In vivo feasibility study of ultrasound potentiated collagenase therapy of chronic total occlusions.
Arterial chronic total occlusions (CTOs) pose considerable challenges for percutaneous interventions, due primarily to the presence of stiff proximal fibrous caps (PFCs) which act as a barrier to the penetration of guide wires. A new approach under development for improving the success rate of guide wire crossing in CTOs is to employ collagenase to degrade the mechanical integrity of the PFCs. This has been shown to be feasible in preclinical work and in a Phase 1 clinical trial. In a recent study we demonstrated using ex vivo experimental CTO specimens that ultrasound-stimulated microbubbles (USMBs) could potentiate the effects of collagenase and result in increased mechanical degradation of the PFCs of CTOs. Here we report the results of the first in vivo study examining the feasibility of this approach, which demonstrates that the force required to puncture through the PFCs of CTOs is reduced with combined USMB+collagenase treatments relative to collagenase only treatments. This approach has the potential to further improve the efficacy of the emerging technique of collagenase facilitation of percutaneous interventions for CTO.
Department of Medical Biophysics, University of Toronto, Canada; Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Canada. Electronic address: goertz@sri.utoronto.ca.
David E
DE
Goertz
Amandeep S
AS
Thind
Raffi
R
Karshafian
Michelle
M
Ladouceur
Cari M
CM
Whyne
F Stuart
FS
Foster
Bradley H
BH
Strauss
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D017364:Collagenases / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D004357:Drug Synergism; D005240:Feasibility Studies; D005263:Femoral Artery / Q000000981:diagnostic imaging* / Q000187:drug effects*; D011817:Rabbits; D011859:Radiography; D013010:Sonication / Q000379:methods*; D016896:Treatment Outcome; D014464:Ultrasonic Therapy / Q000379:methods*; D014463:Ultrasonography
D017364:Collagenases
Atherosclerosis; Chronic total occlusion; Microbubbles; Percutaneous intervention; Therapeutic ultrasound