated with respect to the arterial and venous pressures, as well as the heart rate. Saline solution was used as a control. Three different volumes (0.1, 0.5, and 1.0 mL) were infused rapidly. An increase in arterial pressure and concomitant decrease in venous pressure, which we considered as signs of a cardiovascular toxicity, were observed to a differing extent for all organic solvents. Changes in heart rate were negligible. Based on the intensity of arterial pressure change after a 1-mL infusion, a classification of the toxicity of the solvents following intra-arterial infusion is proposed: Solvents devoid of significant cardiovascular toxicity: dimethyl isosorbide (DMI), Glycofurol 75, polyethylene glycol 200 (PEG 200), diglyme. Solvents with moderate cardiovascular toxicity: tetrahydrofurfuryl alcohol (THFA), ethanol, acetone, Solketal, glycerol formal, dimethyl sulfoxide (DMSO). Solvents with marked cardiovascular toxicity: propylene glycol, ethyl lactate, N-methyl-2-pyrrolidone (NMP). Emphasis is put on the relative character of the proposed ranking and on the lack for certain solvents, at least in the open literature, of data pertaining at other forms of toxic effects (e.g., undesirable pharmacological action, carcinogenicity, teratogenicity, mutagenicity, and irritating and sensitizing properties), all factors that have to be considered when selecting a proper solvent.

Fungal internal carotid artery aneurysms: successful embolization of an Aspergillus-associated case and review.

BACKGROUND: Fungal aneurysms of the carotid artery are rare. We report here a case of Aspergillus fumigatus invasive sphenoidal sinusitis complicated by carotid artery aneurysms in a severely neutropenic patient who was successfully treated with a combination of antifungal therapy and embolization of all aneurysms. METHODS AND RESULTS: Carotid aneurysms were suspected when severe epistaxis occurred during follow-up for sinusitis. MRI angiograph and cerebral angiograph revealed 5 aneurysms involving the right intracavernous carotid artery. Coil endovascular embolization was successfully used for the first time in this context, and the patient is alive 2 years later. We also reviewed the literature and identified 10 cases of fungal carotid artery aneurysms. Aspergillus species was the most common fungal organism. All patients were immunocompromised and had to be treated surgically. CONCLUSIONS: Internal carotid arterial involvement is a rare but life-threatening complication of invasive fungal sinusitis. Fungal aneurysms should be diagnosed early, so that the embolization procedure can be performed before the occurrence of severe bleeding.

Arterial distribution of calibrated tris-acryl gelatin and polyvinyl alcohol microspheres in a sheep kidney model.

OBJECTIVE: The objective of this study was to compare the repartition in the renal arterial vasculature of tris-acryl gelatin microspheres (TGMS) and polyvinyl alcohol microspheres (PVAMS) of 3 calibers (500-700, 700-900, and 900-1200 microm). MATERIALS AND METHODS: Twelve kidneys from 6 adult sheep were embolized and histologically analyzed. The number and size of microspheres and vessels were measured, as well as the deformation of TGMS and PVAMS, and the histologic location according to a classification in 5 zones of the kidney. RESULTS: Two hundred eighty-four vessels were measured. The diameter of the occluded vessels increased when the caliber used for embolization was larger for TGMS and for PVAMS (P < 0.0001, each). The location of TGMS and PVAMS within the vasculature was different for each caliber, because PVAMS blocked significantly more distally than TGMS (P < 0.0001 each). The deformation within the tissue was greater for PVAMS (18.0 +/- 12.3%) than for TGMS (9.0 +/- 8.3%) in general (P < 0.001) and for each caliber of injected microspheres (P < 0.001 each). CONCLUSION: The repartition of a spherical embolic agent in a given vascular network can be influenced by its size and also by its deformation within the vascular bed.

Partition of calibrated tris-acryl gelatin microspheres in the arterial vasculature of embolized nasopharyngeal angiofibromas and paragangliomas.

PURPOSE: To determine the location of calibrated tris-acryl gelatin microspheres (TGMs) in the arterial vasculature of nasopharyngeal angiofibromas (NAFs) and paragangliomas (PGs). MATERIALS AND METHODS: Forty-nine specimens (25 PGs and 24 NAFs) treated operatively after embolization with TGMs of various sizes (100-300 microm to 900-1200 microm) were stained with hematoxylin and eosin saffron and analyzed at an objective magnification of 10 or 20 with a micrometric eyepiece (magnification, x12.5). The diameter of occluded vessels, their localization (intra- or extratumoral), and the number and diameter of TGMs they contained were determined. RESULTS: Embolized vessels (N = 1125) were measured: 440 in PGs and 685 in NAFs. Vessels were 89% intratumoral and 11% extratumoral. The diameter of the occluded vessels increased significantly with the size range of TGMs used for embolization for each tumor type (P < .0001). Intratumoral occluded vessels were significantly smaller than extratumoral vessels (P < .0001). Distribution of TGMs within the vascular network (intratumoral or extratumoral location) were similar for NAFs and PGs. The intratumoral and extratumoral dissemination of TGMs was different when comparing 100-300-microm TGMs versus 500-700-microm TGMs (P = .0006) as well as 300-500-microm TGMs versus 500-700-microm TGMs (P = .0001). CONCLUSIONS: The size of the vessels occluded by TGMs and their intra- or extratumoral location directly depend on the size of the injected TGMs. The vessels located inside the tumors were smaller than those located outside the tumors. A threshold for the intratumoral penetration of TGMs in the vasculature can be proposed from these data. There was no evidence of different behavior of TGMs in NAFs versus PGs.

