Konstantin Kotliar

Rationale and study design of the prospective, longitudinal, observational cohort study “rISk strAtification in end-stage renal disease” (ISAR) study

BackgroundThe ISAR study is a prospective, longitudinal, observational cohort study to improve the cardiovascular risk stratification in endstage renal disease (ESRD). The major goal is to characterize the cardiovascular phenotype of the study subjects, namely alterations in micro- and macrocirculation and to determine autonomic function.Methods/designWe intend to recruit 500 prevalent dialysis patients in 17 centers in Munich and the surrounding area. Baseline examinations include: (1) biochemistry, (2) 24-h Holter Electrocardiography (ECG) recordings, (3) 24-h ambulatory blood pressure measurement (ABPM), (4) 24xa0h pulse wave analysis (PWA) and pulse wave velocity (PWV), (5) retinal vessel analysis (RVA) and (6) neurocognitive testing. After 24xa0months biochemistry and determination of single PWA, single PWV and neurocognitive testing are repeated. Patients will be followed up to 6xa0years for (1) hospitalizations, (2) cardiovascular and (3) non-cardiovascular events and (4) cardiovascular and (5) all-cause mortality.Discussion/conclusionWe aim to create a complex dataset to answer questions about the insufficiently understood pathophysiology leading to excessively high cardiovascular and non-cardiovascular mortality in dialysis patients. Finally we hope to improve cardiovascular risk stratification in comparison to the use of classical and non-classical (dialysis-associated) risk factors and other models of risk stratification in ESRD patients by building a multivariable Cox-Regression model using a combination of the parameters measured in the study.Clinical trials identifierClinicalTrials.gov NCT01152892 (June 28, 2010)

Altered neurovascular coupling as measured by optical imaging: a biomarker for Alzheimer’s disease

Neurovascular coupling can be directly assessed by retinal vessel response to flickering light using optical imaging methods. The response is altered in a number of ocular and cardiovascular diseases. Whether it is altered in Alzheimer’s disease (AD) is investigated. Retinal vessel reaction to monochromatic flicker stimulation was examined by Dynamic Vessel Analyzer independent of the commercial software in elderly subjects: 15 patients with mild-to-moderate dementia due to AD (ADD); 24 patients with mild cognitive impairment due to AD (MCI); 15 cognitively healthy controls (HC). Retinal vessels in ADD showed a more emphasized and delayed reactive dilation as compared to HC. In MCI, these aspects still differed from those seen in ADD. Maximal arterial reaction was increased and dilation was delayed in ADD as compared to HC (pu2009=u20090.004 and pu2009<u20090.001) and to MCI (pu2009=u20090.058 and pu2009=u20090.004), respectively. Maximal venous reaction was increased in ADD as compared to HC (pu2009=u20090.001) and to MCI (pu2009=u20090.007), respectively. This finding suggests that retinal neuronal activity is either increased or feed-back loop of neurovascular coupling is damaged with differentiating alterations across the spectrum of AD. Thus, retinal vessel reaction to flicker stimulation is considered a promising non-invasive, widely available and easy-to-administer future biomarker for the diagnosis and monitoring of AD.

Unconjugated bilirubin modulates neuronal signaling only in wild-type mice, but not after ablation of the R-type/Cav2.3 voltage-gated calcium channel

The relationship between blood metabolites and hemoglobin degradation products (BMHDPs) formed in the cerebrospinal fluid and the development of vasospasm and delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) has been the focus of several previous studies, but their molecular and cellular targets remain to be elucidated.

Vasoconstriction and Impairment of Neurovascular Coupling after Subarachnoid Hemorrhage: a Descriptive Analysis of Retinal Changes

Impaired cerebral autoregulation and neurovascular coupling (NVC) contribute to delayed cerebral ischemia after subarachnoid hemorrhage (SAH). Retinal vessel analysis (RVA) allows non-invasive assessment of vessel dimension and NVC hereby demonstrating a predictive value in the context of various neurovascular diseases. Using RVA as a translational approach, we aimed to assess the retinal vessels in patients with SAH. RVA was performed prospectively in 24 patients with acute SAH (group A: day 5–14), in 11 patients 3xa0months after ictus (group B: day 90xa0±xa035), and in 35 age-matched healthy controls (group C). Data was acquired using a Retinal Vessel Analyzer (Imedos Systems UG, Jena) for examination of retinal vessel dimension and NVC using flicker-light excitation. Diameter of retinal vessels—central retinal arteriolar and venular equivalent—was significantly reduced in the acute phase (pxa0<xa00.001) with gradual improvement in group B (pxa0<xa00.05). Arterial NVC of group A was significantly impaired with diminished dilatation (pxa0<xa00.001) and reduced area under the curve (pxa0<xa00.01) when compared to group C. Group B showed persistent prolonged latency of arterial dilation (pxa0<xa00.05). Venous NVC was significantly delayed after SAH compared to group C (A pxa0<xa00.001; B pxa0<xa00.05). To our knowledge, this is the first clinical study to document retinal vasoconstriction and impairment of NVC in patients with SAH. Using non-invasive RVA as a translational approach, characteristic patterns of compromise were detected for the arterial and venous compartment of the neurovascular unit in a time-dependent fashion. Recruitment will continue to facilitate a correlation analysis with clinical course and outcome.

THE USEFULNESS OF DYNAMIC RETINAL VESSEL REACTION TO FLICKERING LIGHT AS A BIOMARKER FOR ALZHEIMER'S DISEASE

VESSEL REACTION TO FLICKERING LIGHTAS A BIOMARKER FOR ALZHEIMER’S DISEASE Konstantin Kotliar, Christine Hauser, Marion Ortner, Claudia Muggenthaler, Christoph Schmaderer, Arno SchmidtTrucksaess, Timo Grimmer, Aachen University of Applied Sciences, Aachen, Germany; 2 Klinikum rechts der Isar, Technische Universitaet Muenchen, Munich, Germany; Institute of Exercise and Health Sciences, Basel University, Basel, Switzerland. Contact e-mail: kotliar@fh-aachen.de

Computer simulation of the cornea-scleral shell as applied to pressure-volume relationship in the human eye

Relationship between intraocular pressure (IOP) and the intraocular volume (IOV) was obtained for three mechanical models with following problem statements: 1) the eyeball shell is assumed to be ellipsoidal transversal isotropic shell; 2) the corneoscleral shell of the eye is modeled as a conjugated shell consisting of two segments (sclera and cornea); 3) in the third model the coupled fluid-structure interactions in the eye are taken into account.