Microvascular Function In Humans Research Articles

Arterial stiffness mediates the association between age and processing speed at low levels of microvascular function in humans across the adult lifespan.

The function of micro- and macrovessels within the peripheral vasculature has been identified as a target for the investigation of potential cardiovascular-based promoters of cognitive decline. However, little remains known regarding the interaction of the micro- and macrovasculature as it relates to cognitive function, especially in cognitively healthy individuals. Therefore, our purpose was to unravel peripheral factors that contribute to the association between age and processing speed. Ninety-nine individuals (51 men, 48 women) across the adult life span (19-81 yr) were used for analysis. Arterial stiffness was quantified as carotid-femoral pulse-wave velocity (cfPWV) and near-infrared spectroscopy assessed maximal tissue oxygenation (Sto2max) following a period of ischemia. Processing speed was evaluated with Trail Making Test (TMT) Parts A and B. Measures of central (cPP) and peripheral pulse pressure (pPP) were also collected. Moderated mediation analyses were conducted to determine contributions to the age and processing speed relation, and first-order partial correlations were used to assess associations while controlling for the linear effects of age. A P ≤ 0.05 was considered statistically significant. At low levels of Sto2max, there was a significant positive (b = 1.92; P = 0.005) effect of cfPWV on time to completion on TMT part A. In addition, cPP (P = 0.028) and pPP (P = 0.027) remained significantly related to part A when controlling for age. These results suggested that the peripheral microvasculature may be a valuable target for delaying cognitive decline, especially in currently cognitively healthy individuals. Furthermore, we reinforced current evidence that pulse pressure is a key endpoint for trials aimed at preventing or delaying the onset of cognitive decline.NEW & NOTEWORTHY Arterial stiffness partially mediates the association between age and processing speed in the presence of low microvascular function, as demarcated by maximum tissue oxygenation following ischemia. Central and peripheral pulse pressure remained associated with processing speed even after controlling for age. Our findings were derived from a sample that was determined to be cognitively healthy, which highlights the potential for these outcomes to be considered during trials aimed at the prevention of cognitive decline.

Ischemic Preconditioning Improves Microvascular Endothelial Function in Remote Vasculature by Enhanced Prostacyclin Production.

BACKGROUNDThe mechanisms underlying the effect of preconditioning on remote microvasculature remains undisclosed. The primary objective was to document the remote effect of ischemic preconditioning on microvascular function in humans. The secondary objective was to test if exercise also induces remote microvascular effects.METHODS AND RESULTSA total of 12 healthy young men and women participated in 2 experimental days in a random counterbalanced order. On one day the participants underwent 4×5 minutes of forearm ischemic preconditioning, and on the other day they completed 4×5 minutes of hand‐grip exercise. On both days, catheters were placed in the brachial and femoral artery and vein for infusion of acetylcholine, sodium nitroprusside, and epoprostenol. Vascular conductance was calculated from blood flow measurements with ultrasound Doppler and arterial and venous blood pressures. Ischemic preconditioning enhanced (P<0.05) the remote vasodilator response to intra‐arterial acetylcholine in the leg at 5 and 90 minutes after application. The enhanced response was associated with a 6‐fold increase (P<0.05) in femoral venous plasma prostacyclin levels and with a transient increase (P<0.05) in arterial plasma levels of brain‐derived neurotrophic factor and vascular endothelial growth factor. In contrast, hand‐grip exercise did not influence remote microvascular function.CONCLUSIONSThese findings demonstrate that ischemic preconditioning of the forearm improves remote microvascular endothelial function and suggest that one of the underlying mechanisms is a humoral‐mediated potentiation of prostacyclin formation.