Vascular anomalies and the growth of limbs: a review.

Growth of the limb in a child can be impaired, with the coexistence of a vascular malformation. In these vascular bone syndromes, altered growth is manifest as overgrowth or hypotrophy. The vascular malformation is usually complex and gets progressively worse with time. The two types of vascular anomalies in limbs, fast-flow and slow-flow, can be associated with limb length discrepancies. The fast-flow vascular malformations together with arteriovenous fistulae are part of Parkes Weber syndrome, characterized by congenital red cutaneous staining, hypertrophy in girth and increasing of limb length, lymphedema, increasing skin alterations due to a distal vascular steal, and pain, all of which develop during childhood. Treatment is generally conservative. An affected lower extremity can be complicated by pelvic tilting and scoliosis because leg length discrepancy may reach 10 cm. To avoid such a course, stapling epiphysiodesis of the knee cartilages is often performed, but this orthopedic procedure may augment the worsening of the arterial venous malformation in the limb. Therefore, less aggressive orthopedic management is preferable. Slow-flow vascular anomalies associated with limb growth alteration include (1) a diffuse capillary malformation (port-wine stain) with congenital hypertrophy of the involved extremity which is non-progressive; (2) purely venous malformations invading skin, muscles and joints, with pain, functional impairment, a chronic localized intravascular coagulopathy requiring distinctive management, and usually a slight undergrowth of the affected extremity and progressing amyotrophy; (3) the triad of a port-wine stain, anomalous veins and overgrowth of the limb, often known as Klippel-Trenaunay syndrome, which requires orthopedic management to decide the optimal timing for epiphysiodesis (i.e. when leg length discrepancy is >2.5 cm). Varicose veins are sometimes surgically removed after ultrasonographic and Doppler evaluation has confirmed a normal deep venous system. Capillary malformations can be effectively treated with pulsed dye laser, but results are usually poor in distal extremities.

Location of vessel occlusion of calibrated tris-acryl gelatin microspheres for tumor and arteriovenous malformation embolization.

PURPOSE: To evaluate (i). the presence and number of calibrated tris-acryl gelatin microspheres (TGMS) in targeted organs after embolization of tumors or arteriovenous malformations (AVMs) and (ii). the possible correlations among the size of TGMS used for embolization, the size of TGMS found in specimens, and the size of the occluded vessels. MATERIALS AND METHODS: Histologic slides were reviewed of 92 specimens from 80 patients with primarily head and neck tumors or AVMs operatively treated after embolization with TGMS of various sizes (40-120 microm, 100-300 microm, 300-500 microm, 500-700 microm, 700-900 microm, and 900-1200 microm). The diameters of the vessels containing TGMS, the size of TGMS, and the thickness of the inflammatory reactions developed around them were measured, and the location of the microspheres was recorded. RESULTS: TGMS were found in 88% of the specimens; 1985 embolized vessels containing TGMS were analyzed. The median number of TGMS per vessel was one (mean +/- SD, 3.1 +/- 6.9). The diameter of the occluded vessels increased significantly (P <.0001) with increased size of TGMS used for embolization. In tumors, 92% of the occluded vessels were located inside the tumor. CONCLUSION: There is an obvious correspondence between the size of the TGMS used for embolization and the diameter of the occluded vessels. This correlation confirms the possibility that the vessels to be occluded can be precisely targeted with the use of a proper TGMS size range.

[Treatment by embolization of small uterine myomata]. / Traitement par embolisation des leiomyomes utérins symptomatiques de volume modéré.

We examined the effectiveness of uterine artery embolization (UAE) as a primary treatment for small symptomatic myomatas (<50 mm diameter). One hundred patients aged from 29 to 68 years underwent UAE between 01/01/99 and 12/31/2002. Efficacy was judged by physical examination and imaging studies at 6 to 12 months. All the patients were evaluated. Treatment failed in five cases, while symptoms resolved in all the other patients. Five patients became pregnant. The main complication was amenorrhea. No serious adverse effects were observed. The efficacy and safety of this method make it a possible preventive treatment for pre-symptomatic myomata. If these findings are confirmed, they will open a new era in the treatment of fibroids.

