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Objectives: The goal of this study was to evaluate a new drug-eluting stent (DES) comprising a bioabsorbable polymer eluting a moderate dose of paclitaxel in a clinically relevant animal model., Background: Although DES limit restenosis, adverse vascular pathologies and toxicities continue to be of major concern. Optimization of DES components, especially completely absorbable polymers, may reduce these toxicities., Methods: Bare-metal (BM), absorbable polymer coating only (POLY), and polymer-based paclitaxel-eluting (PACL) stents were implanted in porcine coronary arteries using intravascular ultrasound (IVUS) to optimize stent apposition. The dose density of paclitaxel was 0.30-0.35 mcg/mm2, with in vitro elution studies demonstrating a gradual elution over 6-8 weeks. The animals were terminated at 1 week, 1 month and 3 months. Histopathologic and histomorphometric analyses were perform., Results: The arteries with PACL showed extensive smooth muscle cell necrosis at 1 week and poor apposition of stent struts at 1 month (malapposition measured as gap width between strut and internal elastic lamina), with greater gap width compared to the BM and POLY groups (0.22 mm +/- 0.02 vs. 0.03 mm +/- 0.02 and 0.02 mm +/- 0.01, respectively; p < 0.001). At 3 months, the PACL group showed rebound neointimal thickness and histological percent stenosis compared to the BM group (0.48 mm +/- 0.14 vs. 0.07 mm +/- 0.02, respectively; p < 0.001 and 59% +/- 11 vs. 17% +/- 2, respectively; p < 0.001)., Conclusions: Despite in vitro data showing slow, sustained release of paclitaxel from a bioabsorbable polymer, the porcine coronary artery model demonstrated a sequence of medial necrosis, stent malapposition and late neointimal thickening. Since the therapeutic window for paclitaxel may be narrower than currently inferred, thorough preclinical testing coupled with the polymer development process for stents eluting paclitaxel is needed.

Objectives: To assess the impact of intraaortic balloon counterpulsation on coronary, renal and aortic blood flow in an animal heart failure model., Background: Heart failure exacerbations are still often treated with inotropic medications despite a lack of evidence demonstrating any benefit with these drugs. Intraaortic balloon counterpulsation may be considered in certain cases a bridge to recovery., Methods: Four juvenile pigs underwent pacemaker implantation to induce a rapid-pacing mediated dilated cardiomyopathy. After approximately 4 weeks of rapid pacing, the mean ejection fraction was reduced to 28.8+/-9.5% with a mean systolic blood pressure of 64/44 mmHg. The pigs then underwent surgical placement of flow probes around the circumflex coronary artery, renal artery and infrarenal aorta. A Millar catheter was used to calculate Dp/Dt and a Swan-Ganz to calculate cardiac output. Data were recorded at baseline and after 10 minutes of balloon pumping. The pigs were euthanized post-procedure., Results: Coronary blood flow was increased 9.7% by balloon counterpulsation from 38.3 +/- 12.0 to 42.0+/-11.4 ml/s (p=NS). Renal blood flow was reduced 11.9% by counterpulsation from 130.0+/-88.6 ml/s to 114.5+/-76.6 ml/s (p=NS). Infrarenal aortic blood flow was not changed (mean of 900 ml/s with and without counterpulsation); blood pressure, cardiac output and Dp/Dt were not changed after 10 minutes of pumping. There was little impact observed by changing the position of the balloon closer to or farther away from the apex of the aortic arch., Conclusion: Intraaortic balloon counterpulsation did not significantly improve hemodynamics in the pig heart failure model. This may be attributed to the high compliance of the juvenile pig's aorta, thus attenuating the pressure wave generated by counterpulsation. A larger volume balloon would merit investigation for this application.