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The value of volume substitution in patients with septic and haemorrhagic shock with respect to the microcirculation.
Siegemund, M, Hollinger, A, Gebhard, EC, Scheuzger, JD, Bolliger, D
Swiss medical weekly. 2019;:w20007
Abstract
After decades of ordinary scientific interest, fluid resuscitation of patients with septic and haemorrhagic shock took centre stage in intensive care research at the turn of the millennium. By that time, resuscitation fluids were the mainstay of haemodynamic stabilisation, avoidance of vasopressors and treatment of hypovolaemia in patients in shock, but were accompanied by adverse events such as excessive tissue oedema. With the spread of early goal-directed therapy research intensified and it was realised that type, volume and timing of resuscitation fluids might affect the course and outcome of critically ill patients. At the same time, the importance of microvascular blood flow as target of resuscitation was accepted. Today, once-forbidden albumin is the recommended colloid in severe sepsis and septic shock, and the European Medical Agency is considering the removal of starch solutions from the European market because of an increased incidence of acute kidney injury and mortality. This is unprecedented, especially because the administration of low-molecular-weight starches seems to have advantages in indications other than sepsis, and because practices in fluid resuscitation have changed fundamentally since the negative starch studies. Crystalloids are still the mainstay of hypovolaemia treatment in critically ill patients, but awareness is increasing that electrolyte composition, strong ion gap, tonicity and the bicarbonate-substituting anion may have an effect on adverse effects and outcome. In haemorrhagic shock, the utilisation of crystalloids and colloids is retreating, and plasma and erythrocyte concentrates are gaining more importance in the resuscitation of the patient with acute bleeding. However, there are still influential voices warning against the liberal usage of plasma concentrates and erythrocytes in trauma and haemorrhagic shock. This review describes the evidence relating to fluid resuscitation in sepsis, septic shock and massive haemorrhage. Beside the scientific evidence based on clinical trials, possible effects on the microcirculation and, therefore, organ function will be illustrated and areas of future research highlighted. The critical appraisal of the existing evidence should enable the reader to choose the optimal volume substitution for an individual patient.
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N-Acetylcysteine's Role in Sepsis and Potential Benefit in Patients With Microcirculatory Derangements.
Chertoff, J
Journal of intensive care medicine. 2018;(2):87-96
Abstract
OBJECTIVE To review the data surrounding the utility of N-acetylcysteine (NAC) in sepsis and identify areas needed for additional research. DATA SOURCES A review of articles describing the mechanisms of action and clinical use of NAC in sepsis. SUMMARY OF REVIEW Despite many advances in critical care medicine, still as many as 50% of patients with septic shock die. Treatments thus far have focused on resuscitation and restoration of macrocirculatory targets in the early phases of sepsis, with less focus on microcirculatory dysfunction. N-acetylcysteine, due to its anti-inflammatory and antioxidative properties, has been readily investigated in sepsis and has yielded largely incongruous and disappointing results. In addition to its known anti-inflammatory and antioxidative roles, one underappreciated property of NAC is its ability to vasodilate the microcirculation and improve locoregional blood flow. Some investigators have sought to capitalize on this mechanism with promising results, as evidenced by microcirculatory vasodilation, improvements in regional blood flow and oxygen delivery, and reductions in lactic acidosis, organ failure, and mortality. CONCLUSION In addition to its antioxidant and anti-inflammatory properties, N-acetylcysteine possesses vasodilatory properties that could benefit the microcirculation in sepsis. It is imperative that we investigate these properties to uncover NAC's full potential for benefit in sepsis.
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Microvascular Vasodilator Plasticity After Acute Exercise.
Robinson, AT, Fancher, IS, Mahmoud, AM, Phillips, SA
Exercise and sport sciences reviews. 2018;(1):48-55
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Abstract
Endothelium-dependent vasodilation is reduced after acute exercise or after high intraluminal pressure in isolated arterioles from sedentary adults but not in arterioles from regular exercisers. The preserved vasodilation in arterioles from exercisers is hydrogen peroxide (H2O2) dependent, whereas resting dilation is nitric oxide (NO) dependent. We hypothesize chronic exercise elicits adaptations allowing for maintained vasodilation when NO bioavailability is reduced.
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Looking into the eye of patients with chronic obstructive pulmonary disease: an opportunity for better microvascular profiling of these complex patients.
