Trabecular Meshwork Motion Profile from Pulsatile Pressure Transients: A New Platform to Simulate Transitory Responses in Humans and Nonhuman Primates

Trabecular meshwork (TM) motion abnormality is the leading cause of glaucoma. With technique limitations, how TM moves is still an enigma. This study describes a new laboratory platform to investigate TM motion responses to ocular transients in ex vivo eyes. The anterior segments of human cadaver and primate eyes were mounted in a perfusion system fitting. Perfusion needles were placed to establish mean baseline pressure. A perfusion pump was connected to the posterior chamber and generated an immediate transient pressure elevation. A phase-sensitive optical coherent tomography system imaged and quantified the TM motion. The peak-to-peak TM displacements (ppTMD) were determined, a tissue relaxation curve derived, and a time constant obtained. This study showed that the ppTMD increased with a rise in the pulse amplitude. The ppTMD was highest for the lowest mean pressure of 16 mmHg and decreased with mean pressure increase. The pulse frequency did not significantly change ppTMD. With a fixed pulse amplitude, an increase in mean pressure significantly reduced the time constant of recoil from maximum distension. Our research platform permitted quantitation of TM motion responses to designed pulse transients. Our findings may improve the interpretation of new TM motion measurements in clinic, aiding in understanding mechanisms and management.

Modulation of Arterial Stiffness Gradient by Acute Administration of Nitroglycerin

Background: Physiologically, the aorta is less stiff than peripheral conductive arteries, creating an arterial stiffness gradient, protecting microcirculation from high pulsatile pressure. However, the pharmacological manipulation of arterial stiffness gradient has not been thoroughly investigated. We hypothesized that acute administration of nitroglycerin (NTG) may alter the arterial stiffness gradient through a more significant effect on the regional stiffness of medium-sized muscular arteries, as measured by pulse wave velocity (PWV). The aim of this study was to examine the differential impact of NTG on regional stiffness, and arterial stiffness gradient as measured by the aortic-brachial PWV ratio (AB-PWV ratio) and aortic-femoral PWV ratio (AF-PWV ratio).Methods: In 93 subjects (age: 61 years, men: 67%, chronic kidney disease [CKD]: 41%), aortic, brachial, and femoral stiffnesses were determined by cf-PWV, carotid-radial (cr-PWV), and femoral-dorsalis pedis artery (fp-PWV) PWVs, respectively. The measurements were repeated 5 min after the sublingual administration of NTG (0.4 mg). The AB-PWV and AF-PWV ratios were obtained by dividing cf-PWV by cr-PWV or fp-PWV, respectively. The central pulse wave profile was determined by radial artery tonometry through the generalized transfer function.Results: At baseline, cf-PWV, cr-PWV, and fp-PWV were 12.12 ± 3.36, 9.51 ± 1.81, and 9.71 ± 1.89 m/s, respectively. After the administration of NTG, there was a significant reduction in cr-PWV of 0.86 ± 1.27 m/s (p < 0.001) and fp-PWV of 1.12 ± 1.74 m/s (p < 0.001), without any significant changes in cf-PWV (p = 0.928), leading to a significant increase in the AB-PWV ratio (1.30 ± 0.39 vs. 1.42 ± 0.46; p = 0.001) and AF-PWV ratio (1.38 ± 0.47 vs. 1.56 ± 0.53; p = 0.001). There was a significant correlation between changes in the AF-PWV ratio and changes in the timing of wave reflection (r = 0.289; p = 0.042) and the amplitude of the heart rate-adjusted augmented pressure (r = − 0.467; p < 0.001).Conclusion: This study shows that acute administration of NTG reduces PWV of muscular arteries (brachial and femoral) without modifying aortic PWV. This results in an unfavorable profile of AB-PWV and AF-PWV ratios, which could lead to higher pulse pressure transmission into the microcirculation.

