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Critical Care Clinics Apr 2020Oxygen (O2) delivery, which is fundamental to supporting patients with critical illness, is a function of blood O2 content and flow. This article reviews red blood cell... (Review)
Review
Oxygen (O2) delivery, which is fundamental to supporting patients with critical illness, is a function of blood O2 content and flow. This article reviews red blood cell (RBC) physiology and dysfunction relevant to disordered O2 delivery in the critically ill. Flow is the focus of O2 delivery regulation: O2 content is relatively fixed, whereas flow fluctuates greatly. Thus, blood flow volume and distribution vary to maintain coupling between O2 delivery and demand. This article reviews conventional RBC physiology influencing O2 delivery and introduces a paradigm for O2 delivery homeostasis based on coordinated gas transport and vascular signaling by RBCs.
Topics: Adenosine Triphosphate; Critical Illness; Erythrocyte Deformability; Erythrocytes; Hemorheology; Homeostasis; Humans; Microcirculation; Nitric Oxide
PubMed: 32172813
DOI: 10.1016/j.ccc.2019.12.008 -
European Journal of Pharmaceutical... Dec 2023During septic shock, impairment of microcirculation leads to enhanced permeability of intestinal mucosa triggered by generalized vasodilation and capillary leak....
INTRODUCTION
During septic shock, impairment of microcirculation leads to enhanced permeability of intestinal mucosa triggered by generalized vasodilation and capillary leak. Intravenous angiotensin II (AT-II) has been approved for the treatment of septic shock; however, no in-vivo data exist on the influence of AT-II on hepatic and intestinal microcirculation.
MATERIAL AND METHODS
Sixty male Lewis rats were randomly assigned to six study groups (each n = 10): sham, lipopolysaccharide-induced septic shock, therapy with low- or high-dose AT-II (50 or 100 ng/kg/min, respectively), and septic shock treated with low- or high-dose AT-II. After median laparotomy, hepatic and intestinal microcirculation measures derived from micro-lightguide spectrophotometry were assessed for 3 h and included oxygen saturation (SO), relative blood flow (relBF) and relative hemoglobin level (relHb). Hemodynamic measurements were performed using a left ventricular conductance catheter, and blood samples were taken hourly to analyze blood gasses and systemic cytokines.
RESULTS
AT-II increased mean arterial pressure in a dose-dependent manner in both septic and non-septic animals (p < 0.001). Lower hepatic and intestinal SO (both p < 0.001) were measured in animals without endotoxemia who received high-dose AT-II treatment, however, significantly impaired cardiac output was also reported in this group (p < 0.001). In endotoxemic rats, hepatic relBF and relHb were comparable among the treatment groups; however, hepatic SO was reduced during low- and high-dose AT-II treatment (p < 0.001). In contrast, intestinal SO remained unchanged despite treatment with AT-II. Intestinal relBF (p = 0.028) and interleukin (IL)-10 plasma levels (p < 0.001) were significantly elevated during treatment with high-dose AT-II compared with low-dose AT-II.
CONCLUSIONS
A dose-dependent decrease of hepatic and intestinal microcirculation during therapy with AT-II in non-septic rats was observed, which might have been influenced by a corresponding reduction in cardiac output due to elevated afterload. While hepatic microcirculation was reduced during endotoxemia, no evidence for a reduction in intestinal microcirculation facilitated by AT-II was found. In contrast, both intestinal relBF and anti-inflammatory IL-10 levels were increased during high-dose AT-II treatment.
Topics: Rats; Male; Animals; Endotoxemia; Shock, Septic; Angiotensin II; Microcirculation; Rats, Inbred Lew; Hemodynamics
PubMed: 37734468
DOI: 10.1016/j.ejps.2023.106588 -
Sensors (Basel, Switzerland) Nov 2022: Microcirculation is a vital sign that supplies oxygen and nutrients to maintain normal life activities. Sepsis typically influences the operation of microcirculation,...
