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.
Thoracoscopic spinal instrumentation compares favorably with posterior fusion in terms of coronal plane curve correction and balance, sagittal contour, the rate of complications, pulmonary function, and patient-based outcomes. The advantages of the procedure include the need for fewer levels of spinal fusion, less operative blood loss, lower transfusion requirements, and improved cosmesis as a result of small, well-hidden incisions. However, the operative time for the thoracoscopic procedure was nearly twice that for the posterior approach. Additional study is needed to determine the precise role of thoracoscopic spinal instrumentation in the treatment of thoracic adolescent idiopathic scoliosis.
SummaryUltrasound accelerates fibrinolysis in vitro and in animal models of thrombosis. Since transport of fibrinolytic enzymes into clots by permeation may be an important determinant of the rate of fibrinolysis, we examined the effect of ultrasound on permeation through fibrin gels in vitro. Gels of purified fibrin were prepared in plastic tubes, and the rate of pressure-mediated fluid permeation was measured. Exposure to 1 MHz ultrasound at 2 W/cm2 and a duty cycle of 5 msec on, 5 msec off resulted in a significant (p = .005) increase in flow through the gel of 29.0 ± 4.2% (SEM). The ultrasound-induced flow increase was intensity-dependent, increasing from 17.0 ± 1.2% at 1 W/cm2 to 30.1 ± 1.9% at 2.3 W/cm2. Increased flow was not due to heating, detachment of fibrin from the tube wall or fragmentation of the gel resulting in channeling. However, degassing the fluid by autoclaving significantly reduced the ultrasound-induced increase in flow. We conclude that exposure of fibrin gels to ultrasound increases pressure-mediated permeation. This effect may be related to cavitation-induced changes in fibrin gel structure, and could contribute to the accelerated fibrinolysis observed in an ultrasound field.
Ultrasound reversibly alters the structure of polymerized fibrin, an effect that could influence tissue-plasminogen activator (t-PA) binding. We have, therefore, characterized the effects of ultrasound on binding of t-PA to fibrin using a novel system in which radiolabeled, active-site blocked, single chain tissue-plasminogen activator flowed through a fibrin gel at constant rate, and specific binding was determined by monitoring incorporation of radiolabel. Results using polymerized fibrin were compared with those using a surface of fibrin immobilized on Sepharose beads in a similar system. Interaction of t-PA with surface-immobilized fibrin involved two classes of binding sites (Kd = 31 nmol/L and 244 nmol/L) and a maximum binding ratio of 3.8 mol t-PA/mol fibrin. Ultrasound increased Kd for the high affinity site to 46 nmol/L (P < .0001), but it had no significant effects on the Kd 244 nmol/L site nor on Bmax. Tissue-plasminogen activator binding to noncrosslinked fibrin involved two sites with Kds of 267 nmol/L and 952 nmol/L, while a single Kd 405 nmol/L site was identified for crosslinked fibrin. Ultrasound had no significant effect on the binding affinity for noncrosslinked fibrin, but Bmaxwas increased in the presence of ultrasound, from 31 μmol/L to 43 μmol/L (P < .0001). Ultrasound decreased the Kd for crosslinked fibrin to 343 nmol/L (P = .026) and also increased Bmax from 22 μmol/L to 25 μmol/L (P = .015). Ultrasound also affected the kinetics of t-PA binding to fibrin, significantly accelerating the rate of dissociation by 77% ± 5% for noncrosslinked fibrin and by 69% ± 3% for crosslinked fibrin (P < .001 for each). These results indicate that ultrasound exposure accelerates t-PA binding, alters binding affinity, and increases maximum binding to polymerized fibrin, effects that may result from ultrasound-induced changes in fibrin structure.
Ultrasound reversibly alters the structure of polymerized fibrin, an effect that could influence tissue-plasminogen activator (t-PA) binding. We have, therefore, characterized the effects of ultrasound on binding of t-PA to fibrin using a novel system in which radiolabeled, active-site blocked, single chain tissue-plasminogen activator flowed through a fibrin gel at constant rate, and specific binding was determined by monitoring incorporation of radiolabel. Results using polymerized fibrin were compared with those using a surface of fibrin immobilized on Sepharose beads in a similar system. Interaction of t-PA with surface-immobilized fibrin involved two classes of binding sites (Kd = 31 nmol/L and 244 nmol/L) and a maximum binding ratio of 3.8 mol t-PA/mol fibrin. Ultrasound increased Kd for the high affinity site to 46 nmol/L (P < .0001), but it had no significant effects on the Kd 244 nmol/L site nor on Bmax. Tissue-plasminogen activator binding to noncrosslinked fibrin involved two sites with Kds of 267 nmol/L and 952 nmol/L, while a single Kd 405 nmol/L site was identified for crosslinked fibrin. Ultrasound had no significant effect on the binding affinity for noncrosslinked fibrin, but Bmaxwas increased in the presence of ultrasound, from 31 μmol/L to 43 μmol/L (P < .0001). Ultrasound decreased the Kd for crosslinked fibrin to 343 nmol/L (P = .026) and also increased Bmax from 22 μmol/L to 25 μmol/L (P = .015). Ultrasound also affected the kinetics of t-PA binding to fibrin, significantly accelerating the rate of dissociation by 77% ± 5% for noncrosslinked fibrin and by 69% ± 3% for crosslinked fibrin (P < .001 for each). These results indicate that ultrasound exposure accelerates t-PA binding, alters binding affinity, and increases maximum binding to polymerized fibrin, effects that may result from ultrasound-induced changes in fibrin structure.
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