Algimantas Krisciukaitis

Small Aβ1–42 oligomer-induced membrane depolarization of neuronal and microglial cells: Role of N-methyl-D-aspartate receptors

Although it is well documented that soluble beta amyloid (Aβ) oligomers are critical factors in the pathogenesis of Alzheimers disease (AD) by causing synaptic dysfunction and neuronal death, the primary mechanisms by which Aβ oligomers trigger neurodegeneration are not entirely understood. We sought to investigate whether toxic small Aβ1–42 oligomers induce changes in plasma membrane potential of cultured neurons and glial cells in rat cerebellar granule cell cultures leading to neuronal death and whether these effects are sensitive to the N‐methyl‐D‐aspartate receptor (NMDA‐R) antagonist MK801. We found that small Aβ1–42 oligomers induced rapid, protracted membrane depolarization of both neurons and microglia, whereas there was no change in membrane potential of astrocytes. MK801 did not modulate Aβ‐induced neuronal depolarization. In contrast, Aβ1−42 oligomer‐induced decrease in plasma membrane potential of microglia was prevented by MK801. Small Aβ1–42 oligomers significantly elevated extracellular glutamate and caused neuronal necrosis, and both were prevented by MK801. Also, small Aβ1–42 oligomers decreased resistance of isolated brain mitochondria to calcium‐induced opening of mitochondrial permeability transition pore. In conclusion, the results suggest that the primary effect of toxic small Aβ oligomers on neurons is rapid, NMDA‐R‐independent plasma membrane depolarization, which leads to neuronal death. Aβ oligomers‐induced depolarization of microglial cells is NMDA‐R dependent.

Prognosis of in-hospital myocardial infarction course for diabetic and nondiabetic patients using a noninvasive evaluation of hemodynamics and heart rate variability.

BACKGROUND AND OBJECTIVE The objective of our study was to investigate whether the combination of markers of heart rate variability (HRV) and impedance cardiography (ICG) help evaluate the risk of in-hospital death, ventricular arrhythmia, or complicated course secondary to myocardial infarction (STEMI) and to clarify whether combined analysis of HRV and ICG improve prognosis of STEMI, comparing 3 groups: 1) diabetic, 2) nondiabetic, and 3) diabetes-unselected patients. MATERIAL AND METHODS The parameters reflecting heart rate variability and central hemodynamics were estimated from a 24-hour synchronic electrocardiogram and thoracic impedance signal recordings in 232 patients (67 diabetic) on the third day after myocardial infarction. Logistic regression analysis was used to determine the predictors of selected outcomes. Different prognostic models were compared with the receiver operating characteristic curve analysis. RESULTS The model consisting of low- and high-frequency power ratio (LF/HF) and cardiac output (CO) was elaborated for the prognosis of in-hospital death in the group 3 (odds ratios [ORs] were 9.74 and 4.85, respectively). Very low-frequency power (VLF), cardiac index (CIN), and cardiac power output (CPO) were the predictors of ventricular arrhythmia in the group 2 (ORs of 1.005, 5.09, and 66.7, respectively) and the group 3 (ORs of 1.004, 3.84, and 37.04, respectively). The predictors of the complicated in-hospital course in the group 1 were the baseline width of the minimum square difference triangular interpolation of the highest peak of the histogram of all NN intervals (TINN) and stroke volume (SV) (ORs of 1.006, and 1.009, respectively); in the group 2, the mean of the standard deviations of all NN intervals for all 5-minute segments of the recording (SDNN index) and CPO (ORs of 1.06 and 2.44, respectively); and in the group 3, SDNN index, VLF, LF/HF, CIN (ORs of 1.04, 1.004, 2.3, and 3.49, respectively). CONCLUSIONS The patients with decreased HRV and low estimates of central hemodynamics evaluated by ICG are at an increased risk of the adverse in-hospital course of STEMI. The combined analysis of HRV and ICG hemodynamic estimates contributes to the risk assessment of the complicated in-hospital course of STEMI, in-hospital hemodynamically significant ventricular arrhythmia, and in-hospital death secondary to STEMI. The in-hospital prognostic value of the combined estimates of HRV and ICG is lower in the STEMI patients with diabetes mellitus as compared with the nondiabetic patients.

Multistage principal component analysis based method for abdominal ECG decomposition.

