BJR
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Blann, A D
Right arrow Articles by McCollum, C N
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Blann, A D
Right arrow Articles by McCollum, C N
British Journal of Radiology 74 (2001),811-817 © 2001 The British Institute of Radiology

Full paper

Changes in endothelial, leucocyte and platelet markers following contrast medium injection during angiography in patients with peripheral artery disease

A D Blann, PhD1, R Adams, PhD1, R Ashleigh, MD2, S Naser, MSc1, U Kirkpatrick, MD1 and C N McCollum, MD1

Departments of 1Surgery and 2Radiology, South Manchester University Hospital, Nell Lane, Manchester M20 8LR, UK

Correspondence: Dr Andrew Blann, Haemostasis, Thrombosis and Vascular Biology Unit, University Department of Medicine, The City Hospital, Dudley Road, Birmingham B18 7QH, UK. Tel/Fax: 00 44 121 507 5076


   Abstract
Top
 Abstract
Introduction
 Material and methods
 Results
 Discussion
 References
 
Peripheral artery angiography, a common diagnostic procedure, may cause early and late adverse reactions, such as anaphylaxis, thrombosis and possible progression of the underlying arterial disease. To test the hypothesis that radiographic contrast medium may contribute to these events by adversely affecting the endothelium, leucocytes and/or platelets, 19 subjects undergoing angiography for the investigation and/or treatment of lower limb atherosclerosis were recruited. Blood was obtained from the external iliac vein before, and at serial intervals after, the injection of radiographic contrast medium into the ipsilateral femoral artery for diagnostic use. Markers of endothelial cell injury (von Willebrand factor (vWf)), platelet activation (soluble P-selectin) and leucocyte activation (neutrophil elastase and soluble L-selectin) were measured in citrated plasma. Soluble intercellular adhesion molecule-1 (sICAM-1) and thromboxane B2, which are non-specific markers of inflammation, were also measured. Compared with the sample prior to angiography, levels of soluble L-selectin and sICAM-1 were reduced (p<0.02) immediately after passage of the last bolus of contrast medium. 15 min later, levels returned to normal but the level of vWf had increased (p<0.02). After 30 min, only levels of thromboxane B2 were increased (p<0.05). The following day both vWf (p<0.01) and soluble P-selectin (p<0.05) were increased. These data point to both early and late effects of contrast medium on markers of endothelial, platelet and leucocyte function.


   Introduction
Top
 Abstract
 Introduction
Material and methods
 Results
 Discussion
 References
 
Diagnostic angiography is an essential investigation in the planning of surgical or interventional radiology treatment for abdominal and lower limb atherosclerotic disease. The use of intravascular contrast media may be associated with unfavourable reactions, such as a feeling of mild warmth or discomfort in the lower limbs, although serious adverse reactions such as anaphylactic shock are very rare. Various alterations in the functional properties of different blood cells and endothelial cells, such as in coagulation, have been reported [1, 2]. Some of these reactions may be owing to adverse or cytotoxic effects of radiographic contrast medium, the catheterization process, the X-rays themselves, or any combination of these on the endothelium, coagulation system, leucocytes and platelets [3]. Evidence for this hypothesis comes from in vitro experiments in which blood and contrast media are simply mixed and the properties of the resultant complex analysed [4–7], studies with cultured human and bovine endothelial cells [8–10], and animal experiments [11–16].

There have also been reports of the effects of contrast medium on humans in vivo. These include evidence of increased thrombotic and coagulation activity (raised thrombin–antithrombin III complexes, prothombin fragments 1+2 and D-dimers [6, 17]), reduced levels of alpha-2-antiplasmin [6], the consumption of complement components and a neutrophil leucocytosis [18], and increased tissue plasminogen activator (arising from platelets and endothelial cells) and beta-thromboglobulin (a platelet-specific marker) [19]. Studies of endothelium, platelets and neutrophil leucocytes (cells fundamental to the pathogenesis of atherosclerosis) in vivo are limited in this respect.

We hypothesized that there would be both early (within 30 min) and late (overnight) effects of contrast medium on endothelial cell, platelet and leucocyte function. To test this we measured levels of certain specific, relevant, recognized and well characterized markers of these cells. These were endothelial product von Willebrand factor (vWf), platelet product soluble P-selectin (sP-selectin) and leucocyte markers soluble L-selectin (sL-selectin) and neutrophil elastase. We also measured levels of soluble intercellular adhesion molecule-1 (sICAM-1) arising from the endothelium, activated lymphocytes and other cells, and thromboxane B2 released from the endothelium, neutrophils and platelets.

