Evaluation of vascular aging on measures of cardiac function and mechanical efficiency: insights from in-silico modeling.

Introduction: This study evaluated the hypothesis that vascular aging (VA) reduces ventricular contractile function and mechanical efficiency (ME) using the left ventricular pressure-volume (PV) construct. Methods: A previously published in-silico computational model (CM) was modified to evaluate the hypothesis in two phases. In phase I, the CM included five settings of aortic compliance (CA) from normal to stiff, studied at a heart rate of 80 bpm, and phase II included the normal to stiff CA settings evaluated at 60, 100, and 140 bpm. The PV construct provided steady-state and transient data through a simulated vena caval occlusion (VCO). The steady-state data included left ventricular volumes (EDV and ESV), stroke work (SW), and VCO provided the PV area (PVA) data in addition to the three measures of contractile state (CS): end-systolic pressure-volume relationship (ESPVR), dP/dtmax-EDV and preload recruitable stroke work (PRSW). Finally, ME was calculated with the SW/PVA parameter. Results: In phase I, EDV and ESV increased, as did SW and PVA. The impact on the CS parameters demonstrated a small decrease in ESPVR, no change in dP/dtmax-EDV, and a large increase in PRSW. ME decreased from 71.5 to 60.8%, respectively. In phase II, at the normal and stiff CA settings, across the heart rates studied, EDV and ESV decreased, ESPVR and dP/dtmax-EDV increased and PRSW decreased. ME decreased from 76.4 to 62.6% at the normal CA and 65.8 to 53.2% at the stiff CA. Discussion: The CM generated new insights regarding how the VA process impacts the contractile state of the myocardium and ME.

Evaluation of ventricular-vascular coupling with critical care metrics: An in silico approach.

Mean arterial pressure and cardiac output provide insufficient guidance for the management of intraoperative hypotension (IOH). In silico models offer additional insights into acute changes in hemodynamic parameters that may be encountered during IOH. A computational model (CM) generated parameters quantifying ventricular-vascular coupling, and pressure-volume construct across levels of aortic compliance (CA ). We studied how a loss from normal-to-stiff CA impacts critical care metrics of hemodynamics during vascular occlusion. Pulse pressure (PP), end-systolic pressure (Pes ), arterial compliance (Art-ca), arterial elastance (Art-ea), and dynamic arterial elastance (Eadyn), along mechanical efficiency (ME) were measured at five levels of CA . A loss in CA impacted all variables. During steady-state conditions, PP, Pes , and stroke work increased significantly as CA decreased. Art-ca decreased and Art-ea increased similarly; Eadyn increased and ME decreased. During a decrease in preload across all CA levels, arterial dynamics measures remained linear. The CM demonstrated that a loss in CA impacts measures of arterial dynamics during steady-state and transient conditions and the model demonstrates that critical care metrics are sensitive to changes in CA . While Art-ca and Art-ea were sensitive to changes in preload, Eadyn did not change.

A Microstrip Transmission Line Biosensor to Measure the Interaction between Microliter Aqueous Solutions and 1.0-17.0 GHz Radio Frequencies.

Radio frequency (RF) biosensors are an expanding field of interest because of the ability to design noninvasive, label-free, low-production-cost sensing devices. Previous works identified the need for smaller experimental devices, requiring nanoliter to milliliter sampling volumes and increased capability of repeatable and sensitive measurement capability. The following work aims to verify a millimeter-sized, microstrip transmission line biosensor design with a microliter well operating on a broadband radio frequency range of 1.0-17.0 GHz. Three successive experiments were performed to provide evidence for (1) repeatability of measurements after loading/unloading the well, (2) sensitivity of measurement sets, and (3) methodology verification. Materials under test (MUTs) loaded into the well included deionized water, Tris-EDTA buffer, and lambda DNA. S-parameters were measured to determine interaction levels between the radio frequencies and MUTs during the broadband sweep. MUTs increasing in concentration were repeatably detected and demonstrated high measurement sensitivity, with the highest error value observed being 0.36%. Comparing Tris-EDTA buffer versus lambda DNA suspended in Tris-EDTA buffer suggests that introducing lambda DNA into the Tris-EDTA buffer repeatably alters S-parameters. The innovative aspect of this biosensor is that it can measure interactions of electromagnetic energy and MUTs in microliter quantities with high repeatability and sensitivity.

A Systematic Review of In Vitro and In Vivo Radio Frequency Exposure Methods.

