Cardiologie clinique et expérimentale
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Abstrait

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

Azriel B Osherov, Sang Yup Lim, Jagdish Butany, Beiping Qiang, Ronen Jaffe, Ilana Erlich and Bradley H Strauss

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.