Sharon Zlochiver

Tel Aviv University, Tell Afif, Tel Aviv, Israel

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Publications (51)152.07 Total impact

  • Ani Amar · Sharon Zlochiver · Ofer Barnea ·
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    ABSTRACT: A biophysical detailed multiscale model of the myocardium is presented. The model was used to study the contribution of interrelated cellular mechanisms to global myocardial function. The multiscale model integrates cellular electrophysiology, excitation propagation dynamics and force development models into a geometrical fiber based model of the ventricle. The description of the cellular electrophysiology in this study was based on the Ten Tusscher-Noble-Noble-Panfilov heterogeneous model for human ventricular myocytes. A four-state model of the sarcomeric control of contraction developed by Negroni and Lascano was employed to model the intracellular mechanism of force generation. The propagation of electrical excitation was described by a reaction-diffusion equation. The 3D geometrical model of the ventricle, based on single fiber contraction was used as a platform for the evaluation of proposed models. The model represents the myocardium as an anatomically oriented array of contracting fibers with individual fiber parameters such as size, spatial location, orientation and mechanical properties. Moreover, the contracting ventricle model interacts with intraventricular blood elements linking the contractile elements to the heart's preload and afterload, thereby producing the corresponding pressure-volume loop. The results show that the multiscale ventricle model is capable of simulating mechanical contraction, pressure generation and load interactions as well as demonstrating the individual contribution of each ion current.
    10/2015; 6(4). DOI:10.1007/s13239-015-0247-5
  • Hila Dvir · Sharon Zlochiver ·
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    ABSTRACT: A single isolated sinoatrial pacemaker cell presents intrinsic interbeat interval (IBI) variability that is believed to result from the stochastic characteristics of the opening and closing processes of membrane ion channels. To our knowledge, a novel mathematical framework was developed in this work to address the effect of current fluctuations on the IBIs of sinoatrial pacemaker cells. Using statistical modeling and employing the Fokker-Planck formalism, our mathematical analysis suggests that increased stochastic current fluctuation variance linearly increases the slope of phase-4 depolarization, hence the rate of activations. Single-cell and two-dimensional computerized numerical modeling of the sinoatrial node was conducted to validate the theoretical predictions using established ionic kinetics of the rabbit pacemaker and atrial cells. Our models also provide, to our knowledge, a novel complementary or alternative explanation to recent experimental observations showing a strong reduction in the mean IBI of Cx30 deficient mice in comparison to wild-types, not fully explicable by the effects of intercellular decoupling. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.
    Biophysical Journal 03/2015; 108(5):1281-92. DOI:10.1016/j.bpj.2015.01.010 · 3.97 Impact Factor
  • Hila Dvir · Sharon Zlochiver ·
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    ABSTRACT: Low pacing variabilty in the heart has been clinically reported as a risk factor for lethal cardiac arrhythmias and arrhythmic death. In a previous simulation study, we demonstrated that stochastic pacing sustains an antiarrhythmic effect by moderating the slope of the action potential duration (APD) restitution curve, by reducing the propensity of APD alternans, converting discordant to concordant alternans, and ultimately preventing wavebreaks. However, the dynamic mechanisms relating pacing stochasticity to tissue stability are not yet known. In this work, we develop a mathematical framework to describe the APD signal using an autoregressive stochastic model, and we establish the interrelations between stochastic pacing, cardiac memory, and cardiac stability, as manifested by the degree of APD alternans. Employing stability analysis tools, we show that increased stochasticity in the ventricular tissue activation sequence works to lower the maximal absolute eigenvalues of the stochastic model, thereby contributing to increased stability. We also show that the memory coefficients of the autoregressive model are modulated by pacing stochasticity in a nonlinear, biphasic way, so that for exceedingly high levels of pacing stochasticity, the antiarrhythmic effect is hampered by increasing APD variance. This work may contribute to establishment of an optimal antiarrhythmic pacing protocol in a future study.
