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Do clinically relevant circulating concentrations of radiographic contrast agents inhibit platelet-dependent arterial
Yanhong Zhu1, Richard Tomasiak, William P Fay
1Department of Internal Medicine (Cardiology), University of Michigan Medical School, and the Ann Arbor Veterans Affairs Hospital, Ann Arbor, MI, USA.
Objectives:
The purpose of this study was to determine if radiographic contrast agents (RCAs) inhibit thrombosis in a rat carotid artery injury model.
Background:
Whether ionic and nonionic RCAs differentially affect thrombus formation during coronary artery angioplasty is controversial. Although there are numerous in vitro studies and clinical trials addressing this issue, it is unknown whether clinically relevant plasma concentrations of RCA inhibit platelet-dependent thrombosis after injury of medium-sized arteries.
Methods:
Rats received RCA or control solution by bolus (0.7 ml/kg) and constant (0.04 ml/kg/min) intravenous infusion. Carotid arteries were injured with ferric chloride. Blood flow was monitored for 1 h. In vitro platelet aggregation and plasma clotting were studied.
Results:
After injury, mean times free from formation of an occlusive, platelet-rich thrombus were 16.2+/-2.3, 49.6+/-18.9, 47.9+/-21.0, and 37.1+/-22.8 min for rats (n=5/group) that received saline, diatrizoate (P<.002 vs. saline), ioxaglate (P<.002 vs. saline), and iohexol (P=.06 vs. saline), respectively. Reperfusion after initial occlusion did not occur in saline-treated animals, but was common in rats that received RCA. The antithrombotic properties of RCA were not explained by their high osmolarities or by detectable effects on in vitro platelet aggregation and plasma clotting. Plasma concentrations of RCA were <1%.
Conclusions:
Systemic administration of RCA at doses that achieve low, clinically relevant plasma concentrations can inhibit platelet-rich thrombus formation after arterial injury. Antithrombotic properties of ionic RCA appear to be greater than those of nonionic RCA.