The Role of Coronary Physiology Assessment in the Diagnosis and Treatment of Stable Angina. Dive Inside Recent Findings of Diffuse Coronary Disease Treatment.

Coronary physiology is widely used to assess epicardial coronary lesions in patients with stable angina. Based on the available evidence, physiology plays a crucial role in diagnosing and treating patients. There have been invasive methods for determining cardiac physiology, such as fractional flow reserve and instantaneous wave-free ratio. Still, new non-invasive approaches provide extra anatomical information, such as fractional flow reserve computed tomography (FFR-CT) based on computed tomography and physiology based on angiography. Even though FFR-guided percutaneous coronary intervention (PCI) is clinically beneficial, one-third of patients retain suboptimal FFR after the procedure, associated with severe adverse events, rendering PCI in diffuse coronary artery disease questionable. Using the pullback pressure gradient (PPG), we can analyze the magnitude and extent of pressure losses; a lower value may indicate diffuse disease, while a high value with an abrupt curve may indicate focal disease. Since PCI is not the best option for treating diffuse coronary disease, current strategies focus on conservatively using medical therapy or bypass surgery. It has been demonstrated that patients with diffuse disease of the left anterior descending (LAD) are at a greater risk of developing occlusion of the left internal mammary artery graft than those with focal disease and that maximal medical therapy may be the most effective treatment for these patients.

Molecular mechanisms of endothelial dysfunction in coronary microcirculation dysfunction.

Coronary microvascular endothelial cells (CMECs) react to changes in coronary blood flow and myocardial metabolites and regulate coronary blood flow by balancing vasoconstrictors-such as endothelin-1-and the vessel dilators prostaglandin, nitric oxide, and endothelium-dependent hyperpolarizing factor. Coronary microvascular endothelial cell dysfunction is caused by several cardiovascular risk factors and chronic rheumatic diseases that impact CMEC blood flow regulation, resulting in coronary microcirculation dysfunction (CMD). The mechanisms of CMEC dysfunction are not fully understood. However, the following could be important mechanisms: the overexpression and activation of nicotinamide adenine dinucleotide phosphate oxidase (Nox), and mineralocorticoid receptors; the involvement of reactive oxygen species (ROS) caused by a decreased expression of sirtuins (SIRT3/SIRT1); forkhead box O3; and a decreased SKCA/IKCA expression in the endothelium-dependent hyperpolarizing factor electrical signal pathway. In addition, p66Shc is an adapter protein that promotes oxidative stress; although there are no studies on its involvement with cardiac microvessels, it is possible it plays an important role in CMD.

Acute Complications in Patients with Myocardial Infarction with Non-Obstructive Coronary Arteries: A Systematic Review with Special Focus on Mechanical Complications.

Background: Recently, we have observed an increasing focus on myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA) patients. MINOCA incidence is estimated to be within the range of 5-15% of all MI cases. Unfortunately, MINOCA relates to various conditions that are not rarely hard to identify, including coronary microcirculation dysfunction, epicardial coronary spasm, or plaque erosion. Our systematic review aimed to identify and appraise previous studies which characterized acute complications, with particular focus on mechanical complications, in patients with MINOCA. Methods: Applying the MeSH strategy in PubMed and Embase, two operators independently and systematically reviewed published studies on patients diagnosed with MINOCA and in whom acute complications were described. Papers published in the last 10 years (June 2012-June 2022) to reflect the introduction of the MINOCA definition as well as the current clinical practice were analyzed. The research was conducted in July 2022. Results: The search yielded 192 records. After abstract review, 79 papers were left, and after full-text analysis, we finally included 20 studies. Among 20 studies, there were: one randomized controlled trial, one prospective study, five retrospective studies, 1 case series, and 12 case reports with a total number of 337,385 patients. In the identified literature, we revealed 7 cases of intraventricular septal rupture, 3 cases of free wall rupture with pericardial effusion or cardiac tamponade, and 3 cases of bleeding complications (intracerebral or intestinal bleeding). Moreover, the ventricular arrhythmia incidence ranged from 2% to 13.8%, and the in-hospital death rate ranged from 0.9% to 6.4%. Conclusions: These findings suggest that MINOCA patients should be treated as standard MI patients with watchful monitoring, especially in the first few days.

Coronary Physiology: Delivering Precision Medicine?

