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Item A Flexible Near-Field Biosensor for Multisite Arterial Blood Flow Detection(MDPI, 2022-11-01) Mohammed, Noor; Cluff, Kim; Sutton, Mark; Villafana-Ibarra, Bernardo; Loflin, Benjamin E.; Griffith, Jacob L.; Becker, Ryan; Bhandari, Subash; Alruwaili, Fayez; Desai, Jaydip; Orthopaedic Surgery, School of MedicineModern wearable devices show promising results in terms of detecting vital bodily signs from the wrist. However, there remains a considerable need for a device that can conform to the human body's variable geometry to accurately detect those vital signs and to understand health better. Flexible radio frequency (RF) resonators are well poised to address this need by providing conformable bio-interfaces suitable for different anatomical locations. In this work, we develop a compact wearable RF biosensor that detects multisite hemodynamic events due to pulsatile blood flow through noninvasive tissue-electromagnetic (EM) field interaction. The sensor consists of a skin patch spiral resonator and a wearable transceiver. During resonance, the resonator establishes a strong capacitive coupling with layered dielectric tissues due to impedance matching. Therefore, any variation in the dielectric properties within the near-field of the coupled system will result in field perturbation. This perturbation also results in RF carrier modulation, transduced via a demodulator in the transceiver unit. The main elements of the transceiver consist of a direct digital synthesizer for RF carrier generation and a demodulator unit comprised of a resistive bridge coupled with an envelope detector, a filter, and an amplifier. In this work, we build and study the sensor at the radial artery, thorax, carotid artery, and supraorbital locations of a healthy human subject, which hold clinical significance in evaluating cardiovascular health. The carrier frequency is tuned at the resonance of the spiral resonator, which is 34.5 ± 1.5 MHz. The resulting transient waveforms from the demodulator indicate the presence of hemodynamic events, i.e., systolic upstroke, systolic peak, dicrotic notch, and diastolic downstroke. The preliminary results also confirm the sensor's ability to detect multisite blood flow events noninvasively on a single wearable platform.Item Arterial stiffness is not acutely modified by consumption of a caffeinated soft drink sweetened with high‐fructose corn syrup in young healthy adults(Wiley, 2021) Freemas, Jessica A.; Greenshields, Joel T.; Baker, Tyler; Carter, Stephen J.; Johnson, Blair D.; Schlader, Zachary J.; Medicine, School of MedicineWe tested the hypothesis that ingestion of a caffeinated soft drink sweetened with high-fructose corn syrup acutely increases arterial stiffness. In a randomized counterbalanced, crossover design, fourteen healthy adults (25 ± 3 years, 6 women) reported to the laboratory for two experimental visits where 500 ml of tap water (H2 O) or 500 ml of Mountain Dew® (a caffeinated soft drink sweetened with high-fructose corn syrup (HFCS)) were consumed. Arterial stiffness (carotid-to-femoral pulse wave velocity (cfPWV)), peripheral and central blood pressures were measured pre-consumption, 30 min post-consumption, and 120 min post-consumption. Prior to each measurement period, beat-to-beat hemodynamic measures were collected. Changes in heart rate, blood pressure, and cardiac output from pre-consumption did not differ between trials at any timepoint (p ≥ 0.06). Moreover, changes in peripheral or central blood pressures from pre-consumption did not differ between trials (p ≥ 0.84). Likewise, changes in cfPWV from pre-consumption to 30 min post-consumption (HFCS: 0.2 ± 0.3 m/s, H2 O: 0.0 ± 0.3 m/s, p = 0.34) and 120 min post-consumption (HFCS: 0.3 ± 0.4 m/s, H2 O: 0.2 ± 0.3 m/s, p = 0.77) did not differ. Changes in aortic augmentation pressure, augmentation index, augmentation index corrected to a heart rate of 75 bpm, and reflection magnitude did not differ between conditions at 30 min post- (p ≥ 0.55) or 120 min post- (p ≥ 0.18) consumption. In healthy young adults, ingesting 500 ml of a commercially available caffeinated soft drink sweetened with high-fructose corn syrup does not acutely change indices of arterial stiffness and wave reflection.Item Chronic Embolic