Magnesium sulfate neither potentiates nor inhibits tissue plasminogen activator-induced thrombolysis.
BACKGROUND
Increasing circulating magnesium concentrations to 2-fold over normal baseline may afford a neuroprotective effect in patients with acute cerebral ischemia.


OBJECTIVE
As patients receiving magnesium sulfate (MgSO(4)) in human clinical trials may also be candidates for subsequent thrombolytic therapy with tissue plasminogen activator (t-PA), preclinical assessment of possible inhibition or potentiation of fibrinolytic activity by MgSO(4) has important clinical relevance.


METHODS
We utilized an in vitro system, in which D-dimer release served as a reflection of t-PA-induced clot lysis, to measure the effect of magnesium at the target concentration being tested in human stroke clinical trials, and at 2- and 3-fold higher levels. Clots from normal volunteers were exposed to t-PA at concentrations that correspond to therapeutic or endogenous plasma t-PA levels.


RESULTS
MgSO(4) had no effect on t-PA-induced clot lysis at up to 3-fold target magnesium concentration (6x normal serum concentration).


CONCLUSIONS
MgSO(4) concentrations well above the targeted level in therapeutic stroke trials does not affect t-PA-induced fibrinolytic activity, and therefore is a suitable agent for trials of combined neuroprotective and thrombolytic therapy in patients with acute ischemic stroke.
Stewart
D
D
Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Marder
V J
VJ
Starkman
S
S
Saver
J L
JL
D004305:Dose-Response Relationship, Drug; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008278:Magnesium Sulfate / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D020521:Stroke / Q000188:drug therapy; D015912:Thrombolytic Therapy / Q000379:methods*; D010959:Tissue Plasminogen Activator / Q000494:pharmacology* / Q000627:therapeutic use
D005338:Fibrin Fibrinogen Degradation Products; D018696:Neuroprotective Agents; C036309:fibrin fragment D; D008278:Magnesium Sulfate; D010959:Tissue Plasminogen Activator