Noninvasive, Transthoracic, Low-Frequency Ultrasound Augments Thrombolysis in a Canine Model of Acute Myocardial Infarction

Siegel, Robert J.; Atar, Shaul; Fishbein, Michael C.; Brasch, Andrea V.; Peterson, Thomas; Nagai, Tomoo; Pal, Dharmendra; Nishioka, Toshihiko; Chae, Jang Seong; Birnbaum, Yochai; Zanelli, Claudio I.; Luo, Hao

doi:10.1161/01.cir.101.17.2026

Cited by 83 publications

(68 citation statements)

References 18 publications

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“…In a canine coronary artery thrombus model, transcutaneous 27-kHz US along with rt-PA demonstrated significant recanalization (Siegel et al 2000). Microbubble potentiation of thrombolysis in intracranial arteries was demonstrated in a porcine model by Culp et al (2003) using 1-MHz US.…”

Section: Discussionmentioning

confidence: 89%

Ultrasound-Enhanced Thrombolysis Using Definity® as a Cavitation Nucleation Agent

Datta

Coussios

Ammi

et al. 2008

Ultrasound in Medicine & Biology

226

200

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Ultrasound has been previously shown to act synergistically with a thrombolytic agent, such as recombinant tissue plasminogen activator (rt-PA) to accelerate thrombolysis. In this in vitro study, a commercial contrast agent, Definity ® , was used to promote and sustain the nucleation of cavitation during pulsed ultrasound exposure at 120 kHz. Ultraharmonic signals, broadband emissions, and harmonics of the fundamental were measured acoustically by using a focused hydrophone as a passive cavitation detector and utilized to quantify the level of cavitation activity. Human whole blood clots suspended in human plasma were exposed to a combination of rt-PA, Definity ® , and ultrasound at a range of ultrasound peak-to-peak pressure amplitudes, which were selected to expose clots to various degrees of cavitation activity. Thrombolytic efficacy was determined by measuring clot mass loss before and after the treatment and correlated with the degree of cavitation activity. The penetration depth of rt-PA and plasminogen was also evaluated in the presence of cavitating microbubbles using a dual antibody fluorescence imaging technique. The largest mass loss (26.2%) was observed for clots treated with 120 kHz ultrasound (0.32 MPa peak-to-peak pressure amplitude), rt-PA and stable cavitation nucleated by Definity ® . A significant correlation was observed between mass loss and ultraharmonic signals (r=0.8549, p<0.0001, n=24). The largest mean penetration depth of rt-PA (222 µm) and plasminogen (241 µm) was observed in the presence of stable cavitation activity. Stable cavitation activity plays an important role in enhancement of thrombolysis and can be monitored to evaluate the efficacy of thrombolytic treatment.

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Section: Discussionmentioning

confidence: 89%

Ultrasound-Enhanced Thrombolysis Using Definity® as a Cavitation Nucleation Agent

Datta

Coussios

Ammi

et al. 2008

Ultrasound in Medicine & Biology

226

200

View full text Add to dashboard Cite

show abstract

“…In a canine model, they demonstrated that application of transcutaneous ultrasound near the site of an occluded femoral artery, when used in conjunction with tPA infusion, resulted in an 80% decrease in time for recanalization [30]. Similarly, in canine models of acute coronary occlusions, transcutaneous ultrasound augmented the efficacy of tPA-facilitated thrombolysis, regardless of whether the anterior or posterior coronary circulations were involved [31,32]. For the clinical application of noninvasive ultrasound therapy, it may be advantageous to determine the exact location of the clot in order to selectively insonify the area of interest, thus limiting potential harmful bioeffects to surrounding tissues.…”

Section: Discussionmentioning

confidence: 99%

Ultrasound-facilitated thrombolysis using tissue-plasminogen activator-loaded echogenic liposomes

Tiukinhoy-Laing¹,

Huang²,

Klegerman³

et al. 2007

Thrombosis Research

122

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Introduction-Targeted delivery of thrombolytics to the site of occlusion is an attractive concept, with implications for the treatment of many thrombo-occlusive diseases. Ultrasound enhances thrombolysis, which can be augmented by the addition of a contrast agent. We have previously reported development of echogenic liposomes (ELIP) for targeted highlighting of structures with potential for drug and gene delivery. This study evaluated the potential of ELIP for thrombolytic loading, and the effect of ultrasound exposure of thrombolytic-loaded ELIP on thrombolytic efficacy.

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“…Stable cavitation is characterized by bubbles pulsating gently in response to the time-varying acoustic pressure in an ultrasound field. Siegel et al found that noninvasive transthoracic application of low-frequency (27 kHz) ultrasound augmented the efficacy of t-PA-mediated thrombolysis in a canine model, and improved coronary patency without increasing the risk of bleeding [23].…”

Section: Introductionmentioning

confidence: 99%

Ultrasound-enhanced tissue plasminogen activator thrombolysis in an in vitro porcine clot model

Holland

Vaidya

Datta

et al. 2008

Thrombosis Research

100

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Noninvasive, Transthoracic, Low-Frequency Ultrasound Augments Thrombolysis in a Canine Model of Acute Myocardial Infarction

Abstract: In vivo, the noninvasive transthoracic application of low-frequency ultrasound (1) greatly augments the efficacy of t-PA-mediated thrombolysis, (2) seems safe, and (3) has substantial potential as a noninvasive adjunct to improve coronary patency without increasing the risk of bleeding.

Cited by 83 publications

References 18 publications

Ultrasound-Enhanced Thrombolysis Using Definity® as a Cavitation Nucleation Agent

Ultrasound-Enhanced Thrombolysis Using Definity® as a Cavitation Nucleation Agent

Ultrasound-facilitated thrombolysis using tissue-plasminogen activator-loaded echogenic liposomes

Ultrasound-enhanced tissue plasminogen activator thrombolysis in an in vitro porcine clot model

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