Pulmonary Hypertension Caused by Pulmonary Embolism and Vascular Endothelial Growth Factor Inhibition(Elsevier, 2017-04) Neto-Neves, Evandro M.; Brown, Mary B.; Zaretskaia, Maria V.; Rezania, Samin; Goodwill, Adam G.; McCarthy, Brian P.; Persohn, Scott A.; Territo, Paul R.; Kline, Jeffrey A.; Emergency Medicine, School of MedicineOur understanding of the pathophysiological basis of chronic thromboembolic pulmonary hypertension (CTEPH) will be accelerated by an animal model that replicates the phenotype of human CTEPH. Sprague-Dawley rats were administered a combination of a single dose each of plastic microspheres and vascular endothelial growth factor receptor antagonist in polystyrene microspheres (PE) + tyrosine kinase inhibitor SU5416 (SU) group. Shams received volume-matched saline; PE and SU groups received only microspheres or SU5416, respectively. PE + SU rats exhibited sustained pulmonary hypertension (62 ± 13 and 53 ± 14 mmHg at 3 and 6 weeks, respectively) with reduction of the ventriculoarterial coupling in vivo coincident with a large decrement in peak rate of oxygen consumption during aerobic exercise, respectively. PE + SU produced right ventricular hypokinesis, dilation, and hypertrophy observed on echocardiography, and 40% reduction in right ventricular contractile function in isolated perfused hearts. High-resolution computed tomographic pulmonary angiography and Ki-67 immunohistochemistry revealed abundant lung neovascularization and cellular proliferation in PE that was distinctly absent in the PE + SU group. We present a novel rodent model to reproduce much of the known phenotype of CTEPH, including the pivotal pathophysiological role of impaired vascular endothelial growth factor-dependent vascular remodeling. This model may reveal a better pathophysiological understanding of how PE transitions to CTEPH in human treatments.Item Comparison of isoflurane and α-chloralose in an anesthetized swine model of acute pulmonary embolism producing right ventricular dysfunction(American Association for Laboratory Animal Science, 2015-02) Beam, Daren M.; Neto-Neves, Evandro M.; Stubblefield, William B.; Alves, Nathan J.; Tune, Johnathan D.; Kline, Jeffrey A.; Department of Emergency Medicine, IU School of MedicinePulmonary embolism (PE) is a leading cause of sudden cardiac death, and a model is needed for testing potential treatments. In developing a model, we compared the hemodynamic effects of isoflurane and α-chloralose in an acute swine model of PE because the choice of anesthesia will likely affect the cardiovascular responses of an animal to PE. At baseline, swine that received α-chloralose (n = 6) had a lower heart rate and cardiac output and higher SpO2, end-tidal CO2, and mean arterial pressure than did those given isoflurane (n = 9). After PE induction, swine given α-chloralose compared with isoflurane exhibited a lower heart rate (63 ± 10 compared with 116 ± 15 bpm) and peripheral arterial pressure (52 ± 12 compared with 61 ± 12 mm Hg); higher SpO2 (98% ± 3% compared with 95% ± 1%), end-tidal CO2 (35 ± 4 compared with 32 ± 5), and systolic blood pressure (121 ± 8 compared with 104 ± 20 mm Hg); and equivalent right ventricular:left ventricular ratios (1.32 ± 0.50 compared with 1.23 ± 0.19) and troponin I mean values (0.09 ± 0.07 ng/mL compared with 0.09 ± 0.06 ng/mL). Isoflurane was associated with widely variable fibrinogen and activated partial thromboplastin time. Intraexperiment mortality was 0 of 6 animals for α-chloralose and 2 of 9 swine for isoflurane. All swine anesthetized with α-chloralose survived with sustained pulmonary hypertension, RV-dilation-associated cardiac injury without the confounding vasodilatory or coagulatory effects of isoflurane. These data demonstrate the physiologic advantages of α-chloralose over isoflurane for anesthesia in a swine model of severe submassive PE.Item Endothelial colony-forming cells ameliorate endothelial dysfunction via secreted factors following ischemia-reperfusion injury(American Physiological Society, 2017-05-01) Collett, Jason A.; Mehrotra, Purvi; Crone, Allison; Shelley, W. Christopher; Yoder, Mervin C.; Basile, David P.; Cellular and Integrative Physiology, School of MedicineDamage to endothelial cells contributes to acute kidney injury (AKI) by leading to impaired