Reliability of transcardiopulmonary thermodilution cardiac output measurement in experimental aortic valve insufficiency.

Monitoring cardiac output (CO) is important to optimize hemodynamic function in critically ill patients. The prevalence of aortic valve insufficiency (AI) is rising in the aging population. However, reliability of CO monitoring techniques in AI is unknown. The aim of this study was to investigate the impact of AI on accuracy, precision, and trending ability of transcardiopulmonary thermodilution-derived COTCPTD in comparison with pulmonary artery catheter thermodilution COPAC.Sixteen anesthetized domestic pigs were subjected to serial simultaneous measurements of COPAC and COTCPTD. In a novel experimental model, AI was induced by retraction of an expanded Dormia basket in the aortic valve annulus. The Dormia basket was delivered via a Judkins catheter guided by substernal epicardial echocardiography. High (HPC), moderate (MPC) and low cardiac preload conditions (LPC) were induced by fluid unloading (20 ml kg-1 blood withdrawal) and loading (subsequent retransfusion of the shed blood and additional infusion of 20 ml kg-1 hydroxyethyl starch). Within each preload condition CO was measured before and after the onset of AI. For statistical analysis, we used a mixed model analysis of variance, Bland-Altman analysis, the percentage error and concordance analysis.Experimental AI had a mean regurgitant volume of 33.6 ± 12.0 ml and regurgitant fraction of 42.9 ± 12.6%. The percentage error between COTCPTD and COPAC during competent valve function and after induction of substantial AI was: HPC 17.7% vs. 20.0%, MPC 20.5% vs. 26.1%, LPC 26.5% vs. 28.1% (pooled data: 22.5% vs. 24.1%). The ability to trend CO-changes induced by fluid loading and unloading did not differ between baseline and AI (concordance rate 95.8% during both conditions).Despite substantial AI, transcardiopulmonary thermodilution reliably measured CO under various cardiac preload conditions with a good ability to trend CO changes in a porcine model. COTCPTD and COPAC were interchangeable in substantial AI

Pre-Analytical Parameters Affecting Vascular Endothelial Growth Factor Measurement in Plasma: Identifying Confounders

Background Vascular endothelial growth factor-A (VEGF-A) is intensively investigated in various medical fields. However, comparing VEGF-A measurements is difficult because sample acquisition and pre-analytic procedures differ between studies. We therefore investigated which variables act as confounders of VEGF-A measurements. Methods Following a standardized protocol, blood was taken at three clinical sites from six healthy participants (one male and one female participant at each center) twice one week apart. The following pre-analytical parameters were varied in order to analyze their impact on VEGF-A measurements: analyzing center, anticoagulant (EDTA vs. PECT/CTAD), cannula (butterfly vs. neonatal), type of centrifuge (swing-out vs. fixed-angle), time before and after centrifugation, filling level (completely filled vs. half-filled tubes) and analyzing method (ELISA vs. multiplex bead array). Additionally, intrapersonal variations over time and sex differences were explored. Statistical analysis was performed using a linear regression model. Results The following parameters were identified as statistically significant independent confounders of VEGF-A measurements: analyzing center, anticoagulant, centrifuge, analyzing method and sex of the proband. The following parameters were no significant confounders in our data set: intrapersonal variation over one week, cannula, time before and after centrifugation and filling level of collection tubes. Conclusion VEGF-A measurement results can be affected significantly by the identified pre-analytical parameters. We recommend the use of CTAD anticoagulant, a standardized type of centrifuge and one central laboratory using the same analyzing method for all samples

Hemodynamic changes related to induction of aortic insufficiency and cardiac preload changes (mixed model).

<p>Hemodynamic changes related to induction of aortic insufficiency and cardiac preload changes (mixed model).</p

Porcine model for experimental aortic valve insufficiency.

<p>(A) A Judkins catheter was used as a guiding catheter to deliver a Dormia basket, (B) The Judkins catheter was introduced via an introducer sheath in the carotid artery and advanced through the brachiocephalic trunk into the ascending aorta (AscAo), (C) A compressed Dormia basket was delivered via the Judkins catheter through the aortic valve (AoV) in the left ventricle (LV). Subsequently the expanded Dormia basket was retracted in the aortic valve annulus, (D) Targeted tip position for the Dormia basket to induce substantial aortic valve regurgitation verified by epicardial echocardiography (E).</p

Four-quadrant plots.

