Modulation by the Noble Gas Helium of Tissue Plasminogen Activator: Effects in a Rat Model of Thromboembolic Stroke
| Autor: | Jean-Eric Blatteau, Jacques H. Abraini, Benoit Haelewyn, Nicolas Vallée, Cédric Meckler, Hélène N. David, Jean-Jacques Risso |
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| Rok vydání: | 2015 |
| Předmět: |
inorganic chemicals
Male genetic structures chemistry.chemical_element Thromboembolic stroke Pharmacology Critical Care and Intensive Care Medicine Tissue plasminogen activator Neuroprotection Helium Brain Ischemia Brain ischemia 03 medical and health sciences 0302 clinical medicine Antifibrinolytic agent Thromboembolism medicine Animals Stroke Dose-Response Relationship Drug business.industry 030208 emergency & critical care medicine respiratory system Hypothermia medicine.disease Antifibrinolytic Agents respiratory tract diseases Rats Disease Models Animal chemistry Anesthesia Tissue Plasminogen Activator Drug Therapy Combination medicine.symptom business Intracranial Hemorrhages 030217 neurology & neurosurgery circulatory and respiratory physiology medicine.drug |
| Zdroj: | Critical care medicine. 44(6) |
| ISSN: | 1530-0293 |
| Popis: | Helium has been shown to provide neuroprotection in mechanical model of acute ischemic stroke by inducing hypothermia, a condition shown by itself to reduce the thrombolytic and proteolytic properties of tissue plasminogen activator. However, whether or not helium interacts with the thrombolytic drug tissue plasminogen activator, the only approved therapy of acute ischemic stroke still remains unknown. This point is not trivial since previous data have shown the critical importance of the time at which the neuroprotective noble gases xenon and argon should be administered, during or after ischemia, in order not to block tissue plasminogen activator-induced thrombolysis and to obtain neuroprotection and inhibition of tissue plasminogen activator-induced brain hemorrhages.We show that helium of 25-75 vol% inhibits in a concentration-dependent fashion the catalytic and thrombolytic activity of tissue plasminogen activator in vitro and ex vivo. In vivo, in rats subjected to thromboembolic brain ischemia, we found that intraischemic helium at 75 vol% inhibits tissue plasminogen activator-induced thrombolysis and subsequent reduction of ischemic brain damage and that postischemic helium at 75 vol% reduces ischemic brain damage and brain hemorrhages.In a clinical perspective for the treatment of acute ischemic stroke, these data suggest that helium 1) should not be administered before or together with tissue plasminogen activator therapy due to the risk of inhibiting the benefit of tissue plasminogen activator-induced thrombolysis; and 2) could be an efficient neuroprotective agent if given after tissue plasminogen activator-induced reperfusion. |
| Databáze: | OpenAIRE |
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