    Biophysical Journal 08/2014; 107(4):1023-1034. DOI:10.1016/j.bpj.2014.07.004 · 3.97 Impact Factor
  • Ariel Greisas · Zohar Zafrir · Sharon Zlochiver ·
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    ABSTRACT: Electrogram-guided ablation has been recently developed for allowing better detection and localization of abnormal atrial activity that may be the source of arrhythmogeneity. Nevertheless, no clear indication for the benefit of using electrograms guided ablation over empirical ablation was established thus far, and there is a clear need of improving the localization of cardiac arrhythmogenic targets for ablation. In this work we propose a new approach for detection and localization of irregular cardiac activity during ablation procedures that is based on dimension reduction algorithms and principal component analysis (PCA). Using an 8x8 electrode-array, our method produces manifolds that allow easy visualization and detection of possible arrhythmogenic ablation targets characterized by irregular conduction. We employ mathematical modeling and computer simulations to demonstrate the feasibility of the new approach for two well established arrhythmogenic sources for irregular conduction - spiral waves and patchy fibrosis. Our results show that the PCA method can differentiate between focal ectopic activity and spiral wave activity, as these two types of activity produce substantially different manifold shapes. Moreover, the technique allows the detection of spiral wave cores and their general meandering and drifting pattern. Fibrotic patches larger than 2 mm2 could also be visualized using the PCA method, both for quiescent atrial tissue and for tissue exhibiting spiral wave activity. We envision that this method, contingent to further numerical and experimental validation studies in more complex, realistic geometrical configurations and with clinical data, can improve existing atrial ablation mapping capabilities, thus increasing success rates and optimizing arrhythmia management.
    IEEE transactions on bio-medical engineering 07/2014; 62(1). DOI:10.1109/TBME.2014.2342792 · 2.35 Impact Factor
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    Conrado J Calvo · Makarand Deo · Sharon Zlochiver · José Millet · Omer Berenfeld ·
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    ABSTRACT: Maintenance of paroxysmal atrial fibrillation (AF) by fast rotors in the left atrium (LA) or at the pulmonary veins (PVs) is not fully understood. To gain insight into this dynamic and complex process, we studied the role of the heterogeneous distribution of transmembrane currents in the PVs and LA junction (PV-LAJ) in the localization of rotors in the PVs. We also investigated whether simple pacing protocols could be used to predict rotor drift in the PV-LAJ. Experimentally observed heterogeneities in IK1, IKs, IKr, Ito, and ICaL in the PV-LAJ were incorporated into two- and pseudo three-dimensional models of Courtemanche-Ramirez-Nattel-Kneller human atrial kinetics to simulate various conditions and investigate rotor drifting mechanisms. Spatial gradients in the currents resulted in shorter action potential duration, minimum diastolic potential that was less negative, and slower upstroke and conduction velocity for rotors in the PV region than in the LA. Rotors under such conditions drifted toward the PV and stabilized at the shortest action potential duration and less-excitable region, consistent with drift direction under intercellular coupling heterogeneities and regardless of the geometrical constraint in the PVs. Simulations with various IK1 gradient conditions and current-voltage relationships substantiated its major role in the rotor drift. In our 1:1 pacing protocol, we found that among various action potential properties, only the minimum diastolic potential gradient was a rate-independent predictor of rotor drift direction. Consistent with experimental and clinical AF studies, simulations in an electrophysiologically heterogeneous model of the PV-LAJ showed rotor attraction toward the PV. Our simulations suggest that IK1 heterogeneity is dominant compared to other currents in determining the drift direction through its impact on the excitability gradient. These results provide a believed novel framework for understanding the complex dynamics of rotors in AF.
