General dynamics of the physical-chemical systems in mammals

Biodynamic regulator chain models for physical chemical systems in mammal

CrossTalk proposal: Blood flow pulsatility in left ventricular assist device patients is essential to maintain normal brain physiology

For the first time in history, some humans live without a palpable pulse (Purohit et al. 2018). This remarkable physiology is the consequence of surgical implantation of a continuous‐flow left ventricular assist device (CF‐LVAD) in patients with end‐stage heart failure. Blood flow produced by CF‐LVADs has a low oscillatory profile in the aorta that results in significantly reduced pulsatility in all arterial compartments (Castagna et al. 2017; Fig. 1). Despite remarkable gains in quality of life and longevity, complications that affect not only morbidity, such as gastrointestinal bleeding, but also mortality, such as strokes, are still prevalent in CF‐LVAD patients. Low pulsatility has been proposed as a major culprit in contributing to these adverse events (Mancini & Colombo, 2015; Goldstein et al. 2018). In this CrossTalk proposal, we present the current arguments in favour of maintaining an appropriate amount of arterial pulsatility, in particular in the cerebral circulation, to lower risk in these patients

Laser doppler perfusion imaging of the normal and diseased vulva.

Vulval lichen sclerosus (LS) and high-grade intraepithelial neoplasia (VIN 3) are two common and distressing diseases. Significant morbidity is caused by symptoms of persistent pruritus and surgical treatment of skin areas suspicious of malignancy. The risk of developing cancer in a background of LS and VIN 3 is poorly defined. The methods currently available for clinical assessment of the vulva are limited. There is abundant research on the application of the LASER Doppler technique - laser Doppler Flowmetry (LDF) - showing changes in perfusion within the small blood vessels of the skin as a useful parameter for more accurate disease classification. There is also research on immunohistochemical microvessel density (MVD) studies showing increases in blood supply in tissues prone to develop cancer or as a prognostic marker of cancer outcome. The Laser Doppler perfusion imager (LDPI) provides a rapid, real time, non-invasive and non-contact method to measure skin blood flow in an area as opposed to a single point by the LDF, making the LDPI more suitable for application to the vulva. This thesis reports for the first time, the application of the LDPI to the vulva. Initially the LDPI was applied to the clinically normal vulva to study perfusion variance related to menstrual cycle, age and local skin temperature provocation. The application was then extended to vulval disease, LS and VIN 3, and validated against morphological differences in MVD. The LDPI and MVD studies suggest that in VIN 3 there is an actual increase in skin perfusion. In LS the situation is more complex and suggests that the LDPI measured perfusion at a greater depth than the MVD. Studies on base line perfusion variance of vulval LS to topical therapy show that there is no overall difference in baseline perfusion in spite of symptom improvement. Temperature provocation studies suggest differences in skin blood flow response in diseased compared to the normal vulva

Quantification of myocardial blood flow with cardiovascular magnetic resonance throughout the cardiac cycle

BACKGROUND: Myocardial blood flow (MBF) varies throughout the cardiac cycle in response to phasic changes in myocardial tension. The aim of this study was to determine if quantitative myocardial perfusion imaging with cardiovascular magnetic resonance (CMR) can accurately track physiological variations in MBF throughout the cardiac cycle. METHODS: 30 healthy volunteers underwent a single stress/rest perfusion CMR study with data acquisition at 5 different time points in the cardiac cycle (early-systole, mid-systole, end-systole, early-diastole and end-diastole). MBF was estimated on a per-subject basis by Fermi-constrained deconvolution. Interval variations in MBF between successive time points were expressed as percentage change. Maximal cyclic variation (MCV) was calculated as the percentage difference between maximum and minimum MBF values in a cardiac cycle. RESULTS: At stress, there was significant variation in MBF across the cardiac cycle with successive reductions in MBF from end-diastole to early-, mid- and end-systole, and an increase from early- to end-diastole (end-diastole: 4.50 ± 0.91 vs. early-systole: 4.03 ± 0.76 vs. mid-systole: 3.68 ± 0.67 vs. end-systole 3.31 ± 0.70 vs. early-diastole: 4.11 ± 0.83 ml/g/min; all p values <0.0001). In all cases, the maximum and minimum stress MBF values occurred at end-diastole and end-systole respectively (mean MCV = 26 ± 5%). There was a strong negative correlation between MCV and peak heart rate at stress (r = -0.88, p < 0.001). The largest interval variation in stress MBF occurred between end-systole and early-diastole (24 ± 9% increase). At rest, there was no significant cyclic variation in MBF (end-diastole: 1.24 ± 0.19 vs. early-systole: 1.28 ± 0.17 vs.mid-systole: 1.28 ± 0.17 vs. end-systole: 1.27 ± 0.19 vs. early-diastole: 1.29 ± 0.19 ml/g/min; p = 0.71). CONCLUSION: Quantitative perfusion CMR can be used to non-invasively assess cyclic variations in MBF throughout the cardiac cycle. In this study, estimates of stress MBF followed the expected physiological trend, peaking at end-diastole and falling steadily through to end-systole. This technique may be useful in future pathophysiological studies of coronary blood flow and microvascular function

Fluctuation in Shear Rate, with Unaltered Mean Shear Rate, Improves Brachial Artery Flow-Mediated Dilation in Healthy, Young Men.