Increased plasma levels of vWf found in cancer, atherosclerosis and connective tissue disease reflect endothelial cell damage/injury and are associated with the development of adverse events such as myocardial infarction and stroke. However, it is unclear whether this added risk is a direct consequence of endothelial dysfunction and/or an increased risk of thrombosis, which vWf can promote by cross-linking platelets [20]. Increased levels of sP-selectin are becoming recognized as reflecting platelet activation, and therefore thrombotic potential, in vivo [21, 22] and, like vWf, are present in atherosclerosis and cancer. They may also carry an increased risk of cardiovascular events [23, 24]. The membrane-bound form of L-selectin, found on leucocytes, mediates binding of these cells to the endothelium. Although sL-selectin in the plasma retains biological activity and inhibits this adhesion in vitro, other functions are yet to be clarified [25, 26]. sICAM-1 and thromboxane B2, both non-specific markers of inflammation and both raised in the plasma of patients with peripheral artery disease [27, 28], were included to determine a possible inflammatory effect of the contrast medium, as atherosclerosis is believed to have an inflammatory component [29]. Our experimental approach was broadly similar to those of other workers [6, 17–19], i.e. taking serial plasma samples before and after the injection of contrast medium in the diagnosis and treatment of atherosclerosis.


   Material and methods
Top
 Abstract
 Introduction
 Material and methods
Results
 Discussion
 References
 
This project was approved by the Ethics Committee of South Manchester Health Authority. Informed, written consent was obtained from all participants. The project conformed to the guidelines of the Declaration of Helsinki [30].

Subjects
19 patients were recruited from among those scheduled to undergo diagnostic radiography and/or angioplasty to investigate and/or treat presumed lower limb peripheral artery disease. Clinical and demographic details of the subjects are presented in Table 1Go. 45% of the interventions were performed on the left side. 70% of subjects were men and the mean±SD age of all subjects was 63±12 years. 24 age- (mean±SD, 59±9 years) and sex-matched (67% men) healthy control subjects were drawn from attenders for endoscopy, hernia repair or minor operations, and from healthy hospital staff. None of the control subjects displayed symptoms of vascular disease or signs, e.g. carotid bruit, on clinical examination. Exclusion criteria for all subjects were venous ulceration, serological evidence of hepatitis B virus or HIV infection, malignancy, acute or chronic liver and kidney disease, connective tissue disease, as well as the treatment or use of aspirin, thienopyridines, gpIIb/IIIa blockers, Warfarin, vasopression, or immunosuppressive or cytotoxic drugs. Systolic and diastolic blood pressure was recorded in each subject following a minimum of 5 min rest. Subjects were asked if they regularly smoked cigarettes, were ex-smokers or if they had never smoked.


View this table:
[in this window]
[in a new window]
  		Table 1. Clinical, angiographic and demographic details of the 19 patients

 
Protocol
Following local anaesthesia using lignocaine, a 5 F catheter was inserted into the distal external iliac vein on the side that the investigation was to be performed. A blood sample (sample 1) was taken. The ipsilateral femoral artery was then punctured under local anaesthesia and the aorta was catheterized with a 4 F straight catheter with eight side holes. Diagnostic catheters and guidewires were flushed with heparinized saline. Up to 11 20 ml boluses of the contrast medium iohexol (Omnipaque 350, containing 350 mg iodine ml-1 (Nycomed Amersham plc, Chesham, UK)) diluted with heparinized saline (2000 U l-1) to 240 mgI ml-1 were then injected by an automated pressure syringe (Medrad) at 6 ml s-1. All procedures were performed by a single radiologist (R Ashleigh). Eight patients had angioplasty with an appropriately sized 5 F balloon catheter following the diagnostic angiogram, with a median of four (range two to eight) inflations. Thrombolytic agents were not used. A second blood sample (sample 2) was obtained after injection of the final bolus of contrast medium. Additional blood samples were taken from the venous line at 15 min (sample 3) and 30 min (sample 4) after last passage of the contrast medium. The femoral vein catheter was then removed and the patient returned to the ward. A final sample (sample 5) was taken from an antecubital vein the following morning on the ward.

