title: Reduced diagnostic value of lactate dehydrogenase (LDH) in the presence of radiographic contrast media.
abstract: Isoforms of the enzyme lactate dehydrogenase (LDH) were found in almost all cells of the organism and an elevated activity of LDH in the circulation is thought to be a clear indicator of elevated cell destruction coinciding with an increased release of components from the cellular cytoplasm, e.g. LDH. Here, we report on an in-vitro examination to test whether radiographic contrast media (RCM) could induce cell destruction followed by an increase in LDH release. The RCM were tested in non-flow cultures of human umbilical venous endothelial cells (HUVEC) of the fourth passage seeded on extracellular matrix and the results were compared to those from control cultures not exposed to contrast media. The examination revealed that the addition of contrast media to the cell culture media supplemented with pooled human serum (HSP) as source of exogenous LDH was followed by a strong decrease in LDH activity both in the absence and presence of HUVEC. Within 1.5 min after the addition of contrast media to the culture medium supplemented with HSP (30% vol of the culture medium were replaced by either of two contrast media, Iodixanol or Iopromide) the LDH activity decreased about 80% compared to the initial values. In contrast, the LDH activity did not change in cell culture media not supplemented with RCM. The partial replacement of HSP supplemented cell culture medium by RCM will cause a dilution of cell culture medium constituents. The decrease of LDH activity, however, was much stronger than the decrease thought to be attributable to the effects of dilution of cell culture medium, so that the role of dilution seems to be a minor one in this case. It has to be assumed that the RCM could interact with the LDH available in the culture medium as well as with the substrates delivered with the measurement system for the assessment of LDH activity, so that both, the amount of LDH and the activities of enzymes involved might be influenced. In the presence of HUVEC a similar effect was observed. Here, a little less strong decrease of LDH activity occurred compared to the decrease in cell culture medium without HUVEC. This was unexpected because a considerable amount of HUVEC were detached after the addition of contrast media and many of these cells were damaged seriously so that a significant amount of endogenous LDH should have been released. These unexpected results make it necessary to re-evaluate those past time examinations focussed on cell damage/destruction in the presence of contrast media, where the measurement of LDH activity was used as indicator or cell vitality and where cell decease rates were correlated to questionable toxic influences. According to the results of the examination reported here it is difficult to uphold the interpretation of recently published findings that contrast media almost exclusively induce cellular apoptosis and not necrosis.
authors.affiliation: Department of Biomaterials, University of Ulm, Central Institute for Biomedical Engineering, Ulm, Germany.
authors.forename: R-P
authors.initials: RP
authors.lastname: Franke
authors.forename: R
authors.initials: R
authors.lastname: Fuhrmann
authors.forename: C
authors.initials: C
authors.lastname: Mrowietz
authors.forename: D
authors.initials: D
authors.lastname: Rickert
authors.forename: B
authors.initials: B
authors.lastname: Hiebl
authors.forename: F
authors.initials: F
authors.lastname: Jung
mesh_terms: D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D003287:Contrast Media / Q000494:pharmacology* / Q000633:toxicity; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000032:analysis* / Q000187:drug effects; D011859:Radiography / Q000009:adverse effects / Q000379:methods*
chemical_list: D003287:Contrast Media; D007770:L-Lactate Dehydrogenase