    Biophysical Journal 04/2014; 106(8):1811-21. DOI:10.1016/j.bpj.2014.02.030 · 3.97 Impact Factor
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    ABSTRACT: An optical lensless configuration for a remote noncontact measuring of mechanical contractions of a vast number of cardiac myocytes is proposed. All the myocytes were taken from rats, and the measurements were done in an in vitro mode. The optical method is based on temporal analysis of secondary reflected speckle patterns generated in lensless microscope configuration. The processing involves analyzing the movement and the change in the statistics of the secondary speckle patterns that are created on top of the cell culture when it is illuminated by a spot of laser beam. The main advantage of the proposed system is the ability to measure many cells simultaneously (∼1000 cells) and to extract the statistical data of their movement at once. The presented experimental results also include investigation of the effect of isoproteranol on cell contraction process.
    Journal of Biomedical Optics 10/2013; 18(10):101310. DOI:10.1117/1.JBO.18.10.101310 · 2.86 Impact Factor

  • SPIENewsroom 08/2013; DOI:10.1117/2.1201308.004974
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    Hila Dvir · Sharon Zlochiver ·
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    ABSTRACT: The ventricular tissue is activated in a stochastic rather than in a deterministic rhythm due to the inherent heart rate variability (HRV). Low HRV is a known predictor for arrhythmia events and traditionally is attributed to autonomic nervous system tone damage. Yet, there is no model that directly assesses the antiarrhythmic effect of pacing stochasticity per se. One-dimensional (1D) and two-dimensional (2D) human ventricular tissues were modeled, and both deterministic and stochastic pacing protocols were applied. Action potential duration restitution (APDR) and conduction velocity restitution (CVR) curves were generated and analyzed, and the propensity and characteristics of action potential duration (APD) alternans were investigated. In the 1D model, pacing stochasticity was found to sustain a moderating effect on the APDR curve by reducing its slope, rendering the tissue less arrhythmogenic. Moreover, stochasticity was found to be a significant antagonist to the development of concordant APD alternans. These effects were generally amplified with increased variability in the pacing cycle intervals. In addition, in the 2D tissue configuration, stochastic pacing exerted a protective antiarrhythmic effect by reducing the spatial APD heterogeneity and converting discordant APD alternans to concordant ones. These results suggest that high cardiac pacing stochasticity is likely to reduce the risk of cardiac arrhythmias in patients.
    Biophysical Journal 07/2013; 105(2):533-42. DOI:10.1016/j.bpj.2013.06.012 · 3.97 Impact Factor
  • Hila Dvir · Sharon Zlochiver ·
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    ABSTRACT: The physiological heart rate is not deterministic but rather varies in time; those variations are termed heart rate variability (HRV). It is well known that low HRV is often seen in patients prone to arrhythmias. The ability of HRV to predict arrhythmia events is traditionally attributed to an impaired balance between the autonomic sympathetic and parasympathetic tone. However, there is no concrete model that directly relates low HRV to the electrical conduction in the cardiac tissue and to arrhythmogenic dynamic properties. We simulated stochastic cardiac pacing with Gaussian distribution using 2D human ventricular tissue model. Conduction stabilization was obtained with stochastic pacing owing to reduced propensity of the appearance of action potential duration (APD) discordant alternans and reduced APD spatial heterogeneity.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 07/2013; 2013:1514-1517. DOI:10.1109/EMBC.2013.6609800
  • Zohar Zafrir · Sharon Zlochiver ·
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    ABSTRACT: Although computational modeling of the prospective electrical activity in the cardiac tissue is well established and robust, the retrospective extrapolation of this activity has not been explored to date. Here, we establish an algorithm for the backward-in-time extrapolation of electrical activity from measurements taken in the present. Using minimal human cardiac kinetic models and a modified Newton-Raphson algorithm, we demonstrate the feasibility of past activity reconstruction in a single cell and in a linear strand. In a single cell, reconstruction of state variables' shape, the action potential morphology, and the time of stimulation was successful for up to 1300 ms poststimulation and for data with signal-to-noise ratio levels higher than 40 dB. For linear strands, the action potential morphology was reconstructed for 500 ms poststimulation, and the reconstructed conduction velocity remained unaffected for signal-to-noise ratio levels higher than 50 dB. Moreover, tissue restitution properties due to various pacing rates were successfully reconstructed by the backward-in-time algorithm. These preliminary results demonstrate that past cardiac activity may be reconstructed from measurements in the present. We envision that this methodology could be implemented in future clinical applications, for example to trace the location and timing of ectopic foci during ablation procedures. Copyright © 2013 John Wiley & Sons, Ltd.