Endovascular treatment of basilar tip aneurysms with Guglielmi detachable coils: predictors of immediate and long-term results with multivariate analysis 6-year experience.

PURPOSE: To analyze anatomic and clinical results and factors predictive of outcome in treatment of basilar tip aneurysms with Guglielmi detachable coils (GDCs). MATERIALS AND METHODS: During 6 years, 55 unselected consecutive saccular aneurysms in 53 patients (mean age, 47 years) were treated with GDC occlusion. Forty-one (75%) aneurysms were ruptured (Hunt-Hess and Fisher grades were assigned in patients); 14 (25%), unruptured. Clinical and angiographic evaluations were performed 6 months after treatment and during follow-up (mean follow-up, 2 years). Multivariate analysis was used to determine factors predictive of outcome. RESULTS: GDC occlusion was a success in 52 (95%) aneurysms, a failure in two (4%), and not attempted in one (2%). Occlusion at final follow-up, evaluated in 44 aneurysms, was complete in 34 (77%), near complete in four (9%), and incomplete in six (14%). At 6-12 months, mean aneurysmal occlusion rate significantly worsened because of revascularization (P <.001) but improved at final follow-up because of reembolization in 10 aneurysms (P =.009); it remained stable (P =.351) between initial and final follow-up. Multivariate binary logistic regression indicated that before treatment started, aneurysmal neck size was the only independent predictor of initial occlusion rate (P =.002) and revascularization (P =.004). After the initial procedure, sac size and initial occlusion rate were independent predictors of revascularization (P =.004 and.008, respectively), irrespective of neck size. Occlusion rate at 6-12-month follow-up was the only independent predictor of that at final follow-up (P =.021), regardless of shape of aneurysm. Overall morbidity was 2% (one of 51); mortality, 6% (three of 51). Mortality correlated significantly with Hunt-Hess grade 4 at admission (P =.003) and incidence of vasospasm (P =.058). CONCLUSION: GDC occlusion proved to be a safe effective therapeutic alternative to surgery in patients with ruptured or unruptured basilar tip aneurysms. Morphologic and clinical factors were respectively identified as predictors of the optimal anatomic and clinical outcomes.

Transcranial approach for venous embolization of dural arteriovenous fistulas.

OBJECT: Transvenous embolization is effective in the treatment of an intracranial dural arteriovenous fistula (DAVF). Access to the fistula via the internal jugular vein (IJV) may be limited by associated dural sinus thrombosis; a transcranial approach has been developed for venous embolization in such a situation. The authors report their experiences with the use of a transcranial approach for venous embolization of DAVFs. METHODS: Ten patients with DAVFs underwent craniectomy and embolization procedures in which direct sinus puncture was performed. The DAVFs were located inside the dura mater that constituted the walls of the transverse sinus in five cases, the superior sagittal sinus in four cases, and the superior petrosal sinus in one case. All DAVFs drained directly into a sinus with secondary reflux into leptomeningeal veins. In all cases, the fistula could not be accessed from the IJVs. Craniectomy was performed in an operating room and, in seven cases, subsequent enlargement of the craniectomy was required. Sinus catheterization was performed after the patient had been transferred to the angiography room. The DAVFs were embolized using coils only in five patients, glue only in two patients, and both coils and glue in three patients. Angiographic confirmation that embolization of the fistula was successful was obtained in all cases. A transient complication occurred during the first case after sinus catheterization was attempted in the operating room. CONCLUSIONS: The transcranial approach allows straightforward access to DAVFs located on superficial dural sinuses that are inaccessible from the IJVs. The effectiveness of this approach is similar to that of the standard retrograde venous approach. The correct location and adequate extent of the craniectomy are essential for success to be achieved using this technique.

Uterine artery embolization in sheep: comparison of acute effects with polyvinyl alcohol particles and calibrated microspheres.

PURPOSE: To compare the effects on the myometrium of polyvinyl alcohol (PVA) particles and calibrated microspheres (MS) in embolization of the uterine arteries in sheep. MATERIALS AND METHODS: Superselective and bilateral embolization of the uterine arteries was performed with PVA particles and calibrated MS within 24 hours after artificial ovulation in 26 adult nonpregnant sheep. PVA particles of four diameters, 150-250, 250-400, 400-600, and 600-1,000 microm, were compared with calibrated MS of similar diameters, 100-300, 300-500, 500-700, and 700-900 microm, in eight groups of sheep. Evaluation was based on histopathologic study of uterus, ovaries, and vascular pedicles after sacrifice 5 days after embolization. The scores of necrosis, the diameter of occluded arteries, and the number of particles were determined. The scores of uterine necrosis were compared by using nonparametric tests (Mann-Whitney U and Kruskal-Wallis). Spearman rank test was used for correlations. RESULTS: PVA particles clumped more readily than did MS. Small particles had a higher score (P =.02) of uterine necrosis than did large particles. PVA particles produced more necrosis than did MS. Size of MS and diameter of occluded arteries showed significant correlation (rho = 0.762, P <.001). Size of PVA particles and diameter of occluded arteries showed no correlation. PVA particles occluded vessels of a wider range of size than did calibrated MS. CONCLUSION: PVA particles are associated with intense uterine necrosis and extensive arterial occlusion regardless of size. Calibrated MS, which are associated with less uterine necrosis, permit a segmental arterial occlusion correlated with size.