Special Issue No. – 10, June, 2020 Journal &gt; Special Issue &gt; Special Issue No. – 10, June, 2020 &gt; Page 5 “Quantative Methods in Modern Science” organized by Academic Paper Ltd, Russia MORPHOLOGICAL AND ANATOMICAL FEATURES OF THE GENUS GAGEA SALISB., GROWING IN THE EAST KAZAKHSTAN REGION Authors: Zhamal T. Igissinova,Almash A. Kitapbayeva,Anargul S. Sharipkhanova,Alexander L. Vorobyev,Svetlana F. Kolosova,Zhanat

Special Issue No. – 10, June, 2020 Journal &gt; Special Issue &gt; Special Issue No. – 10, June, 2020 &gt; Page 5 “Quantative Methods in Modern Science” organized by Academic Paper Ltd, Russia MORPHOLOGICAL AND ANATOMICAL FEATURES OF THE GENUS GAGEA SALISB., GROWING IN THE EAST KAZAKHSTAN REGION Authors: Zhamal T. Igissinova,Almash A. Kitapbayeva,Anargul S. Sharipkhanova,Alexander L. Vorobyev,Svetlana F. Kolosova,Zhanat

Polyphenols and Microvascular Function in Humans: A Systematic Review.

Polyphenol-rich dietary sources are acknowledged to have potential cardiovascular health benefits, particularly in reducing cardiovascular disease risk. This systematic review sought to determine the effect of polyphenol-rich foods and beverages upon microvascular function, which is of considerable importance in its contribution towards the pathophysiology of microvascular-related complications but also in the future development of (macro-vessel) cardiovascular disease. Overall, consumption of polyphenol-rich foods and beverages demonstrate improved microvascular function, although this is dependent upon the polyphenol source, the dose of the product, the duration of consumption and the population group studied. Most subgroups reviewed suggest an overall beneficial effect on microvascular function, particularly grape-derived products, cocoa, tea, pine bark and Rutaceae aurantiae. Other groups remain equivocal and require further study due to the limited research performed to date. Polyphenols are abundant in the human diet and this systematic review demonstrates that they are an inexpensive, non-pharmacological approach for improving cardiovascular health in currently healthy individuals and in populations with microvascular dysfunction.

Assessing Microvascular Function in Humans from a Chronic Disease Perspective

Microvascular dysfunction (MVD) is considered a crucial pathway in the development and progression of cardiometabolic and renal disease and is associated with increased cardiovascular mortality. MVD often coexists with or even precedes macrovascular disease, possibly due to shared mechanisms of vascular damage, such as inflammatory processes and oxidative stress. One of the first events in MVD is endothelial dysfunction. With the use of different physiologic or pharmacologic stimuli, endothelium-dependent (micro)vascular reactivity can be studied. This reactivity depends on the balance between various mediators, including nitric oxide, endothelin, and prostanoids, among others. The measurement of microvascular (endothelial) function is important to understand the pathophysiologic mechanisms that contribute to MVD and the role of MVD in the development and progression of cardiometabolic/renal disease. Here, we review a selection of direct, noninvasive techniques for measuring human microcirculation, with a focus on methods, interpretation, and limitations from the perspective of chronic cardiometabolic and renal disease.

Non‐invasive Assessment of Skin Microvascular Function in Humans: An Insight Into Methods

For more than two decades, methods for the non-invasive exploration of cutaneous microcirculation have been mainly based on optical microscopy and laser Doppler techniques. In this review, we discuss the advantages and drawbacks of these techniques. Although optical microscopy-derived techniques, such as nailfold videocapillaroscopy, have found clinical applications, they mainly provide morphological information about the microvessels. Laser Doppler techniques coupled with reactivity tests are widespread in the field of microvascular function research, but many technical issues need to be taken into account when performing these tests. Post-occlusive reactive hyperemia and local thermal hyperemia have been shown to be reliable tests, although their underlying mechanisms are not yet fully understood. Acetylcholine and sodium nitroprusside iontophoresis, despite their wide use as specific tests of endothelium-dependent and -independent function, respectively, show limitations. The influence of the skin site, recording conditions, and the way of expressing data are also reviewed. Finally, we focus on promising tools such as laser speckle contrast imaging.

Regulation of the human coronary microcirculation

Atherosclerosis of conduit epicardial arteries is the principal culprit behind the complications of coronary heart disease, but a growing body of literature indicates that the coronary microcirculation also contributes substantially to the pathophysiology of cardiovascular disease. An understanding of mechanisms regulating microvascular function in humans is an essential foundation for understanding the role in disease, especially since these regulatory mechanisms vary substantially across species and vascular beds. In fact all subjects whose coronary tissue was used in the studies described have medical conditions that warrant cardiac surgery, thus relevance to the normal human must be inferential and is based on tissue from subjects without known arteriosclerotic disease. This review will focus on recent advances in the physiological and pathological mechanisms of coronary microcirculatory control, describing a robust plasticity in maintaining endothelial control over dilation, including mechanisms that are most relevant to the human heart. This article is part of a Special Issue entitled "Coronary Blood Flow".

