Pulsatile System Research Articles

Formulation, In-vitro and In-vivo Evaluation of Chronology-based Mucoadhesive Drug Delivery System of an Antihypertensive Drug

Current research aimed to prepare and estimate chronology-based mucoadhesive PDDS of antihypertensive drug losartan potassium through formulation of fast-dissolving core tablet and incorporation of core tablet to polymer coating to formulate bioadhesive PDDS through direct compression system. The coating was done by using polymers ethyl cellulose and carbopol 934. Pre-compression and post-compression parameters, drug release, lag time and mucoadhesive examination was assessed for the formulation. The expected lag time for hypertension is 8 hours; hence, this lag time was achieved by using a bioadhesive pulsatile system. The optimized formulation showed 8 hours lag time with appropriate mucoadhesion for an equivalent period. Moreover, in-vitro as well as in-vivo mucoadhesion investigations reflected the positive outcomes. Consequently, the BPDDS was the finest preventative substitute for drugs with the highest absorption in the stomach and for drugs used to treat diseases related to circadian rhythm

The Double Sequential Actions of the Angiotensin II Receptor Blockers and Mineralocorticoid Receptor Antagonists Therapy on the Renin Angiotensin Aldosterone System Produce a Better Reduction of Both Blood Pressure and Central Haemodynamic Parameters and Can Prevent the Appearance of the Atrial Fibrillation

Hypertension is a complex, multifactorial disease that has a significant positive association with adverse cardiovascular outcomes, such as myocardial infarction, stroke, kidney disease, and death. Research studies on hypertension have, so far, generally focused on vascular resistance and small arteries. The development of hypertension is usually accompanied by arterial structural remodelling, such as large artery stiffness, and increased both central systolic blood pressure and pulse pressure. Also, is well-established that hypertension is an important risk factor for atrial fibrillation. The goal of antihypertensive therapy is to prevent cardiovascular complications. Therefore, treatment with combination of antihypertensive agents acting on multiple targets is necessary for successful in the majority of patients. New therapeutics models are necessary to reduce both arterial stiffness and volume cardiovascular to ameliorate the stress of the arterial-ventricular-atrial dynamic coupling and the abnormal pulsatile system. The objective of the study was to assess the levels reached on both the systolic and diastolic blood pressure, and the central haemodynamic parameters into each one of the three groups of patients during the angiotensin II receptor blockers therapy alone, associated with hydrochlorothiazide or mineralocorticoid receptor antagonists, and observing the presence of episodes of atrial fibrillation during 24-hour Holter monitoring. The results suggest that the latter association of sequential double blockade on the renin angiotensin aldosterone system achieves the best haemodynamic conditions to avoid or reduce the presence of brief phases of atrial fibrillation on hypertensive patients with normal kidney function.

PULSATILE DRUG DELIVERY: A STRATEGY FOR TREATING CHRONOTHERAPEUTIC AILMENTS

Modern drug delivery systems have been promoted to a unique notion of chronopharmacology, i.e., the ability to provide the medicament to a patient in a staggered profile, as the discipline of chronobiology has advanced. The main disadvantage of developing such a delivery system that fits the circadian cycle is the lack of accurate technology (Pulsatile drug delivery system, PDDS). Pulsatile devices are gaining popularity because they deliver the medicine to the correct region of action at the correct time, allowing for spatial and temporal dosing and compliance among patients. These technologies are meant to work with the body's natural circadian cycle. The circadian rhythm affects various biological systems in humans, including metabolism, physiology, behaviour, sleep patterns, hormone synthesis, and so on. This article addresses several methods, such as osmotic systems, capsular systems, single and multiple-unit programable devices that rely on soluble or erodible polymer coatings, and the usage of rupturable membranes. The present review covered the rationale for the creation of pulsatile drug delivery systems, benefits, limitations the types of diseases that require pulsatile release, categorization, and assessments of pulsatile system of drug delivery.

