title: Thrombolysis with tissue plasminogen activator (tPA) is temperature dependent.
abstract: Thrombolysis with tissue plasminogen activator (tPA) and hypothermia are two potential treatment modalities for acute ischemic stroke. Many investigators are studying these modalities both in the laboratory and in clinical trials. Because these modalities each appear to show benefit in animal models, there is considerable interest in studying combined therapy with both thrombolysis and hypothermia. However, it is known that alterations in the coagulation system can occur with decreased body temperature. Clinicians have frequently observed bleeding problems when patients are subjected to hypothermia for a variety of reasons. Hypothermia induced coagulopathy has been attributed to a variety of factors. Hypothermia can cause platelet dysfunction, inhibition of clotting factors, increased fibrinolysis and endogenous production of a heparin-like factor. Groups who studied fibrinolysis and temperature, however, found the opposite to be the case. Clot lysis studies with streptokinase showed increased fibrinolysis at higher temperatures. Data by Mumme suggested that the peak fibrinolytic activity of streptokinase was at 40 degrees C, but at 43 degrees C fibrinolytic activity was decreased. Rijken et al studied plasminogen activation with tissue plasminogen activator (tPA), urokinase and streptokinase at extremely low temperatures. They found less plasminogen activation and fibrinogen degradation at 25 degrees C compared to 37 degrees C, but negligible differences at 10 degrees C, 0 degrees C and -8 degrees C. To our knowledge, there is no data studying the fibrinolytic activity of tissue plasminogen activator (tPA) at temperature ranges between 25-37 degrees C which is the range of temperatures used clinically for therapeutic purposes.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Dept. of Neurology, Stanford University Medical Center, CA 94305, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Yenari
authors.forename: J T
authors.initials: JT
authors.lastname: Palmer
authors.forename: P M
authors.initials: PM
authors.lastname: Bracci
authors.forename: G K
authors.initials: GK
authors.lastname: Steinberg
mesh_terms: D000208:Acute Disease; D000818:Animals; D004195:Disease Models, Animal; D005342:Fibrinolysis / Q000187:drug effects*; D007035:Hypothermia; D008297:Male; D011817:Rabbits; D013696:Temperature; D013927:Thrombosis / Q000628:therapy*; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
chemical_list: D010959:Tissue Plasminogen Activator