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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
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