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Biomedicine & Pharmacotherapy =... Aug 2023Coronary microvascular dysfunction (CMD) is a high-risk factor for a variety of cardiovascular events. Due to its complex aetiology and concealability, knowledge of the... (Review)
Review
Coronary microvascular dysfunction (CMD) is a high-risk factor for a variety of cardiovascular events. Due to its complex aetiology and concealability, knowledge of the pathophysiological mechanism of CMD is still limited at present, which greatly restricts its clinical diagnosis and treatment. Studies have shown that CMD is closely related to a variety of cardiovascular diseases, can aggravate the occurrence and development of cardiovascular diseases, and is closely related to a poor prognosis in patients with cardiovascular diseases. Improving coronary microvascular remodelling and increasing myocardial perfusion might be promising strategies for the treatment of cardiovascular diseases. In this paper, the pathogenesis and functional assessment of CMD are reviewed first, along with the relationship of CMD with cardiovascular diseases. Then, the latest strategies for the treatment of CMD and cardiovascular diseases are summarized. Finally, urgent scientific problems in CMD and cardiovascular diseases are highlighted and future research directions are proposed to provide prospective insights for the prevention and treatment of CMD and cardiovascular diseases in the future.
Topics: Humans; Cardiovascular Diseases; Coronary Circulation; Myocardial Ischemia; Microcirculation
PubMed: 37321056
DOI: 10.1016/j.biopha.2023.115011 -
Function (Oxford, England) 2023When exercising humans increase their oxygen uptake (V̇O) 20-fold above rest the numbers are staggering: Each minute the O transport system - lungs, cardiovascular,... (Review)
Review
When exercising humans increase their oxygen uptake (V̇O) 20-fold above rest the numbers are staggering: Each minute the O transport system - lungs, cardiovascular, active muscles - transports and utilizes 161 sextillion (10 ) O molecules. Leg extension exercise increases the quadriceps muscles' blood flow 100-times; transporting 17 sextillion O molecules per kilogram per minute from microcirculation (capillaries) to mitochondria powering their cellular energetics. Within these muscles, the capillary network constitutes a prodigious blood-tissue interface essential to exchange O and carbon dioxide requisite for muscle function. In disease, microcirculatory dysfunction underlies the pathophysiology of heart failure, diabetes, hypertension, pulmonary disease, sepsis, stroke and senile dementia. Effective therapeutic countermeasure design demands knowledge of microvascular/capillary function in health to recognize and combat pathological dysfunction. Dated concepts of skeletal muscle capillary (from the Latin meaning 'hair') function prevail despite rigorous data-supported contemporary models; hindering progress in the field for future and current students, researchers and clinicians. Following closely the 100th anniversary of August Krogh's 1920 Nobel Prize for capillary function this Evidence Review presents an anatomical and physiological development of this dynamic field: Constructing a scientifically defensible platform for our current understanding of microcirculatory physiological function in supporting blood-mitochondrial O transport. New developments include: 1. Putative roles of red blood cell aquaporin and rhesus channels in determining tissue O diffusion. 2. Recent discoveries regarding intramyocyte O transport. 3. Developing a comprehensive capillary functional model for muscle O delivery-to-V̇O matching. 4. Use of kinetics analysis to discriminate control mechanisms from collateral or pathological phenomena.
Topics: Humans; Oxygen; Microcirculation; Capillaries; Oxygen Consumption; Muscle, Skeletal; Mitochondria
PubMed: 37168497
DOI: 10.1093/function/zqad013 -
Journal of Cerebral Blood Flow and... Oct 2023Temporal lobe epilepsy (TLE) is increasingly associated with blood-brain barrier dysfunction and microvascular alterations, yet the pathophysiological link is missing....
Temporal lobe epilepsy (TLE) is increasingly associated with blood-brain barrier dysfunction and microvascular alterations, yet the pathophysiological link is missing. An important barrier function is exerted by the glycocalyx, a gel-like layer coating the endothelium. To explore such associations, we used intraoperative videomicroscopy to quantify glycocalyx and microcirculation properties of the neocortex and hippocampus of 15 patients undergoing resective brain surgery as treatment for drug-resistant TLE, and 15 non-epileptic controls. Fluorescent lectin staining of neocortex and hippocampal tissue was used for blood vessel surface area quantification. Neocortical perfused boundary region, the thickness of the glycocalyx' impaired layer, was higher in patients (2.64 ± 0.52 µm) compared to controls (1.31 ± 0.29 µm), 0.01, indicative of reduced glycocalyx integrity in patients. Moreover, erythrocyte flow velocity analysis revealed an impaired ability of TLE patients to (de-)recruit capillaries in response to changing metabolic demands ( = 0.75, 0.01), indicating failure of neurovascular coupling mechanisms. Blood vessel quantification comparison between intraoperative measurements and resected tissue showed strong correlation ( = 0.94, 0.01). This is the first report on assessment of glycocalyx and microcirculation properties in TLE patients, confirming the pivotal role of cerebrovascular changes. Further assessment of the cerebral microcirculation in relation to epileptogenesis might open avenues for new therapeutic targets for drug-resistant epilepsy.
