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Circulation Jan 2024Angina with nonobstructive coronary arteries is a common condition for which no effective treatment has been established. We hypothesized that the measurement of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Angina with nonobstructive coronary arteries is a common condition for which no effective treatment has been established. We hypothesized that the measurement of coronary flow reserve (CFR) allows identification of patients with angina with nonobstructive coronary arteries who would benefit from anti-ischemic therapy.
METHODS
Patients with angina with nonobstructive coronary arteries underwent blinded invasive CFR measurement and were randomly assigned to receive 4 weeks of amlodipine or ranolazine. After a 1-week washout, they crossed over to the other drug for 4 weeks; final assessment was after the cessation of study medication for another 4 weeks. The primary outcome was change in treadmill exercise time, and the secondary outcome was change in Seattle Angina Questionnaire summary score in response to anti-ischemic therapy. Analysis was on a per protocol basis according to the following classification: coronary microvascular disease (CMD group) if CFR<2.5 and reference group if CFR≥2.5. The study protocol was registered before the first patient was enrolled (International Standard Randomised Controlled Trial Number: ISRCTN94728379).
RESULTS
Eighty-seven patients (61±8 years of age; 62% women) underwent random assignment (57 CMD group and 30 reference group). Baseline exercise time and Seattle Angina Questionnaire summary scores were similar between groups. The CMD group had a greater increment (delta) in exercise time than the reference group in response to both amlodipine (difference in delta, 82 s [95% CI, 37-126 s]; <0.001) and ranolazine (difference in delta, 68 s [95% CI, 21-115 s]; =0.005). The CMD group reported a greater increment (delta) in Seattle Angina Questionnaire summary score than the reference group in response to ranolazine (difference in delta, 7 points [95% CI, 0-15]; =0.048), but not to amlodipine (difference in delta, 2 points [95% CI, -5 to 8]; =0.549).
CONCLUSIONS
Among phenotypically similar patients with angina with nonobstructive coronary arteries, only those with an impaired CFR derive benefit from anti-ischemic therapy. These findings support measurement of CFR to diagnose and guide management of this otherwise heterogeneous patient group.
Topics: Female; Humans; Male; Amlodipine; Coronary Artery Disease; Coronary Circulation; Cross-Over Studies; Microcirculation; Microvascular Angina; Myocardial Ischemia; Phenotype; Ranolazine; Middle Aged; Aged
PubMed: 37905403
DOI: 10.1161/CIRCULATIONAHA.123.066680 -
Advances in Clinical and Experimental... Mar 2024The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused high morbidity and mortality and has been a source of substantial challenges for... (Review)
Review
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused high morbidity and mortality and has been a source of substantial challenges for healthcare systems globally. Despite a full recovery, a significant proportion of patients demonstrate a broad spectrum of cardiovascular, pulmonary and neurological symptoms that are believed to be caused by long-term tissue damage and pathological inflammation, which play a vital role in disease development. Microvascular dysfunction also causes significant health problems. This review aimed to critically appraise the current data on the long-term cardiovascular sequelae of coronavirus disease 2019 (COVID-19), with a primary focus on cardiovascular symptoms such as chest pain, fatigue, palpitations, and breathlessness, and more significant disease entities including myocarditis, pericarditis and postural tachycardia syndrome. Potential risk factors identified in recent studies that contribute towards the development of long COVID are also included alongside a summary of recent advances in diagnostics and putative treatment options.
Topics: Humans; COVID-19; SARS-CoV-2; Post-Acute COVID-19 Syndrome; Cardiovascular System; Arrhythmias, Cardiac
PubMed: 37386857
DOI: 10.17219/acem/167482 -
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 -
Pathophysiology : the Official Journal... Aug 2023Diabetes Mellitus (DM) is a complex metabolic disorder associated with multiple microvascular complications leading to nephropathy, retinopathy, and neuropathy. Mounting... (Review)
Review
Diabetes Mellitus (DM) is a complex metabolic disorder associated with multiple microvascular complications leading to nephropathy, retinopathy, and neuropathy. Mounting evidence suggests that red blood cell (RBC) alterations are both a cause and consequence of disturbances related to DM-associated complications. Importantly, a significant proportion of DM patients develop varying degrees of anemia of confounding etiology, leading to increased morbidity. In chronic hyperglycemia, RBCs display morphological, enzymatic, and biophysical changes, which in turn prime them for swift phagocytic clearance from circulation. A multitude of endogenous factors, such as oxidative and dicarbonyl stress, uremic toxins, extracellular hypertonicity, sorbitol accumulation, and deranged nitric oxide metabolism, have been implicated in pathological RBC changes in DM. This review collates clinical laboratory findings of changes in hematology indices in DM patients and discusses recent reports on the putative mechanisms underpinning shortened RBC survival and disturbed cell membrane architecture within the diabetic milieu. Specifically, RBC cell death signaling, RBC metabolism, procoagulant RBC phenotype, RBC-triggered endothelial cell dysfunction, and changes in RBC deformability and aggregation in the context of DM are discussed. Understanding the mechanisms of RBC alterations in DM provides valuable insights into the clinical significance of the crosstalk between RBCs and microangiopathy in DM.
PubMed: 37606388
DOI: 10.3390/pathophysiology30030026 -
The Journal of Investigative Dermatology Oct 2023Severe psoriasis is associated with an increased cardiovascular risk, which may be independent of the traditional risk factors. Coronary microvascular dysfunction (CMD)...
Severe psoriasis is associated with an increased cardiovascular risk, which may be independent of the traditional risk factors. Coronary microvascular dysfunction (CMD) has been shown to predict a poor cardiovascular prognosis in the general population and in patients with psoriasis. In this study, we assessed the prevalence and predictors of CMD in a large cohort of patients with psoriasis without clinical cardiovascular disease. A total of 503 patients with psoriasis were enrolled and underwent transthoracic Doppler echocardiography to evaluate coronary microcirculation. Of these, 55 patients were excluded from the analyses because of missing data. Of the 448 patients in this study, 31.5% showed CMD. Higher PASI, longer disease duration, the presence of psoriatic arthritis, and hypertension were independently associated with CMD. An increase of 1 point of PASI and 1 year of psoriasis duration were associated with a 5.8% and 4.6% increased risk of CMD, respectively. In our study, CMD was associated with the severity and duration of psoriasis. This supports the role of systemic inflammation in CMD and suggests that the coronary microcirculation may represent an extracutaneous site involved in the immune-mediated injury of psoriasis. We should diagnose and actively search for CMD in patients with severe psoriasis.
Topics: Humans; Psoriasis; Arthritis, Psoriatic; Cardiovascular Diseases; Heart Disease Risk Factors; Hypertension
PubMed: 37739764
DOI: 10.1016/j.jid.2023.02.037 -
ESC Heart Failure Aug 2023Coronary microvascular dysfunction (CMD) has been proposed as an important pathophysiological mechanism in Takotsubo syndrome (TTS). Our aims were (i) to evaluate and...
AIMS
Coronary microvascular dysfunction (CMD) has been proposed as an important pathophysiological mechanism in Takotsubo syndrome (TTS). Our aims were (i) to evaluate and compare levels of CMD in patients with TTS and patients with ischaemia and no obstructive coronary arteries (INOCA) and (ii) to investigate associations between CMD and clinical parameters, left ventricular function, and coronary atherosclerosis in TTS.
