No abstract

BACKGROUND Cardiac troponin T (cTnT) is widely used for the diagnosis of acute myocardial infarction (AMI). However, it is still unclear whether degraded cTnT forms circulate in the patient's blood. We therefore aimed to elucidate which cTnT forms are detected by the clinical assay. METHODS Separation of cTnT forms by gel filtration chromatography (GFC) was performed in sera from 13 AMI patients to examine cTnT degradation. The GFC eluates were subjected to Western blot analysis with the original antibodies from the Roche immunoassay used to mimic the clinical cTnT assay. To investigate the degradation pattern with time, standardized serum samples of 18 AMI patients collected 0–72 h after admission were analyzed by Western blot analysis. RESULTS GFC analysis of AMI patients' sera revealed 2 cTnT peaks with retention volumes of 5 and 21 mL. Western blot analysis identified these peaks as cTnT fragments of 29 and 14–18 kDa, respectively. Furthermore, the performance of direct Western blots on standardized serum samples demonstrated a time-dependent degradation pattern of cTnT, with fragments ranging between 14 and 40 kDa. Intact cTnT (40 kDa) was present in only 3 patients within the first 8 h after hospital admission. CONCLUSIONS These results demonstrate that the Roche cTnT immunoassay detects intact as well as degraded cTnT forms in AMI patients' sera during the period of diagnostic testing. Moreover, following AMI, cTnT is degraded in a time-dependent pattern.

We found that cTnT forms in ESRD patients are small (<18 kDa) and different from forms seen in AMI patients. These insights may prove useful for development of a more specific cTnT immunoassay, especially for the acute and diagnostic phase of myocardial infarction.

The transverse cross-sectional area and reflectivity of the peroneal nerve on the US images could be viable tools in the diagnosis of PN after weight loss.

HL-1 cardiomyocytes subjected to simulated ischemia released cTnI and cTnT only in combination with the release of LDH. We find no evidence of cTn release from viable cardiomyocytes, but did observe a significant decrease in cTn content, before the onset of cell death. Intracellular decrease of cTn in viable cardiomyocytes can have important consequences for the interpretation of cTn values in clinical practice.

Prolonged endurance-type exercise is associated with elevated cardiac troponin (cTn) levels in asymptomatic recreational athletes. It is unclear whether exercise-induced cTn release mirrors a physiological or pathological underlying process. The aim of this study was to provide a direct comparison of the release kinetics of high-sensitivity cTnI (hs-cTnI) and T (hs-cTnT) after endurance-type exercise. In addition, the effect of remote ischemic preconditioning (RIPC), a cardioprotective strategy that limits ischemia-reperfusion injury, was investigated in a randomized controlled crossover manner. Twenty-five healthy volunteers completed an outdoor 30-km running trial preceded by RIPC (4 × 5 min 220 mm Hg unilateral occlusion) or control intervention. hs-cTnT, hs-cTnI, and sensitive cTnI (s-cTnI) concentrations were examined before, immediately after, 2 and 5 hours after the trial. The completion of a 30-km run resulted in a significant increase in circulating cTn (time: all p <0.001), with maximum hs-cTnT, hs-cTnI, and s-cTnI levels of 47 ± 27, 69 ± 62, and 82 ± 64 ng/L (mean ± SD), respectively. Maximum hs-cTnT concentrations were measured in 60% of the participants at 2 hours after exercise, compared with maximum hs-cTnI and s-cTnI concentrations at 5 hours in 84% and 80% of the participants. Application of an RIPC stimulus did not reduce exercise-induced cTn release (time × trial: all p >0.5). In conclusion, in contrast to acute myocardial infarction, maximum hs-cTnT levels after exercise precede maximum hs-cTnI levels. Distinct release kinetics of hs-cTnT and hs-cTnI and the absence of an effect of RIPC favors the concept that exercise-induced cTn release may be mechanistically distinct from cTn release in acute myocardial infarction.

Elevated concentrations of cardiac troponin T (cTnT; ±37 kDa) and I (cTnI; ±24 kDa), and the N-terminal fragment of the prohormone brain-type natriuretic peptide (NTproBNP; ±8.5 kDa) have been reported in end-stage renal disease patients and are associated with cardiovascular morbidity and mortality [1,2]. Also, cTnT, cTnI and NTproBNP correlate with glomerular filtration rate, suggesting a significant role of renal removal and consequences for the clinical interpretation of these cardiac markers [3]. The influence of hemodialysis (HD) on cardiac biomarkers itself remains contradictory. Previous studies have demonstrated intra-dialytic decreases [4] and increases in NTproBNP [5]. Also, significant reductions as well as increases in cTnT and cTnI concentrations have been reported following dialysis [5][6][7][8]. These differences can be attributed to the use of different dialysis modalities and membrane filters [5,8].Currently, most patients are treated with 4-h high-flux HD. However, it has been shown that uremic toxins were better removed when patients were treated with hemodiafiltration (HDF) and extended 8-h dialysis treatments resulted in more hemodynamic stability [9]. The aim of the present study was therefore to assess the acute effects of conventional and extended high-flux HD and HDF on cardiac biomarkers in the same population as previously described [9], especially focusing on high-sensitivity (hs-) cTnT and hs-cTnI results.Prevalent conventional HD patients were recruited receiving chronic conventional HD treatments, without residual urine production and acute illness, such as infection or cardiovascular events. All patients underwent one mid-week session in random order: 4-h HD (HD4), 8-h HD (HD8), 4-h online HDF (HDF4) and 8-h online HDF (HDF8) sessions; with a 2-week interval between the study sessions. Between the study sessions, these patients received conventional HD (HD4) treatments. All treatments were performed with the Fresenius 5008 Therapy System (Fresenius Medical Care). High-flux FX80 and FX800 dialysers (both Fresenius) were used for HD and HDF, respectively. Blood flow and dialysate flow were 300 and 600 mL/min, respectively. Substitution flow was 83.3 mL/min to achieve a total substitution volume of 15 L for HDF4 and 30 L for HDF8. Dialysate composition was 1.5 mmol/L calcium, 2 mmol/L potassium, 136-138 mmol/L sodium and 35-38 mmol/L bicarbonate and remain unchanged during the study period. This study (NL34908.068.10/MEC10-2-098) was approved by the Local Ethics Committee, and written informed consent was obtained from each patient.Blood was drawn from the inlet bloodlines in serum tubes, immediately before and after dialysis. Serum samples were aliquoted, stored at −80 °C and thawed prior to analysis. For HDF8, hs-cTnI and NTproBNP could not be measured in three patients due to a lack of

No abstract