Coronary physiological assessment is now widely used to assess epicardial coronary lesions in cath lab. Based on clinical evidence, fractional flow reserve (FFR) is the gold standard method to select whether epicardial coronary lesions need revascularization. While additional epicardial indexes, such as instantaneous wave-free ratio (iFR), are also used for revascularization decision-making, several indexes are now also available to explore the coronary microcirculation. Therefore, coronary physiological assessment now allows to explore the entire coronary tree and offer the potential of precision medicine for patients affected by coronary artery disease (CAD). This paper will provide review of the epicardial and microvascular indexes available for the assessment of coronary physiology. More specifically, the already demonstrated contributions of these indexes in the management of CAD and the role they could play in precision medicine will be reviewed with special emphasis on chronic coronary syndrome.

Pathophysiological factors contributing to fractional flow reserve and instantaneous wave-free ratio discordance.

The diagnostic accuracy and clinical benefits of instantaneous wave-free ratio (iFR) compared to fractional flow reserve (FFR) have been well-established in the literature. Despite the advantages of non-hyperemic pressure indices, approximately 20% of iFR and FFR measurements are discordant. Efforts have been made to establish the mechanisms as well as identify causative factors that lead to such a discordance. Recent studies have identified many factors of discordance including sex differences, age differences, bradycardia, coronary artery stenosis location, elevated left ventricular end-diastolic pressure, and diastolic dysfunction. Additionally, discordance secondary to coronary artery microcirculation dysfunction, as seen in diabetics and patients on hemodialysis, has sparked interest amongst experts. As more interventional cardiologists are utilizing iFR independent of FFR to guide percutaneous coronary intervention an emphasis has been placed on identifying factors leading to discordance. The aim of this review is to outline recent studies that have identified factors of FFR and iFR discordance.

Anatomical and Pathological Observation and Analysis of SARS and COVID-19: Microthrombosis Is the Main Cause of Death.

The spread of the coronavirus (SARS-CoV-2, COVID-19 for short) has caused a large number of deaths around the world. We summarized the data reported in the past few months and emphasized that the main causes of death of COVID-19 patients are DAD (Diffuse Alveolar Damage) and DIC (Disseminated intravascular coagulation). Microthrombosis is a prominent clinical feature of COVID-19, and 91.3% of dead patients had microthrombosis.Endothelial damage caused by SARS-CoV-2 cell invasion and subsequent host response disorders involving inflammation and coagulation pathways play a key role in the progression of severe COVID-19. Microvascular thrombosis may lead to microcirculation disorders and multiple organ failure lead to death.The characteristic pathological changes of DAD include alveolar epithelial and vascular endothelial injury, increased alveolar membrane permeability, large numbers of neutrophil infiltration, alveolar hyaline membrane formation, and hypoxemia and respiratory distress as the main clinical manifestations. DAD leads to ARDS in COVID-19 patients. DIC is a syndrome characterized by the activation of systemic intravascular coagulation, which leads to extensive fibrin deposition in the blood. Its occurrence and development begin with the expression of tissue factor and interact with physiological anticoagulation pathways. The down-regulation of fibrin and the impaired fibrinolysis together lead to extensive fibrin deposition.DIC is described as a decrease in the number of platelets and an increase in fibrin degradation products, such as D-dimer and low fibrinogen. The formation of microthrombus leads to the disturbance of microcirculation, which in turn leads to the death of the patient. However, the best prevention and treatment of COVID-19 microthrombosis is still uncertain.This review discusses the latest findings of basic and clinical research on COVID-19-related microthrombosis, and then we proposed the theory of microcirculation perfusion bundle therapy to explore effective methods for preventing and treating COVID-19-related microthrombosis. Further research is urgently needed to clarify how SARS-CoV-2 infection causes thrombotic complications, and how it affects the course and severity of the disease. To cultivate a more comprehensive understanding of the underlying mechanism of this disease. Raise awareness of the importance of preventing and treating microthrombosis in patients with COVID-19.

Salvia miltiorrhiza stem-leaf active components of salvianolic acids and flavonoids improved the hemorheological disorder and vascular endothelial function on microcirculation dysfunction rats.

