[Effects of tissue factor pathway inhibitor-1 on no-reflow in a rabbit model].

OBJECTIVE

To investigate the role of plasma tissue factor (TF) and tissue factor pathway inhibitor-1 (TFPI-1) level and to observe the effect of extrinsic TFPI-1 on no-reflow (NR) in a rabbit model of ischemia/reperfusion.

METHODS

Rabbits were randomized into four groups (n = 10 each): ischemic- reperfusion group (IR, subjected to 120 minutes of coronary artery occlusion and followed by 60 minutes of reperfusion); ischemic- reperfusion TFPI-1 group (100 ng/kg bolus and 1 ng x kg(-1) x min(-1) infusion during reperfusion); ischemic group (subjected to 180 minutes of coronary artery occlusion) and sham group. The NR area and ischemic area were determined by thioflavin S and Evan's blue staining in vivo. Plasma TF and TFPI-1 levels were measured before operation, before and at 120 minutes post coronary artery ligation, 10 and 60 minutes after reperfusion by ELISA.

RESULTS

Plasma TF and TFPI-1 levels before and at 120 minutes post coronary artery ligation were similar among the four groups (all P > 0.05). At 10 and 60 minutes after reperfusion, the plasma TF levels in the IR group was significantly higher than those in ischemic group and sham group [10 minutes: (20.7 + or - 4.1) pg/ml vs. (13.9 + or - 2.2) pg/ml (P < 0.001), (20.7 + or - 4.1) pg/ml vs. (13.2 + or - 2.6) pg/ml (P < 0.001); 60 minutes: (15.8 + or - 2.6) pg/ml vs. (13.5 + or - 1.6) pg/ml (P < 0.05), (15.8 + or - 2.6) pg/ml vs. (12.1 + or - 0.7) pg/ml (P < 0.001)] while the plasma TFPI-1 levels were similar among IR, ischemic and sham groups at 10 minutes after reperfusion and at 60 minutes after reperfusion (all P > 0.05). TFPI-1 level [(9.7 + or - 1.6) ng/ml] was significantly lower in the IR group than in the ischemic group [(11.6 + or - 1.6) ng/ml, P < 0.05] and sham group [(10.1 + or - 1.3) ng/ml, P < 0.01]. TF mRNA expression in the NR area in IR group was significantly up-regulated compared to the ischemic group (P < 0.05) and sham group (P < 0.001) while TFPI-1 mRNA expression was similar between IR group and ischemic group (P > 0.05). NR severity in the ischemic-reperfusion TFPI-1 group was significantly attenuated compared to IR group (0.39 + or - 0.11 vs. 0.54 + or - 0.06, P < 0.01).

CONCLUSION

Upregulated TF mRNA expression in the NR area and increased plasma TF level during reperfusion period, reduced plasma TFPI-1 level during reperfusion period as well as attenuated NR severity by extrinsic application of human rTFPI-1 in this model suggested an important role in the pathogenesis of the NR phenomenon.