A pilot study of streptokinase-induced endothelial injury and platelet activation following acute myocardial infarction.
OBJECTIVE
To relate the changes in serum vitamin E, an essential antioxidant, to changes in fibrinogen, as well as indices of endothelial damage [as indicated by plasma markers, soluble thrombomodulin (sTM) and von Willebrand factor (vWf), and an index of platelet activation (soluble P selectin (sPsel)], in myocardial infarction treated with thrombolytic therapy.


METHODS
Prospective longitudinal pilot study in a teaching hospital Coronary Care Unit.


METHODS
Seventeen patients (12 men: mean age (62 years +/- SD 11 years) admitted with acute myocardial infarction (AMI), who were given thrombolytic therapy, and 59 healthy controls.


RESULTS
Baseline levels of fibrinogen (Mann-Whitney test, P = 0.0055) and vWf (P < 0.001) were significantly higher than controls, but sPsel, sTM or vitamin E levels were not significantly different. Following thrombolysis, as expected, median concentrations of plasma fibrinogen fell profoundly (Friedman ANOVA P < 0.001) so that after 45 min, levels were undetectable in 13 patients. At 24-h median fibrinogen concentration had recovered to approximately 30% of baseline (P < 0.01) and was still undetectable in three patients. Levels of vWf and sPsel increased steadily, reaching significance after three hours (both P < 0.05). However, levels of sTM rose immediately after thrombolysis, peaking between 1 and 3 h, and remained elevated at 24 h. These increases corresponded to a simultaneous early fall in serum vitamin E concentrations.


CONCLUSIONS
The present pilot study demonstrates significant endothelial damage and platelet activation in association with increased oxidative stress following streptokinase therapy for AMI.
Lip
G Y
GY
University Department of Medicine, City Hospital, Birmingham, UK. G.Y.H.LIP@bham.ac.uk
Lydakis
C
C
Nuttall
S L
SL
Landray
M J
MJ
Watson
R D
RD
Blann
A D
AD
D000368:Aged; D000704:Analysis of Variance; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D005340:Fibrinogen / Q000187:drug effects / Q000378:metabolism*; D005343:Fibrinolytic Agents / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000188:drug therapy*; D018384:Oxidative Stress / Q000187:drug effects; D019007:P-Selectin / Q000097:blood* / Q000187:drug effects; D010865:Pilot Projects; D015539:Platelet Activation / Q000187:drug effects*; D011446:Prospective Studies; D013300:Streptokinase / Q000009:adverse effects*; D018180:Thrombomodulin / Q000097:blood* / Q000187:drug effects; D014810:Vitamin E / Q000097:blood*; D014841:von Willebrand Factor / Q000187:drug effects / Q000378:metabolism*
D005343:Fibrinolytic Agents; D019007:P-Selectin; D018180:Thrombomodulin; D014841:von Willebrand Factor; D014810:Vitamin E; D005340:Fibrinogen; D013300:Streptokinase