Biochemical basis of angioedema associated with recombinant tissue plasminogen activator treatment: an in vitro experimental approach.

نویسندگان

  • Giuseppe Molinaro
  • Nicole Gervais
  • Albert Adam
چکیده

BACKGROUND Angioedema has been reported during recombinant tissue plasminogen activator (rtPA) treatment of acute ischemic stroke, often with concomitant use of angiotensin I-converting enzyme inhibitor treatment. Angioedema has been partly attributed to the nonapeptide bradykinin (BK), although its precise role has been poorly documented until now. The purposes of this report are 2-fold. First, we sought to define and characterize the in vitro kinin-forming capacity of rtPA when incubated with human plasma at a concentration within the therapeutic concentration range of rtPA attained in blood in vivo during fibrinolysis. Second, we sought to define the mechanism by which rtPA liberates BK from purified human single-chain high-molecular-weight kininogen, a key constituent of the contact system of plasma and the precursor of BK. SUMMARY OF REPORT When incubated with human plasma, in the presence of an angiotensin I-converting enzyme inhibitor, rtPA generates BK, which is further metabolized to des-Arg9-BK. The quantity of kinins generated by rtPA is similar to that observed during the activation of the contact system of plasma with a negatively charged surface, suggesting that it is physiologically relevant. The total amount of des-Arg9-BK liberated during the incubation period depends on the aminopeptidase P activity, its main degrading peptidase. Additionally, incubations using purified proteins of the fibrinolytic and the contact system pathways show that the rtPA kinin-forming capacity is mediated by plasmin. CONCLUSIONS We conclude that rtPA used in vitro at a therapeutic concentration has the capacity to generate significant quantities of kinins from human plasma. This kinin-forming activity depends on the activation of the fibrinolytic pathway. These data suggest that angioedema associated with rtPA treatment of ischemic stroke results directly from plasmin-mediated release of BK.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Optimizing refolding condition for recombinant tissue plasminogen activator

Low molecular size additives such as L-arginine and the redox compounds have been used both in the culturemedium and in vitro refolding to increase recombinant proteins production. Additives increase proteinrefolding and yield of active proteins by suppressing aggregate formation or enhancing refolding process.In this work, a comparative study was performed on refolding of rec...

متن کامل

A clinical study investigating the three months prognosis of patients with ischemic stroke treated with recombinant tissue plasminogen activator (rt-PA) and its effective factors

Objective: Currently, treating ischemic stroke by intravenous thrombolytic therapy has acceptable results in patients with stroke. This study aimed to evaluate the three months prognosis of patients treated with recombinant tissue plasminogen activator (rt-PA).Methods: This cross-sectional prospective study was conducted on 30 patients with cerebral ischemic stroke with the National Insti...

متن کامل

Destruction of Recombinant Tissue Plasminogen Activator (rtPA) -Loaded Echogenic Liposomes under Dual Frequency Sonication

Background:Echogenic liposomes (ELIPs) encapsulate drugs and gas bubbles within lipid vesicles. The destruction of ELIPs in response to MHz and kHz ultrasound waves has been studied previously. Applying ultrasound above a certain threshold causes encapsulated gas bubbles destruct rapidly by fragmentation or more slowly by acoustically driven diffusion. This study compares the d...

متن کامل

Dual frequency ultrasound-enhanced tissue plasminogen activator thrombolysis in an in vitro human clot model

Introduction: Stroke causes death and disability in patients throughout the world. At present, the only FDA- approved drug for ischemic stroke is recombinant tissue plasminogen activator (rt- PA). Unfortunately, rtPA can cause intracerebral hemorrhage and must use within limited time window (within 3-4.5 hour after onset of stroke). Ultrasound with rtPA loaded liposomes (rtPA_L...

متن کامل

The Outcome of Treatment With Recombinant Tissue Plasminogen Activator in Acute Ischemic Stroke

Background: Thrombolytic therapy is the recommended treatment of acute ischemic stroke. It is crucial to evaluate the treatment results with recombinant Tissue Plasminogen Activator (r-TPA) in patients with acute stroke. Objectives: This study aimed to evaluate treatment outcomes with r-TPA in patients with acute stroke in a referral stroke center in Iran. Materials & Methods: In this retrosp...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Stroke

دوره 33 6  شماره 

صفحات  -

تاریخ انتشار 2002