Is It Good to Have a Stiff Aorta with Aging? Causes and Consequences

Aortic stiffness increases with advancing age more than doubling during the human lifespan and is a robust predictor of cardiovascular disease (CVD) clinical events independent of traditional risk factors. The aorta increases in diameter and length to accommodate growing body size and cardiac output in youth, but in middle- and older age the aorta continues to remodel to a larger diameter thinning the pool of permanent elastin fibers increasing intramural wall stress resulting in the transfer of load bearing onto stiffer collagen fibers. While aortic stiffening in early middle-age may be a compensatory mechanism to normalize intramural wall stress and therefore theoretically 'good' early in the lifespan, the negative clinical consequences of accelerated aortic stiffening beyond middle-age far outweigh any earlier physiological benefit. Indeed, aortic stiffness and the loss of the "Windkessel effect" with advancing age results in elevated pulsatile pressure and flow in downstream microvasculature that is associated with subclinical damage to high flow, low resistance organs such as brain, kidney, retina and heart. The mechanisms of aortic stiffness include alterations in extracellular matrix proteins (collagen deposition, elastin fragmentation), increased vasodilator tone (oxidative stress and inflammation-related reduced vasodilators and augmented vasoconstrictors; enhanced sympathetic activity), arterial calcification, vascular smooth muscle cell stiffness and extracellular matrix glycosaminoglycans. Given the rapidly aging population of the U.S., aortic stiffening will likely contribute to substantial CVD burden over the next 2-3 decades unless new therapeutic targets and interventions are identified to prevent the potential avalanche of clinical sequelae related to age-related aortic stiffness.

The Mechanobiology of Endothelial-to-Mesenchymal Transition in Cardiovascular Disease

Endothelial cells (ECs) lining the cardiovascular system are subjected to a highly dynamic microenvironment resulting from pulsatile pressure and circulating blood flow. Endothelial cells are remarkably sensitive to these forces, which are transduced to activate signaling pathways to maintain endothelial homeostasis and respond to changes in the environment. Aberrations in these biomechanical stresses, however, can trigger changes in endothelial cell phenotype and function. One process involved in this cellular plasticity is endothelial-to-mesenchymal transition (EndMT). As a result of EndMT, ECs lose cell-cell adhesion, alter their cytoskeletal organization, and gain increased migratory and invasive capabilities. EndMT has long been known to occur during cardiovascular development, but there is now a growing body of evidence also implicating it in many cardiovascular diseases (CVD), often associated with alterations in the cellular mechanical environment. In this review, we highlight the emerging role of shear stress, cyclic strain, matrix stiffness, and composition associated with EndMT in CVD. We first provide an overview of EndMT and context for how ECs sense, transduce, and respond to certain mechanical stimuli. We then describe the biomechanical features of EndMT and the role of mechanically driven EndMT in CVD. Finally, we indicate areas of open investigation to further elucidate the complexity of EndMT in the cardiovascular system. Understanding the mechanistic underpinnings of the mechanobiology of EndMT in CVD can provide insight into new opportunities for identification of novel diagnostic markers and therapeutic interventions.

Study of Magnetohydrodynamic Pulsatile Blood Flow through an Inclined Porous Cylindrical Tube with Generalized Time-Nonlocal Shear Stress

The effects of pulsatile pressure gradient in the presence of a transverse magnetic field on unsteady blood flow through an inclined tapered cylindrical tube of porous medium are discussed in this article. The fractional calculus technique is used to provide a mathematical model of blood flow with fractional derivatives. The solution of the governing equations is found using integral transformations (Laplace and finite Hankel transforms). For the semianalytical solution, the inverse Laplace transform is found by means of Stehfest’s and Tzou’s algorithms. The numerical calculations were performed by using Mathcad software. The flow is significantly affected by Hartmann number, inclination angle, fractional parameter, permeability parameter, and pulsatile pressure gradient frequency, according to the findings. It is deduced that there exists a significant difference in the velocity of the flow at higher time when the magnitude of Reynolds number is small and large.

