Dissolution of Thrombotic Arterial Occlusion by High Intensity, Low Frequency Ultrasound and Dodecafluoropentane Emulsion: An In Vitro and In Vivo Study

Nishioka, Toshihiko; Luo, Hao; Fishbein, Michael C.; Cercek, Bojan; Forrester, James S.; Kim, Chong‐Jin; Berglund, Hans; Siegel, Robert J.

doi:10.1016/s0735-1097(97)00182-4

Cited by 126 publications

(76 citation statements)

References 35 publications

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“…Ultrasound at 20 kHz applied transdermally in combination with an echo contrast agent induced reperfusion in thrombosed rabbit femoral arteries without administration of any plasminogen activator, presumably by causing mechanical fragmentation, but excessive heating was a problem. 22 Transdermal application of ultrasound at Ϸ37 kHz in combination with intravenous stabilized microbubbles was effective in recanalizing thrombosed rabbit iliofemoral arteries in comparison with either ultrasound alone or microbubbles alone. 23 Our approach is different in concept and uses low-intensity ultrasound to accelerate enzymatic fibrinolysis.…”

Section: Discussionmentioning

confidence: 97%

Enhancement of Fibrinolysis With 40-kHz Ultrasound

et al. 1998

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Background-Ultrasound at frequencies of 0.5 to 1 MHz and intensities of Ն0.5 W/cm 2 accelerates enzymatic fibrinolysis in vitro and in some animal models, but unacceptable tissue heating can occur, and limited penetration would restrict application to superficial vessels. Tissue heating is less and penetration better at lower frequencies, but little information is available regarding the effect of lower-frequency ultrasound on enzymatic fibrinolysis. We therefore examined the effect of 40-kHz ultrasound on fibrinolysis, tissue penetration, and heating. Methods and Results-125 I-fibrin-radiolabeled plasma clots in thin-walled tubes were overlaid with plasma containing tissue plasminogen activator (tPA) and exposed to ultrasound. Enzymatic fibrinolysis was measured as solubilization of radiolabel. Tissue attenuation and heating were examined in samples of porcine rib cage. Fibrinolysis was increased significantly in the presence of 40-kHz ultrasound at 0.25 W/cm 2 , reaching 39Ϯ7% and 93Ϯ11% at 60 minutes and 120 minutes, compared with 13Ϯ8% and 37Ϯ4% in the absence of ultrasound (PϽ0.0001). The acceleration of fibrinolysis increased at higher intensities. Attenuation of the ultrasound field was only 1.7Ϯ0.5 dB/cm through the intercostal space and 3.4Ϯ0.9 dB/cm through rib. Temperature increments in rib were Ͻ1°C/(W/cm 2 ). Conclusions-These findings indicate that 40-kHz ultrasound significantly accelerates enzymatic fibrinolysis at intensities of Ն0.25 W/cm 2 with excellent tissue penetration and minimal heating. Externally applied 40-kHz ultrasound at low intensities is a potentially useful therapeutic adjunct to enzymatic fibrinolysis with sufficient tissue penetration for both peripheral vascular and coronary applications.

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Section: Discussionmentioning

confidence: 97%

Enhancement of Fibrinolysis With 40-kHz Ultrasound

et al. 1998

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“…Ultrasound-mediated thrombolysis may be enhanced by the addition of a contrast agent as cavitation nuclei [36][37][38]. It is hypothesized that the contrast agent adheres to the clot with resultant shearing effect during bubble destruction [13].…”

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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“…In addition, US reversibly alters fibrin fiber structure, generating a larger number of thinner fibers, 19 and this may contribute to changes in equilibrium binding of activator to fibrin. 20 The physical mechanism by which US accelerates fibrinolysis is nonthermal, and the ability of stabilized microbubbles to augment the effect 21 suggests that Figure 4. Effects of US on tissue perfusion and pH.…”

Section: Discussionmentioning

confidence: 99%

“…Externally applied highintensity US alone without plasminogen activator at 20 kHz has been used to recanalize femoral artery thrombi in a rabbit model, but excessive heating also occurred. 21 In considering therapeutic application, the choice of US frequency is of particular importance, because tissue penetration declines and heating increases at higher frequencies. We have previously demonstrated excellent transmission of US through bone at 40 kHz, 5 and others have demonstrated that 40-kHz 29 and 211.5-kHz 30 US transmitted through the skull can accelerate fibrinolysis in vitro.…”

Section: Suchkova Et Al Ultrasound Increases Thrombolysis and Perfusionmentioning

confidence: 99%

Effect of 40-kHz Ultrasound on Acute Thrombotic Ischemia in a Rabbit Femoral Artery Thrombosis Model

2000

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Background —We have shown previously that 40-kHz ultrasound (US) at low intensity accelerates fibrinolysis in vitro with little heating and good tissue penetration. These studies have now been extended to examine the effects of 40-kHz US on thrombolysis and tissue perfusion in a rabbit model. Methods and Results —Treatment was administered with either US alone at 0.75 W/cm 2 , streptokinase alone, or the combination of US and streptokinase. US or streptokinase resulted in minimal thrombolysis, but reperfusion was nearly complete with the combination after 120 minutes. US also reversed the ischemia in nonperfused muscle in the absence of arterial flow. Tissue perfusion decreased after thrombosis from 13.7±0.2 to 6.6±0.8 U and then declined further to 4.5±0.4 U after 240 minutes. US improved perfusion to 10.6±0.5 and 12.1±0.5 U after 30 and 60 minutes, respectively. This effect was reversible and declined to pretreatment values after US was discontinued. Similarly, tissue pH declined from normal to 7.05±0.02 after thrombosis, but US improved pH to 7.34±0.03 after 60 minutes. US-induced improvement in tissue perfusion and pH also occurred after femoral artery ligation, indicating that thrombolysis did not cause these effects. Conclusions —40-kHz US at low intensity markedly accelerates fibrinolysis and also improves tissue perfusion and reverses acidosis, effects that would be beneficial in treatment of acute thrombosis.

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Dissolution of Thrombotic Arterial Occlusion by High Intensity, Low Frequency Ultrasound and Dodecafluoropentane Emulsion: An In Vitro and In Vivo Study

Cited by 126 publications

References 35 publications

Enhancement of Fibrinolysis With 40-kHz Ultrasound

Enhancement of Fibrinolysis With 40-kHz Ultrasound

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

Effect of 40-kHz Ultrasound on Acute Thrombotic Ischemia in a Rabbit Femoral Artery Thrombosis Model

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