DUAL RELEASE CHRONOTHERAPEUTIC SYSTEM OF POORLY WATER SOLUBLE ANTIHYPERTENSIVE DRUG CARVEDILOL: DESIGN, DEVELOPMENT AND IN VITRO CHARACTERIZATION

The current research investigation’s goal was to design a core-in-cup type pulsatile system of an antihypertensive drug (carvedilol phosphate) to reduce the evening and early-morning symptoms of hypertension. An inclusion complex of this drug was prepared with hydroxyl propyl beta cyclodextrin to increase carvedilol solubility. Using direct compression method, various batches of core tablets were formulated using Croscarmellose sodium as a superdisintegrant. Core tablets of the optimized formulation were press coated with backing layer and release-retarding plug layer. An in vitro release research was performed after evaluating the physicochemical characteristics of the core in cup design tablets. Based on the lag time of 8 h between the first and second pulse releases, a batch containing sodium alginate (100 mg) and hydroxypropyl methylcellulose K4M (100 mg) was chosen as the optimum batch. Thus, the dual-release core-in-cup pulsatile tablets may be utilized for managing the hypertension symptoms appearing in chronological order.

CIRCADIAN RHYTHMS REGULATED ASTHMA TREATMENT BY VIRTUE OF PULSATILE DRUG DELIVERY SYSTEM

Asthma, as we all know, is a disease that shows a high tendency of chronic inflammation in the airways, which associates with airflow obstruction. Lung function seems to be decreased in the case of people suffering from asthma. On reviewing many studies from the past, clear statements come out which also revealed that asthma is based on established circadian rhythm. Asthma is considered to be one of the diseases which affects majorly common in adult women than in men; according to numerous studies, 42 percent of persons with active asthma claimed that their asthma started before they were 16 y old. The pulsatile drug delivery system, an innovation in pharmaceutical technology, is generating huge attention these days and is alleged to be the most productive in the treatment of asthma as per many studies. Many pulsatile delivery system components, such as the osmotic system, capsular system, and single and multiple-unit system, are utilized to diagnose and treat diseases caused by biological rhythm disturbances. Various emerging diseases such as cardiovascular, peptic ulcer, asthma, peptic ulcer, diabetes mellitus, cancer, and hypercholesterolemia have been examined by fluctuation in biological rhythms and treated by a pulsatile drug delivery system. During this era, the pulsatile drug delivery system delivers the medicine at the right time duration, in the right place, and the right proportion and the effectiveness of pulsatile drug delivery on asthma have indeed been investigated in this article.

Overview on pulsatile drug delivery system

Traditionally, drugs are released in an immediate or extended fashion. However, in recent years, pulsatile drug release systems are gaining growing interest. Pulsatile drug delivery systems are developed to deliver drug according to circadian behavior of diseases. The product follow a sigmoidal drug release profile characterized by a time period of no release (lag time) followed by a rapid and complete drug release. Pulsatile systems are gaining a lot of interest as they deliver the drug at the right site of action at the right time and in the right amount, thus providing spatial and temporal delivery and increasing patient compliance. Pulsatile release systems can be classified in multiple-pulse and single-pulse systems. A popular class of single-pulse systems is that of rupturable dosage forms. Other systems consist of a drug-containing core, covered by a swelling layer and an outer insoluble, but semipermeable polymer coating or membrane. The potential benefits of chronotherapeutics have been investigated and established for number of diseases like asthma, arthritis, cancer, diabetes, epilepsy, hypertension, ulcer, hypercholesterolemia etc.

Membrane ratcheting directs progressive cell shape changes in a pulsatile system through PIP3 lipid cues

In epithelial sheets, processes that drive cells to change topological relationships can be harnessed by developmental mechanisms to effect changes in tissue architecture. Organisms ranging from humans to Drosophila lengthen their anterior-posterior axis during development. An essential driver of tissue elongation is oriented cell intercalation. In the Drosophila embryonic epithelium, individual cells are able to either consolidate cell-cell contacts or direct neighbor exchange movements through the asymmetric localization of cell adhesion and polarity proteins.

Recent advances in remotely controlled pulsatile drug delivery systems.