Microcirculation, which connects macrocirculation and cells between arterioles and venules, plays a major role in the early onset of a variety of diseases. In this article, a dextran-induced microcirculation dysfunction (MCDF) model rats were adopted to evaluate the effects and mechanism of Salvia miltiorrhiza stem-leaf extracts based on plasma and urine metabonomics. The results showed the effective components of S. miltiorrhiza stem-leaf could significantly improve the hemorheology and coagulation index of MCDF rats and callback the expression of endothelin-1 (ET-1), induciblenitric oxide synthase (iNOS), vascularendothelial growth factor (VEGF), P-Selectin, thromboxane A2, 6-keto-PGF1α , TNF-α, and interleukin-1ß to control group in MCDF rats. The decrease of microvessel density (MVD) in lung and thymus caused by MCDF was upgraded by Salvia miltiorrhiza stem-leaf. Based on the plasma and urine metabolic data, 20 potential biomarkers were identified. These biomarkers are mainly related to linoleic acid metabolism, glutathione metabolism, pantothenate and coenzyme A biosynthesis, pentose and glucuronate interconversions, pyruvate metabolism, glyoxylate and dicarboxylate metabolism, beta-alanine metabolism, and citrate cycle. The results indicated that the effective components of S. miltiorrhiza stem-leaf can improve the hemorheological disorder and vascular endothelial function. Meanwhile, the effective components can regulate potential biomarkers and correlated metabolic pathway, which can provide guidance for the research and development of new drugs for MCDF.

[Advancement of imaging technology for coronary microcirculation dysfunction assessment].

Coronary microcirculation dysfunction (CMVD) is an important risk factor for the prognosis of re-perfused ischemic heart. Recent studies showed that the evaluation of CMVD has significant impact on both the early diagnosis of heart diseases relevant to blood supply and prognosis after myocardial reperfusion. In this review, the definition of CMVD from the perspective of pathophysiology was clarified, the principles and features of the state-of-the-art imaging technologies for CMVD assessment were reviewed from the perspective of engineering and the further research direction was promoted.

Magnesium lithospermate B ameliorates microcirculation perfusion in rats by promoting vascular NO production via activating the PI3K/AKT pathway.

Microcirculation morphologically refers to the blood flow in vessels of less than 150 µm in diameter, including arterioles, capillaries and venules, which provides nutrients and removes metabolic byproducts within tissues. Microcirculation dysfunction is involved in the pathological progress of many diseases, such as obesity, hypertension, and insulin resistance. In this study we investigated the effects of magnesium lithospermate B (MLB), an active compound of the traditional Chinese medicine Slavia miltiorrhiza, on the microcirculation dysfunction in rats and the underlying molecular mechanisms. The effects of MLB on microcirculation were assessed in vivo by measuring the hindlimb blood perfusion in dextran-induced microcirculation dysfunction rats and mesentery blood flow in anesthetized rats. We demonstrated that administration of MLB restored the impaired rat hindlimb blood flow and promoted the mesenteric micoperfusion in vivo. We further revealed in these two animal models that MLB treatment significantly increased the production of total nitrite in vascular tissues (mesentery, aorta, and heart), which was confirmed in human microvascular endothelial cells (HMEC-1) treated with MLB in vitro. Moreover, we showed that MLB treatment significantly increased the phosphorylation of endothelium nitric oxide synthase (eNOS) via inducing AKT phosphorylation in vivo and in vitro. Co-administration of the eNOS inhibitor L-NAME (20 mg/kg) abolished the protective effects of MLB against dextran-induced microcirculation dysfunction in rats, whereas pretreatment with PI3K inhibitor LY294002 (10 µM) prevented eNOS activation in MLB-treated HMEC-1 cells. Our results suggest that MLB can restore the microcirculation dysfunction via activating eNOS, and in turn enhancing the vascular nitric oxide production, which is medicated by MLB-caused activation of the PI3K/AKT pathway.

Comparative pharmacokinetic study on phenolic acids and flavonoids in normal and microcirculation dysfunction rats plasma by UPLC-TQ/MS/MS after oral administration of Salvia miltiorrhiza stem-leaf extracts.

