Glubran 2: a new acrylic glue for neuroradiological endovascular use. Experimental study on animals.

SUMMARY: A new acrylic glue, Glubran 2, is now available on the European market. It bears the CE mark with several surgical indications and the specific indication for neuroradiological endovascular use. Despite this approval, to our knowledge its use is still limited to surgery and no injections have been made in human patients. This study was designed to evaluate the behavior of Glubran 2 in endovascular injection in a simulation of brain AVM. Six sheep were operated on opening a fistula between the right common carotid artery and the jugular vein. This fistula modifies blood flow in the skull base rete mirabilis, which then functions as an AVM. In two sheep, the rete mirabilis was occluded by injection of 1.5 ml of Histoacryl diluted 1:1 and 1:3 with Lipiodol. In two sheep, the rete was embolized by injection of 1.5 ml of Glubran 2 diluted 1:1 with Lipiodol. The last two sheep were embolized by injection of Glubran 2 diluted 1:3 with Lipiodol. The procedures were documented by DSA angiographic acquisitions and by fluoroscopic VHS. The sheep were killed immediately after the procedures and the rete mirabilis isolated for histologic examination. Embolization was obtained with both kinds of glue. Glubran 2 diffuses in a very similar way to Histoacryl with an apparently more complete diffusion. Reflux in the ascending pharyngeal artery showed that Glubran 2 tended not to produce bubbles but diffused more homogeneously. The subjective conclusion of this work is that Glubran 2 can be used in endovascular embolizations. Before approaching brain AVMs, a further study will investigate embolization of the external carotid territory.

Ischemia-reperfusion syndrome: an alternative experimental model.

OBJECTIVE: To design an alternative experimental model of ischemia-reperfusion syndrome. Our model mimics the clinical pattern of the syndrome and also assesses the efficacy of therapeutical protocols. EXPERIMENTAL DESIGN: Ischemia was induced under general anaesthesia in the posterior limbs of 10 sheep by occluding the aorta and vena cava by means of two-way balloon catheters. Ischemia was stopped after 4 hours and blood and histologic parameters determined in the first three hours of revascularization. The animals were divided into three groups: a group of 3 sheep in which a sham operation was performed; a control group (5) to assess the efficacy of induced ischemia; the third group (5) to determine the effect of antioxidant and membrane protective drugs to assess the reliability of the model to study the ischemia-reperfusion syndrome. RESULTS: At the end of ischemia, skin temperature was decreased (p < 0.04) both in control and treated groups, pH decreased significantly soon after reperfusion in the control group (p < 0.04). Reperfusion in control sheep, compared with treated animals, was followed by a significant increase in CPK blood levels (p < 0.009), related to marked muscle damage, in particular after reperfusion. Tissue damage detected at TEM was less severe in treated animals. CONCLUSIONS: This model is an effective experimental strategy and a means of assessing preventive treatment.

Prevention of reperfusion syndrome in acute muscular ischaemia with free radical scavengers and membrane-protecting compounds: an experimental study.

The prevention of oxidant-induced damage following reperfusion was experimentally evaluated. Two pharmacological regimens containing different combinations of antioxidant factors and membrane-stabilizing compounds, such as alpha-tocopherol (vitamin E), methionine, dexamethasone, mannitol and cysteine, were administered. The reduced/oxidized glutathione (GSH/GSSG) ratio in muscle was used to evaluate oxidative stress. Ischaemia was induced by occluding the aorta and the inferior vena cava with an irrigation-occlusion catheter. After 4 h of ischaemia, five sheep were reperfused without any treatment (control group) and five treated with an endoaortic bolus administered at declamping (treatment 1). In five other sheep, treatment started during ischaemia (treatment 2). Ischaemia and, in particular, reperfusion significantly reduced the muscle GSH content, compared with the basal value in the control group; thus the GSH/GSSG ratio decreased significantly in the control group from 10.5(2.2) (mean(s.e.) basal value) to 0.687(0.3) at reperfusion (P < 0.009). Both treatments 1 and 2 significantly prevented a reduction in GSH content induced by reperfusion following ischaemia; the GSH/GSSG ratio (10.5(2.2) basal value) increased to 19.67(4.6) with reperfusion in the treatment group 1, mainly because of a lower decrease of GSH and a lower level of GSSG while it did not change in treatment group 2 (10.7(5.0)). Levels of creatine phosphokinase did not change in the treated groups, although they increased significantly in the control group (P < 0.006). Although oxidative stress is not the only cause of damage in revascularization, this study confirms the protective ability of treatment with free radical scavengers and membrane-stabilizing compounds.

Interaction between vascular prostheses and rifampicin in the prevention of the grafts infection. An experimental study.

Infections caused by synthetic prostheses are relatively rare (1.5-6%) but serious complication in vascular surgery. There is no doubt that during and immediately after surgery bacterial contamination may occur. An in vitro study was carried out in the Vascutek laboratories, which revealed a high affinity between prostheses in Dacron gel and Rifampicin. This affinity, the result of an ionic bond, was demonstrated by the fact that after 5 days Rifampicin was still present on the prostheses. Encouraged by this result, an experimental study was carried out in sheep. Five sheep were operated on making a prosthetic graft in both of the common carotid arteries: on one side a Gelseal Dacron prosthesis was implanted after being soaked for 15 minutes in a solution containing 1 mg/ml Rifampicin. A Knitted Dacron prosthesis was implanted in the contralateral carotid artery, again after pretreatment with Rifampicin. Explants were made after 2, 24, 48, 72 and 96 hours, and the concentration of Rifampicin on the prostheses was assessed on the basis of the diameter of the inhibition area on Staphylococcus aureus cultures. The results showed that the Gelseal Dacron prostheses maintained Rifampicin concentrations with an antibacterial activity up to 72 hours; this property disappears with the Knitted Dacron prostheses after only 24 hours. These results confirm the high affinity of Gelseal Dacron and Rifampicin also in in vivo experimental models.

Local haemofiltration with free radical scavenger treatment during revascularisation of severe muscular ischaemia induced in sheep limbs.

Many treatments have been proposed for the prevention of the revascularisation syndrome following embolectomy or thrombectomy in patients with severe ischaemia. These include the administration of diuretics, bicarbonate, buffer solutions, free radical scavengers, washing out the venous blood from the ischaemic leg, or systemic dialysis. The aim of our study was to investigate the effect of combining haemofiltration with a treatment using compound oxy-radical scavengers in order to prevent or to reduce the appearance of the revascularisation syndrome. The study was performed on 13 sheep. Eight animals underwent 4 h of aortic and vena cava occlusion using irrigation-occlusion catheters, followed by normal reperfusion (control group). Five sheep underwent the same period of ischaemia, followed by 1 h of local haemofiltration and re-oxygenation and 2 h of normal revascularisation. The priming solution for the ECC circuit consisted of 500 ml of 20% mannitol and 500 ml of 18/1000 HCO3- contained: superoxide dismutase (150,000 I.U.), methylprednisolone, 1 g, and heparin, 10,000 I.U. After the 3rd h of ischaemia, 2.1 g of acetate alpha-tocopherol (30 mg kg-1) were injected i.m. The treatment produced good protection against oxidative stress, shown by an increase in the glutathione ratio (GSH/GSSG), and reduced muscular damage, confirmed by a moderate increase in creatine phosphokinase (CPK) levels (significantly higher in the control group). Diuresis was significantly higher in the treated group, and the acid-basic and potassium balance returned to normal more rapidly. Our data suggest that this combined treatment could be effective in the prevention of the ischaemia-reperfusion syndrome.