Pharmaceutical technology is drastically developing to enhance the efficacy and safety of drug therapy. Pulsatile delivery systems, in turn, gained attraction for their ability to deliver the right drug amount to the right body site, at the right time which is advantageous over conventional dosage forms. Their use is associated with increased patient compliance and allows on-demand drug delivery as well as customizable therapy. Recent technologies have been implemented to further develop pulsatile delivery systems for more precise determination of the dosage timing and duration as well as the location of drug release. Great interests are directed towards externally regulated pulsatile release systems which will be the focus of this review. The recent advances will be highlighted in remotely controlled delivery systems. This includes electro responsive, light-responsive, ultrasound responsive, and magnetically induced pulsatile systems as well as wirelessly controlled implantable systems. The current status of these technologies will be discussed as well as the recent investigations and future applications.

Abstract 12817: Experimental Analysis of Bicuspid Aortic Valve Hemodynamics: Effect of Mild Aortic Dilatation on Systolic Flow Characteristics

Introduction: Aortic diameter is a determinant index in deciding surgical intervention for aortic aneurysm with bicuspid aortic valve (BAV). However, the treatment of a mildly dilated ascending aorta remains controversial. We experimentally investigated influence of mild dilatation of the ascending aorta on BAV-related hemodynamics in 3 BAV morphologies. Methods: An MRI-compatible pulsatile flow circulation system incorporating an aortic valve model and aortic arch model was developed. Tricuspid aortic valve (TAV) and 3 asymmetric BAV models including RL-, RN-, and LN-BAV were constructed by suturing bovine pericardium as cusps to aorta. The aortic arch models with the ascending diameters of 30 mm (non-dilatation) and 40 mm (mildly dilatation) were compared. Streamlines and the circulations (m 2 /s) of peak systolic flow in non- and mildly dilated ascending aorta were assessed using 4D-flow MRI in each BAV morphology (Fig). Results: Streamlines showed eccentric aortic valvular outflow jets impinging on the outer curvature of the ascending aorta, proximal arch, and left-anterior supra-valvular aortic wall in RL-, RN-, and LN-BAV, respectively. Regardless of the non-dilated or mildly dilated aorta, the circulations of peak systolic flow were larger in the BAVs than the TAV model (non-dilated aorta, TAV 0.005; RL- 0.016; RN- 0.026; LN-BAV 0.011 m 2 /s, mildly dilated aorta, TAV 0.009; RL- 0.017; RN- 0.028; LN-BAV 0.025 m 2 /s). Right-handed rotation was observed in RL- and RN-BAV, whereas LN-BAV presented left-handed rotation. In LN-BAV, the circulation markedly increased in the mildly dilated ascending aorta. Conclusions: Asymmetric BAV morphology was associated with highly eccentric aortic valvular outflow jet that directly impinged on the aortic wall, and the large circulation of peak systolic flow. The dilatation of the ascending aorta, even mild dilatation, might induce further increase in the circulation of systolic flow, especially in LN-BAV morphology.

Evaluation of the efficiency of a new pulsatile flow‑generating circulatory-assist system in rotary blood pumps. Research on a mathematical model

Objective: to study the effect of a pulsatile flow-generation (PFG) device on the basic hemodynamic parameters of the circulatory system using a mathematical model.Results. Modelling and simulation showed that the use of PFG significantly (76%) increases aortic pulse pressure. The proposed mathematical model adequately describes the dynamics of the circulatory system and metabolism (oxygen debt) on physical activity in normal conditions and heart failure, and the use of non-pulsatile and pulsatile circulatory-assist systems. The mathematical model also shows that the use of PFG device blocks the development of rarefaction in the left ventricular cavity associated with a mismatch of blood inflow and outflow in diastolic phase when there is need to increase systemic blood flow by increasing the rotary pump speed.

Establishment of a resazurin-based aortic valve tissue viability assay for dynamic culture in a microphysiological system.

