Andrea Willfort-Ehringer

Targeted profiling of atherogenic phospholipids in human plasma and lipoproteins of hyperlipidemic patients using MALDI-QIT-TOF-MS/MS

OBJECTIVES Phospholipids (PLs) are increasingly recognized as key molecules with potential diagnostic value in acute inflammation, CVD and atherosclerosis. We introduce a pioneer mass spectrometry (MS)-based approach aiming to investigate the relationship of specific plasma PL-subsets with atherogenic blood parameters in young patients with familial hyperlipidemia representing high-CVD-risk groups. METHODS Plasma of carefully phenotyped FH and FCH patients as well as normolipidemic subjects (age 13 ± 5 years, n = 20) was used. Clinical parameters were assessed using standard laboratory techniques and lipids were subjected to a direct targeted monitoring using LC-ESI-SRM- and MALDI-QIT-TOF-MS/MS, respectively. Statistical analysis was performed to evaluate correlations between PL data and the clinical parameters. RESULTS Most characteristically significant differences of SM/PC and PC/LPC ratios and positive correlations between SM vs. LDL-C (r = 0.946; p = 0.004) and LPC vs. VLDL-C (r = 0.669; p = 0.218) were observed in FH in contrast to the other study groups. OxPC levels were found in the range of ∼2-20 μmol/L with predominance of short-chain aldehydic species (e.g. SOVPC). A positive correlation of OxPCs with IMT (r = 0.952; p = 0.052) and HDL-C (r = 0.893; p = 0.016) but negative correlation with OxLDL (r = -0.910; p = 0.096) was observed. CONCLUSIONS Our study was a first attempt to use a MALDI-QIT-TOF-MS/MS based clinical lipidomics approach to investigate atherogenic dyslipidemia in young patients with familial hyperlipidemia. This technique represents a promising platform for clinical screening of lipid biomarkers in the future.

Microvascular function is impaired in children with morbid obesity

Children’s obesity is a growing problem in Western societies. We hypothesized that morbid obesity (body mass index [BMI] > 99.5th percentile) might affect microvascular function at an early stage. Therefore, we assessed the microvascular function of 41 obese children (13.2 ± 2.8 years, BMI 32.9 ± 6.6) in comparison to 91 healthy controls (12.7 ± 2.1 years, BMI 18.2 ± 2.5) by post-occlusive reactive hyperemia measured by a laser Doppler: baseline perfusion, biological zero (defined as ‘no-flow’ laser Doppler signal during suprasystolic occlusion), peak perfusion (following occlusion), time to peak perfusion and recovery time (time until resuming baseline perfusion) were recorded and compared between both groups. Peak perfusion was higher in children with morbid obesity than in controls (1.67 ± 0.76 AU [arbitrary units] vs 1.26 ± 0.5 AU, p < 0.001). Consecutively, recovery time was longer in children with morbid obesity (118.21 ± 34.64 seconds) than in healthy children (83.18 ± 35.08 seconds, p < 0.001). In conclusion, higher peak perfusion and prolonged recovery time in children with morbid obesity seem to reflect microvascular dysfunction due to an impaired vasoconstrictive ability of precapillary sphincters.

Microcirculation in mixed arterial/venous ulcers and the surrounding skin: Clinical study using a laser Doppler perfusion imager and capillary microscopy

To treat mixed skin ulcers effectively, it is important to investigate skin microcirculation in greater detail. Therefore, we used laser Doppler perfusion imaging and capillary microscopy for assessing both subpapillary and nutritive microcirculation in four defined regions of the skin in 17 patients with mixed ulcers caused by a combination of peripheral arterial occlusive disease and chronic venous insufficiency. Laser Doppler area flux was significantly higher in the ulcer areas than in the areas without granulation tissue and those in intact skin. The flux in the scars was higher than that in the intact skin or in the ulcer areas without granulation tissue. Capillary density in the intact skin was higher than the densities in nongranulation tissue areas, granulation areas, and scar areas (p<0.001 for all comparisons). To conclude, the ulcer areas without granulation tissue did not show a healing tendency due to poor subpapillary and nutritive perfusion; the granulation tissue exhibited high subpapillary perfusion as a sign of healing. In the scars, sufficient blood supply could be detected in both layers as a sign of an almost complete healing process. Blood supply in the intact skin is, however, already affected by distorted microcirculation in the ulcers.

