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

Holland, Christy K.; Vaidya, Sampada S.; Datta, Saurabh; Coussios, Constantin C.; Shaw, George J.

doi:10.1016/j.thromres.2007.07.006

Cited by 100 publications

(87 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is important to note that fully retracted clots (3-14 d old) were employed in this study. These clots tend to be more resistant to lysis than newly formed clots (Holland et al , 2007.…”

Section: Discussionmentioning

confidence: 95%

“…Several mechanistic in vitro studies have been conducted to investigate the interaction of US with thrombolytic drugs , Blinc et al 1993, Francis 1995, Suchkova et al 1998, Akiyama et al 1998, Behrens et al 1999, Everbach et al 2000, Holland et al 2007. Some of these studies have shown that US potentiation of fibrinolysis is related to increased transport of reactants through cavitation-related mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…The treatment times were fixed at 30 min. The rt-PA dose and clinically relevant treatment duration is consistent with previous studies (Datta et al 2006;Holland et al 2007). Following exposure, each clot was weighed again and the extent of thrombolysis was determined as a percent mass loss.…”

Section: Clot Formation Protocolmentioning

confidence: 91%

“…Clots were prepared by aliquoting 1.5 ml of fresh human blood into 1.3 cm inner diameter Vacutainer tubes, incubating the tubes in a 37 °C water bath for 3 h and storing the clots in a 5 °C in refrigerator for at least 72 h prior to use in the experiments in order to allow complete clot retraction. The clot formation and handling protocol has been described previously (Shaw et al 2006;Datta et al 2006;Holland et al 2007). The clots were weighed initially before any treatment and were placed in the sample chamber containing 30 ml of thawed human fresh frozen plasma and held at 37°C.…”

Section: Clot Formation Protocolmentioning

confidence: 99%

See 3 more Smart Citations

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

Datta

Coussios

Ammi

et al. 2008

Ultrasound in Medicine & Biology

Self Cite

218

200

View full text Add to dashboard Cite

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.

show abstract

“…It is important to note that fully retracted clots (3-14 d old) were employed in this study. These clots tend to be more resistant to lysis than newly formed clots (Holland et al , 2007.…”

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Clot Formation Protocolmentioning

confidence: 91%

Section: Clot Formation Protocolmentioning

confidence: 99%

See 2 more Smart Citations

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

Datta

Coussios

Ammi

et al. 2008

Ultrasound in Medicine & Biology

Self Cite

218

200

View full text Add to dashboard Cite

show abstract

“…The temperature vs time history was obtained by solving the bio-heat equation proposed by Pennes numerically [22]. The explicit form of this equation is given by:…”

Section: Simulation Modelmentioning

confidence: 99%

Temperature estimation of focused ultrasound exposures for stroke treatment

Hadjisavvas¹,

Damianou²

2011

JBiSE

View full text Add to dashboard Cite

Introduction: in this paper a simulation model for predicting the temperature during the application of focused ultrasound (FUS) for stroke treatment using pulsed ultrasound is presented. Materials and methods: a single element spherically focused transducer of 5 cm diameter, focusing at 10 cm and operating at either 0.5 MHz or 1 MHz was considered. The power field was estimated using the Khokhlov-Zabolotskaya-Kuznetzov (KZK) model. The temperature was estimated using the bioheat equation. The goal was to extract the acoustic parameters (frequency, power, and duty factor) that maintain a temperature increase of less than 1˚C during the application of a pulse ultrasound protocol. Results: it was found that the temperature change increases linearly with duty factor. The higher the power, the lower the duty factor needed to keep the temperature change to the safe limit of 1˚C. The higher the frequency the lower the duty factor needed to keep the temperature change to the safe limit of 1˚C. Finally, the shallow the target, the lower the duty factor needed to keep the temperature change to the safe limit of 1˚C. The simulation model was tested in brain tissue during the application of pulse ultrasound and the measured temperature was in close agreement with the simulated temperature. Conclusions: This simulation model is considered to be very useful tool for providing acoustic parameters (frequency, power, and duty factor) during the application of pulsed ultrasound at various depths in tissue so that a safe temperature is maintained during the treatment. This model will be tested eventually during stroke clinical trials.

show abstract

Heparin but not tissue plasminogen activator improves outcomes in donation after circulatory death liver transplantation in a porcine model

et al. 2018

View full text Add to dashboard Cite

Ischemic-type biliary lesions (ITBLs) arise most frequently after donation after circulatory death (DCD) liver transplantation and result in high morbidity and graft loss. Many DCD grafts are discarded out of fear for this complication. In theory, microvascular thrombi deposited during donor warm ischemia might be implicated in ITBL pathogenesis. Herein, we aim to evaluate the effects of the administration of either heparin or the fibrinolytic drug tissue plasminogen activator (TPA) as means to improve DCD liver graft quality and potentially avoid ITBL. Donor pigs were subjected to 1 hour of cardiac arrest (CA) and divided among 3 groups: no pre-arrest heparinization nor TPA during postmortem regional perfusion; no pre-arrest heparinization but TPA given during regional perfusion; and pre-arrest heparinization but no TPA during regional perfusion. In liver tissue sampled 1 hour after CA, fibrin deposition was not detected, even when heparin was not given prior to arrest. Although it was not useful to prevent microvascular clot formation, pre-arrest heparin did offer cytoprotective effects during CA and beyond, reflected in improved flows during regional perfusion and better biochemical, functional, and histological parameters during posttransplantation follow-up. In conclusion, this study demonstrates the lack of impact of TPA use in porcine DCD liver transplantation and adds to the controversy over whether the use of TPA in human DCD liver transplantation really offers any protective effect. On the other hand, when it is administered prior to CA, heparin does offer anti-inflammatory and other cytoprotective effects that help improve DCD liver graft quality. Liver Transplantation 24 665-676 2018 AASLD.

show abstract

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

Abstract: Introduction-Thrombolytics such as recombinant tissue plasminogen activator (rt-PA) have advanced the treatment of ischemic stroke, myocardial infarction, deep vein thrombosis and pulmonary embolism.

Cited by 100 publications

References 48 publications

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

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

Temperature estimation of focused ultrasound exposures for stroke treatment

Heparin but not tissue plasminogen activator improves outcomes in donation after circulatory death liver transplantation in a porcine model

Contact Info

Product

Resources

About