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Researchers Develop Model That Aids in Treating Stroke Patients

Researchers at the University of Cincinnati have developed a model that could improve the treatment of ischemic stroke patients by helping physicians combine current clot-busting medication with below-normal body temperatures hypothermia.

It is already known that lowering a patients temperature reduces the metabolic activity of ischemic clot-causing cells, which in turn reduces cell damage and death.

The FDA-approved stroke medication is an enzyme called tissue plasminogen activator tPA.

Researchers led by George Shaw, MD, PhD, used the Celsius (centigrade) scale, normal human body temperature is 37 degrees to test tPA, which like most enzymes is very temperature dependent, to see how well it broke up clots at temperatures ranging from 30 to 39.5 degrees Celsius.

The researchers used blood samples from ten healthy donors to form 226 small clots, exposed the clots to fresh-frozen human plasma and tPA at various temperatures, then measured how much mass the clots lost.

Shaw says that while he and his colleagues fully expected to find that tPA is less effective at lower temperatures, their study enabled them to develop a model to explain the mechanism of how tPA gets into the clot and subsequently breaks it up.

The researchers found that at 33 degrees Celsius, clots exposed to tPA lose only 8.8 percent of their mass, compared with 12 percent at 37 degrees Celsius.

So, if youre administering therapeutic hypothermia and tPA at the same time, you might want a higher tPA dosing, since it is less effective at lower temperatures, Shaw said.

Another consideration, however, is the role of the body enzyme plasminogen, which tPA converts into plasmin, a so-called proteolytic enzyme that actually does the work of dissolving the clots.

Without sufficient plasminogen more tPA won't help, so I suspect if one wants to use hypothermia and tPA at the same time , something else might be needed to help the tPA work better, Shaw says.

Shaw says the model of the tPA-hypothermia interaction that his team has developed from the study may be useful in helping researchers predict the efficacy of tPA over a wide range of temperatures.

Knowing the effectiveness of tPA at various temperatures could allow a physician to adjust tPA dosing in a stroke patient if hypothermia is being induced as well, says Shaw.

There are multiple medications and treatments for heart attacks, but not for stroke because stroke therapies are still in their infancy. This study offers another potential option for treatment, he added.

The work is reported in the May 2007 issue of Physics in Medicine and Biology.


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