    06/2013; 29(6). DOI:10.1002/cnm.2553
  • Conrado J Calvo · Makarand Deo · Sharon Zlochiver · Jose Millet · Omer Berenfeld ·
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    ABSTRACT: Maintenance of paroxysmal atrial fibrillation (AF) by fast rotors near or at the pulmonary veins (PVs) is not fully understood. We believe that heterogeneous distribution of transmembrane currents in the PVs and LA junction (PV-LAJ) play a major in the localization of rotors in the PVs. We seek for pacing protocols and measurements that could be used to predict drift direction. Experimentally observed heterogeneities in the PV-LAJ were incorporated into 2D and pseudo-3D models of Courtemanche-Ramirez-Nattel-Kneller human atrial kinetics to simulate various conditions and investigate rotor drifting mechanisms and electrophysiological pacing predictors. Simulations with various IK1 gradient conditions and various current-voltage relationships, substantiated its major role in the rotor drift. Among various action potential properties tested, only MDP gradient was found to be a pacing-rate independent predictor of rotor drift direction. Our simulations suggest that IK1 heterogeneity is dominant in conveying the drift direction through its impact on the global excitability and refractoriness gradients and more importantly it is only reflected in pacing studies in a frequency dependent manner. Our results call out for precaution when extrapolating results determined from pacing studies, commonly performed at 2 Hz.
    Computing in Cardiology Conference (CinC), 2013; 01/2013
  • Sharon Zlochiver ·

    Heart rhythm: the official journal of the Heart Rhythm Society 12/2012; 10(3). DOI:10.1016/j.hrthm.2012.12.007 · 5.08 Impact Factor
  • Benny Yusupov · Sharon Zlochiver ·
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    ABSTRACT: The accurate navigation and location of a biopsy needle is of main clinical interest in cases of image-guided biopsies for patients with suspected cancerous lesions. Magnetic induction (MI) imaging is a relatively new simple and low-cost noninvasive imaging modality that can be used for measuring the changes of electrical conductivity distribution inside a biological tissue. The feasibility of using MI principles for measuring and imaging the location of a biopsy needle in a tissue with suspected lesion was studied in simulations and with an experimental system. A contactless excitation/sensing unit was designed, and raster scan was performed on a thin tissue slab with an inserted standard 22 gauge stainless steel biopsy needle. A 30-mA, 50-kHz excitation field was employed, and the secondary-induced electromotive force (emf(s)) was measured and plotted on a 2-D plane in order to yield an image of the needle location. The simulations demonstrated the significance of utilizing a ferrimagnetic core for the excitation coil in order to increase induced currents magnitude and scanning resolution. The experimental reconstructed images of the emf(s) spatial distribution revealed the needle position and orientation, with an accuracy of 0.1 mm and a signal-to-background ratio of ~30 dB. High correlation (R(2) = 0.89) between the experimental and simulation results was observed. We conclude that MI principles exhibit a potential alternative to existing imaging modalities for needle biopsy procedures.
