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.

Risk Factors of Influenza-Associated Necrotizing Encephalopathy in Children

“…There were statistically significant differences in serum LDH, CSF LDH and CSF Pro between the two groups (P <0.001), and the IANE group was significantly higher than the IAE group. LDH in serum and cerebrospinal fluid of the IANE group was significantly higher than that of the IAE group, the reason being that LDH could be overexpressed in cell necrosis [24][25][26]. The assessment of LDH in serum and cerebrospinal fluid is helpful for the assessment of peripheral and brain cell necrosis.…”

Discovery of Therapeutic Candidates for Diabetic Retinopathy Based on Molecular Switch Analysis: Application of a Systematic Process

“…LDH reflects the membrane damage of HRMECs [ 37 ], endothelial nitric oxide synthase (eNOS) is crucial in vascular leakage and endothelial junction stability [ 38 ]. LDH release upregulated, and NOS3 mRNA expression downregulated by t-BHP.…”

NMR-Based Metabolomic Analysis on the Protective Effects of Apolipoprotein A-I Mimetic Peptide against Contrast Media-Induced Endothelial Dysfunction

“…Previous works indicated that almost all CM exclusively induce cell apoptosis and destroy the integrity of endothelial cell membrane [ 46 ], and choline plays an important role in cell division and proliferation [ 47 ]. Our work showed that iodixanol treatment decreased PC levels and increased GPC levels, while D-4F pretreatment contrarily increased PC levels and decreased GPC levels, indicating that D-4F could promote the catabolism of glycerophosphate choline and partially restore the intracellular phospholipid metabolism impaired by iodixanol.…”