Blood processing
Blood was collected into EDTA, sodium citrate or no anticoagulant. Plasma or serum was obtained by centrifugation at 2500g for 10 min at 4 °C and then frozen at -70 °C to allow batch analysis. vWf and sP-selectin were measured by a commercial ELISA (Dako, Denmark, and Takara Shuzo, Shiga, Japan, respectively) of the citrated sample. sL-selectin and sICAM-1 (R&D Systems, Abingdon, UK) were measured in the serum sample. Thromboxane B2 was measured in citrated plasma by an ELISA from Cascade Biochemicals (Reading, Berkshire, UK). Fibrinogen in the initial and final citrated plasma samples wasmeasured by the Clauss technique with thrombin (Baxter, Deerfield, IL). Plasma elastase was measured in EDTA-plasma by an ELISA using sheep anti-human elastase and peroxidase-conjugated sheep anti-human antitrypsin (The Binding Site, Birmingham, UK), and a polymorphonuclear leucocyte elastase calibrator (Merck Ltd, West Drayton, UK) [31]. Intra-assay and inter-assay variancesof all assays were <5% and <10%, respectively.

Data analysis and statistics
Raw data were analysed by the Ryan–Joiner normality test to determine the nature of its distribution. sP-selectin, elastase and thromboxane B2 were non-normally distributed and are therefore presented as median and range; all other data were normally distributed and so are presented as mean and standard deviation. Data between the cases and controls were compared with a t-test or the Mann–Whitney U-test. Fibrinogen data from samples 1 and 5 were analysed by paired t-test. Data from all samples were analysed by Friedman's repeated measures (two-way) analysis of variance, following log transformation where necessary.


   Results
Top
 Abstract
 Introduction
 Material and methods
 Results
Discussion
 References
 
Table 2Go and Figure 1Go show levels of sICAM-1, vWf and sP-selectin in control subject and patient samples. Levels of sICAM-1 were reduced (p<0.01) immediately after angiography (sample 2). There was a transient rise in levels of vWf (p<0.025) after 15 min (sample 3). The following morning (sample 5), sICAM-1 was normal but levels of vWf (p<0.01) and sP-selectin (p<0.05) were increased (Figure 1Go). Levels of vWf (p=0.031), sICAM-1 (p=0.028) and sP-selectin (p=0.042) were all slightly higher in the patients' baseline blood samples compared with the controls' samples.


View this table:
[in this window]
[in a new window]
  		Table 2. Levels of soluble intercellular adhesion molecule-1 (sICAM-1), von Willebrand factor (vWf) and soluble P-selectin (sP-selectin) levels in the 19 patients and 24 control subjects

 


View larger version (10K):
[in this window]
[in a new window]
  		Figure 1. Changes in levels of soluble intercellular adhesion molecule-1 (•) von Willebrand factor ({circ}) and soluble P-selectin ({square}) in blood samples 1–5, expressed in terms of baseline levels at the start of the procedure. *p<0.05.

 
Table 3Go and Figure 2Go show levels of sL-selectin, elastase and thromboxane B2 in control subject and patient samples. Levels of sL-selectin were reduced in samples 2 (p<0.05) and 4 (p<0.05). There were no significant changes in levels of elastase, but levels of thromboxane B2 were increased at 30 min post contrast (sample 4) (p<0.05). None of the levels were significantly altered in the sample taken the following morning. There was no significant difference in levels of sL-selectin (p=0.652) or elastase (p=0.210) between patients and controls, but thromboxane B2 was slightly higher in the patients' samples (p=0.041).


View this table:
[in this window]
[in a new window]
  		Table 3. Levels of soluble L-selectin (sL-selectin), thromboxane B2 and elastase levels in the 19 patients and 24 control subjects

 


View larger version (9K):
[in this window]
[in a new window]
  		Figure 2. Changes in levels of soluble L-selectin (•), thromboxane B2 ({square}), and elastase ({circ}) in blood samples 1–5, expressed in terms of baseline levels at the start of the procedure. *p<0.05.

 
Plasma fibrinogen was not significantly different in patients' sample 5 (3.8±1.2 g l-1) compared with sample 1 (3.5±1.1 g l-1, p=0.21), but was higher compared with the control subjects' levels (3.0±0.6 g l-1, p=0.022). None of the clinical, angiographic or demographic factors described in Table 1Go, or age or sex, had an influence on any of the plasma markers. For example, the amount of contrast medium used or the number of balloon inflations or their duration all failed to correlate with the absolute levels of the six study indices or their relative increase or decrease from the initial sample. This is not surprising in view of the small number of patients. The small numbers also prevent meaningful subanalyses, such as angiography alone compared with angiography and angioplasty.


