Activated protein C and antithrombin-III activity during arterial thrombolysis with recombinant tissue-type plasminogen activator in rabbits.
BACKGROUND
Protein C and antithrombin III (AT-III) are endogenous anticoagulants that regulate thrombotic processes. This experimental study examined the effect of recombinant tissue-type plasminogen activator (rt-PA) thrombolysis on the activity of these natural anticoagulants.


METHODS
Blood clots were produced in the femoral artery segments of six rabbits with endothelial damage and stenosis (group A). Five rabbits with only surgical dissection served as controls (group B). Both groups received an infusion of rt-PA at 30 micrograms/kg/min for 60 min. The plasma activity of activated protein C (APC) and AT-III was determined using chromogenic assays. Blood samples were taken at baseline (t1), after surgical dissection with (group A) or without (group B) thrombosis induction (t2), after rt-PA infusion (t3), and 1 h later (t4).


RESULTS
In group A rabbits, the mean (+/- SEM) APC activity rose significantly (P = 0.02) from 2.2 +/- 0.3 and 3.7 +/- 1.5 mOD units/min at t1 and t2, respectively, to 59.3 +/- 17.8 mOD units/min at t3 and decreased to 8.0 +/- 3.4 mOD units/min at t4. In group B rabbits, the mean (+/- SEM) APC activity rose (P = 0.01) from 1.1 +/- 0.1 and 1.2 +/- 0.1 mOD units/min at t1 and t2 to 17.1 +/- 3.2 mOD units/min at t3 and decreased to 2.4 +/- 0.2 at t4, (P = 0.011 for comparison between groups using two-way analysis of variance). The mean APC value at t3 was higher for group A than for group B (P = 0.06). A slight but statistically significant decrease (P < 0.01) in AT-III activity was noted in both groups, from 92 +/- 3% and 96 +/- 2% at t1 in groups A and B, respectively, to 79 +/- 3% and 86 +/- 2% at t4 (P = 0.028 for comparison between groups).


CONCLUSIONS
These data show a transient rise in APC and a slight decrease in AT-III activity during rt-PA thrombolysis. Whether these changes influence thrombolysis outcome remains to be determined.
Kornowski
R
R
Neufeld Cardiac Research Institute, Sackler School of Medicine, Tel-Aviv University, Sheba Medical Center, Tel Hashomer, Israel.
Battler
A
A
D000818:Animals; D000990:Antithrombin III / Q000032:analysis / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects*; D005263:Femoral Artery; D007262:Infusions, Intravenous; D008954:Models, Biological; D009842:Oligopeptides / Q000097:blood / Q000187:drug effects*; D011817:Rabbits; D011994:Recombinant Proteins; D015912:Thrombolytic Therapy; D013927:Thrombosis / Q000097:blood* / Q000188:drug therapy; D010959:Tissue Plasminogen Activator / Q000494:pharmacology* / Q000627:therapeutic use
D009842:Oligopeptides; D011994:Recombinant Proteins; C047135:protein C activator peptide; D000990:Antithrombin III; D010959:Tissue Plasminogen Activator