Combined central retinal arterial and venous obstruction: emergency ophthalmic arterial fibrinolysis.

PURPOSE: To investigate the role of urokinase selectively perfused into the ophthalmic artery as an emergency treatment for combined central retinal arterial obstruction (CRAO) and central retinal venous obstruction (CRVO). MATERIALS AND METHODS: Over a 6-year period, 11 consecutive patients presented with recent combined CRAO and CRVO (< or =72 hours). Urokinase (300,000 IU) was selectively perfused via the femoral artery into the ophthalmic artery for 40 minutes. Evaluation criteria were Snellen visual acuity with best correction, funduscopic results, and retinal arteriovenous transit time assessed over a mean 3.5-year follow-up. Mean vision and retinal perfusion were tested by means of repeated-measures analysis of variance. The correlation between visual improvement and retinal perfusion improvement was evaluated by means of Spearman rank correlation. RESULTS: Substantial improvement in vision and retinal perfusion was noted in seven of the 11 patients treated. Mean vision improvement was significant (P =.009) within 24-48 hours after fibrinolysis, increased until 1 month after (P =.006), then remained stable throughout the follow-up (P >.10). Visual improvement correlated with retinal perfusion improvement during the period from before fibrinolysis to 24-48 hours after (P =.028). In all patients with improved results, retinal hemorrhages transiently increased. One patient had intravitreal hemorrhage shortly after fibrinolysis. CONCLUSION: For this uncommon clinical entity, which typically has a poor visual outcome, these results suggest that ophthalmic arterial fibrinolysis may restore retinal perfusion, which leads to rapid substantial visual improvement in many cases of combined CRAO and CRVO, without systemic complications, but it may be responsible for intravitreal hemorrhage.

Thromboaspiration in the basilar artery: report of two cases.

Recanalization of the basilar artery is not always achieved with intraarterial fibrinolysis. We report two cases of thromboaspiration in the basilar artery in which recanalization with fibrinolysis was successful. Thromboaspiration requires favorable anatomy and a fresh nonadhesive clot. It reduces the time for recanalization, has no hemorrhagic risk, and may prevent distal clot migration. Thromboaspiration may be attempted as an adjunct or alternative to intraarterial fibrinolysis for basilar artery recanalization.

Endovascular treatment of cerebral mycotic aneurysms.

PURPOSE: To evaluate the endovascular treatment (EVT) of mycotic aneurysms (MAs). MATERIALS AND METHODS: Clinical and radiologic data of 18 MAs treated with EVT were retrospectively reviewed. There were 14 patients (11 men, three women), ranging in age from 28 to 64 (mean age, 44 years). All patients had endocarditis and positive blood culture. The aneurysms were located within the distal cerebral circulation (n = 13) or in the circle of Willis (n = 5). There were 12 ruptured aneurysms and six unruptured aneurysms. Distal or fusiform aneurysms were treated by means of parent vessel occlusion. Proximal saccular aneurysms were selectively treated. RESULTS: Endovascular treatment was successful for all aneurysms. No aneurysm bled after embolization during clinical follow-up. Follow-up angiograms obtained in 11 of 14 patients 6 months to 2 years after the procedures showed stable occlusions. Transient complications occurred in two cases, with worsening of hemiparesis and quadrantanopia. Five patients underwent surgical cardiac valve replacement within 1 week of EVT without neurologic complications. The late clinical outcome was normal neurologic status (n = 9) or permanent disability that was related to the initial stroke (n = 5). CONCLUSION: EVT is a reliable and safe technique that should be considered at the time of diagnosis of cerebral mycotic aneurysms.

Coil embolization of an aortic arch false aneurysm.

PURPOSE: To report the endovascular occlusion of an anastomotic false aneurysm of the ascending aorta. CASE REPORT: A 51-year-old patient developed an anastomotic false aneurysm at the level of the aortic arch after surgical replacement of the aortic root and arch for aortic dissection. The aneurysm expanded after 6 months and because of its saccular shape was treated by selective occlusion with detachable microcoils. Magnetic resonance angiography showed the stability of the occlusion after 2 years. CONCLUSIONS: Endovascular treatment with coils may be a good alternative to surgery for saccular anastomotic false aneurysms.