Ultrasound Enhanced Thrombolysis

By Zac Hafez, Graduate Student

Occlusion of blood vessels by way of ischemic blockage results in the restriction of blood flow to the affected area. With any instance of ischemia, the re-supply of blood flow to the effected tissues is a time-sensitive process. The longer that tissue is deprived of oxygen, the less chance that it will live and fully function. The effects of oxygen depravation are most seen with ischemic stroke, where blood supply to the brain has been affected or blocked completely. In stroke victims, re-supply of blood flow is definitive of how affected the patient will be. The current clinical treatment of occlusions is to administer a class of drugs called t-Pas, or recombinase tissue plasminogen activators within three hours of the onset of symptoms. T-Pas are naturally occurring, serine proteases that are physiologically identical to the naturally occurring endogenous plasminogen activator in humans. In its natural state, t-Pa is produced by vascular endothelium (Ohman et al 2001). In its native amounts, it is harmless to the body and keeps blood from pooling and forming clots. However, when a traumatic event occurs that results in a large thrombus which develops into an ischemic blockage, a higher amount of t-Pa is necessary to dissolve the thrombus and re-supply blood flow before cell and tissue death.

In place of injecting large, dangerous amounts of t-Pa into the body, it has been shown experimentally that stimulation by ultrasound aides in the dissolution of blot clots in vitro (Olson et al 1994, Suchkova et al 2002, Schafer et al 2005). However, the mechanism of action remains poorly understood and often unknown in cases of thrombolysis. It is known that there are duty factor dependences, with continues wave being the optimal conditions, yet frequency, pulse repetition frequency and cycle dependencies remain poorly understood.

Research into these mechanisms can help in clinical application of ultrasound to increase the patency of blood flow during an ischemic blockage. By decreasing the amount of time that there is a blockage, the side effects of oxygen depravation can be limited. With the inclusion of the impact of Ultrasound Contrast Agents, ultrasound enhanced thrombolysis could provide a revolutionary way to treat strokes.