: Microcirculation is a vital sign that supplies oxygen and nutrients to maintain normal life activities. Sepsis typically influences the operation of microcirculation, which is recovered by the administration of medicine injection. : Sepsis-induced variation and recovery of microcirculation are quantitatively detected using microcirculation images acquired by a non-contact imaging setup, which might assist the clinical diagnosis and therapy of sepsis. : In this study, a non-contact imaging setup was first used to record images of microcirculation on the back of model rats. Specifically, the model rats were divided into three groups: (i) the sham group as a control group; (ii) the cecum ligation and puncture (CLP) group with sepsis; and (iii) the CLP+thrombomodulin (TM) group with sepsis and the application of TM alfa therapy. Furthermore, considering the sparsity of red blood cells (RBCs), the blood velocity is estimated by robust principal component analysis (RPCA) and U-net, and the blood vessel diameter is estimated by the contrast difference between the blood vessel and tissue. : In the experiments, the continuous degradation of the estimated blood velocity and blood vessel diameter in the CLP group and the recovery after degradation of those in the CLP+TM group were quantitatively observed. The variation tendencies of the estimated blood velocity and blood vessel diameter in each group suggested the effects of sepsis and its corresponding therapy.
Topics: Rats; Animals; Microcirculation; Sepsis; Punctures
PubMed: 36366167
DOI: 10.3390/s22218471 -
Current Cardiology Reviews 2022Invasive assessment of coronary physiology has radically changed the paradigm of myocardial revascularization in patients with coronary artery disease. Despite the... (Review)
Review
Invasive assessment of coronary physiology has radically changed the paradigm of myocardial revascularization in patients with coronary artery disease. Despite the prognostic improvement associated with ischemia-driven revascularization strategy, functional assessment of angiographic intermediate epicardial stenosis remains largely underused in clinical practice. Multiple tools have been developed or are under development in order to reduce the invasiveness, cost, and extra procedural time associated with the invasive assessment of coronary physiology. Besides epicardial stenosis, a growing body of evidence highlights the role of coronary microcirculation in regulating coronary flow with consequent pathophysiological and clinical and prognostic implications. Adequate assessment of coronary microcirculation function and integrity has then become another component of the decision-making algorithm for optimal diagnosis and treatment of coronary syndromes. This review aims at providing a comprehensive description of tools and techniques currently available in the catheterization laboratory to obtain a thorough and complete functional assessment of the entire coronary tree (both for the epicardial and microvascular compartments).
Topics: Coronary Angiography; Coronary Artery Disease; Coronary Stenosis; Fractional Flow Reserve, Myocardial; Humans; Microcirculation; Percutaneous Coronary Intervention
PubMed: 34521331
DOI: 10.2174/1573403X17666210908114154 -
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 -
Microcirculation (New York, N.Y. : 1994) Apr 2021Kidneys are highly vascular organs that despite their relatively small size receive 20% of the cardiac output. The highly intricate, delicately organized structure of... (Review)
Review
Kidneys are highly vascular organs that despite their relatively small size receive 20% of the cardiac output. The highly intricate, delicately organized structure of renal microcirculation is essential to enable renal function and glomerular filtration rate through the local modulation of renal blood flow and intraglomerular pressure. Not surprisingly, the dysregulation of blood flow within the microvessels (abnormal vasoreactivity), fibrosis driven by disordered vascular-renal cross talk, or the loss of renal microvasculature (rarefaction) is associated with kidney disease. In addition, kidney disease can cause microcirculatory dysfunction in distant organs such as the heart and brain, mediated by mechanisms that remain to be elucidated. The objective of this review is to highlight the role of renal microvasculature in kidney disease. The overview will outline the impetus to study renal microvasculature, the bidirectional relationship between kidney disease and microvascular dysfunction, the key pathways driving microvascular diseases such as vasoreactivity, the cell dynamics coordinating fibrosis, and vessel rarefaction. Finally, we will also briefly highlight new therapies targeting the renal microvasculature to improve renal function.
