Serial assessment of endothelial function 1, 6, and 12 months after ST-elevation myocardial infarction.

Knowledge about the changes in endothelial function after ST-elevation myocardial infarction (STEMI) is of substantial interest, but serial data are scarce. The aim of the present study was to noninvasively evaluate whether endothelial function, as assessed shortly after primary percutaneous coronary intervention (PPCI) for STEMI, may improve until 12-month follow-up. This prospective observational cohort study was performed in patients in the RESPONSE randomized trial who participated in a substudy and underwent noninvasive assessment of endothelial function at 1 (baseline), 6, and 12-month follow-up after treatment of a STEMI by PPCI. The reactive hyperemia peripheral artery tonometry (RH-PAT) method was used to assess endothelial function (higher RH-PAT index signifies better function). Of the 70 study participants, who were 57.4 ± 9.7 years of age, 55 (78.6%) were male and 9 (13%) had diabetes. The endothelial function deteriorated significantly during follow-up: the RH-PAT index at baseline, 6, and 12-month follow-up was 1.90 ± 0.58, 1.81 ± 0.57, and 1.69 ± 0.49, respectively (p = 0.04). Although patients were carefully treated in outpatient clinics and adequate pharmacological therapy was prescribed, we noted an increase in total cholesterol (p = 0.001), LDL cholesterol (p = 0.002), HbA1C (p = 0.054), and diastolic blood pressure (p = 0.047) However, multivariate analysis revealed that this increase in cardiovascular risk factors could not explain the observed deterioration in endothelial function. In patients with STEMI, we observed a significant deterioration in endothelial function during 12 months after PPCI that could not be explained by changes in the traditional cardiovascular risk profile.

Nephrotoxicity and Kidney Transport Assessment on 3D Perfused Proximal Tubules.

Proximal tubules in the kidney play a crucial role in reabsorbing and eliminating substrates from the body into the urine, leading to high local concentrations of xenobiotics. This makes the proximal tubule a major target for drug toxicity that needs to be evaluated during the drug development process. Here, we describe an advanced in vitro model consisting of fully polarized renal proximal tubular epithelial cells cultured in a microfluidic system. Up to 40 leak-tight tubules were cultured on this platform that provides access to the basolateral as well as the apical side of the epithelial cells. Exposure to the nephrotoxicant cisplatin caused a dose-dependent disruption of the epithelial barrier, a decrease in viability, an increase in effluent LDH activity, and changes in expression of tight-junction marker zona-occludence 1, actin, and DNA-damage marker H2A.X, as detected by immunostaining. Activity and inhibition of the efflux pumps P-glycoprotein (P-gp) and multidrug resistance protein (MRP) were demonstrated using fluorescence-based transporter assays. In addition, the transepithelial transport function from the basolateral to the apical side of the proximal tubule was studied. The apparent permeability of the fluorescent P-gp substrate rhodamine 123 was decreased by 35% by co-incubation with cyclosporin A. Furthermore, the activity of the glucose transporter SGLT2 was demonstrated using the fluorescent glucose analog 6-NBDG which was sensitive to inhibition by phlorizin. Our results demonstrate that we developed a functional 3D perfused proximal tubule model with advanced renal epithelial characteristics that can be used for drug screening studies.

Endothelial function after ST-elevation myocardial infarction in patients with high levels of high-sensitivity CRP and Lp-PLA2: A substudy of the RESPONSE randomized trial.

BACKGROUND: The combination of high levels of high-sensitive C-reactive protein (hs-CRP) and lipoprotein-associated phospholipase-A2 (Lp-PLA2) was recently shown to correlate with increased cardiovascular risk. Endothelial dysfunction is also known to be a risk factor for cardiovascular events. AIM: To test among patients with previous ST-elevation myocardial infarction (STEMI) the hypothesis that high levels of both hs-CRP and Lp-PLA2 may be associated with impaired endothelium-dependent vasodilatation. METHODS: In this substudy of the RESPONSE randomized trial, we used reactive hyperemia peripheral artery tonometry (RH-PAT) 4 to 6weeks after STEMI and primary percutaneous coronary intervention (PPCI) to non-invasively assess endothelial function (RH-PAT index <1.67 identified endothelial dysfunction). Reliable measurements of RH-PAT, hs-CRP, and Lp-PLA2 were obtained in 68 patients, who were classified as high-risk if levels of both hs-CRP and Lp-PLA2 were in the upper tertile (≥3.84mg/L and >239µg/L, respectively). RESULTS: Patients were 57.4±9.7years and 53 (77.9%) were men. 11 (16%) patients were classified as high-risk and 57 (84%) as low-to-intermediate-risk. The RH-PAT index was 1.68±0.22 in high-risk and 1.95±0.63 in low-to-intermediate-risk patients (p=0.17). Endothelial dysfunction was present in 8 (72.7%) high-risk and 26 (45.6%) low-to-intermediate-risk patients (p=0.09). Framingham risk score, NT-proBNP and fibrinogen levels were higher in high-risk patients (p≤0.03). CONCLUSION: In this population of patients with recent STEMI and PPCI, we observed between patients with high hs-CRP and Lp-PLA levels and all other patients no more than numerical differences in endothelial function that did not reach a statistical significance. Nevertheless, further research in larger study populations may be warranted.