Topics: Humans; Epilepsy, Temporal Lobe; Glycocalyx; Microcirculation; Blood-Brain Barrier; Capillaries
PubMed: 37231664
DOI: 10.1177/0271678X231179413 -
Minerva Anestesiologica May 2003Microcirculatory alterations have been widely described in experimental models of sepsis, however the microcirculation have long been neglected in septic patients as... (Review)
Review
Microcirculatory alterations have been widely described in experimental models of sepsis, however the microcirculation have long been neglected in septic patients as traditional techniques do not allow the visualisation of the microcirculation. The Orthogonal Polarization Spectral (OPS) imaging technique allows the direct visualisation of the microcirculation at the bedside. A selected review of the articles on the microcirculation in patients with sepsis using the OPS imaging technique, is made. Patients severe sepsis present a decrease in capillary density and a decrease in the proportion of the perfused capillaries. The severity of these alterations is more pronounced in non survivors than in survivors, and is related with the development of multiple organ failure. These alterations can be reversed by vasodilators, either topically applied or administered intravenously. Microvascular blood flow alterations are frequently observed in patients with sepsis and can have major pathophysiological implications.
Topics: Capillaries; Critical Illness; Diagnostic Imaging; Humans; Microcirculation; Point-of-Care Systems
PubMed: 12768172
DOI: No ID Found -
Critical Reviews in Biomedical... 2013The microvasculature is a dynamic cellular system necessary for tissue health and function. Therapeutic strategies that target the microvasculature are expanding and... (Review)
Review
The microvasculature is a dynamic cellular system necessary for tissue health and function. Therapeutic strategies that target the microvasculature are expanding and evolving, including those promoting angiogenesis and microvascular expansion. When considering how to manipulate angiogenesis, either as part of a tissue construction approach or a therapy to improve tissue blood flow, it is important to know the microenvironmental factors that regulate and direct neovessel sprouting and growth. Much is known concerning both diffusible and matrix-bound angiogenic factors, which stimulate and guide angiogenic activity. How the other aspects of the extravascular microenvironment, including tissue biomechanics and structure, influence new vessel formation is less well known. Recent research, however, is providing new insights into these mechanisms and demonstrating that the extent and character of angiogenesis (and the resulting new microcirculation) is significantly affected. These observations and the resulting implications with respect to tissue construction and microvascular therapy are addressed.
Topics: Animals; Cellular Microenvironment; Hemodynamics; Humans; Microcirculation; Microvessels; Models, Cardiovascular; Neovascularization, Physiologic
PubMed: 24580565
DOI: 10.1615/critrevbiomedeng.2013008077 -
The Journal of Physiological Sciences :... Sep 2013The microcirculation is a major topic in current physiology textbooks and is frequently explained with schematics including the precapillary sphincters and... (Review)
Review
The microcirculation is a major topic in current physiology textbooks and is frequently explained with schematics including the precapillary sphincters and metarterioles. We re-evaluated the validity and applicability of the concepts precapillary sphincters and metarterioles by reviewing the historical context in which they were developed in physiology textbooks. The studies by Zweifach up until the 1950s revealed the unique features of the mesenteric microcirculation, illustrated with impressive schematics of the microcirculation with metarterioles and precapillary sphincters. Fulton, Guyton and other authors introduced or mimicked these schematics in their physiology textbooks as representative of the microcirculation in general. However, morphological and physiological studies have revealed that the microcirculation in the other organs and tissues contains no metarterioles or precapillary sphincters. The metarterioles and precapillary sphincters were not universal components of the microcirculation in general, but unique features of the mesenteric microcirculation.
Topics: Anal Canal; Animals; Arterioles; Humans; Microcirculation; Splanchnic Circulation
PubMed: 23824465
DOI: 10.1007/s12576-013-0274-7 -
Circulation Research Jan 2016The microcirculation is responsible for orchestrating adjustments in vascular tone to match local tissue perfusion with oxygen demand. Beyond this metabolic dilation,... (Review)
Review
The microcirculation is responsible for orchestrating adjustments in vascular tone to match local tissue perfusion with oxygen demand. Beyond this metabolic dilation, the microvasculature plays a critical role in modulating vascular tone by endothelial release of an unusually diverse family of compounds including nitric oxide, other reactive oxygen species, and arachidonic acid metabolites. Animal models have provided excellent insight into mechanisms of vasoregulation in health and disease. However, there are unique aspects of the human microcirculation that serve as the focus of this review. The concept is put forth that vasculoparenchymal communication is multimodal, with vascular release of nitric oxide eliciting dilation and preserving normal parenchymal function by inhibiting inflammation and proliferation. Likewise, in disease or stress, endothelial release of reactive oxygen species mediates both dilation and parenchymal inflammation leading to cellular dysfunction, thrombosis, and fibrosis. Some pathways responsible for this stress-induced shift in mediator of vasodilation are proposed. This paradigm may help explain why microvascular dysfunction is such a powerful predictor of cardiovascular events and help identify new approaches to treatment and prevention.