Tissue pathogenesis of aortic valve (AV) stenosis is research focus in cardiac surgery. Model limitations of conventional 2D culture of human or porcine valvular interstitial/endothelial cells (VIC/VECs) isolated from aortic valve tissues but also limited ability of (small) animal models to reflect human (patho)physiological situation in AV position raise the need to establish an in vitro setup using AV tissues. Resulting aim is to approximate (patho)physiological conditions in a dynamic pulsatile Microphysiological System (MPS) to culture human and porcine AV tissue with preservation of tissue viability but also defined ECM composition. A tissue incubation chamber (TIC) was designed to implement human or porcine tissues (3×5 mm2) in a dynamic pulsatile culture in conventional cell culture ambience in a MPS. Cell viability assays based on lactate dehydrogenase (LDH)-release or resazurin-conversion were tested for applicability in the system and applied for a culture period of 14 days with interval evaluation of tissue viability on every other day. Resazurin-assay setup was compared in static vs. dynamic culture using varying substance saturation settings (50-300μM), incubation times and tissue masses and was consequently adapted. Sterile dynamic culture of human and porcine AV tissue segments was established at a pulsatile flow rate range of 0.9-13.4μl/s. Implementation of tissues was realized by stitching the material in a thermoplastic polyurethane (TPU)-ring and insertion in the TIC-MPS-system. Culture volume of 2 ml caused LDH dilution not detectable in standard membrane integrity assay setup. Therefore, detection of resazurin-conversion of viable tissue was investigated. Optimal incubation time for viability conversion was determined at two hours at a saturated concentration of 300μM resazurin. Measurement in static conditions was shown to offer comparable results as dynamic condition but allowing optimal handling and TIC sterilization protocols for long term culture. Preliminary results revealed favourable porcine AV tissue viability over a 14 day period confirmed via resazurin-assay comparing statically cultured tissue counterparts. Human and porcine AV tissue can be dynamically cultured in a TIC-MPS with monitoring of tissue viability using an adapted resazurin-assay setup. Preliminary results reveal advantageous viability of porcine AV tissues after dynamic TIC-MPS culture compared to static control.

The Development of an ex vivo Flow System to Assess Acute Arterial Drug Retention of Cardiovascular Intravascular Devices.

Purpose: The goal of this study was to develop an ex vivo system capable of rapidly evaluating arterial drug levels in living, isolated porcine carotid arteries.Methods: A vascular bioreactor system was developed that housed a native porcine carotid artery under physiological flow conditions. The ex vivo bioreactor system was designed to quantify the acute drug transfer of catheter-based drug delivery devices into explanted carotid arteries. To evaluate our ex vivo system, a paclitaxel-coated balloon and a perfusion catheter device delivering liquid paclitaxel were utilized. At 1-h post-drug delivery, arteries were removed, and paclitaxel drug levels measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Parallel experiments were performed in a pig model to validate ex vivo measurements.Results: LC-MS/MS analysis demonstrated arterial paclitaxel levels of the drug-coated balloon-treated arteries to be 48.49 ± 24.09 ng/mg and the perfusion catheter-treated arteries to be 25.42 ± 9.74 ng/mg at 1 h in the ex vivo system. Similar results were measured in vivo, as arterial paclitaxel concentrations were measured at 59.23 ± 41.27 ng/mg for the drug-coated balloon-treated arteries and 23.43 ± 20.23 ng/mg for the perfusion catheter-treated arteries. Overall, no significant differences were observed between paclitaxel measurements of arteries treated ex vivo vs. in vivo.Conclusion: This system represents the first validated ex vivo pulsatile system to determine pharmacokinetics in a native blood vessel. This work provides proof-of-concept of a quick, inexpensive, preclinical tool to study acute drug tissue concentration kinetics of drug-releasing interventional vascular devices.

Antihypertensives’ Rock around the Clock

Although homeostasis is a commonly accepted concept, there is incontrovertible evidence that biological processes and functions are variable and that variability occurs in cycles. In order to explain and understand dysregulation, which has not been embraced by homeostatic principles, the allostatic model has emerged as the first serious challenge to homeostasis, going beyond its homeostatic roots. Circadian rhythm is the predominant variation in the body, and it is a pattern according to which many physiological and pathological events occur. As there is strong experimental and clinical evidence that blood pressure fluctuations undergo circadian rhythm, there is equally strong evidence that targeted time therapy for hypertension provides a better outcome of the disease. The research has gone even further throughout the development and approval process for the use of pulsatile drug release systems, which can be considered as an option for an even more convenient dosage regimen of the medicines needed.

