BACKGROUND: Chronic total occlusions (CTOs) are associated with significant angina, impaired left ventricular function, and worse long-term outcomes. Percutaneous coronary interventions in CTO are unsuccessful in up to 50% of cases, primarily because of inability to cross the lesion with a guide wire. Collagen is the predominant component of the atherosclerotic plaque. The objective of this study was to determine the efficacy and toxicity of local delivery of a collagen-degrading enzyme to facilitate guide wire crossing in CTO. METHODS AND RESULTS: Type IA collagenase (100 or 450 microg) or placebo was locally administered to 45 CTOs in a rabbit femoral artery model. Mean occlusion duration was 16+/-5 weeks. Attempts to cross the CTO (mean length, 28+/-9 mm) with conventional guide wires were assessed at 72 hours after treatment. An additional 3 arteries per group were assessed for collagenase effects at 24 hours after treatment. Successful guide wire crossings were significantly higher in collagenase-treated arteries (13 of 21, 62%) than in placebo-treated arteries (7 of 24, 29%) (P=0.028). No adverse effects on arterial structure were observed in collagenase-treated arteries. At 24 hours, collagenase-treated arteries demonstrated increased collagenase protein, gelatinase activity, and collagen fragments. CONCLUSIONS: Local delivery of collagenase can safely facilitate guide wire crossing of CTO. This novel approach could lead to higher percutaneous coronary intervention success rates in CTO.
BACKGROUND: Chronic total occlusions (CTOs) are associated with significant angina, impaired left ventricular function, and worse long-term outcomes. Percutaneous coronary interventions in CTO are unsuccessful in up to 50% of cases, primarily because of inability to cross the lesion with a guide wire. Collagen is the predominant component of the atherosclerotic plaque. The objective of this study was to determine the efficacy and toxicity of local delivery of a collagen-degrading enzyme to facilitate guide wire crossing in CTO. METHODS AND RESULTS: Type IA collagenase (100 or 450 microg) or placebo was locally administered to 45 CTOs in a rabbit femoral artery model. Mean occlusion duration was 16+/-5 weeks. Attempts to cross the CTO (mean length, 28+/-9 mm) with conventional guide wires were assessed at 72 hours after treatment. An additional 3 arteries per group were assessed for collagenase effects at 24 hours after treatment. Successful guide wire crossings were significantly higher in collagenase-treated arteries (13 of 21, 62%) than in placebo-treated arteries (7 of 24, 29%) (P=0.028). No adverse effects on arterial structure were observed in collagenase-treated arteries. At 24 hours, collagenase-treated arteries demonstrated increased collagenase protein, gelatinase activity, and collagen fragments. CONCLUSIONS: Local delivery of collagenase can safely facilitate guide wire crossing of CTO. This novel approach could lead to higher percutaneous coronary intervention success rates in CTO.
Authors: Bradley H Strauss; Azriel B Osherov; Sam Radhakrishnan; G B John Mancini; Allison Manners; John D Sparkes; Robert J Chisholm Journal: Circulation Date: 2011-12-16 Impact factor: 29.690
Authors: Nan Yeol Kim; Kyung Seob Lim; Myung Ho Jeong; In Ho Bae; Jun-Kyu Park; Jae-Woon Nah; Dae Sung Park; So Youn Lee; Eun Jae Jang; Jong Min Kim; Jung Ha Kim; Hae Jin Kee; Soo-Na Cho; Doo Sun Sim; Keun-Ho Park; Young Joon Hong; Sang-Gi Oh; Sang-Hyung Kim; Youngkeun Ahn; Jung Chaee Kang Journal: J Mater Sci Mater Med Date: 2015-03-25 Impact factor: 3.896
Authors: Ronen Jaffe; General Leung; Nigel R Munce; Amandeep S Thind; Howard Leong-Poi; Kevan J T Anderson; Xiuling Qi; Judy Trogadis; Ariella Nadler; Davida Shiff; Jamie Saperia; Julia Lockwood; Chaim Jacobs; Beiping Qiang; Aaron Teitelbaum; Alexander J Dick; John D Sparkes; Jagdish Butany; Graham A Wright; Bradley H Strauss Journal: J Am Coll Cardiol Date: 2009-03-31 Impact factor: 24.094