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Journal of Clinical Medicine Oct 2023Hypertrophic cardiomyopathy (HCM) is a genetic disease characterized by an increased left ventricular wall thickness in the absence of increased afterload conditions. In... (Review)
Review
Hypertrophic cardiomyopathy (HCM) is a genetic disease characterized by an increased left ventricular wall thickness in the absence of increased afterload conditions. In addition to diastolic dysfunction, obstruction of the left ventricular outflow tract is common in HCM and has an important influence on symptoms and outcome. Over the last five decades or two decades, respectively, surgical myectomy and alcohol septal ablation were the only therapeutic options if standard medical care was not sufficient. Recently, a new option has become available that has the potential to revolutionize the therapeutic strategies for patients with HCM. Mavacamten is a myosin inhibitor that belongs to a completely new drug class and targets the excessive actin-myosin cross-bridging that is the underlying pathology of HCM. By reducing the actin-myosin interactions, mavacamten not only reduces the left ventricular outflow tract (LVOT) obstruction but also seems to have positive effects on the diastolic function, microcirculation, and cardiac structure. This article summarizes the current evidence on alcohol septal ablation and reviews the preclinical and clinical data on mavacamten for the treatment of patients with obstructive HCM.
PubMed: 37892766
DOI: 10.3390/jcm12206628 -
Frontiers in Medicine 2023
PubMed: 37809341
DOI: 10.3389/fmed.2023.1285005 -
Frontiers in Physiology 2023
PubMed: 38089480
DOI: 10.3389/fphys.2023.1336150 -
The Journal of Clinical Investigation Dec 2023Reactivation and dysregulation of the mTOR signaling pathway are a hallmark of aging and chronic lung disease; however, the impact on microvascular progenitor cells...
Reactivation and dysregulation of the mTOR signaling pathway are a hallmark of aging and chronic lung disease; however, the impact on microvascular progenitor cells (MVPCs), capillary angiostasis, and tissue homeostasis is unknown. While the existence of an adult lung vascular progenitor has long been hypothesized, these studies show that Abcg2 enriches for a population of angiogenic tissue-resident MVPCs present in both adult mouse and human lungs using functional, lineage, and transcriptomic analyses. These studies link human and mouse MVPC-specific mTORC1 activation to decreased stemness, angiogenic potential, and disruption of p53 and Wnt pathways, with consequent loss of alveolar-capillary structure and function. Following mTOR activation, these MVPCs adapt a unique transcriptome signature and emerge as a venous subpopulation in the angiodiverse microvascular endothelial subclusters. Thus, our findings support a significant role for mTOR in the maintenance of MVPC function and microvascular niche homeostasis as well as a cell-based mechanism driving loss of tissue structure underlying lung aging and the development of emphysema.
Topics: Mice; Humans; Animals; Lung; TOR Serine-Threonine Kinases; Stem Cells; Wnt Signaling Pathway; Aging
PubMed: 37874650
DOI: 10.1172/JCI171430 -
Deutsches Arzteblatt International Nov 2023Coronary microvascular dysfunction (CMD) comprises a variety of pathogenic mechanisms that impair the microcirculation of the heart. Clinical studies have shown that... (Review)
Review
BACKGROUND
Coronary microvascular dysfunction (CMD) comprises a variety of pathogenic mechanisms that impair the microcirculation of the heart. Clinical studies have shown that 30-50% of patients suffering from myocardial ischemia without significant coronary artery stenosis have CMD. The disease is associated with ele - vated mortality and poor quality of life. Whenever a patient presents with symptoms of angina pectoris and no underlying disease is detected by the usual methods, CMD should be considered a possible cause.
METHODS
This review is based on publications retrieved by a selective search in PubMed and on current international guidelines and recommendations of specialty societies.
RESULTS
The diagnosis of CMD is based on objective evidence of a microvascular origin of symptoms. The guidelines contain a class IIa recommendation for invasive coronary flow reserve and microvascular resistance measurements. Noninvasive tests such as positron emission tomography and cardiac magnetic resonance imaging are less accurate and are given a class IIb recommendation. No highquality therapeutic trials are available to date, and the treatment of CMD is thus based on that of chronic coronary syndrome. Lifestyle modification is performed to reduce risk factors. Patients with an abnormal coronary flow reserve or elevated microvascular resistance can be treated with an ACE inhibitor or angiotensin receptor blocker. Beta-blockers and calcium channel antagonists can relieve angina pectoris. Statins lower the LDL level and have positive pleiotropic effects. First-line treatment can be supplemented with further medications.
CONCLUSION
Approximately 25% of patients with CMD have symptoms that do not respond to intensive treatment with the currently available modalities. New treatments, including interventional therapies, are being studied. Their long-term benefit remains to be assessed and compared to that of the existing methods.