Abstract 14618: Bicuspid Aortic Valve Morphology and Risk Factors of Abnormal Hemodynamics: An Experimental Investigation of Velocity, Vorticity and Eccentricity of Systolic Jet Stream, Using a Magnetic Resonance Imaging Compatible Pulsatile Flow Circulation System

Introduction: Abnormal hemodynamics with bicuspid aortic valve (BAV) is influenced by the BAV morphology. However, due to the morphological variety, the relationship between BAV morphology and hemodynamics has not been well clarified. We experimentally investigated influences of BAV morphology on hemodynamics. Methods: An MRI compatible pulsatile flow circulation system incorporating an aortic valve model and morphologically relevant aortic arch model was developed. Two types of BAV models with cusp angles of 240-120 (asymmetric BAV) and 180-180 (symmetric BAV) were prepared using bovine aorta and pericardium. The vorticity and eccentricity of jet in the aortic arch model in systolic phase were assessed using 4D-flow MRI. Streamlines at peak systole were compared among 5 BAV morphologies defined based on the symmetry and the position of leaflets (Fig). Results: Eccentric supra-valvular jets directed to the aortic wall faced to the smaller leaflet were present in the 3 asymmetric BAVs. In the ABAV-1, a markedly eccentric jet impinging on the aortic outer curvature was present. In the ABAV-2, a left-posterior directed jet shifting to the outer curvature of proximal arch was present. The asymmetric BAVs induced larger flow vorticity in the ascending aorta than the symmetric BAVs (ABAV-1 vs -2 vs -3 vs SBAV-1 vs -2, 0.018 vs 0.019 vs 0.014 vs 0.010 vs 0.011 m 2 /s). The ABAV-2 had a larger vortex in the middle arch than the ABAV-1 (ABAV-2 vs -1, 0.010 vs 0.005 m 2 /s). Conclusion: Our study indicated that the angles and orientations of the BAV impacted on the locations of jets impinging on the aortic wall and magnitudes of vorticities in systole. In the asymmetric BAVs, the direction of jet was influenced by the position of smaller leaflet. Our data suggests that the ABAV-1 morphology may be a risk factor inducing asymmetric aneurysm bulged toward the aortic outer curvature, while the ABAV-2 morphology may be a risk factor of an aortic aneurysm involving the transvers arch.

The Efficacy Between Conventional Lid Hygiene and Additional Thermal Pulsatile System in Meibomian Gland Dysfunction Patients Treated with Long-Term Anti-Glaucoma Medications in a Randomized Controlled Trial.

PurposeTo evaluate the efficacy of additional thermal pulsatile system compared to standard lid hygiene alone in meibomian gland dysfunction (MGD) patients who are using long-term anti-glaucoma medications.Patients and MethodsWell-controlled glaucoma patients who used anti-glaucoma medications for at least 1 year and had MGD were enrolled and randomized between a study group who received thermal pulsatile system (Lipiflow®) treatment and standard lid hygiene, and a control group who received standard lid hygiene alone. The primary outcome was meibomian gland expression score, and the secondary outcomes were the Ocular Surface Disease Index (OSDI) score, Schirmer test score, tear break-up time (TBUT), corneal staining score, lipid layer thickness (LLT), and meibography score. All the outcomes were re-evaluated at 1 week, then at 1, 3, and 6 months after treatment.ResultsOf 60 participants who underwent randomization, 48 completed the study. At the 6-month mark, this study could not demonstrate any significant difference between groups in both primary and secondary outcomes. However, there was significant improvement from baseline in both groups of the following outcomes: meibomian gland expression score, OSDI score, LLT, and meibography score. No serious adverse event was found in this study.ConclusionAn additional single thermal pulsatile system treatment with standard lid hygiene significantly improved meibomian gland assessment score and subjective symptoms at 6 months. Any difference between additional thermal pulsatile system treatment and lid hygiene alone was not found in this study. The results may suggest more chronic MGD and more damaged meibomian gland induced by long-term anti-glaucoma medications.