   Discussion
Top
 Abstract
 Introduction
 Material and methods
 Results
 Discussion
References
 
The injection of radiographic contrast medium is associated with a variety of adverse events [1, 2, 32, 33]. We have found early (approx. 30 min) and late (approx. 24 h) changes in markers of endothelial cell and platelet function in vivo. Although all subjects were exposed to localized short bursts of ionizing radiation, it is generally considered that changes are mainly owing to the contrast medium [1–19]. Levels of sL-selectin (derived from leucocytes [26]) and sICAM-1 (derived from many cells, including the endothelium and activated leucocytes [27]) both fell immediately after injection of the contrast medium bolus. Soluble adhesion molecules retain functional activity [26] and may be important in modulating adhesion of blood cells to the endothelium. The fall in sL-selectin and sICAM-1 levels seen here could reflect increased binding, and thus sequestration from the plasma, owing to activation-induced expression of ligands such as CD11a/CD18 on leucocytes and/or the endothelium [34]. Theoretically, any dilution effects of the contrast medium may contribute to this 13–18% reduction in sL-selectin and sICAM-1. However, this alone is unlikely to be the sole cause as, for example, elastase fell by only 5% and levels of vWf and thromboxane B2 both increased.

Raised levels of vWf were present 15 min after contrast medium injection, suggesting an acute endothelial response. The high levels of vWf and sP-selectin after 24 h are probably owing to a late effect on the endothelium and platelets, respectively, complementing the report that contrast media induce increased expression of membrane P-selectin by platelets in vitro [35]. No change in levels of fibrinogen at this time implies the lack of an acute phase response so, as vWf may behave as an acute phase reactant [36], the increased levels are unlikely to be owing to a non-specific inflammatory increase. However, Tschopl et al [17] noted raised plasma vWf and fibrinogen after 48 h, but no increase after 1 h or 24 h, interpreting the fibrinogen increase as an acute phase response or as owing to increased synthesis by the liver, and the rise in vWf as increased synthesis by endothelial cells. Levels of the inflammatory mediator and vasoconstrictor thromboxane B2, possibly deriving from the endothelium, platelets and neutrophils [28], rose markedly during the procedure, reaching significance after 30 min. Thromboxane B2 has several effects, such as regulating vascular tone and resistance, although increased plasma levels may not necessarily indicate changes in the function of abluminal medial smooth muscle cells.

Our protocol is similar to that used by others [6, 17–19, 37]. Polanowska et al [19] investigated 26 men with peripheral artery disease and found a 20% increase in platelet marker beta thromboglobulin and a 32% increase in tissue plasminogen activator. They concluded that angiography may be responsible for partial stimulation or damage both of platelets and endothelial cells. We found no immediate effect on our platelet marker sP-selectin, although changes in other platelet markers ex vivo have been reported [38]. Hoffman et al [37] reported changes in several haemostatic markers 5 min and 30 min after exposure to contrast medium. Unlike us, they found no increase in vWf after 30 min but did find an increase in a different platelet marker (beta thromboglobulin) after 30 min. However, both our own study and that of Hoffman et al failed to find differences in leucocyte elastase, and so are to some extent complementary. Others have reported a reversible fall [39], or no acute change [40] in levels of beta thromboglobulin after the use of contrast medium, but Kolarov et al [41] reported platelet activation and consumption up to 2 h after the use of contrast medium.

One major difference between our own study and those outlined above is that we have attempted to localize any influence of contrast medium by obtaining our samples from the draining venous circulation of the limb most likely to be affected. In this way we hoped to avoid any haemodilution likely to occur when using a cubital vein. Consequently, our samples up to 30 min seem likely to be more sensitive to the effects of the contrast medium. The overnight sample carries with it the haemodilution issue so that we cannot say if the changes in levels of vWf and sP-selectin are due to systemic or local effects on the endothelium and platelets. A further deficiency in our study is the lack of a control group, although it would be impossible to subject patients to catheterization without the use of contrast medium or to use contrast medium without imaging. We are also unable to answer the point that our results may be owing only to the catheters and/or X-rays and not the contrast medium as we assume. However, we consider this unlikely in light of other in vitro data. Our single control group is of healthy, age- and sex-matched subjects that simply demonstrate what levels of markers would be expected in the absence of atherosclerosis—no direct case-control study is implied by these data. A further caveat is the possibility that the changes observed are simply owing to the effect of venepuncture/arteriopuncture alone and not necessarily the effect of the contrast medium. Cousins et al [42] found that arterial puncture, not the use of contrast medium, caused an increase in coagulation parameter fibrinopeptide A.