Vaes, AW, Spruit, MA, Theunis, J, Goswami, N, Vanfleteren, LE, Franssen, FME, Wouters, EFM, De Boever, P
Acta ophthalmologica. 2018;(6):539-549
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Abstract
Chronic obstructive pulmonary disease (COPD) is a complex disease with many patients suffering from cardiovascular comorbidity. However, cardiovascular diseases remain often undiagnosed in COPD. Assessment of the retinal microvasculature can provide value in cardiovascular profiling of these patients. Retinal microvascular assessment carried out via a noninvasive eye exam represents an easy to use tool when examining patients with COPD. The purpose of this review was to provide an overview of studies assessing structural and functional changes in the retinal microvasculature of patients with COPD. Findings demonstrated that structural and functional microvascular changes were more common and severe in COPD patients as compared to non-COPD controls, although few retinal investigations have been performed in patients with COPD. As cardiovascular comorbidities are highly prevalent in COPD, we advocate more research to investigate the value of an eye exam for microvascular phenotyping of COPD patients.
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Assessment of flow dynamics in retinal and choroidal microcirculation.
Wei, X, Balne, PK, Meissner, KE, Barathi, VA, Schmetterer, L, Agrawal, R
Survey of ophthalmology. 2018;(5):646-664
Abstract
Alterations in ocular blood flow have been implicated in mechanisms that lead to vision loss in patients with various ocular disorders such as diabetic retinopathy, glaucoma, and age-related macular degeneration. Assessment of retinal and choroidal blood flow is also a window to evaluate systemic diseases that affect microvasculature. Quantification and qualification of the blood flow in the retina and choroid help us understand pathophysiology, stratify disease risk, and monitor disease progression in these disorders. Multiple methods are used by researchers for assessment of blood flow, but a gold standard is lacking. We review commonly used methods, both invasive and noninvasive, for evaluation of blood flow, including intravital microscopy, laser Doppler velocimetry, laser Doppler flowmetry, laser interferometry, confocal scanning laser Doppler flowmetry, laser speckle flowgraphy, Doppler optical coherence tomography, blue-field entoptic simulation, retinal vessel caliber assessment, optical coherence tomography angiography, retinal function imaging, color Doppler imaging, and scanning laser ophthalmoscope angiogram. As technology evolves, better evaluation of blood flow in various ocular and systemic diseases will likely bring new perspectives into clinical practice and translate to better diagnosis and treatment.
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Coronary No-Reflow Phenomenon in Clinical Practice.
Scarpone, M, Cenko, E, Manfrini, O
Current pharmaceutical design. 2018;(25):2927-2933
Abstract
Timely delivered coronary revascularization with no residual anatomical stenosis does not always lead to prompt restoration of anterograde coronary flow and complete myocardial reperfusion. This condition is known as coronary no-reflow and is associated with major clinical adverse events and poor prognosis. The pathophysiology of no-reflow phenomenon is still poorly understood. Proposed mechanisms include distal microembolization of thrombus and plaque debris, ischemic injury, endothelial dysfunction and individual susceptibility to microvascular dysfunction/obstruction. Older age, diabetes, hypercholesterolemia, prolonged ischemic time, hemodynamic instability, high thrombus burden, complex angiographic lesions and multivessel disease are frequently reported to be associated with the no-reflow phenomenon. There is no general consensus on the correct prevention and management of no-reflow. Non-pharmacological measures such as distal embolic protection devices and manual thrombus aspiration did not result in improved flow or reduction of infarct size. Current preventive measures include reduction of time from symptoms onset to reperfusion therapy, and intracoronary administration of vasodilators such as adenosine, verapamil or nitroprusside.
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Microvascular Dilator Function in Athletes: A Systematic Review and Meta-analysis.