Colon targeting of celecoxib nanomixed micelles using pulsatile drug delivery systems for the prevention of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a debilitating condition characterized by chronic inflammation of the colon which can increase the risk of colon cancer. Celecoxib (CXB), a cyclooxygenase-2 inhibitor, showed potential for the prophylaxis against IBD. However, it suffers from poor aqueous solubility and cardiovascular toxicity on prolonged use. Here, CXB solubility was enhanced using nanomixed micelles (NMMs) and then colon targeted in a pulsatile system to minimize systemic side effects. Pluronic P123 NMMs with bile salts or hydrophilic Pluronics were prepared using the thin film hydration technique. NMMs were characterized for particle size, size distribution and zeta potential before and after freeze drying and for solubility enhancement. The freeze dried NMMs were then loaded in pulsatile systems with varying tablet plugs containing time-dependent polymers at different concentrations. The optimum NMM consisted of Pluronic P123 and sodium taurocholate (1:1) and CXB:surfactant mixture ratio of 1:30. The pulsatile capsules, containing a tablet plug made of 75% Carbopol®, achieved the target release profile with 88.35% of the dose released after an 8 hrs lag period. Finally, the optimum NMM/pulsatile system showed protective effect against experimentally-induced colitis compared to conventional capsules and pulsatile capsules filled with pure CXB.

An Innovative Ex Vivo Vascular Bioreactor as Comprehensive Tool to Study the Behavior of Native Blood Vessels Under Physiologically Relevant Conditions

Abstract Ex vivo systems represent important models to study vascular biology and to test medical devices, combining the advantages of in vitro and in vivo models such as controllability of parameters and the presence of biological response, respectively. The aim of this study was to develop a comprehensive ex vivo vascular bioreactor to long-term culture and study the behavior of native blood vessels under physiologically relevant conditions. The system was designed to allow for physiological mechanical loading in terms of pulsatile hemodynamics, shear stress, and longitudinal prestretch and ultrasound imaging for vessel diameter and morphology evaluation. In this first experience, porcine carotid arteries (n = 4) from slaughterhouse animals were cultured in the platform for 10 days at physiological temperature, CO2 and humidity using medium with blood-mimicking viscosity, components, and stability of composition. As expected, a significant increase in vessel diameter was observed during culture. Flow rate was adjusted according to diameter values to reproduce and maintain physiological shear stress, while pressure was kept physiological. Ultrasound imaging showed that the morphology and structure of cultured arteries were comparable to in vivo. Histological analyses showed preserved endothelium and extracellular matrix and neointimal tissue growth over 10 days of culture. In conclusion, we have developed a comprehensive pulsatile system in which a native blood vessel can be cultured under physiological conditions. The present model represents a significant step toward ex vivo testing of vascular therapies, devices, drug interaction, and as basis for further model developments.

Periodicity, time constants of drainage, and the mechanical determinants of peak cardiac output during exercise.

To analyze mechanical adaptations that must occur in the cardiovascular system to reach the high cardiac outputs known to occur at peak aerobic performance, we adapted a computational model of the circulation by adding a second parallel venous compartment as proposed by August Krogh in 1912. One venous compartment has a large compliance and slow time constant of emptying; it is representative of the splanchnic circulation. The other has a low compliance and fast time constant of emptying and is representative of muscle beds. Fractional distribution between the two compartments is an important determinant of cardiac output. Parameters in the model were based on values from animal and human studies normalized to a 70 kg male. The baseline cardiac output was set at 5 L/min, and we aimed for 25 L/min at peak exercise with a fractional flow to the peripheral-muscle region of 90%. Finally, we added the equivalent of a muscle pump. Adjustments in circuit and cardiac parameters alone increased cardiac output to only 15.6 L/min because volume accumulated in the muscle compartment and limited a higher cardiac output. Addition of muscle contractions decompressed the muscle region and allowed cardiac output to increase to 23.4 L/min. The pulsatility of blood flow imposes important constraints on the adaptations of cardiac and circulatory functions because it fixes the times for filling and emptying. Flow is further limited by the limits of cardiac filling on each beat. Muscle contractions play a key role by decompressing volume that would otherwise accumulate in the muscle vasculature and by decreasing the time for stroke return to the right ventricle.NEW & NOTEWORTHY We used a computational model of the circulation and previous human and animal data to model mechanical changes in the heart and circulation that are needed to reach the known high cardiac output at peak aerobic exercise. Key points are that time constants of drainage of circulatory compartments put limits on peak flow in a pulsatile system. Muscle contractions increase the rate of return to the heart and by doing so prevent accumulation of volume in the muscle compartment and greatly increase circulatory capacity.

