Comparison of methods for local delivery of tissue factor pathway inhibitor to balloon-injured arteries in rabbits.

BACKGROUND: Prolonged intravenous infusions of recombinant tissue factor pathway inhibitor (rTFPI) have been shown to attenuate markedly neointimal formation and stenosis after balloon-induced injury to the carotid arteries in minipigs. DESIGN: Because local delivery of rTFPI to the injury site would be clinically advantageous, we designed this study to compare the local delivery and retention of rTFPI in balloon-injured arteries using three catheter-based systems. METHODS: Similar amounts (range 3-4.5 mg) of a mixture of 125I-labeled and unlabeled rTFPI were delivered by either passive diffusion at moderate pressure (5 x 10(5) Pa with the LocalMed InfusaSleeve, or 4 x 10(5) Pa with the SciMed Dispatch device), or facilitated diffusion combining lower pressure (2 x 10(5) Pa) and electrical current (3.5 mA/cm2; e-MED, iontophoresis) to balloon-injured carotid arteries in anesthetized rabbits. RESULTS: Comparable amounts of rTFPI were retained on the injured vessels immediately after delivery (t = 0) with the LocalMed (628 +/- 68 micrograms/g per cm2, n = 4), SciMed (522 +/- 167 micrograms/g per cm2, n = 4), and e-MED (497 +/- 142 micrograms/g per cm2, n = 4) catheters (NS). However, rTFPI was decreased by 37% after 24 h compared with t = 0 (P < 0.02) in the e-MED group, but was increased 1.5-fold (P = 0.02) and 1.3-fold in the SciMed and LocalMed groups, respectively, presumably because of redistribution of rTFPI from remote endothelial or perivascular sites. Retention of rTFPI was six to nine times higher for injured compared with non-injured arteries, and persisted for at least 48 h after delivery with the LocalMed catheter. CONCLUSIONS: Sustained, marked retention of rTFPI delivered locally at the site of balloon-induced arterial injury appears to result from catheter-based systems that use passive diffusion at moderate pressure.

Pharmacokinetics and tissue localization of antisense oligonucleotides in balloon-injured pig coronary arteries after local delivery with an iontophoretic balloon catheter.

When delivered locally to the arterial wall by passive fluid transfer systems such as perforated balloons, water-soluble compounds in aqueous solution are not readily taken up by tissue, show low levels of cellular localization, and are quickly lost by wash-out. One approach to improve delivery is addition of an "active" component to the catheter system to change the nature of the drug-to-tissue interaction. Using an iontophoretic balloon catheter to deliver antisense oligonucleotide (ODN) to pig coronary arteries after balloon angioplasty, we determined the quantity and localization of ODN in the tissue. By radiolabeling, 7.3 +/- 2.4 micrograms ODN was present at 30 min, 1.5 +/- 0.6 at 2 h, 0.52 +/- 0.35 at 24 h, and 0.26 +/- 0.11 at 7 d. By fluorescent labeling, circumferential medial uptake and adventitial delivery at the site of medial injury was observed, with primarily cellular localization. The iontophoretic catheter thus appears to be a useful device for ODN delivery to arterial tissue.

A survey of cardiopulmonary bypass perfusion practices in Australia in 1992.

Twenty-four cardiopulmonary bypass (CPB) perfusion units around Australia were surveyed to determine the characteristics of CPB perfusion as practised in Australia in 1992. Twenty completed survey forms were received. Findings were compared with those of a similar study performed by one of the authors for the year 1986. The field of CPB perfusion continues to expand both in terms of numbers of cases and increasing technological complexity. The major technological changes evident are the now clear dominance of membrane over bubble oxygenators and the proliferation of inline SvO2 monitoring devices. The greatest change in practice has been to the virtually universal use of cardioplegia. There remains considerable variation in the composition of the cardioplegia solutions used in the responding units. A range of minimum perfusion pressures for CPB is noted, whereas most units employ similar minimum perfusion flows. Methods of central nervous system and renal protection are mainly hypothermia and diuretics, respectively, with a scattering of other techniques. Staffing of CPB perfusion units is essentially unchanged since 1986 and at least five units had no medical perfusionist appointed in 1992.