title: Local delivery of heparin to balloon angioplasty sites with a new angiotherapy catheter: pharmacokinetics and effect on platelet deposition in the porcine model.
abstract: The purpose of this study was to assess the efficacy of local heparin delivery to balloon angioplasty sites in an in vivo porcine model by using a newly designed angiotherapy catheter that allows for prolonged drug infusion while maintaining distal arterial perfusion. Protocols were designed to assess the safety of intracoronary drug delivery, the effect of infusion time and drug concentration on intramural heparin deposition, the distribution of heparin within the arterial wall, the histologic effects of local heparin delivery, the wash-out of intramurally deposited heparin, and the effect of heparin delivery on early platelet deposition following balloon injury in peripheral and coronary vessels. Local intracoronary delivery of heparin was well tolerated in all animals. Between 0.04 and 0.08% of infused heparin was intramurally deposited at the time of drug delivery, with longer infusion durations and higher concentrations of heparin resulting in greater intramural deposition. Autoradiography demonstrated homogenous distribution of heparin throughout the intima, media, and adventitia, with localization in the nuclei, cytoplasm, and extracellular space. Histologic analysis demonstrated no additional vessel trauma from local drug delivery beyond that seen with conventional angioplasty. Wash-out studies demonstrated a biexponential disappearance of intramurally deposited drug, with rapid release of heparin over the first 60 min and persistence of small amounts of drug for at least 7 d. Locally delivered heparin significantly attenuated the deposition of platelets in peripheral vessels, although a similar decrease in platelet deposition in the coronary arteries was not statistically significant. Local delivery of heparin directly to coronary angioplasty sites is possible with the use of a new angiotherapy catheter. Wash-out of heparin from the arterial wall is initially rapid, although drug is detectable for up to 1 wk following delivery. In porcine peripheral arteries, use of this technique significantly decreases early platelet deposition following balloon injury.
authors.affiliation: Department of Internal Medicine, Hartford Hospital, University of Connecticut 06102, USA.
authors.forename: D B
authors.initials: DB
authors.lastname: Fram
authors.forename: J F
authors.initials: JF
authors.lastname: Mitchel
authors.forename: M A
authors.initials: MA
authors.lastname: Azrin
authors.forename: M S
authors.initials: MS
authors.lastname: Chow
authors.forename: D D
authors.initials: DD
authors.lastname: Waters
authors.forename: R G
authors.initials: RG
authors.lastname: McKay
mesh_terms: D015906:Angioplasty, Balloon, Coronary / Q000295:instrumentation*; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001345:Autoradiography; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000295:instrumentation*; D004867:Equipment Design; D006493:Heparin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology; D010974:Platelet Aggregation / Q000187:drug effects*; D013552:Swine; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D006493:Heparin