ABSTRACT
BACKGROUND: Adverse atherogenic lipid profile is associated with an increased risk of major adverse cardiac events in patients after acute coronary syndrome (ACS). Knowledge regarding the impact of statins on lipid profile remains limited. METHODS: We retrospectively analysed multicenter, real-world data from the Chinese Cardiovascular Association Database-iHeart Project. Patients with a primary diagnosis of ACS from 2014 to 2021 during index hospitalisation and having at least one lipid panel record after discharge within 12 months were enrolled. We analysed target achievement of atherogenic lipid profile, including apolipoprotein B (< 80 mg/dL), low-density lipoprotein cholesterol (LDL-C) (< 1.8 mmol/L), lipoprotein(a) [Lp(a)] (< 30 mg/dL), triglycerides (< 1.7 mmol/L), remnant cholesterol (RC) (< 0.78 mmol/L), non-high-density lipoprotein cholesterol (< 2.6 mmol/L) at baseline and follow-up. Multivariate Cox regression models were employed to investigate the association between patient characteristics and target achievement. RESULTS: Among 4861 patients, the mean age was 64.9 years. Only 7.8% of patients had all atherogenic lipids within the target range at follow-up. The proportion of target achievement was for LDL-C 42.7%, Lp(a) 73.3%, and RC 78.5%. Patients with female sex, younger age, myocardial infarction, hypertension, and hypercholesteremia were less likely to control LDL-C, Lp(a), and RC. An increase in the burden of comorbidities was negatively associated with LDL-C and Lp(a) achievements but not with RC. CONCLUSIONS: A substantial gap exists between lipid control and the targets recommended by contemporary guidelines. Novel therapeutics targeting the whole atherogenic lipid profile will be warranted to improve cardiovascular outcomes.
Subject(s)
Acute Coronary Syndrome , Cholesterol, LDL , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Humans , Acute Coronary Syndrome/drug therapy , Acute Coronary Syndrome/blood , Male , Female , Middle Aged , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Aged , Cholesterol, LDL/blood , Retrospective Studies , Triglycerides/blood , Atherosclerosis/blood , Atherosclerosis/drug therapy , Databases, Factual , Lipids/blood , Lipoprotein(a)/blood , China/epidemiology , Risk Factors , East Asian PeopleABSTRACT
Microvascular damage is a key pathological change in myocardial ischemia/reperfusion (I/R) injury. Using a rat model of myocardial I/R, our current study has provided the first evidence that nicotinamide adenine dinucleotide (NAD+) administration can significantly attenuate myocardial I/R-induced microvascular damage, including reduced regional blood perfusion, decreased microvessel density and integrity, and coronary microvascular endothelial cells (CMECs) injury. In studies with primary cultured CMECs under hypoxia/reoxygenation (HR) and a rat model of I/R, our results suggested that the protective effect of NAD+ on CMECs exposed to HR or I/R is at least partially mediated by the NAD+-induced restoration of autophagic flux, especially lysosomal autophagy: NAD+ treatment markedly induced transcription factor EB (TFEB) activation and attenuated lysosomal dysfunction in the I/R or HR-exposed cells. Collectively, our study has provided the first in vivo and in vitro evidence that NAD+ significantly rescued the impaired autophagic flux and cell apoptosis that was induced by I/R in rat CMECs, which is mediated in part through the action of TFEB-mediated lysosomal autophagy.
Subject(s)
Autophagy/drug effects , Myocardial Reperfusion Injury/prevention & control , NAD/therapeutic use , Animals , Cell Separation , Drug Evaluation, Preclinical , Endothelium, Vascular/cytology , Endothelium, Vascular/drug effects , Male , Microvessels/drug effects , NAD/pharmacology , Rats, Sprague-DawleyABSTRACT
OBJECTIVE: Evidence has shown that the ACE2/Ang (1-7)/Mas axis plays an important role in the control of hypertension. Thus, we hypothesized that chemical renal denervation (RDN) could reduce blood pressure by regulating the ACE2/Ang (1-7)/Mas axis in spontaneously hypertensive rats. METHODS: Twelve rats were randomly divided into sham group and chemical RDN group. All the rats were sacrificed 4 weeks later. Plasma samples were collected to measure the renin-angiotensin system (RAS) activities and reactive oxygen species levels by radioimmunoassay, chromatometry and ELISA. Paraventricular nucleus (PVN) tissues were collected to examine the expression of the components of the ACE2/Ang (1-7)/Mas axis by western bolt and immunofluorescence. RESULTS: The systolic blood pressure (169.33 ± 7.50 vs 182.67 ± 7.00 mmHg, p < .05) and the diastolic blood pressure (97.50 ± 4.68 vs 109.33 ± 4.41 mmHg, p < .05) in the RDN group were obviously lower than the baseline levels, whereas the opposite results were observed in the sham group. The RDN group exhibited a significant reduction in the plasma ROS (91.59 ± 13.12 vs 72.34 ± 11.76 U/ml, p < .05) and NADPH oxidase (171.86 ± 1.14 vs 175.75 ± 1.74 nmol/ml, p < .001) compared with the sham group, while the plasma eNOS (3.47 ± 0.42 vs 2.49 ± 0.51 U/ml, p < .05) and NO (55.92 ± 8.10 vs 43.53 ± 4.58 µmol/L, p < .05) were increased. The expression of the components of the ACE2/Ang (1-7)/Mas axis was upregulated while the expression of the components of the ACE/Ang II/AT1 R axis was downregulated in the plasma and PVN in the RDN group. CONCLUSION: Our findings suggested that the reduction in blood pressure was regulated by chemical RDN-induced upregulation of the components of the ACE2/Ang (1-7)/Mas axis.
Subject(s)
Angiotensin I/metabolism , Blood Pressure , Peptide Fragments/metabolism , Peptidyl-Dipeptidase A/metabolism , Proto-Oncogene Proteins/metabolism , Receptors, G-Protein-Coupled/metabolism , Sympathectomy, Chemical , Angiotensin-Converting Enzyme 2 , Animals , Hypertension/physiopathology , Male , NADPH Oxidases/blood , Nitric Oxide/blood , Nitric Oxide Synthase Type III/blood , Paraventricular Hypothalamic Nucleus/metabolism , Proto-Oncogene Mas , Random Allocation , Rats , Rats, Inbred SHR , Reactive Oxygen Species/blood , Renal Artery/innervation , Renin-Angiotensin System , Up-RegulationABSTRACT
Endothelial inflammation and monocyte plays an essential role in the initiation and progression of atherosclerosis. Ghrelin is beneficial for atherosclerosis progression. However, the detailed and precise molecular mechanisms of how ghrelin regulates endothelial inflammation are not clear. In this study, we investigated the regulation mechanism of ghrelin on TNF-α-activated endothelial inflammation and monocyte adhesion. It was found that TNF-α-induced monocyte adhesion on HUVEC was significantly attenuated by ghrelin. Furthermore, we found that ghrelin effectively suppressed TNF-α-induced inflammatory factors' (including ICAM-1, VCAM-1, MCP-1, and IL-1ß) expression through inhibiting AMPK phosphorylation and p65 expression both in HUVEC and THP-1. This phenomenon was further demonstrated by using AMPK agonist AICAR and inhibitor compound C, respectively. Our findings suggest that ghrelin may mediate TNF-α-induced endothelial inflammation and monocyte adhesion, in part via AMPK/NF-κB signaling pathway. These novel anti-inflammatory and immunoregulatory actions of ghrelin may play a certain role in understanding the formation and development of atherosclerosis.
Subject(s)
AMP-Activated Protein Kinases/metabolism , Ghrelin/pharmacology , Inflammation Mediators/metabolism , Signal Transduction/drug effects , Transcription Factor RelA/metabolism , Cytokines/metabolism , Human Umbilical Vein Endothelial Cells , Humans , Inflammation/metabolism , Inflammation/pathology , Intercellular Adhesion Molecule-1/metabolism , THP-1 Cells , Vascular Cell Adhesion Molecule-1/metabolismABSTRACT
Cardiovascular disease is a leading cause of death worldwide, requiring the development of new therapeutic strategies including stem cell therapy. Pentraxins (PTXs) are a superfamily of proteins highly involved in different myocardial disorders, and thus this study aimed to identify the modulation of long pentraxin 3 (PTX3) in the differentiation of mouse embryonic stem cells (mESCs) toward cardiomyocytes. Cell toxicity of PTX3 was detected by MTT and LDH assays in mESCs. Embryoid bodies (EBs) were differentiated using hanging drop method, and the beating was observed under microscope. Expressional levels of early cardiac progenitor marker genes were assessed by qRT-PCR. Expression of marker proteins in early myocardial development and the activation of JNK signaling pathway was evaluated by Western blot. PTX3 treatment at 50 ng/mL significantly promoted the expression of cardiac-specific marker genes including Nkx2.5, Mef2c, Tbx5, dHand, and αMHC, and increased the expression of cardiac maturity indicative markers including connexin 43 and troponin C1. PTX3 enhanced the phosphorylation of JNK across the incubation duration, whereas the activation of p38 remained the same as control group. Co-treatment of JNK signaling pathway inhibitor SP600125 impaired the PTX3-promoted transcription of Nkx2.5, Mef2c, Tbx5, dHand, and αMHC. This study revealed the promotion of PTX3 in the differentiation of mESCs into cardiomyocytes and the underlying mechanism.
Subject(s)
C-Reactive Protein/pharmacology , Cell Differentiation/drug effects , MAP Kinase Signaling System/drug effects , Mouse Embryonic Stem Cells/cytology , Mouse Embryonic Stem Cells/metabolism , Myocardium/cytology , Serum Amyloid P-Component/pharmacology , Animals , Biomarkers/metabolism , Cell Survival/drug effects , Connexin 43/metabolism , Embryoid Bodies/cytology , Embryoid Bodies/drug effects , Embryoid Bodies/metabolism , Gene Expression Regulation/drug effects , Mice , Mouse Embryonic Stem Cells/drug effects , Myocytes, Cardiac/cytology , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Organ Specificity , Troponin C/metabolismABSTRACT
The prevalence of chronic kidney disease (CKD) is high in patients with atrial fibrillation (AF). Left atrial appendage closure (LAAC) has been recognized as an efficient alternative to oral anticoagulation for the prevention of thromboembolic events in patients with non-valvular AF (NVAF); however, the long-term safety and efficacy of LAAC in patients with CKD remain unclear. This study was designed to provide data regarding the safety and efficacy of LAAC in NVAF patients with CKD. A real-world analysis of the safety and efficacy of LAAC was performed on a cohort of 300 NVAF patients with or without CKD who underwent LAAC using the Watchman (WM) device at our center. The patients with CKD (n = 151) were significantly older (77.0 ± 7.2 vs. 73.2 ± 7.8 years, respectively, P < 0.0001) and had a higher CHA2DS2-VASc score (4.3 ± 1.5 vs. 3.4 ± 1.4, respectively, P < 0.0001) and HAS-BLED score (4.0 ± 1.0 vs. 3.0 ± 1.0, respectively, P < 0.0001) than the patients without CKD (n = 149). However, there were no differences between groups with respect to the device implant success rate (98.7 vs. 97.3%, respectively, P = 0.446) or severe periprocedural complications within 7 days. The patients were followed up for 637 ± 398 days, and all patients received repeat transesophageal echocardiography (TEE). Thirteen (4.3%) device-related thrombi, 3 (1.0%) ischemic strokes, and 19 (6.3%) non-procedural major bleeding cases were documented, and there were no differences in these complications between groups. The observed rate of all thromboembolic events by Kaplan-Meier analysis decreased by 68.8% (CKD) and 48.6% (non-CKD); moreover, the observed annual rate of bleeding was reduced by 57.5% (CKD) and 11.4% (non-CKD). Our results indicate that LAAC with the WM device is safe and effective in preventing stroke in NVAF patients with and without CKD.