Reflection of fetal heart electrical activity is present in registered abdominal ECG signals. However this signal component has noticeably less energy than concurrent signals, especially maternal ECG. Therefore traditionally recommended independent component analysis, fails to separate these two ECG signals. Multistage principal component analysis (PCA) is proposed for step-by-step extraction of abdominal ECG signal components. Truncated representation and subsequent subtraction of cardio cycles of maternal ECG are the first steps. The energy of fetal ECG component then becomes comparable or even exceeds energy of other components in the remaining signal. Second stage PCA concentrates energy of the sought signal in one principal component assuring its maximal amplitude regardless to the orientation of the fetus in multilead recordings. Third stage PCA is performed on signal excerpts representing detected fetal heart beats in aim to perform their truncated representation reconstructing their shape for further analysis. The algorithm was tested with PhysioNet Challenge 2013 signals and signals recorded in the Department of Obstetrics and Gynecology, Lithuanian University of Health Sciences. Results of our method in PhysioNet Challenge 2013 on open data set were: average score: 341.503 bpm(2) and 32.81 ms.

Detection and evaluation of ventricular repolarization alternans: an approach to combined ECG, thoracic impedance, and beat-to-beat heart rate variability analysis.

BACKGROUND AND OBJECTIVE Beat-to-beat alteration in ventricles repolarization reflected by alternans of amplitude and/or shape of ECG S-T,T segment (TWA) is known as phenomena related with risk of severe arrhythmias leading to sudden cardiac death. Technical difficulties have caused limited its usage in clinical diagnostics. Possibilities to register and analyze multimodal signals reflecting heart activity inspired search for new technical solutions. First objective of this study was to test whether thoracic impedance signal and beat-to-beat heart rate reflect repolarization alternans detected as TWA. The second objective was revelation of multimodal signal features more comprehensively representing the phenomena and increasing its prognostic usefulness. MATERIALS AND METHODS ECG, and thoracic impedance signal recordings made during 24h follow-up of the patients hospitalized in acute phase of myocardial infarction were used for investigation. Signal morphology variations reflecting estimates were obtained by the principal component analysis-based method. Clinical outcomes of patients (survival and/or rehospitalization in 6 and 12 months) were compared to repolarization alternans and heart rate variability estimates. RESULTS Repolarization alternans detected as TWA was also reflected in estimates of thoracic impedance signal shape and variation in beat-to-beat heart rate. All these parameters showed correlation with clinical outcomes of patients. The strongest significant correlation showed magnitude of alternans in estimates of thoracic impedance signal shape. CONCLUSIONS The features of ECG, thoracic impedance signal and beat-to-beat variability of heart rate, give comprehensive estimates of repolarization alternans, which correlate, with clinical outcomes of the patients and we recommend using them to improve diagnostic reliability.

Methods for evaluation of central hemodynamics and detection of indicators of risk of sudden cardiac death for network based clinical decision support system

Two methods for evaluation of crucial factors describing status of cardiologic patients based on advanced signal processing methods were incorporated into prototype network based clinical decision support system: a) novel method for chest impedance signal analysis enabling reliable evaluation of central hemodynamics in non-invasive way; b) method for automatic detection and evaluation of ECG T-wave alternans - predictor of sudden cardiac death. Both methods supplement each other and improve the quality of monitoring of patient status in intensive care unit.

SCARB1 rs5888 is associated with the risk of age-related macular degeneration susceptibility and an impaired macular area

ABSTRACT Background: Age-related macular degeneration (ARMD), a progressive retinal disease, is responsible for an impaired central vision in about 180 million people worldwide. Current options for ARMD prevention and treatment are limited due to an incomplete understanding of disease etiopathogenesis. We aimed to test the hypothesis that the single nucleotide polymorphism rs5888 of SCARB1 gene reflecting lipid and antioxidant micronutrient metabolism pathways is associated with ARMD susceptibility and to evaluate if there is any relation between SCARB1 rs5888 and the macular lesion area. Materials and methods: The prospective case-control study included patients with ARMD (n = 215) and the reference group (n = 238) drawn from a random sample of the Lithuanian population (n = 1436). The genotyping test of SCARB1 rs5888 was carried out using the real-time polymerase chain reaction method. Results: Regression analysis adjusted by gender and age demonstrated that SCARB1 rs5888 TT genotype significantly decreased the odds for ARMD development (OR: 0.61, 95%; CI: 0.380–0.981, p = 0.04). A smoking habit and leading an outdoor life are associated with larger macular lesion areas in ARMD patients (0.54 (0.00–39.06) vs. 3.09 (0.02–19.30) and 0.27 (0.00–34.57) vs. 0.75 (0.00–39.06), respectively). In late stage ARMD subjects with CT genotype, the macular lesion area was larger than in TT carriers (7.64 (0.49–39.06) mm2 vs. 5.02 (0.03–37.06) mm2, p = 0.006). Conclusions: SCARB1 rs5888 and environmental oxidative stress have a prominent role in ARMD susceptibility, early ARMD progression to advanced stage disease and even in the outcome of the disease—an area of macular lesion.

