alexa Effects of Intracoronary Collagenase Injection in a Porcine Model: A Safety Dose-Finding Study
ISSN: 2155-9880

Journal of Clinical & Experimental Cardiology
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Research Article

Effects of Intracoronary Collagenase Injection in a Porcine Model: A Safety Dose-Finding Study

Azriel B Osherov1,4, Sang Yup Lim1,3, Jagdish Butany2, Beiping Qiang1, Ronen Jaffe1,5, Ilana Erlich1 and Bradley H Strauss1,2*
1Schulich Heart Centre, Sunnybrook Health Sciences Centre, Canada
2University Health Network, University of Toronto, Toronto, Canada
3Korea University Ansan Hospital, Ansan, Korea
4Barzilai Medical Centre, Ben Gurion University, Ashkelon, Israel
5Lady Davis Carmel Medical Centre, Technion-Israel Institute of Technology, Haifa, Israel
Corresponding Author : Bradley H Strauss
Reichmann Chair in Cardiovascular Sciences
Schulich Heart Centre, Sunnybrook Health Sciences Centre
2075 Bayview Avenue, D4-06, Toronto, Ontario, M4N 3M5 Canada
Tel: 4164806066
Fax: 4164806174
E-mail: [email protected]
Received May 21, 2014; Accepted June 24, 2014; Published July 04, 2014
Citation: Osherov AB, Lim SY, Butany J, Qiang B, Jaffe R, et al. (2014) Effects of Intracoronary Collagenase Injection in a Porcine Model: A Safety Dose-Finding Study. J Clin Exp Cardiolog 5:323. doi:10.4172/2155-9880.1000323
Copyright: © 2014 Osherov AB, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Abstract

Objective: Chronic Total Occlusions (CTO) remains a challenge for Percutaneous Coronary Intervention (PCI). Initial studies of bacterial collagenase injections into experimental arterial CTOs and human coronary CTOs have indicated very promising effects to facilitate guide wire crossing in previously failed cases. The aim of the current study was to assess the vascular and cardiac effects of intracoronary collagenase injections in a porcine model.

Methods: Intracoronary injections of collagenase were done in the Left Anterior Descending (LAD) artery of 21 Yorkshire pigs through an over-the-wire balloon catheter. Two groups were studied: 24 hours after injection (n=14) and 30 days after injection (n=6). During balloon inflation, 8 ml of a phosphate buffered solution (PBS) containing either collagenase (range 50-3200 μg) or PBS alone (control) was injected. After sacrifice, hearts were photographed immediately and then fixed in 10% buffered formalin. Myocardial cross-sections were stained with H&E and Movat.

Results: One pig died acutely due to arterial dissection during balloon inflation. In collagenase-treated pigs, localized epicardial and myocardial haemorrhages were evident at 24 hr in the LAD distribution at doses more than 800 μg. The extent of haemorrhages was related to the dose and was generally mild at doses less than1600 μg and moderate at doses more than 1600 μg. At 30 d, no evidence of haemorrhages was present. Mild myocardial fibrosis, likely due to ischemia, was present in both placebo and treatment groups. Balloon damaged LAD arteries showed mild intimal hyperplasia but no specific effects related to collagenase.

Conclusions: A single intracoronary injection of a bacterial collagenase formulation into normal coronary arteries caused dose-related, localized epicardardial and myocardial haemorrhages, which were well tolerated without later sequelae.

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