University of Cincinnati (UC) scientists have developed a model that could help physicians combine current clot-busting medication with below-normal body temperatures (hypothermia) to improve the treatment of ischemic stroke patients.
Thought to be first report of the temperature dependence of the standard, FDA-approved stroke medicationan enzyme called tissue plasminogen activator (tPA)in human clots and plasma, the findings could prove useful in predicting the efficacy of tPA over a wide range of temperatures, the UC researchers say.
The work is reported in the May 2007 issue of Physics in Medicine and Biology.
It is already known that lowering a patient's temperature reduces the metabolic activity of ischemic (clot-causing) cells, which in turn reduces cell damage and death.
But, says George Shaw, MD, PhD, who led the UC team, while several research centers are studying the use of hypothermia treatment for both stroke and heart attacks, little is known about how effective tPA is in the lab or the human body at lower temperatures.
Using the Celsius (centigrade) scale, normal human body temperature is 37 degrees. Shaw and his team tested 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.
"Around 33 Celsius is what most folks would consider the target temperature in cooling for therapeutic hypothermia," Shaw explains, "although there have been suggestions that 35 Celsius would be useful as well."
The UC researchers found, however, 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.