Transvascular transport has been studied with atherogenic, tracer, and inert compounds such as low-density lipoprotein, horseradish peroxidase, and albumin, respectively. Few studies used vasoactive compounds, and virtually all studies examined entry from the lumen and not from the perivascular space. We compared several mechanisms that govern arterial heparin deposition after administration to the perivascular and endovascular aspects of the calf carotid artery in vitro and the rabbit iliac artery in vivo. In the absence of transmural hydrostatic pressure gradients, heparin deposition following endovascular administration was unaffected by deendothelialization and was indistinguishable from perivascular delivery. Deposition in the former was enhanced by the addition of a pressure gradient and to a greater extent in denuded arteries, indicating that convection influences transport but is dampened by the endothelium. Neither the endothelium nor the adventitia pose significant resistances to heparin. Deposition in vivo was greater following endovascular hydrogel release than perivascular application from similar devices to native or denuded arteries. The loss of drug to extra-arterial microvessels exceeded the loss of drug to the lumen flow. These findings are essential for describing vascular pharmacokinetics and for implementing local pharmacotherapies.

Crack turning or delamination behavior of AA 2050-T87 and AA 7050-T7451 ESE(T) and hourglass coupons under cyclic fatigue conditions is presented. Fatigue crack growth rate curves, fracture surface examinations, and the preferred manner of crack growth for each alloy are discussed in an effort to better understand fatigue crack growth behavior of aluminum-lithium alloys in structural components under service conditions.

5525 Background: It has been hypothesized that the presence of extensive adhesions after ovarian cancer resection may limit the distribution of intraperitoneal (IP) chemotherapeutics. The objective of this study was to determine if using a hyaluronate/carboxymethylcellulose (HA/CMC) barrier to prevent adhesions during a simulated tumor resection surgery would increase tissue drug levels following subsequent IP chemotherapy. Methods: A sidewall defect/cecal abrasion model was used to induce adhesion formation and simulate tumor resection trauma in 22 rabbits. Seven rabbits received HA/CMC at the end of the surgery. Four weeks after surgery, cisplatin (2.5mg/kg) was administered IP to HA/CMC treated and untreated animals or IV to untreated controls. Animals were sacrificed 24hrs after infusion and tissue samples were collected from inside the defect (with or without adhesions) and outside the defect on the contralateral sidewall. Samples were cryosectioned and analyzed for platinum content by ICP/MS. Results: Platinum tissue levels in the uppermost peritoneal layer (0–1mm) were significantly higher for IP delivery than IV and were the highest for IP delivery when no adhesions were present inside the defect. Platinum levels were significantly higher in the previously traumatized tissue inside the defect than in untraumatized tissue outside the defect. This was consistent for both IP or IV and HA/CMC treated or untreated animals. The benefit of HA/CMC was underscored by the fact that samples under adhesions could not be obtained for that group due to the significant reduction in adhesion formation compared to untreated controls. Conclusions: Recently traumatized tissue without adhesions had the highest platinum levels following IP cisplatin in this model. The previously traumatized tissue had significantly higher platinum levels than untraumatized tissue likely due to both increased peritoneal diffusion and systemic delivery components. [Table: see text] [Table: see text]

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