Recently, interest in the effects of radio frequency (RF) on biological systems has increased and is partially due to the advancements and increased implementations of RF into technology. As research in this area has progressed, the reliability and reproducibility of the experiments has not crossed multidisciplinary boundaries. Therefore, as researchers, it is imperative to understand the various exposure systems available as well as the aspects, both electromagnetic and biological, needed to produce a sound exposure experiment. This systematic review examines common RF exposure methods for both in vitro and in vivo studies. For in vitro studies, possible biological limitations are emphasized. The validity of the examined methods, for both in vitro and in vivo, are analyzed by considering the advantages and disadvantages of each. This review offers guidance for researchers to assist in the development of an RF exposure experiment that crosses current multidisciplinary boundaries.

A Novel Idea to Improve Cardiac Output of Mechanical Circulatory Support Devices by Optimizing Kinetic Energy Transfer Available in Forward Moving Aortic Blood Flow.

Mechanical circulatory support devices (MCSDs) have gained widespread clinical acceptance as an effective heart failure (HF) therapy. The concept of harnessing the kinetic energy (KE) available in the forward aortic flow (AOF) is proposed as a novel control strategy to further increase the cardiac output (CO) provided by MCSDs. A complete mathematical development of the proposed theory and its application to an example MCSDs (two-segment extra-aortic cuff) are presented. To achieve improved device performance and physiologic benefit, the example MCSD timing is regulated to maximize the forward AOF KE and minimize retrograde flow. The proof-of-concept was tested to provide support with and without KE control in a computational HF model over a wide range of HF test conditions. The simulation predicted increased stroke volume (SV) by 20% (9 mL), CO by 23% (0.50 L/min), left ventricle ejection fraction (LVEF) by 23%, and diastolic coronary artery flow (CAF) by 55% (3 mL) in severe HF at a heart rate (HR) of 60 beats per minute (BPM) during counterpulsation (CP) support with KE control. The proposed KE control concept may improve performance of other MCSDs to further enhance their potential clinical benefits, which warrants further investigation. The next step is to investigate various assist technologies and determine where this concept is best applied. Then bench-test the combination of kinetic energy optimization and its associated technology choice and finally test the combination in animals.

Energy-triggered drug release from polymer nanoparticles for orthopedic applications.

Sequestra, present in many cancers and orthopedic infections, provide a safe harbor for the development of drug resistance. In the face of burgeoning drug resistance, the importance of nanoscale, microenvironment-triggered drug delivery cannot be overestimated. Such strategies may preserve pharmaceutical efficacy and significantly alter the etiology of many orthopedic diseases. Although temperature-, pH- and redox-responsive nanoparticle-based systems have been extensively studied, local drug delivery from polymeric nanoparticles can be triggered by a variety of energy forms. This review offers an overview of the state of the field as well as a perspective on the safety and efficacy of ultrasound, hyperthermia and radio frequency-triggered internal delivery systems in a variety of applications.

Design and In Vivo Test of a Batteryless and Fully Wireless Implantable Asynchronous Pacing System.

Goal: The aim of this study is to develop a novel fully wireless and batteryless technology for cardiac pacing. METHODS: This technology uses radio frequency (RF) energy to power the implanted electrode in the heart. An implantable electrode antenna was designed for 1.2 GHz; then, it was tested in vitro and, subsequently, integrated with the rectifier and pacing circuit to make a complete electrode. The prototype implanted electrode was tested in vivo in an ovine subject, implanting it on the epicardial surface of the left ventricle. The RF energy, however, was transmitted to the implanted electrode using a horn antenna positioned 25 cm above the thorax of the sheep. RESULTS: It was demonstrated that a small implanted electrode can capture and harvest enough safe recommended RF energy to achieve pacing. Electrocardiogram signals were recorded during the experiments, which demonstrated asynchronous pacing achieved at three different rates. CONCLUSION: These results show that the proposed method has a great potential to be used for stimulating the heart and provides pacing, without requiring any leads or batteries. It hence has the advantage of potentially lasting indefinitely and may never require replacement during the life of the patient. SIGNIFICANCE: The proposed method brings forward transformational possibilities in wireless cardiac pacing, and also in powering up the implantable devices.

A far-field radio-frequency experimental exposure system with unrestrained mice.

Many studies have been performed on exploring the effects of radio-frequency (RF) energy on biological function in vivo. In particular, gene expression results have been inconclusive due, in part, to a lack of a standardized experimental procedure. This research describes a new far field RF exposure system for unrestrained murine models that reduces experimental error. The experimental procedure includes the materials used, the creation of a patch antenna, the uncertainty analysis of the equipment, characterization of the test room, experimental equipment used and setup, power density and specific absorption rate experiment, and discussion. The result of this research is an experimental exposure system to be applied to future biological studies.

