Effects of Peptide 6A on Coronary Blood Flow Dynamics in Canine Coronary Thrombosis

Abstract

Intracoronary thrombi resulting in acute myocardial ischemia can often be lysed by thrombolytic agents. We examined the potential of a fibrin(ogen)-degradation product pentapeptide 6A (Ala-Arg-Pro-Ala-Lys), which increases coronary blood flow partly by stimulation of prostacyclin release, in reestablishing coronary blood flow in dogs with experimentally induced thrombus. An occlusive thrombus in the circumflex coronary artery was created by electrical stimulation of the endothelial surface. After the occlusive thrombus was stable without electrical current for at least 15 min, peptide 6A (5 mumol/min for 20 min intracoronary) or tissue-plasminogen activator (t-PA) [10 micrograms/kg/min for 20 min intravenously (i.v.)] was randomly administered. Peptide 6A administration reestablished coronary blood flow (peak 16 +/- 2 ml/min, mean +/- SE) in 6 of 12 animals with occlusive coronary thrombus. Mean time to blood flow reestablishment was 5.3 +/- 2.2 min, but the reflow was short lived (mean duration of reflow: 15.7 +/- 1.6 min). t-PA reestablished coronary blood flow (peak 19 +/- 3 ml/min) in 4 of 10 animals. The time of flow reestablishment was 12.0 +/- 3.9 min and the reflow persisted for 22.0 +/- 3.1 min. Peptide 6A administration was associated with an increase in coronary venous plasma 6-keto-PGF1 alpha, indicating stimulation of prostacyclin release. This study demonstrates the potential of peptide 6A in reestablishing coronary blood flow in a canine model of coronary thrombosis. This transient effect is associated with release of prostacyclin, which may be beneficial because of its vasodilator and platelet inhibitory effects.