We believe this in vivo method provides the opportunity to extend in vitro and in vivo testing of the effects of different types of contrast media [3–7, 17, 37, 39–41]. At least some of the effects of Omnipaque 350 may be detected after 24 h, providing a convenient window for samples from an appropriate venous site. Indeed, our observations of adverse effects on the endothelium and platelets (marked by raised vWf, thromboxane B2 and sP-selectin levels) may be related to both immediate effects such as discomfort and long-term side effects such as thrombosis and restenosis, that could be attributable to contrast media. This therefore supports the recent view of Zhang et al [43], whose in vitro experiments suggest that contrast media induce a degree of endothelial cell injury and apoptosis and that these may be associated with side effects. With our clinical data, we cannot say exactly what type of adverse endothelial perturbation is present, be it damage, injury, activation, frank necrosis or apoptosis [43, 44]. We do not believe our data are simply reflecting an artefact of contrast media induced nephrotoxicity [10, 45] as the changes are clearly specific to certain molecules. If there was a degree of renal impairment, we may perhaps have expected similar changes in all the molecules, or a pattern, possibly related to their size. This was not the case as, for example, the soluble adhesion molecules are all of similar size (approximately 100–200 kDa), elastase is in the region of 27.5 kDa and thromboxane B2 is 370 Da, yet all show different patterns.

The further clinical and cell biology implications of our findings are unclear. However, it may be that these adverse changes to the endothelium and platelets implying increased risk of coagulopathy and thrombosis, may also be related to the risks of restenosis that are common in patients undergoing arterial investigations [32, 33, 46, 47] and therefore warrant additional studies, especially in long-term follow-up. However, despite our focus on the endothelium and platelets, the cytotoxic effects of contrast medium on smooth muscle cells may also be important [48].


   Acknowledgments
 
We would like to thank Nycomed UK for support.


   Footnotes
 
This study was part-supported by Nycomed UK. Back

Received for publication January 2, 2001. Accepted for publication June 6, 2001.


   References
Top
 Abstract
 Introduction
 Material and methods
 Results
 Discussion
 References
 