According to the Standard of Chinese Medicinal Materials of Shaanxi Province (2015 edition), Salvia miltiorrhiza caulis et folium is the dried stems and leaves of Salvia miltiorrhiza, which could activate blood and dispell blood stasis, clear the mind and remove annoyance. In this study, the dynamic absorption changes of phenolic acids (FS) and phenolic acids-flavonoids (FT) in rats after oral administration were studied by UPLC-TQ/MS/MS, to elucidate the pharmacokinetics of seven major bioactive components of the stem-leaf of Salvia miltiorrhiza in vivo. The results showed that the pharmacokinetic parameters of FS and FT were significantly different in normal rats and model rats. Compared with the control group, after injecting 10 % polymer dextran 500 into the tail vein to establish a model of microcirculation disturbance, the Cmax of caffeic acid decreased. The Cmax of rosmarinic acid and lithospermic acid increased. Danshensu showed a decrease in CLz/F, accompanied by an increase in both AUC0-t and AUC0-∞. The AUC0-t of lithospermic acid was also increased. These results indicated that microcirculation disturbance could decrease the absorption of caffeic acid while increasing the absorption of danshensu, rosmarinic acid and lithospermic acid. After oral administration of FT, the Cmax of danshensu and the AUC0-t of caffeic acid were increased significantly, suggesting that the presence of flavonoids may promote the absorption and exposure of phenolic acids in vivo. This study provides a reference for the elucidation of the in vivo substances and the mechanisms of action of FS and FT from the stem-leaf of Salvia miltiorrhiza.

GSEA analysis identifies potential drug targets and their interaction networks in coronary microcirculation disorders.

Coronary microcirculation dysfunction (CMD) is one of the main causes of cardiovascular disease. Traditional treatment methods lack specificity, making it difficult to fully consider the differences in patient conditions and achieve effective treatment and intervention. The complexity and diversity of CMD require more standardized diagnosis and treatment plans to clarify the best treatment strategy and long-term outcomes. The existing treatment measures mainly focus on symptom management, including medication treatment, lifestyle intervention, and psychological therapy. However, the efficacy of these methods is not consistent for all patients, and the long-term efficacy is not yet clear. GSEA is a bioinformatics method used to interpret gene expression data, particularly for identifying the enrichment of predefined gene sets in gene expression data. In order to achieve personalized treatment and improve the quality and effectiveness of interventions, this article combined GSEA (Gene Set Enrichment Analysis) technology to conduct in-depth research on potential drug targets and their interaction networks in coronary microcirculation dysfunctions. This article first utilized the Coremine medical database, GeneCards, and DrugBank public databases to collect gene data. Then, filtering methods were used to preprocess the data, and GSEA was used to analyze the preprocessed gene expression data to identify and calculate pathways and enrichment scores related to CMD. Finally, protein sequence features were extracted through the calculation of autocorrelation features. To verify the effectiveness of GSEA, this article conducted experimental analysis from four aspects: precision, receiver operating characteristic (ROC) curve, correlation, and potential drug targets, and compared them with Gene Regulatory Networks (GRN) and Random Forest (RF) methods. The results showed that compared to the GRN and RF methods, the average precision of GSEA improved by 0.11. The conclusion indicated that GSEA helped identify and explore potential drug targets and their interaction networks, providing new ideas for personalized quality of CMD.

Shexiang Tongxin Dropping Pill Promotes Angiogenesis through VEGF/eNOS Signaling Pathway on Diabetic Coronary Microcirculation Dysfunction.

OBJECTIVE: To study the effect of Shexiang Tongxin Dropping Pill (STDP) on angiogenesis in diabetic cardiomyopathy mice with coronary microcirculation dysfunction (CMD). METHODS: According to a random number table, 6 of 36 SPF male C57BL/6 mice were randomly selected as the control group, and the remaining 30 mice were injected with streptozotocin intraperitoneally to replicate the type 1 diabetes model. Mice successfully copied the diabetes model were randomly divided into the model group, STDP low-dose group [15 mg/(kg·d)], medium-dose group [30 mg/(kg·d)], high-dose group [60 mg/(kg·d)], and nicorandil group [15 mg/(kg·d)], 6 in each group. The drug was given by continuous gavage for 12 weeks. The cardiac function of mice in each group was detected at the end of the experiment, and coronary flow reserve (CFR) was detected by chest Doppler technique. Pathological changes of myocardium were observed by hematoxylin-eosin staining, collagen fiber deposition was detected by masson staining, the number of myocardial capillaries was detected by platelet endothelial cell adhesion molecule-1 staining, and the degree of myocardial hypertrophy was detected by wheat germ agglutinin staining. The expression of the vascular endothlial growth factor (VEGF)/endothelial nitric oxide synthase (eNOS) signaling pathway-related proteins in myocardial tissue was detected by Western blot. RESULTS: Compared with the model group, medium- and high-dose STDP significantly increased the left ventricular ejection fraction and left ventricular fraction shortening (P<0.01), obviously repaired the disordered cardiac muscle structure, reduced myocardial fibrosis, reduced myocardial cell area, increased capillary density, and increased CFR level (all P<0.01). Western blot showed that high-dose STDP could significantly increase the expression of VEGF and promote the phosphorylation of vascular endothelial growth factor receptor 2, phosphoinositide 3-kinase, protein kinase B, and eNOS (P<0.05 or P<0.01). CONCLUSION: STDP has a definite therapeutic effect on diabetic CMD, and its mechanism may be related to promoting angiogenesis through the VEGF/eNOS signaling pathway.

Ticagrelor vs. clopidogrel for coronary microvascular dysfunction in patients with STEMI: a meta-analysis of randomized controlled trials.

Purpose: Approximately half of ST-segment elevation myocardial infarction (STEMI) patients who undergo revascularization present with coronary microvascular dysfunction. Dual antiplatelet therapy, consisting of aspirin and a P2Y12 inhibitor (e.g., clopidogrel or ticagrelor), is recommended to reduce rates of cardiovascular events after STEMI. The present study performed a pooled analysis of randomized controlled trials (RCTs) to compare effects of ticagrelor and clopidogrel on coronary microcirculation dysfunction in STEMI patients who underwent the primary percutaneous coronary intervention. Methods: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched for eligible RCTs up to September 2022, with no language restriction. Coronary microcirculation indicators included the corrected thrombolysis in myocardial infarction (TIMI) frame count (cTFC), myocardial blush grade (MBG), TIMI myocardial perfusion grade (TMPG), coronary flow reserve (CFR), and index of microcirculatory resistance (IMR). Results: Seven RCTs that included a total of 957 patients (476 who were treated with ticagrelor and 481 who were treated with clopidogrel) were included. Compared with clopidogrel, ticagrelor better accelerated microcirculation blood flow [cTFC = -2.40, 95% confidence interval (CI): -3.38 to -1.41, p < 0.001] and improved myocardial perfusion [MBG = 3, odds ratio (OR) = 1.99, 95% CI: 1.35 to 2.93, p < 0.001; MBG ≥ 2, OR = 2.57, 95% CI: 1.61 to 4.12, p < 0.001]. Conclusions: Ticagrelor has more benefits for coronary microcirculation than clopidogrel in STEMI patients who undergo the primary percutaneous coronary intervention. However, recommendations for which P2Y12 receptor inhibitor should be used in STEMI patients should be provided according to results of studies that investigate clinical outcomes.

Invasive Detection of Coronary Microvascular Dysfunction: How It Began, and Where We Are Now.

The landscape of interventional cardiology is ever evolving. Contemporary practice has shifted from a stenosis-centred approach to the total characterisation of both the epicardial and microcirculatory vessels. Microcirculatory dysfunction plays an important role in the pathophysiology of acute and chronic coronary syndromes, and characterisation of the microcirculation has important clinical consequences. Accordingly, the invasive diagnosis of microcirculatory dysfunction is becoming a key feature of the interventional cardiologist's toolkit. This review focuses on the methodology underpinning the invasive diagnosis of microvascular dysfunction and highlights the indices that have arisen from these methodologies.

Influence of fasting plasma glucose-lowering rate on BNP levels in type 2 diabetes mellitus patients with coronary microcirculation dysfunction.

AIM: The aim was to analyze the influence of fasting plasma glucose-lowering rate (FPGLR) on plasma BNP levels in type 2 diabetes mellitus (T2DM) patients with coronary microcirculation dysfunction (CMD) and to determine the optimal FPGLR for these patients. METHODS: A total of 170 T2DM patients who received intensive glucose-lowering therapy during hospitalization in the First Affiliated Hospital of Harbin Medical University were enrolled. Ninety-two patients with CMD and 78 patients without CMD were assigned to a study and a control group, respectively. The study group was stratified as S1 (4.1 ~ 6.0 mmol·L-1·day-1), S2 (2.1 ~ 4.0 mmol·L-1·day-1), and S3 (≤ 2.0 mmol·L-1·day-1) by different FPGLR, and the same in the control group (C1, C2, and C3). The plasma BNP levels with the same FPGLR were compared between the study and the control group, and patients with a different FPGLR in the study group were also compared. RESULTS: In the study and the control group, the BNP level in S1 was significantly higher than that in C1 (87 vs. 12 pg/ml, P < 0.001), although there was no significant difference between S2 and C2, S3 and C3. In the study group, the BNP level in S1 was significantly higher than that in S2 (87 vs. 22 pg/ml, P < 0.001) and S3 (87 vs. 15 pg/ml, P < 0.001), but there was no significant difference between S2 and S3. CONCLUSION: Rapid intensive glucose-lowering may lead to increased plasma BNP levels in T2DM patients with CMD. Optimal FPGLR for these patients was determined to be no more than 4.0 mmol·L-1·day-1.

Correlation Between Retinopathy and Coronary Microcirculation Dysfunction in Patients with Type 2 Diabetes Mellitus.

PURPOSE: The aim of this study is to evaluate the correlation between retinopathy and coronary microcirculation dysfunction (CMD) in type 2 diabetes mellitus (T2DM) patients. METHODS: 198 T2DM patients with left ventricular ejection fraction (LVEF)>50%, no epicardial coronary artery stenosis diagnosis by coronary angiography (CAG) and successfully completed coronary blood flow reserve (CFR) test and laboratory examination were enrolled, and fundus examination was performed on all participants. Two groups were divided according to CFR value, including 86 patients with CMD (CFR≤2.5) in study group and 112 patients without CMD (CFR>2.5) in control group. The composition of various retinopathy in two groups was observed, and the correlation between retinopathy and CMD was analyzed using ordered logistic regression. RESULTS: There were 13 cases with arteriovenous (A/V) nicking, 4 cases with proliferative diabetic retinopathy (PDR), 14 cases with non-proliferative diabetic retinopathy (NPDR), 17 cases with diabetic retinopathy (DR) with A/V nicking, 38 cases without retinopathy in study group, and 18 cases, 7 cases, 20 cases, 4 cases and 63 cases for each in control group. After adjustment for age, gender, hypertension, diabetes duration, dyslipidemia, glycosylated hemoglobin (HbA1c), body mass index (BMI), A/V nicking, PDR and NPDR, the diference of DR with A/V nicking between study and control group remained statistically signifcant (OR 2.0, 95% CI 0.79 to 3.21, p = 0.001). CONCLUSION: DR with A/V nicking could be used as an independent predictor of T2DM patients with CMD. CFR testing should be performed on patients with this kind of eye sign, even if they do not have any symptoms of heart disease. Meanwhile, DR with A/V nicking might be served as a reference indicator of CMD in T2DM patients with chest pain who were unable to be tested for CFR.

Influence of Microcirculatory Dysfunction on Myocardial Injury after Cardiopulmonary Resuscitation.

Objective: This study aimed to examine the effects of microcirculatory dysfunction and 654-1 intervention after cardiopulmonary resuscitation on myocardial injury. Methods: Landrace pigs were divided into a sham operation group (S group, n= 6), ventricular fibrillation control group (VF-C group, n= 8) and 654-1 intervention group (VF-I group, n= 8). Hemodynamics was recorded at baseline, at recovery of spontaneous circulation (ROSC), and 1 h, 2 h, 4 h and 6 h thereafter. Sidestream dark field (SDF) technology was used to evaluate and monitor the microcirculation flow index, total vessel density, perfusion vessel ratio, De-Backer score, and perfusion vessel density in animal viscera at various time points. Results: After administration of 654-1 at 1.5 h post-ROSC, the hemodynamics in the VF-I group, as compared with the VF-C group, was significantly improved. The visceral microcirculation detected by SDF was also significantly improved in the VF-I group. As observed through electron microscopy, significantly less myocardial tissue injury was present in the VF-I group than the VF-C group. Conclusion: Administration of 654-1 inhibited excessive inflammatory by improving the state of visceral microcirculation.

Relationship Between Plasma Total Homocysteine Levels and Mean Corrected TIMI Frame Count in Patients with Acute Myocardial Infarction.