The shear stress of keeping cool: why being in the ‘hot seat’ might actually be good for your blood vessels

An automobile comes off the assembly line stuck with its particular structural and functional traits which may remain inadequate or even dysfunctional in responding to driving challenges, unless public outcry and media coverage demands a recall. Thankfully, biological organisms are capable of constantly modifying themselves to better deal with both external and internal stresses that challenge their structural and functional capacity to maintain homeostasis. How are these stresses coupled to biological structural and functional adaptation? This remains a quintessential question in integrative physiology. Reductionist approaches have done much to identify specifics of signalling pathways that translate a given challenge into adaptations in the functional and structural building blocks of organism response capacity. However, the resurgence of innovative, integrative human in vivo studies in recent years demonstrates the critical contribution this type of research can play in advancing new perspectives on the underpinnings of physiological adaptation. The recent Journal of Physiology study by Green et al. (2010) is a case in point. These investigators set out to test the hypothesis that it is shear stress which couples repeated bouts of local heating (challenge to temperature homeostasis) to improvements in microvascular structure and function (biological response adaptation). The notion that mechanical stresses of blood flow can be a stimulus for vascular adaptation is nothing new and a wealth of findings from reductionist studies demonstrate this (for review see Hudlicka & Brown, 2009). However, no human study designs have been able to demonstrate such a cause–effect in the microvasculature in vivo. Green et al. (2010) measured the forearm skin blood flow response to incremental local heating, which is largely nitric oxide dependent, both before and after 4 and 8 weeks of 30-min-3-times-per-week repeated bilateral forearm heating challenges via water immersion (heat ‘training’). The frequency and duration could be compared to a moderate exercise training intensity for aerobic fitness improvement in sedentary persons. A cuff around the elbow in one arm was inflated during heat training to minimize the increase in skin perfusion during the heating bouts, isolating the impact of skin microvascular hyperaemia and attendant shear stress elevation on microvascular adaptation. Heat training increased the skin blood flow response to incremental heating, but only in the arm which was allowed to experience normal elevations in microvascular perfusion. Some additional key observations should be noted. First, during the heat training challenges skin vasodilatation in the cuffed arm was not different from that in the non-cuffed arm. So, local heating was evoking the normal vasodilatory response even when perfusion was restricted. Yet, the coupling of local temperature change to improvements in microvascular dilatation response did not occur unless mechanical forces of blood flow increased. Second, while the cuff substantially attenuated the increase in skin blood flow with local heating, the increase was still ∼40% of that in the uncuffed arm (∼4-fold vs.∼7-fold), suggesting a threshold shear stress for adaptation. However, it should be acknowledged that shear increase would not be proportional to flow increase because non-shear-mediated dilatation of resistance vessels would attenuate the actual shear experienced. Therefore, it remains to be confirmed what the actual threshold shear for adaptation would be. So why does this study warrant our close attention? First, it has identified increased shear as a stimulus for improving microvascular function in humans, and thereby focuses attention on finding ways to target increased blood flow to vascular regions as part of vascular disease prevention and treatment. But this is not all! This experimental model will allow examination of microvascular adaptations via skin biopsy and microdialysis. An innovative review by Martinez-Lemus and Meininger (Martinez-Lemus et al. 2009) summarizes evidence for repositioning and alignment of vascular smooth muscle cells and cytoskeleton protein rearrangement that rapidly (within a few days) redesigns the mechanical and structural characteristics of the vessel wall to optimize vasoregulatory responsiveness to a new ‘normal’. The approach developed by Green et al. (2010) will allow us to answer the question ‘What is the impact of the type of heat training bouts on structural and functional adaptation and their respective timelines?’ and significantly advance the use of shear stress as a therapeutic approach for vascular health. Second, the lack of vascular adaptation to local heating alone is particularly intriguing. Local heating represents an externally imposed challenge to regulation of temperature. Increases in microvascular perfusion represent a biological response aimed at limiting hyperthermia. Yet, it is coincident shear stress and not heating per se that appears essential for improving microvascular responsiveness to an external heating challenge. So, what aspect(s) of a given challenge to homeostasis actually represent the stimulus for adaptation? This is a question that is sorely lacking answers across a wide range of physiological systems. Perhaps, when investigating this question, the answers will not be found in obvious places.