Topics: Humans; Coronary Circulation; Microcirculation; Quality of Life; Coronary Artery Disease; Angina Pectoris; Myocardial Ischemia
PubMed: 37721132
DOI: 10.3238/arztebl.m2023.0205 -
European Heart Journal Aug 2023
Topics: Humans; Prognosis; Microcirculation; Heart; Coronary Circulation
PubMed: 37358487
DOI: 10.1093/eurheartj/ehad291 -
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 -
BMC Cardiovascular Disorders Aug 2023This study aimed to determine the effect of short-term remote ischemic preconditioning (RIPC) on coronary blood flow and microcirculation function using the quantitative... (Randomized Controlled Trial)
Randomized Controlled Trial
This study aimed to determine the effect of short-term remote ischemic preconditioning (RIPC) on coronary blood flow and microcirculation function using the quantitative flow ratio (QFR) and index of microcirculatory resistance (IMR). We randomly divided 129 patients undergoing coronary angiography (CAG) into RIPC and control groups. Following the first CAG, we randomly divided the patients further into the unilateral upper limb and lower limb groups for four cycles of ischemia/reperfusion circulation; subsequently, we performed the second CAG. During each CAG, contrast-flow QFR (cQFR), fixed-flow QFR (fQFR), and IMR (in patients with cardiac syndrome X) were calculated and compared. We measured 253 coronary arteries in 129 patients. Compared to the control group, the average cQFR of the RIPC group increased significantly after RIPC. Additionally, 23 patients with cardiac syndrome X (IMR > 30) were included in this study. Compared to the control group, IMR and the difference between cQFR and fQFR (cQFR-fQFR) both decreased significantly after receiving RIPC. The application of RIPC can increase coronary blood flow and improve coronary microcirculation function.
Topics: Humans; Cardiovascular Physiological Phenomena; Heart; Ischemic Preconditioning; Microcirculation; Microvascular Angina
PubMed: 37592218
DOI: 10.1186/s12872-023-03419-0 -
BMC Anesthesiology Sep 2023Previous studies indicate supplemental vitamin C improves microcirculation and reduces glycocalyx shedding in septic animals. Our randomized, double-blind,... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of high-dose intravenous ascorbic acid on microcirculation and endothelial glycocalyx during sepsis and septic shock: a double-blind, randomized, placebo-controlled study.
Previous studies indicate supplemental vitamin C improves microcirculation and reduces glycocalyx shedding in septic animals. Our randomized, double-blind, placebo-controlled trial aimed to investigate whether a high dose of intravenous ascorbic acid (AA) might improve microcirculation and affect glycocalyx in septic patients. In our study, 23 septic patients were supplemented with a high dose (50 mg/kg every 6 h) of intravenous AA or placebo for 96 h. Sublingual microcirculation was examined using a handheld Cytocam-incident dark field (IDF) video microscope. A sidestream dark field video microscope (SDF), connected to the GlycoCheck software (GlycoCheck ICU®; Maastricht University Medical Center, Maastricht, the Netherlands), was employed to observe glycocalyx. We found a significantly higher proportion of perfused small vessels (PPV) 6 h after the beginning of the trial in the experimental group compared with placebo. As an indicator of glycocalyx thickness, the perfused boundary region was lower in capillaries of the 5-9 μm diameter in the AA group than placebo after the first dose of AA. Our data suggest that high-dose parenteral AA tends to improve microcirculation and glycocalyx in the early period of septic shock. The study was retrospectively registered in the clinicaltrials.gov database on 26/02/2021 (registration number NCT04773717).
Topics: Ascorbic Acid; Glycocalyx; Microcirculation; Sepsis; Shock, Septic; Humans
PubMed: 37700249
DOI: 10.1186/s12871-023-02265-z -
Pharmacological interventions targeting the microcirculation following traumatic spinal cord injury.Neural Regeneration Research Jan 2024Traumatic spinal cord injury is a devastating disorder characterized by sensory, motor, and autonomic dysfunction that severely compromises an individual's ability to... (Review)
Review
Traumatic spinal cord injury is a devastating disorder characterized by sensory, motor, and autonomic dysfunction that severely compromises an individual's ability to perform activities of daily living. These adverse outcomes are closely related to the complex mechanism of spinal cord injury, the limited regenerative capacity of central neurons, and the inhibitory environment formed by traumatic injury. Disruption to the microcirculation is an important pathophysiological mechanism of spinal cord injury. A number of therapeutic agents have been shown to improve the injury environment, mitigate secondary damage, and/or promote regeneration and repair. Among them, the spinal cord microcirculation has become an important target for the treatment of spinal cord injury. Drug interventions targeting the microcirculation can improve the microenvironment and promote recovery following spinal cord injury. These drugs target the structure and function of the spinal cord microcirculation and are essential for maintaining the normal function of spinal neurons, axons, and glial cells. This review discusses the pathophysiological role of spinal cord microcirculation in spinal cord injury, including its structure and histopathological changes. Further, it summarizes the progress of drug therapies targeting the spinal cord microcirculation after spinal cord injury.
PubMed: 37488841
DOI: 10.4103/1673-5374.375304