Topics: Fibrosis; Humans; Kidney; Kidney Diseases; Microcirculation; Microvessels
PubMed: 33025626
DOI: 10.1111/micc.12661 -
JACC. Cardiovascular Imaging Jul 2022
Topics: Coronary Circulation; Heart; Humans; Microcirculation; Predictive Value of Tests
PubMed: 35798396
DOI: 10.1016/j.jcmg.2022.03.020 -
American Journal of Physiology. Heart... Jun 2021Until recently, epicardial coronary stenosis has been considered the primary outcome of coronary heart disease, and clinical interventions have been dedicated primarily... (Review)
Review
Until recently, epicardial coronary stenosis has been considered the primary outcome of coronary heart disease, and clinical interventions have been dedicated primarily to the identification and removal of flow-limiting stenoses. However, a growing body of literature indicates that both epicardial stenosis and microvascular dysfunction contribute to damaging myocardial ischemia. In this review, we discuss the coexistence of macro- and microvascular disease, and how the structure and function of the distal microcirculation is impacted by the hemodynamic consequences of an epicardial, flow-limiting stenosis. Mechanisms of endothelial dysfunction as well as alterations of smooth muscle function in the coronary microcirculation distal to stenosis are discussed. Risk factors including diabetes, metabolic syndrome, and aging exacerbate microvascular dysfunction in the myocardium distal to a stenosis, and our current understanding of the role of these factors in limiting collateralization and angiogenesis of the ischemic myocardium is presented. Importantly, exercise training has been shown to promote collateral growth and improve microvascular function distal to stenosis; thus, the current literature reporting the mechanisms that underlie the beneficial effects of exercise training in the microcirculation distal to epicardial stenosis is reviewed. We also discuss recent studies of therapeutic interventions designed to improve microvascular function and stimulate angiogenesis in clinically relevant animal models of epicardial stenosis and microvascular disease. Finally, microvascular adaptation to removal of epicardial stenosis is considered.
Topics: Adaptation, Physiological; Aging; Animals; Collateral Circulation; Coronary Circulation; Coronary Stenosis; Diabetes Mellitus; Diabetic Angiopathies; Endothelium; Hemodynamics; Humans; Metabolic Syndrome; Microcirculation; Microvessels; Muscle, Smooth, Vascular; Myocardial Ischemia; Pericardium
PubMed: 33961506
DOI: 10.1152/ajpheart.00992.2020 -
Journal of the American Society of... Sep 2022The glomerular vascular pole is the gate for the afferent and efferent arterioles and mesangial cells and a frequent location of peripolar cells with an unclear...
The glomerular vascular pole is the gate for the afferent and efferent arterioles and mesangial cells and a frequent location of peripolar cells with an unclear function. It has been studied in definitive detail for >30 years, and functionally interrogated in the context of signal transduction from the macula densa to the mesangial cells and afferent arteriolar smooth muscle cells from 10 to 20 years ago. Two recent discoveries shed additional light on the vascular pole, with possibly far-reaching implications. One, which uses novel serial section electron microscopy, reveals a shorter capillary pathway between the basins of the afferent and efferent arterioles. Such a pathway, when patent, may short-circuit the multitude of capillaries in the glomerular tuft. Notably, this shorter capillary route is enclosed within the glomerular mesangium. The second study used anti-Thy1.1-induced mesangiolysis and intravital microscopy to unequivocally establish the long-suspected contractile function of mesangial cells, which have the ability to change the geometry and curvature of glomerular capillaries. These studies led me to hypothesize the existence of a glomerular perfusion rheostat, in which the shorter path periodically fluctuates between being more and less patent. This action reduces or increases blood flow through the entire glomerular capillary tuft. A corollary is that the GFR is a net product of balance between the states of capillary perfusion, and that deviations from the balanced state would increase or decrease GFR. Taken together, these studies may pave the way to a more profound understanding of glomerular microcirculation under basal conditions and in progression of glomerulopathies.
Topics: Microcirculation; Kidney Glomerulus; Glomerular Mesangium; Arterioles; Kidney Tubules
PubMed: 35853715
DOI: 10.1681/ASN.2022030354 -
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