perfusion. Endothelial colony-forming cells (ECFC) are endothelial precursor cells with high proliferative capacity, pro-angiogenic activity, and in vivo vessel forming potential. We hypothesized that ECFC may ameliorate the degree of AKI and/or promote repair of the renal vasculature following ischemia-reperfusion (I/R). Rat pulmonary microvascular endothelial cells (PMVEC) with high proliferative potential were compared with pulmonary artery endothelial cells (PAEC) with low proliferative potential in rats subjected to renal I/R. PMVEC administration reduced renal injury and hastened recovery as indicated by serum creatinine and tubular injury scores, while PAEC did not. Vehicle-treated control animals showed consistent reductions in renal medullary blood flow (MBF) within 2 h of reperfusion, while PMVEC protected against loss in MBF as measured by laser Doppler. Interestingly, PMVEC mediated protection occurred in the absence of homing to the kidney. Conditioned medium (CM) from human cultured cord blood ECFC also conveyed beneficial effects against I/R injury and loss of MBF. Moreover, ECFC-CM significantly reduced the expression of ICAM-1 and decreased the number of differentiated lymphocytes typically recruited into the kidney following renal ischemia. Taken together, these data suggest that ECFC secrete factors that preserve renal function post ischemia, in part, by preserving microvascular function.Item Fetal and neonatal echocardiographic analysis of biomechanical alterations for the systemic right ventricle heart(Public Library of Science, 2024-09-19) Meyers, Brett A.; Bhattacharya, Sayantan; Brindise, Melissa C.; Loke, Yue-Hin; Payne, R. Mark; Vlachos, Pavlos P.; Mechanical and Energy Engineering, Purdue School of Engineering and TechnologyBackground: The perinatal transition's impact on systemic right ventricle (SRV) cardiac hemodynamics is not fully understood. Standard clinical image analysis tools fall short of capturing comprehensive diastolic and systolic measures of these hemodynamics. Objectives: Compare standard and novel hemodynamic echocardiogram (echo) parameters to quantify perinatal changes in SRV and healthy controls. Methods: We performed a retrospective study of 10 SRV patients with echocardiograms at 33-weeks gestation and at day of birth and 12 age-matched controls. We used in-house developed analysis algorithms to quantify ventricular biomechanics from four-chamber B-mode and color Doppler scans. Cardiac morphology, hemodynamics, tissue motion, deformation, and flow parameters were measured. Results: Tissue motion, deformation, and index measurements did not reliably capture biomechanical changes. Stroke volume and cardiac output were nearly twice as large for the SRV compared to the control RV and left ventricle (LV) due to RV enlargement. The enlarged RV exhibited disordered flow with higher energy loss (EL) compared to prenatal control LV and postnatal control RV and LV. Furthermore, the enlarged RV demonstrated elevated vortex strength (VS) and kinetic energy (KE) compared to both the control RV and LV, prenatally and postnatally. The SRV showed reduced relaxation with increased early filling velocity (E) compared prenatally to the LV and postnatally to the control RV and LV. Furthermore, increased recovery pressure (ΔP) was observed between the SRV and control RV and LV, prenatally and postnatally. Conclusions: The novel hydrodynamic parameters more reliably capture the SRV alterations than traditional parameters.Item Fluid Response Evaluation in Sepsis Hypotension and Shock: A Randomized Clinical Trial(Elsevier, 2020) Douglas, Ivor S.; Alapat, Philip M.; Corl, Keith A.; Exline, Matthew C.; Forni, Lui G.; Holder, Andre L.; Kaufman, David A.; Khan, Akram; Levy, Mitchell M.; Martin, Gregory S.; Sahatjian, Jennifer A.; Seeley, Eric; Self, Wesley H.; Weingarten, Jeremy A.; Williams, Mark; Hansell, Douglas M.; Medicine, School of MedicineBackground: Fluid and vasopressor management in septic shock remains controversial. In this randomized controlled trial, we evaluated the efficacy of dynamic measures (stroke volume change during passive leg raise) to guide resuscitation and improve patient outcome. Research question: Will resuscitation that is guided by dynamic assessments of fluid responsiveness in patients with septic