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Effects of peptide 6A on coronary blood flow dynamics in canine coronary thrombosis
J L Mehta1, W W Nichols, T G Saldeen
1Department of Medicine, University of Florida College of Medicine, Gainesville 32610.
Insights
Pentapeptide 6A shows potential in restoring coronary blood flow in dogs with thrombus by stimulating prostacyclin release. This effect was transient but highlights the peptide
Area of Science:
- Cardiovascular Research
- Pharmacology
- Thrombosis Models
Background:
- Intracoronary thrombi cause acute myocardial ischemia.
- Thrombolytic agents are commonly used for treatment.
- Fibrin degradation products may offer therapeutic potential.
Purpose of the Study:
- To evaluate the efficacy of pentapeptide 6A in reestablishing coronary blood flow.
- To investigate the mechanism of action, specifically prostacyclin release.
- To compare peptide 6A with tissue-plasminogen activator (t-PA) in a canine model.
Main Methods:
- Experimentally induced occlusive coronary thrombus in dogs.
- Intracoronary administration of peptide 6A (5 μmol/min for 20 min).
- Intravenous administration of t-PA (10 μg/kg/min for 20 min).
- Measurement of coronary blood flow and 6-keto-PGF1α levels.
Main Results:
- Peptide 6A reestablished coronary blood flow in 6/12 animals (peak 16±2 ml/min) for a mean duration of 15.7±1.6 min.
- t-PA reestablished flow in 4/10 animals (peak 19±3 ml/min) for a mean duration of 22.0±3.1 min.
- Peptide 6A increased coronary venous 6-keto-PGF1α, indicating prostacyclin release.
Conclusions:
- Pentapeptide 6A demonstrates potential in reestablishing coronary blood flow in a canine thrombosis model.
- The transient reflow induced by peptide 6A is associated with prostacyclin release.
- Prostacyclin's vasodilator and antiplatelet effects may contribute to the observed benefits.
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.