Effects of Ionic and Nonionic Contrast Media on Endothelium and on Arterial Thrombus Formation

Abstract

Background:

The aims of the present study were to investigate whether ionic and nonionic contrast media (CM) affect: 1) the procoagulant and fibrinolytic activities of cultured human vessel endothelium; and 2) early events of tissue-factor-induced arterial thrombus formation under conditions which may follow a percutaneous transluminal coronary angioplasty (PTCA) procedure. The following 3 CM were studied: iohexol (nonionic monomer, Omnipaque); iodixanol (nonionic dimer, Visipaque); and ioxaglate (ionic dimer, Hexabrix). Saline (0.9%) and glucose (40 vol%) were used as control.

Methods and Results:

Exposing endothelium to 40 vol% CM for 10 min did not affect the selected parameters of cellular procoagulant (tissue factor), anticoagulant (thrombomodulin), fibrinolytic (tissue plasminogen activator) or antifibrinolytic (plasminogen activator inhibitor-1) activity or antigen. However, ioxaglate had a profound impact on the cell morphology, which was noted already after one minute of exposure. The cells contracted and rounded, exposing large areas of extracellular matrix. Iohexol showed this phenomenon to a considerably lesser extent, whereas iodixanol induced a slight swelling of the cells without detectable exposure of extracellular matrix. The effect of the respective CM on tissue-factor-driven thrombus formation at an arterial shear rate of 2600 s⁻¹ was studied in an ex vivo parallel-plate perfusion chamber device. In this model, human native blood was passed over a tissue factor/phospholipid-rich surface following 30 s exposure to 100% CM. The CM was washed out by nonanticoagulated blood drawn directly from an antecubital vein by a pump positioned distal to the perfusion chamber. Such a pre-exposure of the procoagulant surface to iodixanol reduced the fibrin deposition around the platelet thrombi by 50% (p<0.01). However, iohexol and ioxaglate did not affect fibrin deposition. None of the 3 CM affected the recruitment of platelets in the thrombi, since similar values were obtained with pre-exposure to 40 vol% of saline.

Conclusion:

Iodixanol appears to be most biocompatible with endothelium, and has a moderate inhibitory effect on fibrin deposition in flowing blood. This differs from iohexol, and in particular from ioxaglate, which induce endothelial changes in morphology with no effect on fibrin deposition. Since none of the CM affected the platelet aggregate formation, and since ioxaglate has been reported to have stronger anticoagulant and antithrombotic properties than iodixanol or iohexol in in vitro assays, it is apparent that these properties were not reflected in thrombus formation under the experimental conditions of high arterial shear.

Keywords

Endothelium,contrast media blood flow thrombus formation

Get full access to this article

View all access options for this article.

References

Aznar-Salatti

Anton

Nemerson

Sakariassen

K. S.

: Modulation of procoagulant activity by anti-tissue factor antibody and the synthetic peptide Arg-Gly-Asp Val. Experiments with flowing non-anticoagulated blood. Blood Coag. Fibrinolysis 4 (1993), 881.

Chronos

N. A. F.

Goodall

A. H.

Wilson

D. J.

Sigwart

Buller

N. P.

: Profound platelet degranulation is an important side effect of some types of contrast media used in interventional cardiology. Circulation 88 (1993), 2035.

Colucci

Balconi

Lorenzet

: Cultured human endothelial cells generate tissue factor in response to endotoxin. J. Clin. Invest. 71 (1983), 1893.

Dawson

Hewitt

Mackie

I. J.

Machin

S. J.

Amin

Bradshaw

: Contrast-coagulation and fibrinolysis. Invest. Radiol. 21 (1986), 248.

Grines

C. L.

Schreiber

T. L.

Savas

: A randomized trial of low osmolar ionic versus nonionic contrast media in patients with myocardial infarction or unstable agina undergoing percutaneous transluminal coronary angioplasty. Am. Coll. Cardiol. 27 (1996), 1381.

Hardeman

M. R.

Konijnenberg

Sturk

Reekers

J. A.

: Activation of platelets by low-osmolar contrast media. Differential effects of ionic and non-ionic agents. Radiology 192 (1994), 563.

Jaffe

E. A.

Nachman

R. L.

Becker

C. G.

Minick

C. R.

: Culture of human endothelial cells derived from umbilical veins. J. Clin. Invest. 52 (1973), 2745.

Johnsen

L. W.

Krone

& The Registry Committee of the Society for Cardiac Angiography and Interventions: Cardiac catheterization 1991. A report of the Registry of the Society for Cardiac Angiography and Interventions (SCA&I). Cath. Cardiovasc. Diagn. 28 (1991), 219.