Topics: Animals; Blood Circulation; Cardiovascular Diseases; Endothelium, Vascular; Humans; Microcirculation; Vasodilation
PubMed: 26837746
DOI: 10.1161/CIRCRESAHA.115.305364 -
Frontiers in Endocrinology 2021The pancreas is regarded as consisting of two separate organ systems, the endocrine and exocrine pancreas. While treatment of a disease with either an endocrine or... (Review)
Review
The pancreas is regarded as consisting of two separate organ systems, the endocrine and exocrine pancreas. While treatment of a disease with either an endocrine or exocrine pathogenesis may affect the function of the entire pancreas, the pancreatic diseases have been treated by clinicians in different medical disciplines, including endocrinologists and gastroenterologists. Islet microcirculation has long been considered to be regulated independently from that of the exocrine pancreas. A new model proposes that pancreatic islet blood flow is integrated with the surrounding exocrine capillary network. This recent model may provide revived or contrasting hypotheses to test, since the pancreatic microcirculation has critical implications for the regulation of islet hormones as well as acinar pancreas functions. In this mini-review, practical applications of and studies of islet microcirculation are described with a specific emphasis on large-scale data analysis to ensure sufficient sample size accounting for known islet heterogeneity. For small animal studies, intravital microscopy based on two-photon excitation microscopes is a powerful tool that enables capturing the flow direction and speed of individual fluorescent-labeled red blood cells. Complementarily, for structural analysis of blood vessels, the recent technical advancements of confocal microscopy and tissue clearing have enabled us to image the three-dimensional network structure in thick tissue slices.
Topics: Animals; Cytological Techniques; Hemodynamics; Humans; In Vitro Techniques; Islets of Langerhans; Microcirculation; Models, Biological
PubMed: 34040578
DOI: 10.3389/fendo.2021.602620 -
Revista Brasileira de Terapia Intensiva 2017Parameters related to macrocirculation, such as the mean arterial pressure, central venous pressure, cardiac output, mixed venous saturation and central oxygen... (Review)
Review
Parameters related to macrocirculation, such as the mean arterial pressure, central venous pressure, cardiac output, mixed venous saturation and central oxygen saturation, are commonly used in the hemodynamic assessment of critically ill patients. However, several studies have shown that there is a dissociation between these parameters and the state of microcirculation in this group of patients. Techniques that allow direct viewing of the microcirculation are not completely disseminated, nor are they incorporated into the clinical management of patients in shock. The numerous techniques developed for microcirculation assessment include clinical assessment (e.g., peripheral perfusion index and temperature gradient), laser Doppler flowmetry, tissue oxygen assessment electrodes, videomicroscopy (orthogonal polarization spectral imaging, sidestream dark field imaging or incident dark field illumination) and near infrared spectroscopy. In the near future, the monitoring and optimization of tissue perfusion by direct viewing and microcirculation assessment may become a goal to be achieved in the hemodynamic resuscitation of critically ill patients.
Topics: Critical Illness; Hemodynamics; Humans; Microcirculation; Monitoring, Physiologic; Point-of-Care Systems; Resuscitation
PubMed: 28977264
DOI: 10.5935/0103-507X.20170033 -
Journal of Applied Physiology... Mar 2022Extracorporeal membrane oxygenation (ECMO) is a procedure used to aid respiratory function in critical patients, involving extracorporeal circulation (ECC) of blood....
Extracorporeal membrane oxygenation (ECMO) is a procedure used to aid respiratory function in critical patients, involving extracorporeal circulation (ECC) of blood. There is a limited number of studies quantifying the hemodynamic effects of ECC procedures on the microcirculation. We sought to mimic veno-arterial-ECMO flow conditions by use of a scaled-down circuit primed with either lactate Ringer (LR) or 5% human serum albumin (HSA). The circuit was first tested using benchtop runs with blood, and subsequently used for in vivo experiments in Golden Syrian hamsters instrumented with a dorsal window chamber to allow for quantification of microvascular hemodynamics and functional capillary density (FCD). Results showed significant impairment in FCD, and a reduction of arteriolar and venular blood flow, with HSA providing significant higher blood flows and FCD compared with LR. Changes in hematocrit and RBC labeling after ECC reflected a shift in plasma volume, which may stem from a loss in intravascular oncotic pressure due to priming fluids. The distribution of hemoglobin oxygen saturation in the microvasculature showed a significant decrease in venules after ECC. In addition, major organs such as the kidney and heart showed increases in both inflammatory and damage markers. These results suggest that ECC impairs microvasculature function and promotes ischemia and hypoxia in the tissues, which can be vital to understanding comorbid clinical outcomes from ECC procedures such as acute kidney injury and multiorgan dysfunction. ECC reduces microvascular perfusion, with no full recovery 24 h after ECC. HSA performed better as compared with LR in terms of FCD and venule flow, as well as venule oxygen saturation. Increases in inflammatory and damage markers in key organs were observed within all organs analyzed.
Topics: Animals; Capillaries; Cricetinae; Extracorporeal Circulation; Humans; Microcirculation; Microvessels; Oxygen; Perfusion
PubMed: 35085033
DOI: 10.1152/japplphysiol.00726.2021