The use of ultrasound-stimulated contrast agents as an adjuvant for collagenase therapy in chronic total occlusions

Abstract

To investigate the effectiveness of combining collagenase and ultrasound-stimulated microbubble (USMB) treatments in reducing the mechanical force required for crossing a guidewire through CTOs. Experiments were conducted on ex vivo specimens of a rabbit femoral artery CTO model (n=45 total samples). Four primary groups were employed: control (n=6), collagenase only (n=15), USMB only (1 MHz frequency) (n=5), and collagenase+USMB (n=19). In one set of experiments the force required to puncture through CTO samples was measured and it was found that the puncture force was 2.31-fold lower for the combined treatment group relative to the comparable collagenase-only group (p<0.05). In a second set of experiments, the total protein and hydroxyproline content of the supernatant solution adjacent to the CTO was analysed. Significantly higher hydroxyproline levels were measured in collagenase+USMB treated CTOs (0.065 g/mL) compared to collagenase (0.030 g/mL), USMB (0.003 g/mL) and control (0.004 g/mL) (p<0.05), indicating that the combined treatment augmented collagenase degradation. Ultrasound-stimulated microbubbles improved the effectiveness of collagenase in reducing the force required to cross experimental CTOs. This new approach may have the potential to reduce treatment times and improve the success rates of emerging collagenase-based treatments of CTO.