Author + information
- Ken Kanamasa, MD∗,
- Ikuyoshi Watanabe, MD∗,
- Bojan Cercek, MD∗,
- Juliana Yang, BS,
- Michael C. Fishbein, MD, FACC∗ and
- William Ganz, MD, CSc, FACC†∗
- ↵†Address for reprints: William Ganz, MD, Division of Cardiology, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, California 90048.
The safety of thrombolytic therapy of acute myocardial infarction could be improved if a method were developed to dissolve fresh occlusive coronary thrombus without simultaneously dissolving hemostatic thrombi outside the coronary arteries. This study is based on the assumption that, in a patient with evolving acute myocardial infarction, hemostatic thrombi are likely to be older than the thrombus responsible for occlusion of the coronary artery. It explored whether the relative rates of lysis of fresh and old thrombi could be influenced by the rapidity of recombinant tissuetype plasminogen activator (rt-PA) administration.
In each of 17 dogs, two 1 h and two 24 h old thrombi were produced by inserting copper coils into both jugular and both femoral veins. After 24 h and 1 h, respectively, the coils with the thrombi were removed, weighed and inserted into the adjacent carotid and femoral arteries. A 1 mg/kg body weight dose of rt-PA was given either over 180 or over 30 min. The coils were removed and weights of the residual thrombi determined at the end of the 180 min infusion (Group I), at the end of the 30 min infusion (Group IIA) and 45 min after the 30 min infusion (Group IIB). The 24 h old thrombi were lysed significantly less than the 1 h old thrombi in all three experimental groups: 53.9 ± 4.8% (mean ± SE) versus 86.1 ± 2.5% in Group I (p < 0.001), 16.6 ± 3.5% versus 65.2 ± 6.0% in Group IIA (p < 0.001) and 21.6 ± 5.4% versus 91.7 ± 1.7% in Group IIB (p < 0.001). The 24 h old thrombi were also lysed significantly less by the 30 min infusion than by the 180 min infusion (p < 0.001 for both). The ratio of lysis of 1 and 24 h old thrombi was markedly higher in Groups IIA (7.95 ± 2.16) and IIB (6.52 ± 1.50) than in Group I (1.71 ± 0.17) (p < 0.01 for both).
These findings suggest that rt-PA administered rapidly over a shorter period is less likely to lyse older thrombus, whereas the effect on fresh thrombus is preserved and probably enhanced. Clinical studies are needed to confirm the conclusions of this experimental study.
↵∗ From the Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center and the Department of Medicine, University of California at Los Angeles School of Medicine, Los Angeles, California.
☆ This study was supported in part by NIH SCOR Grant HL 17651 from the National Institutes of Health, Bethesda, Maryland, and was presented in part at the 38th Annual Meeting of the American College of Cardiology, Anaheim, California, March 21, 1989.