Antithrombotic Therapy for Deep Arterial Injury by Angioplasty

Efficacy of Common Platelet Inhibition Compared With Thrombin Inhibition in Pigs

Lam, J. Y.T. MD
Chesebro, J. H. MD
Steele, P. M. MD
Heras, M. MD
Webster, M. W.I. MD
Badimon, L. PhD
Fuster, V. MD

From the Division of Cardiovascular Disease and Internal Medicine (J.Y.T.L., J.H.C., P.M.S., M.H., M.W.LW.), Mayo Clinic and Mayo Foundation, Rochester, Minn.; and the Division of Cardiology (L.B., V.F.), Department of Medicine, Mount Sinai Medical Center, New York.

Address for reprints: James H. Chesebro, MD, Mayo Clinic, 200 First Street, S.W., Rochester, MN 55905.

J.Y.T.L. was a research fellow of the Medical Research Council of Canada. P.M.S. was supported by the National Heart Foundation of Australia. M.H. was the recipient of a research grant from CIRIT-Generalitat de Catalunya, Spain. M.W.I.W. was the recipient of a fellowship from the National Heart Foundation of New Zealand and the Fogarty Center, National Institutes of Health.

Received November 6, 1989; revision accepted March 26, 1991.

Circulation 84(2):p 814-820, August 1991.

Background

Platelet-thrombus formation is a complication of arterial wall deep injury by balloon angioplasty that may lead to acute arterial occlusion and may contribute to restenosis.

Methods and Results

Because common platelet-inhibitor drugs with a heparin bolus (100 units/kg) may be effective in inhibiting platelet-thrombus formation after arterial angioplasty, these were compared with a bolus of heparin alone (control), the specific thrombin inhibitor hirudin (1.0 mg/kg), and saline (hirudin control) in normal pigs after angioplasty of the common carotid arteries. In the presence of deep arterial wall injury (injury exposing the media), indium-111-labeled platelet deposition (X106/cm2) was 68.8 ± f12.3 and 48.1 ± f16.9 in the control animals. This was significantly reduced by pretreatment with low-dose aspirin (1 mg/kg/day), by high-dose aspirin (20 mg/kg/day) plus dipyridamole, and especially by thrombin inhibition with hirudin. Treatment regimens with aspirin alone (20 mg/kg/day), dipyridamole alone, or sulfinpyrazone were ineffective. Likewise, the incidence of mural thrombosis was 75% and 80%o in deeply injured arteries of controls and was significantly reduced to 46% with aspirin plus dipyridamole, 25% with low-dose aspirin, and 0% with hirudin. The incidence of mural thrombosis was unchanged with high-dose aspirin (69%o), dipyridamole (90%), or sulfinpyrazone (92%). This mural thrombosis could not be identified by angiography. In the presence of mild injury (deendothelialization), platelet deposition was low (< 10x 106/cm2, a single layer) and was not changed by any therapy, including hirudin.

Conclusions

These therapies do not affect platelet adhesion to deeply or mildly injured artery. These data suggest a greater role for thrombin inhibition than with thromboxane or cyclooxygenase inhibition in the pathogenesis of platelet-rich mural thrombosis after deep injury during angioplasty. Antithrombotic therapy for arterial thrombosis by thrombin inhibition appears promising.