Montero, D, Walther, G, Diaz-Cañestro, C, Pyke, KE, Padilla, J
Medicine and science in sports and exercise. 2015;(7):1485-94
Abstract
PURPOSE Despite the growing research interest in vascular adaptations to exercise training over the last few decades, it remains unclear whether microvascular function in healthy subjects can be further improved by regular training. Herein, we sought to systematically review the literature and determine whether microvascular dilator function is greater in athletes compared to age-matched healthy untrained subjects. METHODS We conducted a systematic search of MEDLINE, Cochrane, EMBASE, and Web of Science since their inceptions until October 2013 for articles evaluating indices of primarily microvascular endothelium-dependent or endothelium-independent dilation (MVEDD and MVEID, respectively) in athletes. A meta-analysis was performed to determine the standardized mean difference (SMD) in MVEDD and MVEID between athletes and age-matched controls. Subgroup analyses were used to study potential moderating factors. RESULTS Thirty-six studies were selected after systematic review, comprising 521 athletes (506 endurance-trained and 15 endurance- and strength-trained) and 496 age-matched control subjects. After data pooling, athletes presented higher MVEDD (31 studies; SMD, 0.47; P < 0.00001) and MVEID (14 studies; SMD, 0.51; P < 0.00001) compared with the control subjects. Similar results were observed in young (younger than 40 yr) and master (older than 55 yr) athletes when analyzed separately. CONCLUSION Both young and master athletes present enhanced microvascular function compared with age-matched untrained but otherwise healthy subjects. These data provide evidence of a positive association between exercise training and microvascular function in the absence of known underlying cardiovascular disease.
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Endothelial nitric oxide synthase in the microcirculation.
Shu, X, Keller, TC, Begandt, D, Butcher, JT, Biwer, L, Keller, AS, Columbus, L, Isakson, BE
Cellular and molecular life sciences : CMLS. 2015;(23):4561-75
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Abstract
Endothelial nitric oxide synthase (eNOS, NOS3) is responsible for producing nitric oxide (NO)--a key molecule that can directly (or indirectly) act as a vasodilator and anti-inflammatory mediator. In this review, we examine the structural effects of regulation of the eNOS enzyme, including post-translational modifications and subcellular localization. After production, NO diffuses to surrounding cells with a variety of effects. We focus on the physiological role of NO and NO-derived molecules, including microvascular effects on vessel tone and immune response. Regulation of eNOS and NO action is complicated; we address endogenous and exogenous mechanisms of NO regulation with a discussion of pharmacological agents used in clinical and laboratory settings and a proposed role for eNOS in circulating red blood cells.
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Pharmacotherapy for coronary microvascular dysfunction.
Ong, P, Athanasiadis, A, Sechtem, U
European heart journal. Cardiovascular pharmacotherapy. 2015;(1):65-71
Abstract
Coronary microvascular dysfunction (CMD) has been increasingly recognized as an important cardiac condition that can cause signs and symptoms of myocardial ischaemia in various clinical settings. The dysfunction is located on the level of the coronary microcirculation with a vessel diameter of <500 µm and can be characterized by structural as well as functional vascular alterations. The underlying mechanisms are diverse, frequently overlapping and still incompletely understood. A common and often underdiagnosed clinical manifestation of CMD is in patients who have angina symptoms yet no obstructive epicardial coronary artery disease nor myocardial disease. There are still very few data regarding the effectiveness of pharmacological treatments for CMD. The current ESC guidelines on the management of stable coronary artery disease suggest using aspirin and statins as well as β-blockers and/or calcium-channel blockers for the treatment of CMD. This review gives an overview of the currently available pharmacological concepts for the treatment of coronary microvascular dysfunction in patients without epicardial coronary artery disease and without myocardial disease.
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Vascular function in health, hypertension, and diabetes: effect of physical activity on skeletal muscle microcirculation.
Nyberg, M, Gliemann, L, Hellsten, Y
Scandinavian journal of medicine & science in sports. 2015;:60-73
Abstract
Regulation of skeletal muscle blood flow is a complex process, which involves an integration of multiple mechanisms and a number of vasoactive compounds. Overall, muscle blood flow is regulated through a balance between vasoconstrictor and vasodilator signals. In a healthy cardiovascular system, the increase in muscle blood flow required for oxygen supply during exercise is achieved through a substantial increase in vasodilators locally formed in the active muscle tissue that overcome the vasoconstrictor signals. Most of the vasodilator signals are mediated via endothelial cells, which lead to the formation of vasodilators such as nitric oxide (NO) and prostacyclin. In essential hypertension and type II diabetes, the endothelial function and regulation of vascular tone is impaired with consequent increases in peripheral vascular resistance and inadequate regulation of oxygen supply to the skeletal muscle, which can affect muscle function. Central aspects in the vascular impairments are alterations in the formation of prostacyclin, the bioavailability of NO and an increased formation of vasoconstrictors and reactive oxygen species (ROS). Regular physical activity effectively improves vascular function by enhancing vasodilator formation and reducing the levels of vasoconstrictors and ROS.