AIM: Increase in mean shear stress represents an important and potent hemodynamic stimulus to improve conduit artery endothelial function in humans. No previous study has examined whether fluctuations in shear rate patterns, without altering mean shear stress, impacts conduit artery endothelial function. This study examined the hypothesis that 30-minutes exposure to fluctuations in shear rate patterns, in the presence of unaltered mean shear rate, improves brachial artery flow-mediated dilation. METHODS: Fifteen healthy males (27.3±5.0 years) completed the study. Bilateral brachial artery flow-mediated dilation was assessed before and after unilateral exposure to 30-minutes of intermittent negative pressure (10seconds -40mmHg, 7seconds 0mmHg) to induce fluctuation in shear rate, whilst the contra-lateral arm was exposed to a resting period. RESULTS: Negative pressure significantly increased shear rate, followed by a decrease in shear rate upon pressure release (both P<0.001). Across the 30-minute intervention, mean shear rate was not different compared to baseline (P=0.458). A linear mixed model revealed a significant effect of time was observed for flow-mediated dilation (P=0.029), with exploratory post-hoc analysis showing an increase in the intervention arm (∆FMD +2.0%, P=0.008), but not in the contra-lateral control arm (∆FMD +0.5%, P=0.664). However, there was no effect for arm (P=0.619) or interaction effect (P=0.096). CONCLUSION: In conclusion, we found that fluctuations in shear patterns, with unaltered mean shear, improves brachial artery flow-mediated dilation. These novel data suggest that fluctuations in shear pattern, even in the absence of altered mean shear, represents a stimulus to acute change in endothelial function in healthy individuals

Postural vasoconstriction in the human foot

Imperial Users onl

The Influence of Cholesterol-Related Membrane Fluidity on the Shear Stress Control of Neutrophil Adhesion and Its Implications in Hypercholesterolemia

Hypercholesterolemia is a significant risk factor in the development of cardiovascular disease and is associated with chronic leukocyte adhesion in the microvasculature. While the underlying mechanisms behind this have yet to be determined, it may be possible that hypercholesterolemia impairs the fluid shear stress (FSS) inactivation of neutrophils through the rigidifying effect of cholesterol on membrane fluidity. FSS restricts surface expression of CD18 integrins through cathepsin B (ctsB) proteolysis, which minimizes neutrophil adhesivity. If hypercholesterolemia blocks FSS mechanotransduction, then the inhibition of CD18 cleavage may link pathologic blood cholesterol elevations with dysregulated neutrophil adhesion. We hypothesized that elevated cholesterol contributes to dysregulated neutrophil adhesion by impairing ctsB FSS-induced CD18 cleavage through membrane fluidity changes. In the first part of this study, we demonstrated that FSS-induced CD18 cleavage is a robust response of neutrophils and involves selective cleavage of macrophage 1-antigen (Mac1) through ctsB proteolysis. The second part of this study confirmed that ctsB regulates neutrophil adhesion through its proteolytic actions on Mac1, an important integrin involved in adhesion and chemotaxis. Specifically, ctsB accelerated neutrophil motility through an effect on Mac1 integrins during pseudopod retraction. Furthermore, by using a flow-based assay to quantify the mechanoregulation of neutrophil adhesivity, we demonstrated that FSS-induced ctsB release promoted neutrophil detachment from platelet-coated substrates and unstimulated endothelium. For the third part of this study, we linked cholesterol-related membrane fluidity changes with the ability of FSS to restrict neutrophil adhesion through Mac1. We also determined that pathologic cholesterol elevations associated with hypercholesterolemia could block FSS-induced Mac1 cleavage and were linked to disrupted tissue blood flow. This was accomplished using low-density lipoprotein receptor deficient (LDLR-/-) mice fed a high-fat diet. Ultimately, the results provided in the present study confirmed that cholesterol-related changes in membrane fluidity blocked the ability of ctsB to regulate neutrophil adhesion through FSS-induced Mac1 cleavage. This implicates an impaired neutrophil FSS mechanotransduction response in the dysregulation of neutrophil adhesion associated with hypercholesterolemia. Since dysregulated adhesion may be one of the earliest upstream features of cardiovascular disease associated with hypercholesterolemia, the present study provides a foundation for identifying a new mechanobiological factor in the pathobiology of microcirculatory dysfunction

Effect of acute hyperglycemia on clotting time and relative plasma viscosity (RPV) during menstruation

Menstruating females seem to bleed more when they ingest sugar or sugar containing substances. This study was carried out to determine the effect of acute hyperglycemia on clotting time and relative plasma viscosity during menstruation. Forty menstruating females from the St. Philomena School of Midwifery, Benin, Nigeria volunteered for the study. following ethical approval from St. Philomena Catholic Hospital, blood samples were collected from the ante cubital vein; pre-ingestion, one hour and two hours post ingestion of glucose concentrations (39 g/200ml, 78 g/200ml). Fasting blood samples and post glucose ingestion blood samples were analyzed for Sugar, Clotting time and Relative Plasma Viscosity (RPV) using Standard laboratory methods. Results were analyzed with paired t-test and values of p&lt;0.05 were considered statistically significant. The result showed a statistically significant increase (p&lt;0.05) in clotting time and a decrease in relative plasma viscosity (p&lt;0.05) one hour after the intake of both glucose concentrations. Two hours after glucose intake, there was a decrease in clotting time towards the baseline and an increase in RPV towards the baseline. This study thus suggests that acute hyperglycemia increases clotting time and reduced RPV in menstruating girls. This may be the reason for the perceived sense of increased menstrual flow.© 2015 International Formulae Group. All rights reserved.Keywords: Clotting time, Relative Plasma Viscosity (RPV), menstruation, blood suga