Recombinant human, active site-blocked factor VIIa reduces infarct size and no-reflow phenomenon in rabbits

Oxygen free radicals induce de novo synthesis of tissue factor (TF), the in itiator of the extrinsic pathway of coagulation, within the coronary vascul ature during postischemic reperfusion. In the present study we wanted to as sess whether TF expression might cause myocardial injury during postischemi c reperfusion. Anesthetized rabbits underwent 30 min of coronary occlusion followed by 5.5 h of reperfusion. At reperfusion the animals received I) sa line (n = 8), 2) human recombinant, active site-blocked activated factor VI I (FVIIai, 1 mg/kg, n = 8), or 3) human recombinant activated FVII (FVIIa, 1 mg/kg, n = 8). FVIIai binds to TF as native FVII, but with the active sit e blocked it inhibits TF procoagulant activity. The area at risk of infarct ion (AR), the infarct size (IS), and the no-reflow area (NR) were determine d at the end of the experiment. FVIIai resulted in a significant reduction in IS and NR with respect to control animals (28.1 +/- 11.3 and 11.1 +/- 6. 1% of AR vs. 59.8 +/- 12.8 and 24.4 +/- 2.7% of AR, respectively, P < 0.01) , whereas FVIIa resulted in a significant increase in IS and NR to 80.1 +/- 13.1 and 61.9 +/- 13.8% of AR, respectively (P < 0.01). In conclusion, TF- mediated activation of the extrinsic coagulation pathway makes an important contribution to myocardial injury during postischemic reperfusion.