Ex vivo assessment of bicuspidization repair in treating severe functional tricuspid regurgitation: a stereo-scopic PIV study

There has been a resurgence of interest in the treatment of severe functional tricuspid regurgitation (FTR) due to the awareness of its poor outcomes and potential percutaneous therapies. Kay bicuspidization has been adapted in percutaneous therapies but its clinical outcome remains uncertain. The present study evaluates the efficacy of Kay repair in a novel ex vivo pulsatile system. Porcine tricuspid valve (TV) (n = 3) was extracted and incorporated into a patient-specific silicon right ventricle (RV) emulating severe FTR, on which Kay repair was subsequently performed. TV area metrics and RV hemodynamic assessment by means of stereo-scopic particle image velocimetry were quantified in both FTR and post-repair conditions. Bicuspidization led to significant increase in cardiac output although the overall increment due to this approach alone was generally small, possibly due to existence of residual TR and the large reduction in TV opening area. Kinetic energy and viscous loss levels were increased post-repair, especially during diastolic filling. Main vortex structures generally maintained post-procedural. However, there was enhanced swirling motion in larger RV domain. Although this might reduce mural-thrombus risk, the relatively more complex vortex phenomenon likely resulted in elevated viscous loss observed and may potentially impact long-term adaptation. The RV hemodynamic alteration after tricuspid repair could be used to predict the success of these future transcatheter solutions.

Application of Magneto-Rheological Fluids for Investigating the Effect of Skin Properties on Arterial Tonometry Measurements

Accurate, non-invasive measurements of blood pressure and its continuous monitoring are extremely important for personal health care. Arterial tonometry, a method that is used to provide a detailed image of a patient’s cardiovascular health, shows promise for being a non-invasive alternative to current blood pressure measurement methods. However, its measurement accuracy is sensitive to patient variations such as the stiffness of the skin. Thus, this project intends to investigate the effect of skin properties (i.e., stiffness) on the accuracy of tonometric blood pressure measurements. To this end, a test platform, consisting of a pulsatile system and a tunable skin stiffness apparatus (or MR apparatus), is constructed. The cam-follower pulsatile system built based on in vivo testing of human pulses is used to generate realistic pulse waveforms. The MR apparatus is able to adjust its stiffness using Magneto-Rheological (MR) fluid whose apparent viscosity changes with applied magnetic fields. Placed at the surface of the MR apparatus, a cylinder with a frictionless plunger simulates a variable applanation force or “hold-down pressure” of tonometry by adjusting the added weights atop the cylinder. Using this test setup, a series of tests were performed by varying the input magnetic field and the weights, which effectively adjusts the skin stiffness and the hold-down pressure, respectively. The vertical displacement of the plunger caused by the internal pulse pressure was measured using a laser displacement sensor. The output displacement waveforms were analyzed with the focus on the peak amplitude difference of the waveforms, which is related to the augmentation index (a surrogate measure of arterial stiffness). The results show that there exists an “optimal” plunger weight or “hold-down pressure” that provides the most distinct output pulse waveforms. The results further show that the difference in the first two peak values decreases as the skin stiffness increases, indicating that the stiffer the skin property, the less the “hold-down pressure” effects on the accuracy of the tonometry measurements.