Can transcranial ultrasonication increase recanalization flow with tissue plasminogen activator?
OBJECTIVE
In thrombolytic therapy for acute ischemic stroke, it is essential to obtain rapid thrombolysis before ischemic neuronal injury occurs. To develop a new technique of thrombolysis for acute ischemic stroke, the effect of transcranially applied ultrasound (TUS) on thrombolysis was examined.


METHODS
An occlusion model of rabbit femoral artery was produced with thrombin after establishment of stenotic flow and endothelial damage. After stable occlusion was confirmed, monteplase (mtPA) was administered intravenously, and ultrasound (490 kHz, 0.13 W/cm2) was applied through a piece of temporal bone (TUS group; n=9). The control group received mtPA alone (tissue plasminogen activator [tPA] group; n=12). To verify the efficacy of TUS, femoral artery flow was measured during the procedure.


RESULTS
The recanalization ratio was 16.7% (2 of 12) in the tPA group and 66.7% (6 of 9) in the TUS group. The recanalization ratio in the TUS group was higher than that in the tPA group (P=0.03). Patency flow ratio, which was defined as recanalization flow divided by baseline flow, of the TUS group (44.6+/-13.9%) was significantly greater than that of the tPA group (9.9+/-6.8%) at 60 minutes (P=0.025). Patency flow ratio became higher in the TUS group than in the tPA group between 20 and 30 minutes from the start of thrombolysis.


CONCLUSIONS
Low-frequency and low-intensity TUS enhanced thrombolysis by mtPA in a rabbit femoral artery occlusion model. This technique should be clinically useful for thrombolysis in acute ischemic stroke.
Ishibashi
Toshihiro
T
Department of Neurosurgery, Jikei University School of Medicine, Tokyo, Japan. isb@fd6.so-net.ne.jp
Akiyama
Masahiko
M
Onoue
Hisashi
H
Abe
Toshiaki
T
Furuhata
Hiroshi
H
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D004195:Disease Models, Animal; D018450:Disease Progression; D005263:Femoral Artery / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D005343:Fibrinolytic Agents / Q000008:administration & dosage; D007275:Injections, Intravenous; D010960:Plasminogen Activators / Q000008:administration & dosage; D011817:Rabbits; D013696:Temperature; D013927:Thrombosis / Q000473:pathology / Q000628:therapy*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*; D016896:Treatment Outcome; D014464:Ultrasonic Therapy / Q000379:methods*; D017585:Ultrasonography, Doppler, Transcranial
D005343:Fibrinolytic Agents; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator