Author + information
- Received February 27, 1992
- Revision received July 25, 1992
- Accepted July 28, 1992
- Published online February 1, 1993.
- Judith K. Mickelson, MD, FACC∗,
- Paul T. Hoff, MS,
- Jonathon W. Homeister, BA,
- Joseph C. Fantone, MD and
- Benedict R. Lucchesi, PhD, MD
- ↵∗Address for correspondence: Judith K. Mickelson, MD, Baylor College of Medicine, 6025 Annapolis, Houston, Texas 77005.
Objectives. The purpose of this study was to assess the antithrombotic potential of various forms of aspirin administration.
Background. Platelet activation in response to endothelial injury has been implicated in acute coronary syndromes.
Methods. Delivering 100-/gmA anodal direct current to the intima of the left circumtlex coronary artery in dogs at a site of moderate external stenosis provides a thrombogenic model of vascular injury. Animals were treated with aspirin (Group I, 20 mg/kg intravenously [n - 11]; Group II, 4.6 mg/kg intravenously [n = 6]; Group III, 4.6 mg/kg orally 18 h before the experiment [n = 7]J or vehicle (Group IV, control [n = 11]).
Results. The time required for thrombotic occlusion to occur was longer and the incidence of thrombosis was lower in Group 1 (Group I, 238 ± 7 min [n = 2]; Group II, 127 ± 25 min [n = 3]; Group III, 156 ± 35 min [n = 6]; Group IV, 90 ± 11 min [n = 11]) (p < 0.05). Thrombus mass was smaller In Group I (Group 1, 5.0 ± 0.8 mg; Group II, 12.2 ± 2.6 mg; Group HI, 11.6 ± 3.9 mg; Group IV, 9.1 ± 1.6 mg) (p < 0.05). Initial hemodynamic variables did not differ among groups. An increase in mean arterial pressure was noted for several hours after intravenous aspirin administration in Group I(99 ± 5 to 110 ± 4 mm Hg) (p < 0.05). Left circumflex coronary artery blood flow was stable for 5 h in Group I (Group I, 31 ± 2 to 26 ± 4 ml/min) but decreased in all the other groups (Group II, 26 ± 4 to 10 ± 5 ml/min; Group III, 27 ± 5 to 7 ± 7 ml/min; Group IV, 29 ± 4 to 0 ml/min) (p ⩽ 0,05). The in vivo area or left ventricle perfused by the left circumflex coronary artery was not different among groups. Platelet counts were similar and did not change over the course of the protocol. Ex vivo arachidonic acid-induced platelet aggregation decreased in all groups after aspirin (p ⩽ 0.001). Indium-III-labeled platelet adherence to the coronary vasculature was decreased in distal vessel segments after all doses of aspirin (p < 0.05), Platelet deposition in thrombi was similar for all treatment groups.
Conclusions. High dose intravenous aspirin has salutary effects. It stabilizes left circumflex coronary- artery blood flow, prolongs the time to thrombosis, reduces the incidence of thrombolic occlusion, reduces thrombus mass and limits platelet adherence to sites of arterial injury. Low dose aspirin given intravenously or orally was ineffective. When persistent intracoronary thrombi precipitate unstable coronary syndromes, high dose intravenous aspirin may be useful in the acute period even though platelets continue to interact with injured vascular segments through aspirin-insensitive mechanisms.
☆ This work was supported by grants from the National Heart, Lung, and Blood Institute (HL-19782-11), National Institutes of Health, Bethesda, Maryland (B.R.L.), the American Heart Association of Michigan. Ann Arbor (J.K.M.), an Established Inrestigatorship of the American Heart Association, Dallas, Texas (J.K.M.) and the Veterans Administration Merit Review, Washington. D.C. (J.K.M.).
- Received February 27, 1992.
- Revision received July 25, 1992.
- Accepted July 28, 1992.