  1. Ansell G. Complication of intravascular iodinated contrast media. In: Ansell G, Beltman MA, Kienfron JA, Wilkins RA, editors. Complications in diagnostic imaging and interventional radiology (3rd edn). Boston, MA: Blackwell Science, 1996:245–302.
  2. Elroy R, Corot C, Belleville J. Contrast media for angiography: physicochemical properties, pharmacokinetics and biocompatibility. Clin Mater 1991;7:89–197.[Medline]
  3. Fareed J, Moncada R, Messmore HL, Walenga JM, Hoppensteadt D, Wehrmacher WH. Molecular markers of contrast-media induced adverse reactions. Semin Thromb Hemost 1984;10:306–28.[Medline]
  4. Englehart JA, Smith DC, Maloney MD, Westengard JC, Bull BS. A technique for estimating the probability of clots in blood/contrast agent mixtures. Invest Radiol 1988;23:923–7.[Medline]
  5. Carr DH, Walker AC, White RG. Effects of radiographic contrast media on leukocyte locomotion. Invest Radiol 1981;16:133–40.[Medline]
  6. Stormorken H, Skalpe IO, Testart MC. Effect of various contrast media on coagulation, fibrinolysis, and platelet function. An in vitro and in vivo study. Invest Radiol 1986;21:348–54.[Medline]
  7. Corot C, Chronos N, Sabattier V. In vitro comparison of the effects of contrast media on coagulation and platelet activation. Blood Coagul Fibrinolysis 1996;7:602–8.[Medline]
  8. Morgan DM, Bettmann MA. Effects of X-ray contrast media and radiation on human vascular endothelial cell in vitro. Cardiovasc Intervent Radiol 1989;12:154–60.[Medline]
  9. Laerum F. Cytotoxic effects of six angiographic contrast media on human endothelium in culture. Acta Radiol 1987;28:99–105.[Medline]
  10. Haller C, Schick CS, Zorn M, Kubler W. Cytotoxicity of radiocontrast agents on polarised renal epithelial cell monolayers. Cardiovasc Res 1997;33:655–65.[Abstract/Free Full Text]
  11. Heyman SN, Clark BA, Kaiser N, Spokes K, Rosen S, Brezis M, et al. Radiocontrast agents induce endothelin release in vivo and in vitro. J Am Soc Nephrol 1992;3:58–65.[Abstract]
  12. Riemann CD, Massey CV, McCarron DL, Borkowski P, Johnson PC, Ziskind AA. Ionic contrast agent-mediated endothelial injury causes increased platelet deposition to vascular surfaces. Am Heart J 1993;126:71–8.
  13. Marguiles KB, Hildebrand FL, Heublein DM, Burnett JC. Radio-contrast increases plasma and urinary endothelin. J Am Soc Nephrol 1991;2:1041–5.[Abstract]
  14. Fleetwood G, Bettmann MA, Gordon JL. The effects of radiographic contrast media on myocardial contractility and coronary resistance: osmolality, ionic concentration and viscosity. Invest Radiol 1990;25:254–60.[Medline]
  15. Romano M, Di Bello M, Salmona M, Rosati G. Effect of iodinated contrast media on the synthesis and metabolism of leukotriene B4. Invest Radiol 1990;25:S25–6.
  16. Almen T, Aspelin P. Cardiovascular effects of ionic monomeric, ionic dimeric and non-ionic contrast media. Invest Radiol 1975;10:557–63.[Medline]
  17. Tschopl M, Tsakiris DA, Marbet GA, Labs KH, Jager K. Role of hemostatic risk factors for restenosis in peripheral arterial occlusive disease after transluminal angioplasty. Arterioscler Thromb Vasc Biol 1997;17:3208–14.[Abstract/Free Full Text]
  18. Georgsen J, Rasmussen F, Antonsen S, Larsen MG. Influence of radiographic contrast media on granulocyte enzymes and complement during uncomplicated urographies. Eur J Radiol 1991;12:63–6.[Medline]
  19. Polanowska R, Wilczynska M, Stawinski W, Goch JH, Augustyniak W, Cierniewski CS. Changes in platelet activity and tissue plasminogen activator during arteriography in patients with chronic limb ischaemia. Thromb Res 1992;65:663–5.[Medline]
  20. Blann AD. von Willebrand factor and the endothelium in vascular disease. Br J Biomed Sci 1993;50:125–34.[Medline]
  21. Blann AD, Lip GYH. Hypothesis: is soluble P-selectin a new marker of platelet activation? Atherosclerosis 1997;128:135–8.[Medline]
  22. Fijnheer R, Frijns CJM, Korteweg J, Rommes H, Peters JH, Sixma JJ, et al. The origin of P-selectin as a circulating plasma protein. Thromb Haemost 1997;77:1081–5.[Medline]
  23. Blann AD, Wadley M, Stonelake P, Gurney D, Bareford D, Lip GYH. Soluble P-selectin in patients with haematological and solid cancers. Blood Coagul Fibrinolysis 2001;12:9–16.[Medline]
  24. Ridker PM, Buring JE, Rifai N. Soluble P-selectin and the risk of future cardiovascular events. Circulation 2001;103:491–5.[Abstract/Free Full Text]
  25. Kansas GS. Selectin and their ligands: current concepts and controversies. Blood 1996;88:3259–87.[Free Full Text]