    IEEE transactions on bio-medical engineering 06/2012; 59(8):2330-7. DOI:10.1109/TBME.2012.2203132 · 2.35 Impact Factor
  • Ariel Greisas · Sharon Zlochiver ·
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    ABSTRACT: Fibroblasts make for the most common nonmyocyte cells in the human heart and are known to play a role in structural remodeling caused by aging and various pathological states, which can eventually lead to cardiac arrhythmias and fibrillation. Gap junction formed between fibroblasts and myocytes have been recently described and were shown to alter the cardiac electrical parameters, such as action potential duration and conduction velocity, in various manners. In this study, we employed computational modeling to examine the effects of fibroblast-myocyte coupling and ratio on automaticity and electrical wave conduction during reentrant activity, with specific emphasis on dynamic phenomena and stability. Our results show that fibroblast density and coupling impact wave frequency in a biphasic way, first increasing wave frequency and then decreasing it. This can be explained by the dual role of the fibroblast cell as a current sink or a current source, depending on the coupled myocytes intracellular potential. We have also demonstrated that wave stability as manifested by the spiral-wave tip velocity and reentrant activity lifespan depends on fibroblast-myocyte coupling and ratio in a complex way. Finally, our study describes the required conditions in which spontaneous activity can occur, as a result of the fibroblasts depolarizing the myocytes' resting potential sufficiently to induce rhythmic pulses without any stimulation applied.
    IEEE transactions on bio-medical engineering 02/2012; 59(5):1398-407. DOI:10.1109/TBME.2012.2188291 · 2.35 Impact Factor
  • Hila Dvir · Sharon Zlochiver ·
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    ABSTRACT: The physiological heart rate presents a stochastic behavior known as heart rate variability (HRV). In this framework the influence of HRV on the action potential duration (APD) of the atrial myocyte is analyzed in a computer model. We have found that introducing HRV into the myocyte action potential model decreases the APD of the extra beat S2 in an S1-S2 protocol compared to constant heart rate. A possible theoretical explanation for this is also presented and is derived from switched systems theory. It is suggested to consider the myocyte action potential phase 4 and phase 2 as two operation modes of a switching system and analyze the stability of switching between them. Since random switching is known to have a stabilization effect on a switching system, this might explain why HRV has a stabilization effect on the myocyte APD restitution. Implications of this finding include reduced system stability for conditions with low HRV. A possible application for this phenomenon regards artificial pacemakers, where a preset added HRV is predicted to reduce susceptibility to arrhythmias.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 08/2011; 2011:685-8. DOI:10.1109/IEMBS.2011.6090154
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    ABSTRACT: The ionic mechanisms of electrical heterogeneity in the ischemic ventricular epicardium remain poorly understood. This study sought to test the hypothesis that the adenosine triphosphate (ATP)-activated K+ current (I(KATP)) plays an important role in mediating repolarization differences between the right ventricle (RV) and left ventricle (LV) during global ischemia. Electrical activity in Langendorff-perfused guinea pig hearts was recorded optically during control, ischemia, and reperfusion. Patch-clamp experiments were used to quantify I(KATP) density in isolated myocytes. Molecular correlates of I(KATP) (Kir6/SUR) were probed via reverse transcriptase-polymerase chain reaction. The role of I(KATP) in modulating repolarization was studied using computer simulations. Action potential duration (APD) was similar between LV and RV in control hearts, but significantly different in global ischemia. Pretreatment of hearts with 10 μM glibenclamide (I(KATP) blocker) abolished the APD gradient during ischemia. In the absence of ischemia, pinacidil (I(KATP) opener) tended to shorten the APD more in the LV, and caused a small but significant increase in APD dispersion. In voltage clamp experiments, the density of the whole-cell current activated by pinacidil at depolarized potentials was significantly larger in LV, compared with RV epicardial myocytes. The mRNA levels of Kir6.1/Kir6.2 were significantly higher in LV compared with RV. Simulations showed that I(KATP) is the main determinant of LV-RV APD gradient, whereas cell-to-cell coupling modified the spatial distribution of this APD gradient. I(KATP) is an important determinant of the epicardial LV-RV APD gradient during global ischemia, in part due to a higher current density and molecular expression in the LV.