shock improve patient outcomes? Study design and methods: We conducted a prospective, multicenter, randomized clinical trial at 13 hospitals in the United States and United Kingdom. Patients presented to EDs with sepsis that was associated hypotension and anticipated ICU admission. Intervention arm patients were assessed for fluid responsiveness before clinically driven fluid bolus or increase in vasopressors occurred. The protocol included reassessment and therapy as indicated by the passive leg raise result. The control arm received usual care. The primary clinical outcome was positive fluid balance at 72 hours or ICU discharge, whichever occurred first. Results: In modified intent-to-treat analysis that included 83 intervention and 41 usual care eligible patients, fluid balance at 72 hours or ICU discharge was significantly lower (-1.37 L favoring the intervention arm; 0.65 ± 2.85 L intervention arm vs 2.02 ± 3.44 L usual care arm; P = .021. Fewer patients required renal replacement therapy (5.1% vs 17.5%; P = .04) or mechanical ventilation (17.7% vs 34.1%; P = .04) in the intervention arm compared with usual care. In the all-randomized intent-to-treat population (102 intervention, 48 usual care), there were no significant differences in safety signals. Interpretation: Physiologically informed fluid and vasopressor resuscitation with the use of the passive leg raise-induced stroke volume change to guide management of septic shock is safe and demonstrated lower net fluid balance and reductions in the risk of renal and respiratory failure. Dynamic assessments to guide fluid administration may improve outcomes for patients with septic shock compared with usual care.Item Hemodynamic profiles by non-invasive monitoring of cardiac index and vascular tone in acute heart failure patients in the emergency department: External validation and clinical outcomes(PLOS, 2022-03-31) Harrison, Nicholas Eric; Meram, Sarah; Li, Xiangrui; White, Morgan B.; Henry, Sarah; Gupta, Sushane; Zhu, Dongxiao; Pang, Peter; Levy, Phillip; Emergency Medicine, School of MedicineBackground: Non-invasive finger-cuff monitors measuring cardiac index and vascular tone (SVRI) classify emergency department (ED) patients with acute heart failure (AHF) into three otherwise-indistinguishable subgroups. Our goals were to validate these "hemodynamic profiles" in an external cohort and assess their association with clinical outcomes. Methods: AHF patients (n = 257) from five EDs were prospectively enrolled in the validation cohort (VC). Cardiac index and SVRI were measured with a ClearSight finger-cuff monitor (formerly NexFin, Edwards Lifesciences) as in a previous study (derivation cohort, DC, n = 127). A control cohort (CC, n = 127) of ED patients with sepsis was drawn from the same study as the DC. K-means cluster analysis previously derived two-dimensional (cardiac index and SVRI) hemodynamic profiles in the DC and CC (k = 3 profiles each). The VC was subgrouped de novo into three analogous profiles by unsupervised K-means consensus clustering. PERMANOVA tested whether VC profiles 1-3 differed from profiles 1-3 in the DC and CC, by multivariate group composition of cardiac index and vascular tone. Profiles in the VC were compared by a primary outcome of 90-day mortality and a 30-day ranked composite secondary outcome (death, mechanical cardiac support, intubation, new/emergent dialysis, coronary intervention/surgery) as time-to-event (survival analysis) and binary events (odds ratio, OR). Descriptive statistics were used to compare profiles by two validated risk scores for the primary outcome, and one validated score for the secondary outcome. Results: The VC had median age 60 years (interquartile range {49-67}), and was 45% (n = 116) female. Multivariate profile composition by cardiac index and vascular tone differed significantly between VC profiles 1-3 and CC profiles 1-3 (p = 0.001, R2 = 0.159). A difference was not detected between profiles in the VC vs. the DC (p = 0.59, R2 = 0.016). VC profile 3 had worse 90-day survival than profiles 1 or 2 (HR = 4.8, 95%CI 1.4-17.1). The ranked secondary outcome was more likely in profile 1 (OR = 10.0, 1.2-81.2) and profile 3 (12.8, 1.7-97.9) compared to profile 2. Diabetes prevalence and blood urea nitrogen were lower in the high-risk profile 