METHODS AND RESULTS
We conducted a prospective study of 27 female TTS patients and an equally sized, age- and gender-matched, cohort of INOCA patients. Coronary microvascular function was quantified invasively using the index of microcirculatory resistance (IMR), coronary flow reserve (CFR), and resistive reserve ratio (RRR). CMD was defined as IMR ≥ 25 and/or CFR ≤ 2. In the TTS patients, left ventricular function was assessed with echocardiography and cardiovascular magnetic resonance (CMR) imaging, and coronary atherosclerosis was visualized with intravascular ultrasound with near-infrared spectroscopy (IVUS-NIRS). The incidence of CMD was higher in the TTS patients than in the INOCA cohort (78% vs. 44%, P = 0.01), with higher IMR (30 vs. 14, P = 0.002), lower CFR (1.8 vs. 2.8, P = 0.009), and lower RRR (2.1 vs. 3.5, P = 0.003). In apical compared with midventricular TTS, IMR was numerically higher (50 vs. 28, P = 0.20), whereas CFR and RRR were lower (1.5 vs. 2.5, P = 0.003 and 1.6 vs. 2.7, P = 0.01, respectively). Global longitudinal strain and global circumferential strain, assessed with CMR imaging, were more impaired in apical than in midventricular TTS (-11 vs. -14, P < 0.001 and -12 vs. -15, P = 0.049, respectively). In the TTS patients, CFR and RRR correlated with echocardiography-derived (R = 0.15, P = 0.002 and R = 0.18, P = 0.007, respectively) and CMR-derived (R = 0.09, P = 0.025 and R = 0.10, P = 0.038, respectively) ejection fraction. CFR and RRR correlated inversely with CMR-derived end-diastolic volume index, end-systolic volume index, and left ventricular mass index. IMR, CFR, and RRR were not associated with measures of coronary atherosclerosis derived by IVUS-NIRS.
CONCLUSIONS
Coronary microvascular dysfunction is common in patients with TTS and more frequent than in patients with INOCA. CMD in TTS is more severe in the apical compared with the midventricular phenotype of the syndrome, is associated with left ventricular function, but is unrelated to coronary atherosclerosis. Our results support the notion of CMD as a key mediator in TTS.
Topics: Female; Humans; Takotsubo Cardiomyopathy; Coronary Artery Disease; Ventricular Function, Left; Prospective Studies; Microcirculation; Myocardial Ischemia
PubMed: 37218383
DOI: 10.1002/ehf2.14394 -
Frontiers in Immunology 2023The liver is a vital metabolic organ that also performs important immune-regulatory functions. In the context of infections, the liver represents a target site for... (Review)
Review
The liver is a vital metabolic organ that also performs important immune-regulatory functions. In the context of infections, the liver represents a target site for various pathogens, while also having an outstanding capacity to filter the blood from pathogens and to contain infections. Pathogen scavenging by the liver is primarily performed by its large and heterogeneous macrophage population. The major liver-resident macrophage population is located within the hepatic microcirculation and is known as Kupffer cells (KCs). Although other minor macrophages reside in the liver as well, KCs remain the best characterized and are the best well-known hepatic macrophage population to be functionally involved in the clearance of infections. The response of KCs to pathogenic insults often governs the overall severity and outcome of infections on the host. Moreover, infections also impart long-lasting, and rarely studied changes to the KC pool. In this review, we discuss current knowledge on the biology and the various roles of liver macrophages during infections. In addition, we reflect on the potential of infection history to imprint long-lasting effects on macrophages, in particular liver macrophages.
Topics: Humans; Kupffer Cells; Liver; Macrophages; Kinetics; Communicable Diseases
PubMed: 37691953
DOI: 10.3389/fimmu.2023.1238452 -
Anesthesiology May 2024Hemorrhagic shock (HS) and rhabdomyolysis (RM) are two important risk factors of acute kidney injury (AKI) after severe trauma, however the effects of the combination of...
BACKGROUND
Hemorrhagic shock (HS) and rhabdomyolysis (RM) are two important risk factors of acute kidney injury (AKI) after severe trauma, however the effects of the combination of RM and HS on kidney function are unknown. The purpose of this study was to determine the impact of RM and HS on renal function, oxygenation, perfusion and morphology, in a pig model.
METHODS
Forty-seven female pigs were divided into 5 groups: sham, RM, HS, HS and moderate RM (RM4/HS), HS and severe RM (RM8/HS). RM was induced by intramuscular injection of Glycerol 50% with a moderate dose (4 ml/kg for RM4/HS group) or a high dose (8 ml/kg for RM and RM8/HS groups). Among animals with HS, after 90 min of hemorrhage, animals were resuscitated with fluid followed by transfusion of the withdrawn blood. Animals were followed for 48 hours. Macro and microcirculatory parameters measurements were performed.