OBJECTIVE: To explore the relationship between the plasma total homocysteine (tHcy) levels and slow coronary flow (SCF) measured by mean corrected TIMI frame count (CTFC) in patients with acute myocardial infarction (AMI). METHODS: Ninety-one patients with primary myocardial infarction were enrolled in this study. The quantitative measurement of coronary blood flow was performed using the mean CTFC method. Plasma tHcy levels were determined using enzymatic assay from venous blood samples. Multivariable linear regression models indicated were used to estimate the effect size (ß) of plasma tHcy levels on mean CTFC levels. RESULTS: Compared with patients with the mean CTFC ≤23.61 frames per second (FPS) group, there were increased plasma tHcy levels in patients of the second, third and highest mean CTFC quartiles (P < 0.001). Linear regression models indicated that plasma tHcy levels were positively associated with mean CTFC levels (adjusted-ß per SD increase: 1.96, 95% CI 1.20 to 2.73, P < 0.001). Compared to the tHcy ≤12.30 µmol/L group, the third and highest tHcy-quartile groups had higher mean CTFC levels (adjusted-ß: 2.52, 95% CI 0.39 to 4.65, P = 0.023; adjusted-ß: 5.07, 95% CI 2.98 to 7.16, P < 0.001, respectively; P for trend <0.001). Moreover, this positive relationship was modified by diabetes mellitus (P-value for interaction was 0.046). CONCLUSION: We found a positive relationship between plasma tHcy levels and mean CTFC levels in patients with AMI. Moreover, diabetes mellitus played an interactive role in this positive association between the plasma tHcy levels and mean CTFC levels.

Tanshinol Alleviates Microcirculation Disturbance and Impaired Bone Formation by Attenuating TXNIP Signaling in GIO Rats.

Impaired bone formation is the main characteristics of glucocorticoid (GC)-induced osteoporosis (GIO), which can be ameliorated by tanshinol, an aqueous polyphenol isolated from Salvia miltiorrhiza Bunge. However, the underlying mechanism is still not entirely clear. In the present study, we determined the parameters related to microstructure and function of bone tissue, bone microcirculation, and TXNIP signaling to investigate the beneficial effects of tanshinol on skeleton and its molecular mechanism in GIO rats. Male Sprague-Dawley rats aged 4 months were administrated orally with distilled water (Con), tanshinol (Tan, 25 mg kg-1 d-1), prednisone (GC, 5 mg kg-1 d-1) and GC plus tanshinol (GC + Tan) for 14 weeks. The results demonstrated that tanshinol played a significant preventive role in bone loss, impaired microstructure, dysfunction of bone metabolism and poor bone quality, based on analysis of correlative parameters acquired from the measurement by using Micro-CT, histomorphometry, ELISA and biomechanical assay. Tanshinol also showed a significant protective effect in bone microcirculation according to the evidence of microvascular perfusion imaging of cancellous bone in GIO rats, as well as the migration ability of human endothelial cells (EA.hy926, EA cells). Moreover, tanshinol also attenuated GC-elicited the activation of TXNIP signaling pathway, and simultaneously reversed the down-regulation of Wnt and VEGF pathway as manifested by using Western-blot method in GIO rats, EA cells, and human osteoblast-like MG63 cells (MG cells). Collectively, our data highlighted that tanshinol ameliorated poor bone health mediated by activation of TXNIP signaling via inhibiting microcirculation disturbance and the following impaired bone formation in GIO rats.

Effects and mechanisms of PSS-loaded nanoparticles on coronary microcirculation dysfunction in streptozotocin-induced diabetic cardiomyopathy rats.

Coronary microvascular dysfunction (CMD) is the pathological basis and pathogenesis of diabetic cardiomyopathy (DCM). Propylene glycol alginate sodium sulfate (PSS) as heparinoid drug has many biological activities. Here, a novel PSS-loaded nanoparticle (PSS-NP) was prepared to study its effect on the CMD of DCM. We used diabetes mellitus rat induced by STZ to establish the CMD model of DCM, and the study was detected by echocardiography, histological analysis, transmission electron microscopy, immunofluorescence staining, enzyme-linked immunosorbent assay, real time-PCR analysis, liquid-chip analysis, western blot analysis and so on. The experimental results suggested that PSS-NP could improve the survival state of rats, cardiac function, myocardial morphology and coronary microcirculation structure disorders, and increase the number of microvessels. In addition, we demonstrated that PSS-NP could alleviate the CMD by improving endothelial function, anticoagulation and antioxidative stress. The outcomes of this study provided new treatment thoughts for the therapy of coronary microcirculation dysfunction in DCM.