A simple thermodilution technique to assess coronary endothelium-dependent microvascular function in humans: validation and comparison with coronary flow reserve

To validate a novel method for assessment of coronary endothelium-dependent microvascular function and compare this index with the adenosine-derived coronary flow reserve (CFR). We validated use of intra-coronary pressure wire-derived thermodilution to assess changes in coronary flow compared to Doppler flow-wire/quantitative coronary angiography- (QCA) derived data in response to the endothelial agonist substance-P (endothelium-dependent response). There was a close correlation between Doppler/QCA- and thermodilution-derived assessment of endothelium-dependent microvascular function (r = 0.76; P < 0.001). Next, pressure wire-based thermodilution was employed to sequentially compare CFR (hyperaemia achieved with adenosine-140 microg/kg/mL) with changes in coronary flow in response to substance-P (20 pmol/min intra-coronary infusion; 2 min) in 65 unobstructed coronary arteries. There was no correlation between CFR and coronary endothelium-dependent microvascular response (r = 0.08; P = 0.50). Both indices were in turn compared with clinical markers of endothelial dysfunction, namely Framingham risk score (FRS-a marker for cardiovascular risk factor clustering, hence an indirect clinical measure of endothelial dysfunction) and presence/absence of diabetes. Patient's FRS correlated with coronary endothelium-dependent microvascular response (r = -0.48; P < 0.001), but not with CFR (r = 0.14; P = 0.25). Diabetic patients had greater endothelial dysfunction than non-diabetics (P < 0.001) whereas CFR was not influenced by diabetes (P = 0.10). A simple pressure wire-based thermodilution technique can be used to assess coronary endothelium-dependent microvascular function. Adenosine-derived CFR does not adequately interrogate the endothelium-dependent component of coronary microvascular function.

Cigarette smoking is associated with an acute impairment of microvascular function in humans

An effect on microvascular function has been proposed as a possible mechanism explaining the association of acute smoking with increased blood pressure and decreased insulin sensitivity. However, the effects of smoking on microvascular function have not been studied. We have investigated the acute effects of smoking on microvascular function in 12 healthy smokers. Before and after smoking a cigarette, we measured heart rate, blood pressure and capillary recruitment during peak reactive hyperaemia. We also measured endothelium-dependent and endothelium-independent vasodilatation of the skin microcirculation with iontophoresis of acetylcholine and sodium nitroprusside respectively combined with laser Doppler fluxmetry. To exclude non-specific changes, a control study with sham smoking was performed. The smoking and sham smoking studies were conducted in a randomized order. Compared with sham smoking, acute smoking caused increases in heart rate (smoking, 9.3±4.1beats/min; sham, -1.3±3.0beats/min; P&lt;0.001) and systolic blood pressure (smoking, 6.3±8.8mmHg; sham, 0.8±4.4mmHg; P&lt;0.05); decreases in absolute (smoking, -4.9±6.9 per mm2; sham, 0.8±2.1 per mm2; P = 0.01) and relative (smoking, -13.8±21.4%; sham, 1.9±6.9%; P = 0.02) capillary recruitment during peak reactive hyperaemia; and decreases in absolute [smoking, -62.4±47.7 perfusion units (PU); sham, -30.8±32.6PU; P = 0.04] and relative (smoking, -147±163%; sham, 32±225%; P = 0.07) vasodilatation caused by acetylcholine. Absolute (smoking, -31.6±58.5PU; sham, -8.4±44.0PU; P = 0.3) and relative (smoking, -50.2±219.0%; sham, -17.1±139%; P = 0.7) vasodilatation caused by sodium nitroprusside were not affected. Thus acute smoking is associated with impaired capillary recruitment during peak reactive hyperaemia and impaired microvascular endothelium-dependent vasodilatation. These findings may explain the increased blood pressure and decreased insulin sensitivity that have been observed after acute smoking.