Variability of left ventricle outflow tract VTI during breathing cycle may predict fluid responsiveness in the postoperative period for non-cardiac spontaneously breathing patients

Introduction: Different studies show controversial results while discussing which echocardiography parameter is the best to assess fluid responsiveness. The aims of the study were to evaluate the feasibility of echocardiography monitoring in postoperative unit and to assess diagnostic value of different parameters obtained by focused assessed transthoracic echocardiography (FATE) to control non-cardiac patients’ postoperative fluid therapy. Methods: 40 patients who underwent major abdominal surgery and had reduced arterial blood pressure were included in the prospective study. The echocardiography measurements were taken before and immediately after fluid challenge of 500 ml of crystalloids. Positive fluid responsiveness was defined by an increase in stroke volume (SV) of at least 15%. Results: FATE monitoring is feasible in postoperative unit. The identification of fluid responsiveness by clinical signs was significantly lower compared to echocardiography data (p=0.034). Variability of left ventricle outflow tract (LVOT) velocity time integral (VTI) during breathing cycle prognosis fluid responsiveness AUC of the ROC was 0.881. The mitral E wave, E/A ratio and IVC index prognoses fluid responsiveness in spontaneously breathing patients (p=0.006; p<0.001; p<0.001). CI seemed to be not suitable for prognosis of fluid responsiveness (p=0.214). There was no difference between infusion therapy in responders and non-responders neither during operation 2167 ml and 1678 ml (p=0.13) respectively nor in postoperative period 1500 ml and 1678 ml (p=0.344). After FATE the strategy of infusion therapy was changed in 14 (35%) patients. Conclusions: LVOT VTI variability of more than 10% in spontaneously breathing patients had the highest sensitivity and comparable specificity among the parameters used for identification of fluid responders by FATE.

Methods for monitoring and prognosis of clinical status of patients in acute phase of myocardial infarction for computer network based clinical decision support system

Abstract The methods for evaluation of crucial factors describing status of cardiologic patients in intensive care units based on advanced signal processing methods were incorporated into prototype network based clinical decision support system. The methods realize: (a) evaluation of heart rate variability in aim to predict clinical outcome; (b) evaluation of central hemodynamics in non-invasive way by means of chest impedance signal analysis; (c) automatic detection and evaluation of ECG T-wave alternans – predictor of sudden cardiac death. Modern standard monitoring equipment has connection to the computer network and possibility to transfer registered signals and clinical data what could be processed and evaluated with such clinical decision system. The remotely accessed methods of the system can significantly improve the quality of monitoring of patient status using standard equipment.

Hemodynamic studies for prediction of acute myocardial infarction outcomes

Prediction of outcomes after acute myocardial infarction was initiated more than 40 years ago. Improvement of the management options significantly reduced mortality of patients with acute myocardial infarction. In the 1960s, the mortality rate of inpatients was around 25-30%, whereas in 2007, according to the guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes, issued by the European Society of Cardiology, hospital mortality in patients with ST-elevation acute myocardial infarction was 7%, while in patients with non-ST-elevation acute coronary syndrome just 5%, but at 6 months, mortality rates were very similar in both conditions (12% vs. 13%, respectively). There are different criteria for prediction of acute myocardial infarction: demographic, clinical, laboratory, instrumental, and epidemiological. Data of hemodynamic studies are ones of the possible criteria for prediction of outcomes after acute myocardial infarction. Methods and findings of hemodynamic studies used for prediction of the outcomes are presented in this article.