Control strategies for afterload reduction with an artificial vasculature device.

Ventricular assist devices (VADs) have been used successfully as a bridge to transplant in heart failure patients by unloading ventricular volume and restoring the circulation. An artificial vasculature device (AVD) is being developed that may better facilitate myocardial recovery than VAD by controlling the afterload experienced by the native heart and controlling the pulsatile energy entering into the arterial system from the device, potentially reconditioning the arterial system properties. The AVD is a valveless, 80 ml blood chamber with a servo-controlled pusher plate connected to the ascending aorta by a vascular graft. Control algorithms for the AVD were developed to maintain any user-defined systemic input impedance (IM) including resistance, elastance, and inertial components. Computer simulation and mock circulation models of the cardiovascular system were used to test the efficacy of two control strategies for the AVD: 1) average impedance position control (AIPC)-to maintain an average value of resistance during left ventricular (LV) systole and 2) instantaneous impedance force feedback (IIFF) and position control (IIPC)-to maintain a desired value or profile of resistance and compliance. Computer simulations and mock loop tests were performed to predict resulting cardiovascular pressures, volumes, flows, and the resistance and compliance experienced by the native LV during ejection for simulated normal, failing, and recovering LV. These results indicate that the LV volume and pressure decreased, and the LV stroke volume increased with decreasing IM, resulting in an increased ejection fraction. Although the AIPC algorithm is more stable and can tolerate higher levels of sensor errors and noise, the IIFF and IIPC control algorithms are better suited to maintain any instantaneous IM or an IM profile. The developed AVD impedance control algorithms may be implemented with current VADs to promote myocardial recovery and facilitate weaning.

Effect of pacing site on systolic mechanical restitution curves in the in vivo canine model.

INTRODUCTION: Pacing site is known to influence the contractile state of the ventricle. Non-physiologic pacing sites such as the right ventricular apex (RVA) or left ventricular freewall (LVFW) have been shown to decrease the contractile state of normal myocardium, due to abnormal electrical propagation. The impact of pacing at these sites may alter mechanical restitution (MR), a fundamental cardiac property involving the electro-mechanical regulation of contraction. This, in turn, may affect cardiac function. The present study was conducted to determine if pacing site alters the time constant of MR: tau. METHODS AND RESULTS: Anesthetized canines (n = 6) were acutely paced at four sites: right atrium (RA), RVA, right ventricular septum (RVS), and LVFW. MR data was captured by the S1-S2 pacing protocol and used to create MR curves, generating a restitution time constant, tau, at each site. No significant difference in tau was found between pacing sites. A linear regression analysis of MR curves revealed that there was no significant difference in slope between pacing sites. CONCLUSION: Although pacing site has been found to influence the contractile state of the ventricle, this is the first known study to demonstrate no change in tau in an in vivo preparation. This suggests that alteration of electro-mechanical coupling described by MR is not sufficiently robust to provide insight into pacing site and cardiac function in healthy hearts.

Novel means to monitor cardiac performance: the impact of the force-frequency and force-interval relationships on recirculation fraction and potentiation ratio.

Insights into intracellular calcium regulation and contractile state can be accomplished by changing pacing rate. Steady-state increases in heart rate (HR) (force-frequency relationship, FFR), and introduction of extrasystoles (ES) (force-interval relationship, FIR) have been used to investigate this relationship. This study focused on the recirculation fraction (RF) and potentiation ratio (PR), obtained from the recovery of the FFR and FIR. These parameters may provide insight on intracellular Ca(2+) regulation. Left ventricular (LV) pressures and HR were assessed in anesthetized canines (n = 7). Intrinsic data were collected prior to and following HR increases to 150, 180, and 200 bpm, as well as following delivery of an ES at 280 ms. The RF was calculated as the slope of dP/dt(max(n + 1)) vs. dP/dt(max(n)), where n = beat number. The PR was calculated by normalizing dP/dt(max) from the first beat following the ES (or the last paced beat) to the steady-state dP/dt(max). The RF due to an ES was not significantly different than that from a HR of 200 bpm. The PR from an ES was not significantly different than from a HR of 150 bpm. The impact of an ES delivered at an interval of 280 ms produces a PR similar to that from a HR of 150 bpm; yet, it recovers similarly to the termination of pacing at 200 bpm, eliciting a similar RF value. The method of measuring RF by an ES versus an increased HR may provide a safer and more feasible approach to collecting diagnostic information.