Effects of intraarterial thrombin in the swine model

To evaluate the effects of catheter-directed thrombin in the peripheral arterial circulation of swine.

Thrombin was injected into a single femoral artery in 20 domestic swine. Each of five animals from four dose groups received 50, 150, 250, or 1,000 U as a single dose. Bilateral femoral arterial flow was monitored for as long as 4 hours and evaluated relative to baseline and contralateral limb flow. Interval arteriographic results were evaluated by segmental patency and a numeric angiographic score.

Mean baseline flow was 136 mL/min +/- 44, with an internal arterial diameter of 3.4 mm +/- 0.5. A transient increase in blood flow after thrombin administration was followed by diminished flow and thrombosis. These findings varied directly with dose and inversely with baseline flow. Angiographic and flow abnormalities generally improved with time and recovery was generally better in swine that received 50 or 1,000 U than in other groups. However, one animal that received 1,000 U (13.2 U/mL/min) developed stable, complete limb thrombosis. The degree of recovery varied with thrombin dose and thrombus location. At doses greater than 50 U (0.33 U/mL/min +/- 0.05), abnormalities were commonly persistent. Animals receiving the 150-U dose (1.33 U/mL/min +/- 0.41) had a higher incidence of persistent distal occlusion. Distal occlusions were less likely to resolve than proximal occlusions.

The effect of intraarterial thrombin is directly related to dose and inversely related to baseline blood flow. In swine, a threshold for significant flow disruption and thrombosis exists above a dose of 50 U (0.33 U/mL/min +/- 0.05). A threshold dose for irreversible occlusion may also exist. Although small amounts of thrombin in a high-flow vessel may not cause significant complication, administration into the arterial circulation should be avoided.