EFFICACY OF ADJUNCTIVE INTRATHROMBIC HEPARIN WITH PULSE SPRAY THROMBOLYSIS IN RABBIT INFERIOR VENA-CAVA THROMBOSIS

RATIONALE AND OBJECTIVES. The efficacy and speed of pharmacomechanical thrombolysis may be limited by thrombotic effects of activated platelets and thrombin within the lysing clot. The authors designed an animal model of subacute venous thrombosis which was used to evaluate the effect of intrathrombic versus intravenous heparin during thrombolysis. METHODS. Inferior vena cava (IVC) thrombosis was induced in rabbits by balloon catheter injury and placement of steel coils. Venacavagrams were obtained 48 hours later to document clot formation and for angiographic estimation of clot volume. Pulse-spray thrombolysis was performed by forceful injections of various agents through a catheter with multiple side holes spanning the clot. Most animals were given aspirin (30 mg orally) before treatment. After 1 hour of therapy, repeat venacavography was performed. Animals were killed, and residual clot weight was determined. RESULTS. Occlusive IVC thrombi were present in 94% of rabbits at 2 days. Mean residual clot weight per milliliter of estimated initial clot volume (mg/mL) for the various treatment groups was as follows: saline (n = 5) 632 +/- 54; tissue-type plasminogen activator (t-PA) 3 mg, (n = 6) 443 +/- 162; t-PA 3 mg + heparin 750 U intravenously, (n = 7) 408 +/- 128; t-PA 3 mg + heparin 500 U intrathrombic + heparin 250 U intravenously, (n = 8) 213 +/- 166. Differences among these groups (except t-PA alone versus t-PA + intravenous heparin) were significant. The extent of lysis with intrathrombic + intravenous heparin was not significantly retarded by withholding aspirin (n = 6, 194 +/- 72), or improved by giving half the intrathrombic heparin before t-PA injections (n = 6, 280 +/- 158). CONCLUSIONS. The results demonstrate the advantage of adjunctive intrathrombic + intravenous heparin over intravenous heparin alone in increasing the extent of pulse-spray thrombolysis in this IVC thrombosis model.