WINSTON-SALEM,NC - A team of Japanese researchers reported that low-frequency ultrasound speeds the clot-busting power of thrombolytic drugs and may allow physicians to dissolve blood clots deep within the brain with lower doses of medication--reducing the risk of bleeding and other complications.
Dr. Masahiko Akiyama, a neurosurgeon at Jikei University, Daisan Hospital in Tokyo, Japan, said that the group irradiated large one-day-old clots of human blood with low-frequency ultrasound for 12 hours in glass cylinders while also treating the clots with the thrombolytic drug urokinase and measuring the ability of the sonic energy to be transmitted through the skull to potential intracranial clot sites.
They found that the combination of ultrasound and urokinase was more effective than urokinase alone in shrinking clots, dissolving clots by the same amount in four hours that it took the drug itself eight hours to achieve. And they found that the low-frequency soundwaves transmit well through the skull.
The investigators will present their findings August 16th at the International Neurosonology 97 meeting here sponsored by the World Federation of Neurology and the Bowman Gray School of Medicine of Wake Forest University.
"Our results demonstrate that ultrasonic irradiation enhances the power of thrombolytics in vitro and could therefore be a less invasive therapy for treating intracranial lesions that cause strokes or put patients at risk for future attacks," Akiyama said. "Although not part of our study, this method could also be applied for thrombolytic therapy of acute cerebral infarction (stroke).
"The clots we used were relatively older and large, about 30 millimeters in diameter," he said. "If the clots had been relatively small and fresh like you see in acute stroke in the same experimental conditions, dissolution time could have been much shorter."
Akiyama said further studies are planned to evaluate the effect of the experimental combination treatment within the body.
"In spite of these findings, the mechanism underlying the dissolving of clots by ultrasound is still not fully understood," he said. "Ultrasound may accelerate thrombolysis by accelerating the distribution of thrombolytic agents deep inside the clot by a phenomenon known as an acoustic stream (a one-way, unidirectional motion of fluid in an ultrasonic field)," Akiyama said.
"Whatever the mechanism, the results suggest this method could reduce the duration and doses of urokinase and other thrombolytics used in the treatment of intracerebral and subarachnoid hematomas and may be promising for reducing patients' exposure to complications of thrombolytic therapy."
These new findings come amid a clear shift in viewing stroke as the neurological equivalent of a heart attack--a medical emergency requiring treatment within a window of opportunity that may be as narrow as three hours after the first onset of symptoms.
Thrombolytic drugs, which demonstrated their clot-busting prowess first against heart attack, are now being widely used to dissolve blood clots causing strokes and restore blood flow to the brain.The U.S. Food and Drug Administration has approved t-PA for the emergency treatment of acute stroke.
Precisely because of their clot-dissolving powers, thrombolytics are best suited for treating ischemic stroke, or stroke caused when blood clots, plaque and other material shut off the arteries supplying the brain with blood. Improper use in hemorrhagic strokes--caused by ruptured vessels that bleed within the brain--could worsen the bleeding and prove fatal to patients.
But Akiyama said that thrombolytics, even in proper doses and used against ischemic stroke, also carry a risk of bleeding that increases with dose. "Thrombolytic drugs can cause intra- and extra-cranial bleeding in some patients, so reducing dosage of thrombolytic agents would greatly help to minimize these risks."
The findings by Akiyama and his colleagues, Hiroshi Furuhata, Toshihiro Ishibashi, Shogo Tokudome, Takeki Ogawa and Toshiaki Abe, build on similar results in other studies using high-frequency, high-intensity ultrasound in combination with thrombolytics.
In those studies, high-frequency ultrasound--not the low-frequency soundwaves Akiyama's group used in their study--accelerated the action of urokinase and t-PA in experimental animal models of blockages causing heart attacks.
"One previous report in the Japanese literature has suggested that external ultrasound can facilitate thrombolysis in the canine model of acute myocardial infarction (heart attack)," Akiyama said. "However, high-frequency ultrasound is believed to have only limited transmittance though the skull, which would sharply limit the usefulness for external transcranial ultrasound treatments."
For further information, call Mark Wright (email: mwright@bgsm.edu) or Bob Conn (email: rconn@bgsm.edu) at 910-716-4587.
Once the International Neurosonology '97 has begun on August 13, call the conference press room at 910-724-6923.