Author + information
- Athanasios Peppas1,
- Kirk Seward2,
- Karl Van Wygerden3,
- Gerard Conditt4,
- Armando Tellez5,
- Serge Rousselle5,
- Greg Kaluza4 and
- Juan Granada4
- 1CRF Skirball Center for Innovation, New York, New York, United States
- 2Mercator MedSystems, Inc., Emeryville, California, United States
- 3Cardiovascular Research Foundation, New York, New York, United States
- 4CRF Skirball Center for Innovation, Orangeburg, New York, United States
- 5Alizee Pathology, Thurmont, Maryland, United States
Restenosis following endovascular treatment is associated with inflammatory and proliferative responses produced in the artery wall at the time of the procedure which may be ameliorated through delivery of anti-inflammatory or anti-proliferative compounds into the adventitia of the vessel at the time of treatment. The present study aimed to assess the pharmacokinetic profile and vascular response to locally delivered sirolimus analog Torisel (temsirolimus, Pfizer) using the Mercator MedSystems Bullfrog Micro-Infusion Device (Emeryville, CA) to balloon overstretched superficial femoral arteries (SFA) in swine.
Sixteen SFAs of 8 swine were balloon overstretched (1.28±0.16:1 balloon to artery ratio) on day 0 followed by infusion of 357ug Torisel via the Bullfrog catheter at each site and harvested at 1 hour (n=4), 3 days (n=4), 7 days (n=4) or 28 days (n=4). An additional three control animals had bilateral SFA balloon overstretch (1.17±0.08:1 balloon to artery ratio) followed by saline infusion and harvested at 3 days (n=2), 7 days (n=2) or 28 days (n=2). Blood was collected for circulating Torisel evaluation and tissue was harvested for histological analysis and Torisel concentration.
There were no adverse events, signs of toxicity, mural injury or evidence of thrombosis following Torisel or saline administered via the Bullfrog catheter. Quantitative analysis of Ki67-positive nuclei showed cellular proliferation in the control vessels peaking at Day 7 and a Torisel treatment-related decrease in average proliferation values on Day 3, Day 7 and Day 28 that were substantial and consistent along the vessel length. Circulating Torisel concentration peaked at 1 hour post-infusion, were near zero by Day 3 and below limits of quantitation by Day 7. In the treated vessels, Torisel concentration decreased by an order of magnitude from one hour (8440±6956ng/g) to 3 Days (624±398ng/g) and continued to decrease through Day 28 (122±73ng/g) yet remained present at detectable levels.
Torisel has demonstrated ability to inhibit cell proliferation when delivered locally via the Bullfrog catheter which is proven to be a safe, efficient and effective delivery mechanism.
ENDOVASCULAR: Peripheral Vascular Disease and Intervention