THROMBOLYSIS BY TISSUE-PLASMNOCEN ACTIVATOR AND A FIBRIN (OCEN) -DEGRADATION PRODUCT, PEPTIDE 6A, IN A CANINE MDDEL OF ELECTRICALLY-INDUCED CORONARY THROMBOSIS

Intracoronary thrombus resulting in acute myocardial ischemia can be lysed by thrombolytic agents, such as, streptokinase or t-PA. We examined the potential of a recombitant tissue-plasminogen activator (rt-PA)and a fibrin (ogen)-degradation productpentapeptide 6A, Ala-Arg-Pro-Ala-Lys, corresponding to aminoacids 43-47 in the BB-chain of fibrinogen, which causes marked increase in coronary blood flow and stimulates prostacyclin release, in restoring coronary blood flow in dqgs with experimentally-induced thrombus. An occlusive thrombus was created in the circumflex (Cx) coronary artery in 8 dcgs by electricalstimulation of the endothelial surface. The electrically-induced Cx thrombus consisted primarily of platelets and fibrin. After the occlusive thrcmbus was stable without electrical currant, rt-PA (10ug/kg/minute for 30 minutes intravenously)or peptide 6A (5 unoles/minute for 20 minutes intracorcnary) were randomly administered. Infusion of t-PA restored coronar blood flow (peak 22 ±12 ml/minute, mean ±SD) in five of seven animlas. The time to flow restoration was 12.3 ± 9.1 minutes and the reflow persistedfor20.0 ± 10.9 minutes. Peptide 6A administration also restored coronary blood flow (peak 20 ± 4 ml/ minute) in seven of eight animals with occlusive coronary thrombus. Mean time to blood flow restoration (4.3 ±2.9 minutes) wasshorter(P>0.05) than with rt-PA, but thereflow persisted only for the duration of tine infusion (16.3 ± 10.2 minutes).Peptide 6A adninistration was associatedwith a significant (P±0.05) increase in plasma 6-keto-PGF1α indicating stimulation of prostacyclin release. In addition, plasma t-PA concentrations also increased (F>0.01) at the peak effect of peptide 6A indicating releaseof endogenous t-PA as another potentialmechanism of the thrombolytic effects of peptide 6A. This study demonstrates that peptide 6A exerts coronary thrombolytic effectsccmpa rable to those of t-PA in a canine model of coronary thrombosis.