Carotid artery stenting and follow-up: Value of 64-MSCT angiography as complementary imaging method to color-coded duplex sonography

PURPOSE To compare 64-multi-slice-CT angiography (64-MSCTA) to color-coded duplex sonography (CCDS) in the follow-up after carotid artery stenting (CAS). METHODS Thirty patients who had an MSCTA and CCDS examination prior and after CAS were included. Twelve closed-cell and 24 open-cell stents were implanted. Neointimal surface, in-stent-restenosis (ISR), stent expansion, and fracture were evaluated. In addition, the occurrence of atherosclerotic lesions leading to a>50% stenosis in supraaortic vessels was assessed. RESULTS With MSCTA, >50% ISR was found in 5.6% of cases during a mean follow-up of 41.7 months. Comparing MSCTA and CCDS, grading of ISR and absolute diameters of neointimal surface correlated moderately (Spearman=0.402, p=0.015; Pearson=0.404, p=0.03). Assessment of the neointimal surface was significantly better with MSCTA (100% vs. 80.6%; p=0.011). Stent expansion was significant, compared to the basic value, with both modalities and stent types (p<0.001). Of 237 additionally assessed vessel segments, a>50% stenosis was detected in 38 (16.0%) vessel segments. Findings were stable in 25 (10.5%) and progressed in 11 (4.6%) vessel segments. Five small intracranial aneurysms were detected in four (13.3%) patients. Of 21 incidental findings in 16 (51.6%) patients there was one with malignancy (4.8%). CONCLUSION With regard to ISR and stent expansion, no significant difference was found, when MSCTA and CCDS were compared. CTA is quite applicable as a complementary imaging method for the follow-up of patients with carotid artery stents. Additional advantages are the detection of supraaortic vessel pathologies and incidental findings.

Impact of age and gender on microvascular function.

Microcirculatory function can be assessed by postocclusive reactive hyperaemia (PORH) using laser Doppler fluxmetry. Previous studies have shown that PORH reveals microvascular damage at an early stage. In particular, at younger ages, PORH might depend on age and gender. To implement PORH into a larger scale of clinical studies, one has to be aware of the influence of age and gender on microcirculation. The aim of this study was to assess the impact of age and gender on microcirculatory function during adolescence.

Familial hypercholesterolemia affects microvascular autoregulation in children.

OBJECTIVE Familial hypercholesterolemia (FH) impairs macrovascular endothelial function in childhood and causes an increase of cardiovascular risk in later life. Whether microvascular function is affected in children with FH is unknown. The aim of this study was to investigate the impact of FH on microvascular autoregulation in children by post occlusive reactive hyperemia (PORH). METHODS PORH of the skin was assessed using laser Doppler fluxmetry. Baseline perfusion, biological zero, defined as no-flow laser Doppler signal during suprasystolic occlusion, peak perfusion after release of suprasystolic occlusion, as well as time to peak perfusion and recovery time, defined as time until baseline perfusion is resumed, were measured in 16 children, who were diagnosed with FH according to current guidelines, and in 91 healthy controls. RESULTS In children with FH, peak perfusion was higher (FH: 1.60±0.68 vs. controls: 1.26±0.50 AU [arbitrary units], p=0.02), recovery time was longer (110±42.61 vs. 83.18±35.08 s, p=0.01) and biological zero was lower than in controls (0.12±0.04 vs. 0.18±0.05 AU, p<0.001). Baseline perfusion and time to peak were not different between children with FH and controls (baseline perfusion: 0.43±0.21 vs. 0.38±0.15 AU, p=0.18; time to peak: 15.44±12.25 vs. 18.18±17.79 s, p=0.56). CONCLUSION For the first time the present study reveals an impact of FH on microvascular autoregulation in children: the differences of PORH between children with FH and controls indicate an affected autoregulation of microvascular blood flow in FH, which has its onset in childhood.

Transcutaneous oxygen tension monitoring in critically ill patients receiving packed red blood cells.

PURPOSE Whether transfusions of packed red blood cells (PRBCs) affect tissue oxygenation in stable critically ill patients is still matter of discussion. The microvascular capacity for tissue oxygenation can be determined noninvasively by measuring transcutaneous oxygen tension (tcpO2). The aim of this study was to assess tissue oxygenation by measuring tcpO2 in stable critically ill patients receiving PRBC transfusions. METHODS Nineteen stable critically ill patients, who received 2 units of PRBC, were prospectively included into this pilot study. Transcutaneous oxygen tension was measured continuously during PRBC transfusions using Clarks electrodes. In addition, whole blood viscosity and global hemodynamics were determined. RESULTS Reliable measurement signals during continuous tcpO2 monitoring were observed in 17 of 19 included patients. Transcutaneous oxygen tension was related to the global oxygen consumption (r=-0.78; P=.003), the arterio-venous oxygen content difference (r=-0.65; P=.005), and the extraction rate (r=-0.71; P=.02). The transfusion-induced increase of the hemoglobin concentration was paralleled by an increase of the whole blood viscosity (P<.001). Microvascular tissue oxygenation by means of tcpO2 was not affected by PRBC transfusions (P=.46). Packed red blood cell transfusions resulted in an increase of global oxygen delivery (P=.02) and central venous oxygen saturation (P=.01), whereas oxygen consumption remained unchanged (P=.72). CONCLUSIONS In stable critically ill patients, microvascular tissue oxygenation can be continuously monitored by Clarks tcpO2 electrodes. According to continuous tcpO2 measurements, the microvascular tissue oxygenation is not affected by PRBC transfusions.

Measurement of Atherosclerosis in Morbidly Obese Adolescents

Despite remarkable therapeutic advances over the past 50 years, cardiovascular diseases (CVD) are still the major causes of mortality and morbidity in the Western world.