Kjellevand

T. O.

Kløw

N. E.

Vatne

: Coronary angioplasty using a low osmolar nonionic contrast medium. A retrospective angiographic and clinical evaluation. Acta Radiol. 36 (1995), 54.

10.

Levorstad

Vatne

Brodahl

Aakhus

Simonsen

Vik

: Cerebral thromboembolic complications associated with the use of a nonionic contrast medium in coronary angiography. Acta Radiol. 36 (1995), 69.

11.

Marmur

J. D.

Rossikhina

Guha

: Tissue factor activity is rapidly induced in arterial smooth muscle cells after balloon injury. J. Clin. Invest. 91 (1993), 2253.

12.

Nawroth

Stern

: Modulation of endothelial cell haemostatic properties by tumour necrosis factor. J. Exp. Med. 160 (1984), 618.

13.

Ørvim

Roald

H. E.

Stephens

R. W.

Roos

Sakariassen

K. S.

: Tissue-factor-induced coagulation triggers platelet thrombus formation as effciently as fibrillar collagen at arterial blood flow conditions. Arterioscler. Thromb. 14 (1994), 1977.

14.

Owens

M. R.

Ribes

J. A.

Marder

V. J.

Francis

C. W.

: Effects of ionic and non-ionic radiographic contrast agents on endothelial cells in vitro . J. Lab. Clin. Med. 119 (1991), 315.

15.

Piessens

J. H.

Stammen

Vrolix

M. C.

: Effects of an ionic versus a nonionic low osmolar contrast agent on the thrombotic complications of coronary angioplasty. Cathet. Cardiovasc. Diagn. 28 (1993), 99.

16.

Pugh

N. D.

Griffith

T. M.

Karlsson

J. O. G.

: Effects of iodinated contrast media on peripheral blood flow. Acta Radiol. Suppl. 399 (1995), p. 155.

17.

Riemann

C. D.

Massey

C. V.

Maccarron

D. L.

Borkowski

Johnson

P. C.

Ziskind

A. A.

: Ionic contrast agent-mediated endothelial injury increases platelet deposition to vascular surfaces. Am. Heart J. 125 (1993), 71.

18.

Sakariassen

K. S.

Aarts

P. A. M. M.

de Groot

P. G.

Houdijk

W. P. M.

Sixma

J. J.

: A perfusion chamber developed to investigate platelet interaction in flowing blood with human vessel wall cells, their extracellular matrix and purified components. J. Lab. Clin. Med. 102 (1983), 522.

19.

Sakariassen

K. S.

Joss

Muggli

: Collagen type III induced ex vivo thrombogenesis in humans. Role of platelets and leukocytes in deposition of fibrin. Arteriosclerosis 19 (1990), 276.

20.

Sakariassen

K. S.

Kuhn

Muggli

Baumgartner

H. R.

: Growth and stability of thrombi in flowing blood. Assessment of platelet-surface interactions with computer-assisted morphometry. Thromb. Haemost. 60 (1988), 392.

21.

Sakariassen

K. S.

Muggli

Baumgartner

H. R.

: Measurements of platelet interaction with components of the vessel wall in flowing blood. In: Methods in enzymology, vol. 169, p. 33. Edited by Hawiger

Academic Press Inc., New York 1989.

22.

Skalpe

I. O.

: Complications in cerebral angiography with iohexol (Omnipaque) and meglumine metrizoate (Isopaque cerebral). Neuroradiology 30 (1988), 69.

23.

Stormorken

: Present state of contrast media as related to thromboembolic complications. Semin. Hematol. 28 (1991), 69.

24.

Stormorken

Sakariassen

K. S.

: In vitro degranulation by contrast media. Clinical relevance? Circulation 90 (1994), 1580.

25.

Stormorken

Sakariassen

K. S.

: Contrast media. Effects on hemostatic and thrombotic mechanisms. Consequences for practical techniques and prophylactic measures. Acta Radiol. Suppl. 399 (1995), p. 173.

26.

Stormorken

Skalpe

I. O.

Testart

M. C.

: Effect of various contrast media on coagulation, fibrinolysis, and platelet function. An in vitro and in vivo study. Invest. Radiol. 21 (1986), 348.

27.

van Beek

E. J. R.

Levi

Reekers

Hack

C. E.

Buller

H. R.

Cate

J. W. Ten

: Increased plasma levels of PAI-1 after administration of nonionic contrast medium in patients undergoing pulmonary angiography. Radiology 193 (1994), 821.