PREVENTION OF EARLY REOCCLUSION AFTER THROMBOLYSIS OF COPPER COIL-INDUCED THROMBI IN THE CANINE CAROTID-ARTERY - COMPARISON OF PEG-HIRUDIN AND UNFRACTIONATED HEPARIN
K. Rubsamen et W. Hornberger, PREVENTION OF EARLY REOCCLUSION AFTER THROMBOLYSIS OF COPPER COIL-INDUCED THROMBI IN THE CANINE CAROTID-ARTERY - COMPARISON OF PEG-HIRUDIN AND UNFRACTIONATED HEPARIN, Thrombosis and haemostasis, 76(1), 1996, pp. 105-110
Cofactor-independent thrombin inhibitors as adjunctive treatment to th
rombolysis have been found to enhance reperfusion and reduce the incid
ence of early reocclusion more effectively than heparins. However, all
thrombin inhibitors presently available are rapidly cleared from the
circulation which may cause rebound effects after cessation of treatme
nt. To evaluate the effect of PEG-hirudin (LU 87981) a new, long actin
g derivative of hirudin as adjunctive treatment to rt-PA, a thrombotic
occlusion of the carotid artery was induced in mongrel dogs by means
of a copper coil. Vessel patency was continuously monitored with an el
ectromagnetic flow probe. Thrombolysis of the occluded artery was indu
ced by administration of 40 mu g x kg(-1) + 240 mu g x kg(-1) x h(-1)
rt-PA (low dose) or 80 mu g x kg(-1) + 480 mu g x kg(-1) x h(-1) rt-PA
(high dose). With high dose rt-PA treatment, patency was achieved in
all animals within 50 min (range 24 to 75), with low dose rt-PA treatm
ent only in 6 out of 8 animals after 73 min (range 26 to 117). Concomi
tant administration of PEG-hirudin (0.3 mg x kg(-1) bolus + 0.15 mg x
kg(-1) x h(-1) infusion) increased the incidence of reperfusion in the
low dose rt-PA group to 100% while the reperfusion rime was shortened
from 73 min in the corresponding control group to 38 min (range 20 to
75 min) in the group given PEG-hirudin (p = 0.065, Mann-Whitney U-tes
t). The carotid artery blood flow, which rapidly declined to zero with
in 18 to 27 min after discontinuing low or high dose rt-PA infusions r
emained at a sustained level for the whole observation period of 4 h o
nly in the group given PEG-hirudin. Only one animal reoccluded after 2
29 min. Unfractionated heparin (UFH) given at a dose of 0.3 mg x kg(-1
) bolus + 0.3 mg x kg(-1) x h(-1) infusion did not improve the inciden
ce of reperfusion or lower the incidence of reocclusion. Buccal bleedi
ng time was prolonged after high dose rt-PA treatment and after low do
se rt-PA with adjunctive UFH- or PEG-hirudin treatment. Buccal blood l
oss was not significantly affected by either treatment. In conclusion,
these experiments indicate that early reocclusion after thrombolysis
can effectively be diminished by concomitant treatment with the long a
cting thrombin inhibitor PEG-hirudin with moderate effects on bleeding
time and aPTT.