Urokinase treatment preserves endothelial and smooth muscle function in experimental acute arterial thrombosis

Pharmacologic lysis or balloon thrombectomy are options to treat acute arterial thrombosis; however, little is known about their effects on functional changes in the arterial wall. The aim of this study was to determine function of the endothelium and smooth muscle in canine arteries revascularized after acute thrombosis with balloon thrombectomy or lytic therapy.

Acute thrombosis was obtained by bilateral proximal and distal ligation of 8-cm. segments of the femoral arteries in dogs. After 24 hours, the ties were removed and the arteries randomized to treatment groups: group 1, balloon thrombectomy (# 4 Fogarty balloon catheter at 60 grams linear shear x 1 pass, n = 7); group 2, untreated, tie removal only (n = 6); group 3, regional intra-arterial urokinase infusion (4000 U/min x 90 min, n = 6); group 4, regional intra-arterial carrier infusion (0.43 ml/min x 90 min, n = 6); group 5, unoperated normal vessels (n = 5). After treatment, the arteries were removed and endothelial and smooth muscle responses examined in organ chambers. Endothelial loss was graded with light microscopy of vessel rings from each animal by an observer blinded to the treatment group. Findings were confirmed with scanning electron microscopy.

Treatment with urokinase did not alter endothelium-dependent relaxations or smooth muscle contractions compared with carrier infusion or untreated alone. Balloon catheter thrombectomy significantly reduced endothelium-dependent relaxations compared with all other groups in response to acetylcholine, bradykinin, and thrombin (p < 0.001). Contractions of smooth muscle in response to potassium chloride (60 mol/L) and phenylephrine (1 x 10-6 mol/L) were also reduced (p < 0.05). Rings from balloon thrombectomized arteries contracted in response to calcium ionophore A23187 (p < 0.001); these contractions were endothelium dependent and not reduced by indomethacin or blockade of endothelin A and B receptors. No significant differences in percentage of endothelial coverage between groups were assessed by light and electron microscopy.

Thrombolysis with urokinase caused no or minimal abnormalities in endothelial and smooth muscle function. Endothelium present after balloon thrombectomy produces contractile factors. Although the duration and recovery of these abnormalities in function are unknown, these findings support preferential use of urokinase over balloon thrombectomy when possible in acute arterial thrombosis or embolism.