Degeneration of Aortic Valves in a Bioreactor System with Pulsatile Flow

Calcific aortic valve disease is the most common valvular heart disease in industrialized countries. Pulsatile pressure, sheer and bending stress promote initiation and progression of aortic valve degeneration. The aim of this work is to establish an ex vivo model to study the therein involved processes. Ovine aortic roots bearing aortic valve leaflets were cultivated in an elaborated bioreactor system with pulsatile flow, physiological temperature, and controlled pressure and pH values. Standard and pro-degenerative treatment were studied regarding the impact on morphology, calcification, and gene expression. In particular, differentiation, matrix remodeling, and degeneration were also compared to a static cultivation model. Bioreactor cultivation led to shrinking and thickening of the valve leaflets compared to native leaflets while gross morphology and the presence of valvular interstitial cells were preserved. Degenerative conditions induced considerable leaflet calcification. In comparison to static cultivation, collagen gene expression was stable under bioreactor cultivation, whereas expression of hypoxia-related markers was increased. Osteopontin gene expression was differentially altered compared to protein expression, indicating an enhanced protein turnover. The present ex vivo model is an adequate and effective system to analyze aortic valve degeneration under controlled physiological conditions without the need of additional growth factors.

Median nerve compression caused by superficial brachial artery: an unusual clinical case

An iatrogenic pseudoaneurysm of the radial artery and spontaneous venous malformation are associated with median nerve compression. However, the superficial brachial artery (SBA) has rarely been described as the cause of neurological deficits due to median nerve compression. A 61-year-old man was admitted to our clinic with a 1-year history of intermittent aching palsy in the left thumb that had progressed to the first three fingers. Clinical examination revealed mild sensory disturbance and hyperpathia in the first three fingers and weakness of the opponens pollicis. Ultrasound and magnetic resonance imaging confirmed that the SBA was compressing the median nerve by almost one-third. When anomalies of the SBA impinge on the median nerve, pulsatile pressure is applied to the nerve trunk. This may trigger ectopic stimulation of sensory fibers, leading to severe pain, sensory neuropathy, and motor disturbance. Considering the substantial difficulties and risks of a surgical operation as well as the patient’s wish to undergo conservative treatment, we performed muscle relaxation and acupuncture to relieve the pressure of the surrounding soft tissue and in turn decrease the impingement of the SBA on the median nerve. A satisfactory treatment effect was reached in this case.

An update on vessel preparation in lower limb arterial intervention

Background Plain balloon angioplasty has traditionally been used to treat lower limb arterial disease but can be limited by significant residual stenosis, vessel recoil, dissection, and by late restenosis. Appropriate vessel preparation may significantly improve short and long-term outcomes. We aim to give an overview of some of the devices currently available, or under investigation, for vessel preparation in the lower limb. Main text Vessel preparation devices include those that remove plaque (atherectomy devices) and those that modify plaque. The four groups of plaque removing atherectomy devices are defined by their plaque removal method: Directional, rotational orbital and excimer laser are categories of devices investigated for plaque modification. Intravascular lithotripsy devices generate sonic pulsatile pressure waves that pass into the vessel wall cracking calcified plaques whilst sparing soft tissue. This enables dilatation of calcified lesions at low pressure by conventional balloons and enables full stent expansion. Other balloon based vessel preparation devices were designed to modify plaque and produce more controlled, lower pressure luminal expansion without major dissections and potentially with less recoil than conventional angioplasty balloons. Scoring balloons have a helical nitinol element attached to the balloon that scores plaque facilitating uniform luminal enlargement. Further specialty balloons have been developed in recent years, including the Chocolate, Phoenix and Serranator balloons. Finally, the temporary Spur self-expanding retrievable nitinol stent has a series of radially aligned spurs that are driven into the vessel wall by post-dilatation, potentially improving drug delivery. Conclusion Lesion specific vessel preparation aims to improve both short and long term outcomes through improved penetration of anti-proliferative drug, maximising luminal gain, reducing the need for stent placement and minimising intimal injury. Some forms of vessel preparation appear to improve short term outcomes; long-term outcomes remain uncertain. An overview of some of the multiple devices available for vessel preparation is presented.