  26. Schieffenbaum B, Spertini O, Tedder TF. Soluble L-selectin is present in human plasma at high levels and retains functional activity. J Cell Biol 1992;11:229–38.
  27. van de Stolpe A, van der Saag PT. Intercellular adhesion molecule-1. J Mol Med 1996;74:13–33.[Medline]
  28. Patrono C, Patrignani P, Davi G. Thromboxane biosynthesis and metabolism in cardiovascular and renal disease. J Lipid Mediat 1993;6:411–5.[Medline]
  29. Ross R. Atherosclerosis—an inflammatory disease. N Engl J Med 1999;340:115–26.[Free Full Text]
  30. World Medical Association Declaration of Helsinki. Recommendations guiding physicians in biomedical research involving human subjects. Cardiovasc Res 1997;35:2–3.[Free Full Text]
  31. Browser MS, Harpel PC. Alpha-1-antitrypsin-human leukocyte elastase complexes in blood quantified by an ELISA and comparison with alpha-2-plasmin inhibitor-plasmin complexes. Blood 1983;61:842–9.[Abstract/Free Full Text]
  32. Steinberg EP, Moore RD, Powe NR, Gopalan R, Davidoff AJ, Litt M, et al. Safety and cost effectiveness of high-osmolality as compared with low osmolality contrast material in patients undergoing cardiac angiography. N Engl J Med 1992;326:425–30.[Abstract]
  33. Barrett BJ, Parfrey PS, Vavasour HM, O'Dea F, Kent G, Stone E. A comparison of non-ionic, low osmolality radiocontrast agents with ionic high osmolality agents during cardiac catheterisation. N Engl J Med 1992;326:431–6.[Abstract]
  34. Donnelly SC, Haslet C, Dransfield I, Robertson CE, Carter DC, Ross JA, et al. Role of selectins in development of adult respiratory distress syndrome. Lancet 1994;344:215–9.[Medline]
  35. Chronos NAF, Goodall AH, Wilson DJ, Sigwart U, Buller NP. Profound platelet degranulation is an important side-effect of some types of contrast media used in interventional cardiology. Circulation 1993;88:2035–44.[Abstract/Free Full Text]
  36. Pottinger BE, Read RC, Paleolog EM, Higgins PG, Pearson JD. von Willebrand factor is an acute phase reactant in man. Thromb Res 1989;53:387–94.[Medline]
  37. Hoffmann JJML, Tielbeek AV, Krause W. Haemostatic effects of low osmolar non-ionic and ionic contrast media: a double blind comparative study. Br J Radiol 2000;73:248–55.[Abstract]
  38. Grabowski EF, Jang IK, Gold H, Palacios IF, Boor SE, Rodino LJ, et al. Platelet degranulation induced by some contrast media is independent of their non-ionic vs ionic nature. Acta Radiol 1995;36:182–4.[Medline]
  39. Brzosko M, Cyrylowski L, Brzosko I, Domanski Z, Fiedorowicz–Fabrycy I. Effects of ionic and non-ionic contrast medium on platelet function as evaluated by plasma concentrations of beta-thromboglobulin. Br J Radiol 1997;70:1239–44.[Abstract]
  40. Vaitkus PT, Watkins MW, Witmer WT, Tracey RP, Sobel BE. Characterization of platelet activation and thrombin generation accompanying percutaneous transluminal coronary angioplasty. Coron Artery Dis 1995;6:587–92.[Medline]
  41. Kolarov P, Tschoepe D, Nieuwenhuis HK, Gries FA, Strauer B, Schultheiss HP. PTCA: periprocedural platelet activation. Part II of the Duesseldorf PTCA platelet study (DPPS). Eur Heart J 1996;17:1216–22.[Abstract/Free Full Text]
  42. Cousins C, Dutka DP, Bradshaw A, Dawson P. Effect of arterial cannulation and contrast agents on blood coagulation. Acad Radiol 1995;2:663–6.[Medline]
  43. Zhang H, Holt CM, Malik N, Shepherd L, Morcos SK. Effects of radiographic contrast media on proliferation and apoptosis of human vascular endothelial cells. Br J Radiol 2000;73:1034–41.[Abstract]
  44. Blann AD. Viewpoint: endothelial cell activation, injury, damage and dysfunction: separate entities or mutual terms? Blood Coagul Fibrinolysis 2000;11:623–30.[Medline]
  45. Morcos SK. Contrast media-induced nephrotoxicity—questions and answers. Br J Radiol 1998;71:357–65.[Abstract]
  46. Von Andel GJ. Arterial occlusion following angiography. Br J Radiol 1980;53:747–53.[Abstract]
  47. Spencer JA, Fletcher EWL. Deterioration following delay in performing femoral angioplasty. Br J Radiol 1990;63:919–21.[Abstract]
  48. Wang YX, Chan P, Morcos SK. The effect of radiographic contrast medium on human vascular smooth muscle cells. Br J Radiol 1998;71:376–80.[Abstract]




This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Blann, A D
Right arrow Articles by McCollum, C N
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Blann, A D
Right arrow Articles by McCollum, C N

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
BJR DMFR IMAGING  ALL BIR JOURNALS