Biomedical subjects

Heiko Alfke

Publications and source records attributed to Heiko Alfke.

21 records · Page 2Linked to original sources

PubMed2002

Deposition of nanoparticles in the arterial vessel by porous balloon catheters: localization by confocal laser scanning microscopy and transmission electron microscopy.

Restenosis remains the major limitation of percutaneous transluminal angioplasty (PTA) and stenting in the treatment of patients with atherosclerotic disease. Catheter-based local delivery of pharmacologic agents offers a potential therapeutic approach to reducing restenosis and minimizing undesirable systemic side effects. However, the intramural retention of liquid agents is low. Therefore, to achieve a sustained and regional release of the therapeutic agent it must be encapsulated in nanoparticle carrier systems. The purpose of this study was to investigate the size dependence of the penetration of nanoparticles after local delivery into the vessel wall of the aorta abdominalis of New Zealand white rabbits. Two milliliters of a 0.025% fluorescence-labeled polystyrene nanoparticle suspension with diameters ranging from 110 to 514 nm were infused at 2 atm and at constant PTA pressure of 8 atm into the aorta abdominalis. After the infused segments were removed, the location of nanoparticles was visualized using confocal laser scanning microscopy and transmission electron microscopy. The study demonstrates a size-dependent nanoparticle penetration into the intact vessel wall. While nanoparticles of about 100 and 200 nm were deposited in the inner regions of the vessel wall, 514-nm nanoparticles accumulated primarily at the luminal surface of the aorta. The observations confirm that size plays a critical role in the distribution of particles in the arterial vessel wall. It is additionally influenced by the formation of pressure-induced infusion channels, as well as by the existence of anatomic barriers, such as plaques, at the luminal surface of the aorta or the connective elastic tissue.

Animals↗

PubMedDate not supplied

Local administration of NF-kappa B decoy oligonucleotides to prevent restenosis after balloon angioplasty: an experimental study in New Zealand white rabbits.

PURPOSE: To evaluate the efficacy of NF-kappa B oligonucleotides (ODN) administered by local administration with the channeled balloon catheter to prevent restenosis after balloon angioplasty in restenotic iliac arteries of New Zealand white rabbits. MATERIALS AND METHODS: In vitro, 8000 rabbit vascular smooth muscle cells (rVSMC) where transfected with a liposomal carrier (TfX50) with 100 ng of decoy and scrambled ODN. Inhibition of proliferation was measured using a MTT assay after 24 hours in comparison to control. In vivo, 22 male New Zealand White rabbits were fed a 1% cholesterol diet and received denudation of both common iliac arteries with a 3 mm balloon catheter to induce an arterial stenosis. Four weeks after stenosis induction, local application of NF-kappa B in two different concentrations (1 mug: n = 14; 10 mug: n = 8) was performed randomly on one common iliac artery. Scrambled oligonucleotides without specific binding capacities were injected into the contralateral side. The channeled balloon catheter allows simultaneous balloon dilation (8 atm) of the stenosis and local application of a drug solution (2 atm). Four weeks after local drug delivery the animals were killed and the vessels were excised and computerized morphometric measurements were performed. RESULTS: NF-kappa B decoy ODN but not scrambled ODN inhibited proliferation of rVSMC in vitro. Following local ODN application in the animals, no acute vascular complications were seen. NF-kappa B ODN resulted in a statistically non significant reduction of neointimal area compared to the control group. The neointimal area was 0.97 mm(2) using 1 mug NF-kappa B ODN compared to 0.98 mm(2) in the control group. The higher dose resulted in a neointimal area of 0.97 mm(2) compared to 1.07 mm(2) at the control side. CONCLUSIONS: Local drug delivery of NF-kappa B ODN using the "channeled balloon" catheter could not reduce neointimal hyperplasia in stenostic rabbit iliac arteries. Application modalities have to be improved to enhance the effect of the local application to prevent restenosis after balloon angioplasty.

Angioplasty, Balloon↗

PubMedDate not supplied

Cardiovascular risk factors do not predict clinically defined restenosis after percutaneous transluminal angioplasty for lower limb ischemia.

The purpose of this study was to evaluate risk factors predicting restenosis and primary patency after percutaneous transluminal angioplasty. Follow-up data (including cardiovascular risk factor scores according to SCVIR criteria, preinterventional and postinterventional clinical data and patient history) of all patients who underwent successful percutaneous transluminal angioplasty for lower limb ischemia were analyzed retrospectively and patients, relatives, or referring physicians underwent a telephone interview. Patients with incomplete follow-up data were examined by means of a clinical examination, including Doppler measurements and treadmill test. Additionally all angiograms were evaluated to calculate lesion length, number of treated lesions, lesion type (SCVIR score), and runoff. The outcome was categorized into four groups: early recurrence (< 1 month, group I), mean recurrence (1-6 months, group II), late recurrence (>6 months, group III), and no recurrence (group IV). According to common concepts group I was defined as early (thrombotic) reocclusion, group II as clinically defined restenosis, and group III as progression of atherosclerosis. One hundred thirty-seven patients underwent percutaneous transluminal angioplasty of 148 extremities. The groups differ significantly only with respect to a higher diabetes score for group I in comparison to group IV (p=0.002, Kruskal-Wallis test), and a worse runoff of group I compared with group IV (p =0.008). There was a trend toward a higher diabetes score for group II in comparison to group IV (p = 0.014). There were no differences with regard to hyperlipemia, hypertension, and tobacco use between patient groups. Mean primary patency was 436 days. Predictors for lower patency rates were diabetes mellitus (p<0.001), runoff (p=0.005), and number of treated lesions (p=0.007) in a stepwise, multiple regression analysis. Patients with clinically defined restenosis showed no specific risk factor profile in this study. Predictors for lower primary patency were diabetes mellitus, number of treated lesions, and runoff.

Aged↗