RESULTS
RM alone induced a decrease in creatinine clearance at 48 hours (19 (0-41) vs 102 (56-116) ml/min for RM and SHAM respectively; p = 0.0006) without alteration in renal perfusion and oxygenation. HS alone impaired temporarily renal microcirculation, function and oxygenation that were restored with fluid resuscitation. RM4/HS and RM8/HS groups induced greater impairment of renal microcirculation and function than HS alone at the end of blood spoliation that were not improved by fluid resuscitation. Mortality was increased in RM8/HS and RM4/HS groups in the first 48 hours (73% vs 56% vs 9% for RM8/HS, RM4/HS and HS groups respectively).
CONCLUSIONS
The combination of HS and RM induced an early deleterious effect on renal microcirculation, function and oxygenation with decreased response to resuscitation and transfusion compared with HS or RM alone.
PubMed: 38787807
DOI: 10.1097/ALN.0000000000005097 -
CNS Neuroscience & Therapeutics Feb 2024In the field of stroke thrombectomy, ineffective clinical and angiographic reperfusion after successful recanalization has drawn attention. Partial or complete... (Review)
Review
In the field of stroke thrombectomy, ineffective clinical and angiographic reperfusion after successful recanalization has drawn attention. Partial or complete microcirculatory reperfusion failure after the achievement of full patency of a former obstructed large vessel, known as the "no-reflow phenomenon" or "microvascular obstruction," was first reported in the 1960s and was later detected in both experimental models and patients with stroke. The no-reflow phenomenon (NRP) was reported to result from intraluminal occlusions formed by blood components and extraluminal constriction exerted by the surrounding structures of the vessel wall. More recently, an emerging number of clinical studies have estimated the prevalence of the NRP in stroke patients following reperfusion therapy, ranging from 3.3% to 63% depending on its evaluation methods or study population. Studies also demonstrated its detrimental effects on infarction progress and neurological outcomes. In this review, we discuss the research advances, underlying pathogenesis, diagnostic techniques, and management approaches concerning the no-reflow phenomenon in the stroke population to provide a comprehensive understanding of this phenomenon and offer references for future investigations.
Topics: Humans; No-Reflow Phenomenon; Microcirculation; Stroke; Thrombectomy; Reperfusion; Treatment Outcome
PubMed: 38358074
DOI: 10.1111/cns.14631 -
Journal of Clinical Medicine Dec 2023Haemodialysis (HD) is currently the most commonly used method of renal replacement therapy. The process of dialysis involves numerous changes that affect many systems,... (Review)
Review
Haemodialysis (HD) is currently the most commonly used method of renal replacement therapy. The process of dialysis involves numerous changes that affect many systems, including the eye. The changes occurring in the course of HD may affect the ocular parameters, such as intraocular pressure, central corneal thickness, retinal thickness, retinal nerve fibre layer thickness, and choroidal thickness (CT). The choroid, being one of the most vascularized tissues, is characterized by the highest ratio of blood flow to tissue volume in the entire body, may be particularly susceptible to changes occurring during HD, and at the same time reflect the microcirculatory status and its response to HD. Patients with end-stage renal disease subjected to dialysis are highly susceptible to systemic microvascular dysfunction. Moreover, it is considered that the process of HD itself contributes to vascular dysfunction. Nowadays, thanks to the development of imaging techniques, the widely available optical coherence tomography (OCT) tests allow for the assessment of CT, while OCT-angiography allows for a quick, non-invasive, and repeatable assessment of the condition of retinal and choroidal microcirculation, which significantly expands our knowledge regarding the reaction of ocular microcirculation due to HD. The assessment of both retinal and choroidal circulation is even more attractive because retinal circulation is autoregulated, while choroidal circulation is mainly controlled by extrinsic autonomic innervation. Thus, assessment of the choroidal response to an HD session may provide the possibility to indirectly evaluate the functions of the autonomic system in patients subjected to HD. At a time when the importance of microcirculation in systemic and renal diseases is becoming increasingly evident, the assessment of ocular microcirculation appears to be a potential biomarker for assessing the condition of systemic microcirculation. In this work, we present a review of the literature on the effect of the HD session on CT and the retinal and choroidal microcirculation.
PubMed: 38137798
DOI: 10.3390/jcm12247729