    Heart rhythm: the official journal of the Heart Rhythm Society 06/2011; 8(11):1732-9. DOI:10.1016/j.hrthm.2011.06.028 · 5.08 Impact Factor
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    Sharon Zlochiver ·

    Heart rhythm: the official journal of the Heart Rhythm Society 05/2011; 8(5):760-1. DOI:10.1016/j.hrthm.2011.01.004 · 5.08 Impact Factor
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    ABSTRACT: The aim of this paper was to study mechanisms of formation of fractionated electrograms on the posterior left atrial wall (PLAW) in human paroxysmal atrial fibrillation (AF). The mechanisms responsible for complex fractionated atrial electrogram formation during AF are poorly understood. In 24 patients, we induced sustained AF by pacing from a pulmonary vein. We analyzed transitions between organized patterns and changes in electrogram morphology leading to fractionation in relation to interbeat interval duration (systolic interval [SI]) and dominant frequency. Computer simulations of rotors helped in the interpretation of the results. Organized patterns were recorded 31 ± 18% of the time. In 47% of organized patterns, the electrograms and PLAW activation sequence were similar to those of incoming waves during pulmonary vein stimulation that induced AF. Transitions to fractionation were preceded by significant increases in electrogram duration, spike number, and SI shortening (R(2) = 0.94). Similarly, adenosine infusion during organized patterns caused significant SI shortening leading to fractionated electrograms formation. Activation maps during organization showed incoming wave patterns, with earliest activation located closest to the highest dominant frequency site. Activation maps during transitions to fragmentation showed areas of slowed conduction and unidirectional block. Simulations predicted that SI abbreviation that heralds fractionated electrograms formation might result from a Doppler effect on wave fronts preceding an approaching rotor or by acceleration of a stationary or meandering, remotely located source. During induced AF, SI shortening after either drift or acceleration of a source results in intermittent fibrillatory conduction and formation of fractionated electrograms at the PLAW.
    Journal of the American College of Cardiology 03/2011; 57(9):1081-92. DOI:10.1016/j.jacc.2010.09.066 · 16.50 Impact Factor
  • Zohar Zafrir · Sharon Zlochiver ·

    Journal of Electrocardiology 03/2011; 44(2). DOI:10.1016/j.jelectrocard.2010.12.137 · 1.36 Impact Factor
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    Marina Arad · Avraham Adunsky · Sharon Zlochiver · Ofer Barnea · Shimon Abboud ·
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    ABSTRACT: Regular monitoring of pulmonary congestion in car-diogenic pulmonary edema (CPE) patients is neces-sary for its adequate management via pharmaceuti-cal treatment. It is well known that the development of CPE is accompanied with an increase in hema-tocrit, plasma protein concentration and colloid os-motic pressure due to the decrease in the plasma volume. In the present study the mean left and right lung resistivity values taken pre-and post treatment with diuretics using a hybrid bio-impedance electri-cal impedance tomography system were correlate to the measured changes in hematocrit level. A marginal significant correlation was found between the abso-lute mean lung resistivity and hematocrit levels (Pearson's correlation coefficient of R = 0.4, p-value = 0.057). When the change in the mean lung resistivity of a patient was plotted vs. the change in hematocrit readout, a significant linear correlation was found (R = 0.7, p-value = 0.02). These results support the validity of the resistivity measurements using bio-impedance system in monitoring changes of pulmonary edema in CPE patients.
    Journal of biomedical science and engineering 01/2011; 4:76-81. · 0.27 Impact Factor

Publication Stats

833 Citations
152.07 Total Impact Points


  • 2002-2015
    • Tel Aviv University
      • Department of Biomedical Engineering
      Tell Afif, Tel Aviv, Israel
  • 2008-2014
    • University of Michigan
      • • Department of Biomedical Engineering
      • • Center for Arrhythmia Research
      • • Department of Internal Medicine
      Ann Arbor, Michigan, United States
  • 2007
    • State University of New York Upstate Medical University
      • Department of Pharmacology
      Syracuse, New York, United States