title: Efficacy of histotripsy combined with rt-PA in vitro.
abstract: Histotripsy, a form of therapeutic ultrasound that uses the mechanical action of microbubble clouds for tissue ablation, is under development to treat chronic deep vein thrombosis (DVT). We hypothesize that combining thrombolytic agents with histotripsy will enhance clot lysis. Recombinant tissue plasminogen activator (rt-PA) and rt-PA-loaded echogenic liposomes that entrain octafluoropropane microbubbles (OFP t-ELIP) were used in combination with highly shocked histotripsy pulses. Fully retracted porcine venous clots, with similar features of DVT occlusions, were exposed either to histotripsy pulses alone (peak negative pressures of 7-20 MPa), histotripsy and OFP t-ELIP, or histotripsy and rt-PA. Microbubble cloud activity was monitored with passive cavitation imaging during histotripsy exposure. The power levels of cavitation emissions from within the clot were not statistically different between treatment types, likely due to the near instantaneous rupture and destruction of OFP t-ELIP. The thrombolytic efficacy was significantly improved in the presence of rt-PA. These results suggest the combination of histotripsy and rt-PA could serve as a potent therapeutic strategy for the treatment of DVT.
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular Health and Disease, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Bader
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Haworth
authors.forename: Himanshu
authors.initials: H
authors.lastname: Shekhar
authors.forename: Adam D
authors.initials: AD
authors.lastname: Maxwell
authors.forename: Tao
authors.initials: T
authors.lastname: Peng
authors.forename: David D
authors.initials: DD
authors.lastname: McPherson
authors.forename: Christy K
authors.initials: CK
authors.lastname: Holland
mesh_terms: D000818:Animals; D003287:Contrast Media; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D005466:Fluorocarbons; D006801:Humans; D066298:In Vitro Techniques; D008081:Liposomes / Q000008:administration & dosage; D045423:Microbubbles; D011994:Recombinant Proteins / Q000008:administration & dosage; D013552:Swine; D015912:Thrombolytic Therapy / Q000379:methods*; D013927:Thrombosis / Q000000981:diagnostic imaging / Q000628:therapy*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*; D014464:Ultrasonic Therapy / Q000379:methods*
chemical_list: D003287:Contrast Media; D005343:Fibrinolytic Agents; D005466:Fluorocarbons; D008081:Liposomes; D011994:Recombinant Proteins; C042852:perflutren; D010959:Tissue Plasminogen Activator