3 (p<0.05). No significant differences between profiles were observed for other clinical variables or the 3 clinical risk scores. Conclusions: Hemodynamic profiles in ED patients with AHF, by non-invasive finger-cuff monitoring of cardiac index and vascular tone, were replicated de novo in an external cohort. Profiles showed significantly different risks of clinically-important adverse patient outcomes.Item High resolution ultrasound imaging for repeated measure of wound tissue morphometry, biomechanics and hemodynamics under fetal, adult and diabetic conditions(PLOS, 2020-11-23) Gnyawali, Surya C.; Sinha, Mithun; El Masry, Mohamed S.; Wulff, Brian; Ghatak, Subhadip; Soto-Gonzalez, Fidel; Wilgus, Traci A.; Roy, Sashwati; Sen, Chandan K.; Surgery, School of MedicineNon-invasive, repeated interrogation of the same wound is necessary to understand the tissue repair continuum. In this work, we sought to test the significance of non-invasive high-frequency high-resolution ultrasound technology for such interrogation. High-frequency high-resolution ultrasound imaging was employed to investigate wound healing under fetal and adult conditions. Quantitative tissue cellularity and elastic strain was obtained for visualization of unresolved inflammation using Vevo strain software. Hemodynamic properties of the blood flow in the artery supplying the wound-site were studied using color Doppler flow imaging. Non-invasive monitoring of fetal and adult wound healing provided unprecedented biomechanical and functional insight. Fetal wounds showed highly accelerated closure with transient perturbation of wound tissue cellularity. Fetal hemodynamics was unique in that sharp fall in arterial pulse pressure (APP) which was rapidly restored within 48h post-wounding. In adults, APP transiently increased post-wounding before returning to the pre-wounding levels by d10 post-wounding. The pattern of change in the elasticity of wound-edge tissue of diabetics was strikingly different. Severe strain acquired during the early inflammatory phase persisted with a slower recovery of elasticity compared to that of the non-diabetic group. Wound bed of adult diabetic mice (db/db) showed persistent hypercellularity compared to littermate controls (db/+) indicative of prolonged inflammation. Normal skin strain of db/+ and db/db were asynchronous. In db/db, severe strain acquired during the early inflammatory phase persisted with a slower recovery of elasticity compared to that of non-diabetics. This study showcases a versatile clinically relevant imaging platform suitable for real-time analyses of functional wound healing.Item Human CSF movement influenced by vascular low frequency oscillations and respiration(Frontiers Media, 2022-08-19) Nair, Vidhya Vijayakrishnan; Kish, Brianna R.; Inglis, Ben; Yang, Ho-Ching (Shawn); Wright, Adam M.; Wu, Yu-Chien; Zhou, Xiaopeng; Schwichtenberg, Amy J.; Tong, Yunjie; Radiology and Imaging Sciences, School of MedicineCerebrospinal fluid (CSF) movement through the pathways within the central nervous system is of high significance for maintaining normal brain health and function. Low frequency hemodynamics and respiration have been shown to drive CSF in humans independently. Here, we hypothesize that CSF movement may be driven simultaneously (and in synchrony) by both mechanisms and study their independent and coupled effects on CSF movement using novel neck fMRI scans. Caudad CSF movement at the fourth ventricle and hemodynamics of the major neck blood vessels (internal carotid arteries and internal jugular veins) was measured from 11 young, healthy volunteers using novel neck fMRI scans with simultaneous measurement of respiration. Two distinct models of CSF movement (1. Low-frequency hemodynamics and 2. Respiration) and possible coupling between them were investigated. We show that the dynamics of brain fluids can be assessed from the neck by studying the interrelationships between major neck blood vessels and the CSF movement in the fourth ventricle. We also demonstrate that there exists a cross-frequency coupling between these two separable mechanisms. The human CSF system can respond to multiple coupled physiological forces at the same time. This information may help inform the pathological mechanisms behind CSF movement-related disorders.