<p>Trending ability of cardiac output (CO) derived from transcardiopulmonary thermodilution (CO_TCPTP) compaired with CO_PAC (reference method) illustrated by four-quadrant plots. The ability to trend CO changes induced by preload changes was assessed during baseline conditions (left: competent aortic valve) and after induction of aortic valve insufficiency (right). Changes in cardiac preload were induced by fluid unloading (black dots: withdrawal of 20 ml kg^-1 blood) and subsequent fluid loading (white dots: retransfusion of the shed blood and additional infusion of 20 ml kg^-1 hydroxyethyl starch). The concordance analysis gives a concordance rate of 95.8% during both conditions, baseline and aortic valve insufficiency. An exclusion zone of 0.5 l min^-1 (grey area in the center) was applied.</p

Impact of time before (a,b,c) and after (d-g) centrifugation on measured VEGF-A and PF-4 levels.

<p>In some EDTA samples, VEGF-A (a,c,d) and PF-4 levels (b,f) increased with longer incubation times. This was particularly significant when EDTA samples were stored for longer periods of time before centrifugation (c). In PECT samples (c,e,g), VEGF and PF-4 values were not affected by longer sample storage times.</p

Overview of sample acquisition procedures and the distribution of samples from blood acquisition centers to measuring centers and central laboratory.

<p>Overview of sample acquisition procedures and the distribution of samples from blood acquisition centers to measuring centers and central laboratory.</p

(a) Scatter plot for the influence of cannula (neonatal vs. butterfly) on measured VEGF-A plasma levels; (b) Scatter plot for intrapersonal fluctuations in plasma VEGF-A levels over one week; (c) Scatter plot for the impact of filling level of blood collection tubes on the resulting VEGF-A levels.

<p>Location of values near the bisecting line indicates comparable measurement results.</p

Candidate biomarkers for the diagnosis and prognosis of drug-induced liver injury: An international collaborative effort.

To access publisher's full text version of this article click on the hyperlink belowCurrent blood biomarkers are suboptimal in detecting drug-induced liver injury (DILI) and predicting its outcome. We sought to characterize the natural variabilty and performance characteristics of 14 promising DILI biomarker candidates. Serum or plasma from multiple cohorts of healthy volunteers (n = 192 and n = 81), subjects who safely took potentially hepatotoxic drugs without adverse effects (n = 55 and n = 92) and DILI patients (n = 98, n = 28, and n = 143) were assayed for microRNA-122 (miR-122), glutamate dehydrogenase (GLDH), total cytokeratin 18 (K18), caspase cleaved K18, glutathione S-transferase α, alpha-fetoprotein, arginase-1, osteopontin (OPN), sorbitol dehydrogenase, fatty acid binding protein, cadherin-5, macrophage colony-stimulating factor receptor (MCSFR), paraoxonase 1 (normalized to prothrombin protein), and leukocyte cell-derived chemotaxin-2. Most candidate biomarkers were significantly altered in DILI cases compared with healthy volunteers. GLDH correlated more closely with gold standard alanine aminotransferase than miR-122, and there was a surprisingly wide inter- and intra-individual variability of miR-122 levels among healthy volunteers. Serum K18, OPN, and MCSFR levels were most strongly associated with liver-related death or transplantation within 6 months of DILI onset. Prediction of prognosis among DILI patients using the Model for End-Stage Liver Disease was improved by incorporation of K18 and MCSFR levels. Conclusion: GLDH appears to be more useful than miR-122 in identifying DILI patients, and K18, OPN, and MCSFR are promising candidates for prediction of prognosis during an acute DILI event. Serial assessment of these biomarkers in large prospective studies will help further delineate their role in DILI diagnosis and management.National Institute of Diabetes and Digestive and Kidney Diseases Indiana University University of North Carolina University of Michigan Wake Forest University Innovative Medicines Initiative Joint Undertaking European Union's Seventh Framework Programme (FP7/2007-2013) National Institute for Health Research Nottingham Digestive Diseases Biomedical Research Unit at the Nottingham University Hospitals National Health Service Trust University of Nottingha