James E. Leone

Local drug delivery catheters: functional comparison of porous and microporous designs.

BackgroundThe porous (Wolinski) balloon was designed to allow local delivery of compounds targeted to inhibit postintervention restenosis; however, successful use of the device has been hampered by arterial trauma caused by the balloon itself. This study utilized several experimental systems to assess the functional characteristics of the porous balloon catheter. This information was utilized to design and test a new microporous infusion catheter for local intra-arterial drug delivery. MethodsFlow characteristics in fluid and semisolid media as well as arterial trauma by light and electron microscopy were documented for the porous and microporous balloons. In addition, the efficacy of methylene blue delivery in situ and in vitro was documented and quantified for the microporous design. ResultsThe porous balloon exhibits flow characteristics consistent with orifice-related streaming that produces arterial trauma. By maximizing external balloon-pore density and minimizing pore size, the microporous design minimizes streaming in test systems. This is manifested by minimal arterial trauma when applied to intact arteries. The microporous catheter is effective for dye delivery both in situ and in vivo. ConclusionsThe microporous catheter design offers improved functional characteristics when compared with the porous balloon for local intra-arterial drug delivery.

The Double-Tuck Model: A New Animal Model of Arterial Thrombosis

PURPOSE To develop an animal model of a fibrin- and platelet-rich intraluminal arterial thrombus with abnormal mural substrate to simulate in situ thrombosis of human atherosclerotic arteries. MATERIALS AND METHODS Parallel studies of the crush-thrombin model (CT) and double-tuck model (DT) were performed and evaluated with use of angiography and histologic analysis. Ten Yorkshire swine (1-6 months; 20-30 kg; 10 females) underwent right femoral and carotid cutdowns performed after administration of general anesthesia (4 mL intravenous thiopental sodium, isoflurane 2% in 1 L of oxygen). After angiography, the CT model was created in the left carotid artery and the DT model was performed in the right carotid artery. Angiograms were obtained at 20 minutes (n = 1), at 1 hour (n = 3), at 2 hours (n = 4), and at 3 hours (n = 2) before sacrifice. After sacrifice, histologic specimens were stained with hematoxylin-eosin (H-E stain) and phosphotungstic acid hematoxylin for fibrin. The specimens were examined for endothelial irregularity and adhesion, platelet aggregation, fibrin layering, vessel wall injury, and adventitial hemorrhage. The findings were quantified as 0 = absent, 1+ = slight, 2+ = moderate, and 3+ = severe. RESULTS Angiographic results were similar. However, histologic analysis of the CT model showed severe damage to the arterial wall with dissection in nine of 10 animals. In the DT model, no dissection was found (n = 10). Endothelial irregularity was found in six of 10 arteries treated with the CT method, as compared with nine of 10 arteries prepared with the DT model; endothelial adhesion was found in five DT arteries and in four CT arteries. Platelet aggregation was present equally in both methods. A fibrin- and platelet-rich thrombus was created in five of 10 examined arteries by both methods. CONCLUSIONS The DT model creates endothelial irregularity leading to formation of a platelet- and fibrin-rich thrombus, adherent to the vessel wall without damage to the media. This contrasts with the CT method, which created medial dissection in nine of 10 arteries. One hour is the minimum time required to produce a good quality thrombus; 2 hours is the optimum time. The DT model is proposed as a useful tool in the development of new devices, drugs, and biotechnologic advances.