Release of ibuprofen from beads for embolization: in vitro and in vivo studies.

Ibuprofen (IBU) loaded polyvinyl alcohol-based hydrogel beads (IBU-BB) were designed to alleviate side effects such as inflammation and pain following uterine artery embolization for the treatment of leiomyomata. The present in vitro and in vivo study examines whether IBU-BB provide a sustained-release of the drug. In vitro release studies of IBU from IBU-BB (10, 50, 100 mg/mL), IBU solution (PEDEA) and IBU powder were compared using the T apparatus and the beaker method. The pharmacokinetic profile of IBU release was examined in vivo, following sheep uterine artery embolization with 100 mg/mL IBU-BB or after intra-arterial injection of IBU solution. IBU-BB can deliver high concentrations of the drug over time. The in vitro release from IBU-BB was markedly slower compared to IBU solution. Increasing the concentration of loaded IBU from 10 to 100 mg/mL decreased the rate of release. IBU release from the T apparatus was slower than the release in the beaker. In vivo, the release of the drug was progressive, without the early peak observed with IBU solution. A high level of correlation was obtained between in vivo and in vitro (T apparatus) results. Theoretically, IBU-BB could sustainably release high concentrations of IBU at the site of the uterine fibroids, which makes it a promising approach for the control of post-embolization pain.

Thrombosis of angiographic catheters in humans: experimental study.

One of the major problems in the use of catheters is their thrombogenicity since the embolization of clots near the central nervous system or the coronary arteries can cause permanent damage. Catheter thrombogenicity was evaluated in humans during angiographic procedures by their tendency to become occluded. Characterization of catheters was achieved using roughness measurements, FTIR with ATR, DSC and ESCA. The catheters were 5 commercially available catheters, made mainly of polyethylene, Pebax or polyamide sterilized and ready for clinical use. Thirty-one patients due to have an angiographic procedure and with normal blood and hemodynamic parameters were included in the study. The 50 cm catheter test sample was inserted through an introducer into the femoral artery at the beginning of an angiographic procedure. The outcoming blood flow rate (BFR) was continuously monitored by a special computerized device for 15 min or until the total amount of blood reached 30 ml. The angiographic procedure was then normally resumed. DSC and FTIR showed results consistent with the expected composition of catheters. ESCA results showed very high Si/C ratios and could not be explained in all instances. Occlusion of the catheters occurred in 44% of the cases and the average time to obtain occlusion was 8.5 min (3-15 min). Values of the decrease rate of BFR in ml/min2 allowed separation of the catheters into 3 groups of low, medium and high thrombogenicity. However, occlusion occurred at least one time for each type of catheter. Blood volume and BFR curves vs. time allowed the determination of 3 main types of thrombotic behavior: type I shows no significant reduction of BFR; type II shows a progressive decrease in flow rate; type III is much less frequent and shows an abrupt decrease of BFR either quickly followed by a compensatory increase and resuming of a steady flow or by abrupt occlusion. In type II curves the pattern of occlusion follows a classical diffusion model because the Peclet number is greater than 1 and then the classical Higbie solution for diffusion could be used. The most thrombogenic material was the smoothest. There was no correlation between surface chemical composition and thrombogenicity. However, catheters that were based on PE appeared less thrombogenic than PA catheters in this study.

Effects of red blood cell hyperaggregation on the rat microcirculation blood flow.

This study presents the effects of red blood cell (RBC) hyperaggregation on the blood flow and pressure in the rat mesentery and cremaster network. We exclusively studied in situ non-vasodilated organs, in order to maintain the physiological regulation mechanisms. Dextran 500 was injected at different concentrations to increase RBC aggregation. The aggregation rate was measured on very small blood samples with an erythroaggregameter (SEFAM) which evaluated the disaggregating shear stress (tau D) needed to break the RBC aggregates. Microscopic observations and laser Doppler velocimetry were used to quantify the flow rate. The plasmatic dextran concentration (C) increase had different correlated effects: for example, tau D increased from 3 dynes cm-2 (for the control sample) to 14 dynes cm-2 (for C = 75 microM L-1); the flow rate was reduced threefold and very large aggregates were observed in the venules; the arteriolar pressure increased while venular pressure decreased. In order to differentiate the effects of RBC hyperaggregation from those of plasma hyperviscosity (due to dextran 500) on microcirculatory blood flow, we injected an RBC antiaggregating drug (troxerutine) (50 or 100 mg kg-1 i.v.). The consequences were a high reduction for (tau D) (from 14 dynes cm(-2)-9 dynes cm-2), smaller aggregates and higher blood flow in the venules. No effect of troxerutine was observed on plasma viscosity (plasma control: 1.9 cP with or without troxerutine; plasma with dextran at C = 75 microM L-1: 2.45 cP with or without troxerutine). The results strongly suggest that RBC aggregation has a significant influence on blood flow rate in the microcirculatory network.

Theoretical and experimental study of intermittent blood flows in microcirculation: application to the in-vivo determination of compliance.

A new theoretical approach was used to study the nonlinear response of a microvascular segment subjected to a pressure step at one end. The method is suitable for both large and small deformations of the vessel wall in the case of an elastic response of the segment. It is shown that the use of this simulation permits an indirect determination of the compliance of the vessel. The procedure is applied in two cases of major interest: first the in-vivo study of the intermittent blood flow in the microcirculation, and second, the analysis of experiments using micropipettes. The resulting values of the compliance agree with other values found in the previous studies. The theoretical method is particularly adapted to nonlinear equations.