Endothelial Dysfunction After ST-segment Elevation Myocardial Infarction and Long-term Outcome: A Study With Reactive Hyperemia Peripheral Artery Tonometry.

INTRODUCTION AND OBJECTIVES: Long-term data on the relationship between endothelial dysfunction after ST-segment elevation myocardial infarction and future adverse clinical events are scarce. The aim of this study was to noninvasively assess whether endothelial dysfunction 4 weeks to 6 weeks after primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction predicts future clinical events. METHODS: This prospective cohort study was performed in 70 patients of the RESPONSE randomized trial, who underwent noninvasive assessment of endothelial function 4 weeks to 6 weeks after primary percutaneous coronary intervention. Endothelial function was measured by the reactive hyperemia peripheral artery tonometry method; an index<1.67 identified endothelial dysfunction. RESULTS: The reactive hyperemia peripheral artery tonometry index measured on average 1.90±0.58. A total of 35 (50%) patients had endothelial dysfunction and 35 (50%) patients had normal endothelial function. Periprocedural "complications" (eg, cardiogenic shock, total atrioventricular block) were more common in patients with endothelial dysfunction than in those without (25.7% vs 2.9%; P<.01). During 4.0±1.7 years of follow-up, 20 (28.6%) patients had major adverse cardiovascular events: events occurred in 9 (25.7%) patients with endothelial dysfunction and in 11 (31.5%) patients with normal endothelial function (P=.52). There was an association between the prevalence of diabetes mellitus at baseline and the occurrence of major adverse cardiovascular events during follow-up (univariate analysis: hazard ratio=2.8; 95% confidence interval, 1.0-7.8; P<.05), and even in multivariate analyses the risk appeared to be increased, although not significantly (multivariate analysis: hazard ratio=2.5; 95% confidence interval, 0.8-7.5). CONCLUSIONS: In this series of patients who survived an ST-segment elevation myocardial infarction, endothelial dysfunction, as assessed by reactive hyperemia peripheral artery tonometry 4 weeks to 6 weeks after myocardial infarction, did not predict future clinical events during a mean follow-up of 4 years.

Spermometer: electrical characterization of single boar sperm motility.

OBJECTIVE: To study single sperm boar motility using electrical impedance measurements in a microfluidic system. DESIGN: Comparison of the optical data and electrical impedance data. SETTING: Research laboratory at a university. ANIMAL(S): Boar semen sample were used. INTERVENTION(S): A microfluidic system is developed that is able to spatially confine single boar sperm cells and allows noninvasive analysis of their motility on the single cell level. Using this system, the single sperm motility was affected by changing the temperature or adding chemical stimuli (caffeine). The retrieved electrical impedance and video data were processed using Matlab. MAIN OUTCOME MEASURE(S): The sperm beat frequency and amplitude determined from the electrical impedance and video data. RESULT(S): The electrically measured sperm beat frequency was verified by optical analysis and in correspondence. Furthermore the microfluidic platform allowed single sperm analysis by altering the sperm by temperature and chemical stimuli. CONCLUSION(S): This platform could be exploited as a potential tool to study sperm cells on the single cell level and to perform advanced sperm selection for intracytoplasmic sperm injection (ICSI) applications.

A novel side electrode configuration integrated in fused silica microsystems for synchronous optical and electrical spectroscopy.

We present a novel electrode configuration consisting of coplanar side electrode pairs integrated at the half height of the microchannels for the creation of a homogeneous electric field distribution as well as for synchronous optical and electrical measurements. For the integration of such electrodes in fused silica microsystems, a dedicated microfabrication method was utilized, whereby an intermediate bonding layer was applied to lower the temperature for fusion bonding to avoid thereby metal degradation and subsequently to preserve the electrode structures. Finally, we demonstrate the applicability of our devices with integrated electrodes for single cell electrical lysis and simultaneous fluorescence and impedance measurements for both cell counting and characterization.

Assessment of the relation between initial culprit vessel patency in acute ST-elevation myocardial infarction and endothelial function.

AIMS: To assess whether better endothelial function increases the likelihood of patients with acute ST-elevation myocardial infarction (STEMI) having initially patent culprit vessels. Clinical data on the relation between endothelial function and culprit vessel patency in STEMI patients are scarce. METHODS AND RESULTS: In this prospective cohort study in 71 patients with STEMI, endothelial function was non-invasively assessed by use of the reactive hyperaemia peripheral artery tonometry (RH-PAT) method at four to six weeks after the primary percutaneous coronary intervention (PPCI). The RH-PAT index measured on average 1.90±0.58. In patients with patent culprit vessels before PPCI (n=33, 46.5%), endothelial function was significantly better than in patients with occluded vessels (n=38, 53.5%) (RH-PAT index 2.08±0.34 vs. 1.75±0.35; p<0.007). Compared to patients with normal endothelial function, the patients with severe endothelial dysfunction had a fivefold higher risk of presenting with an occluded culprit vessel (OR 5.1, 95% CI: 1.8-14.2). Logistic regression analysis revealed that this relation between endothelial function and vessel patency became even stronger after adjustment for potential confounders (adjusted OR 7.1, 95% CI: 2.1-23.6). CONCLUSIONS: In this series of patients with acute STEMI, better endothelial function was independently associated with a higher likelihood of presenting with an initially patent culprit vessel.