Subject(s)
Atrial Appendage/surgery , Atrial Fibrillation/surgery , Glomerular Filtration Rate/physiology , Prosthesis Implantation/methods , Renal Insufficiency, Chronic/complications , Septal Occluder Device , Stroke/prevention & control , Aged , Atrial Appendage/diagnostic imaging , Atrial Fibrillation/complications , Atrial Fibrillation/diagnosis , Echocardiography, Transesophageal , Female , Follow-Up Studies , Humans , Male , Renal Insufficiency, Chronic/physiopathology , Retrospective Studies , Stroke/etiology , Treatment OutcomeABSTRACT
BACKGROUNDS AND AIMS: This study aims to explore the efficacy of reperfusion strategies on the clinical outcomes of ST-elevation myocardial infarction (STEMI) patients over 80 years old in China. METHODS: A retrospective cohort study was performed on STEMI patients over 80 years old who underwent reperfusion strategies and no reperfusion between January 2014 and December 2021 based on the China Cardiovascular Association (CCA) Database-Chest Pain Center. RESULTS: This study included a total of 42,699 patients (mean age 84.1 ± 3.6 years, 52.2% male) among which 19,280 (45.2%) underwent no reperfusion, 20,924 (49.0%) underwent primary percutaneous coronary intervention (PCI), and 2,495 (5.8%) underwent thrombolytic therapy. After adjusting for potential confounders, multivariable logistic regression analysis revealed that patients who underwent primary PCI strategy showed a significantly lower risk of in-hospital mortality (OR = 0.62, 95% CI: 0.57-0.67, P < 0.001) and the composite outcome (OR = 0.83, 95% CI: 0.79-0.87, P < 0.001) compared to those received no reperfusion. In contrast, patients with thrombolytic therapy exhibited a non-significantly higher risk of in-hospital mortality (OR = 0.99, 95% CI: 0.86-1.14, P = 0.890), and a significantly elevated risk of the composite outcome (OR = 1.15, 95% CI: 1.05-1.27, P = 0.004). During a median follow-up of 6.7 months post-hospital admission, there was a percentage 31.4% of patients died and patients in the primary PCI group consistently demonstrated a reduced incidence of all-cause mortality (HR = 0.58, 95% CI: 0.56-0.61, P < 0.001). CONCLUSION: STEMI patients over 80 years old who underwent the primary PCI strategy are more likely to have favorable clinical outcomes compared to those who received no reperfusion, whereas, thrombolytic therapy warrants careful assessment and monitoring.
ABSTRACT
Background: Microvascular dysfunction in patients with non-obstructive epicardial coronary may aggravate patient's symptoms or lead to various clinical events. Objective: To investigate the correlation between dynamic single photon emission computed tomography (D-SPECT) derived coronary flow reserve (CFR) and TIMI frame count (TFC) in patients with non-obstructive epicardial coronary patients. Methods: Patients with suspected or known stable CAD who were recommended to undergo invasive coronary angiography were prospectively enrolled in this study. Those who had non-obstructive coronary received TIMI frame count (TFC) and D-SPECT. A cut-off value of >40 was defined as slow flow referred to TFC. Results: A total of 47 patients diagnosed with non-obstructive coronary were enrolled. The mean age of patients was 66.09 ± 8.36 years, and 46.8% were male. Dynamic SPECT derived coronary flow reserve (CFR) was significantly correlated with TIMI frame count in 3 epicardial coronary (LAD: r=-0.506, P = 0.0003; LCX: r= -0.532, P = 0.0001; RCA: r= -0.657, P < 0.0001). The sensitivity and specificity of CFR in identifying abnormal TIMI frame count < 40 was 100.0% and 57.6% in LAD, 62.5% and 87.0% in LCX, 83.9% and 75.0% in RCA, respectively. The optimal CFR cut-off values were 2.02, 2.47, and 1.96 among the three vessels. Conclusion: In patients with non-obstructive coronary, CFR derived from D-SPECT was strongly correlated with TFC. This study demonstrates that that CFR may be an alternative non-invasive method for identifying slow flow in non-obstructive coronary.
Subject(s)
Coronary Artery Disease , Coronary Circulation , Humans , Male , Aged , Female , Tomography, Emission-Computed, Single-Photon , Coronary Angiography , Coronary Artery Disease/diagnostic imagingABSTRACT
BACKGROUND: Ascending aortic perivascular adipose tissue (AA-PVAT) mainly comprises brown adipose tissue (BAT), originates from neural crest cells that derive from ectoderm, and plays important role in angiotensin II-induced vascular inflammation and remodeling in mice. However, the characterization and function of human AA-PVAT remains highly unclear. METHODS: Patients with coronary artery disease (CAD) (nâ¯=â¯20) and aortic valve disease (AVD) (nâ¯=â¯23) who underwent cardiac surgery consented to take part in transcriptome and histological studies. Paired samples of AA-PVAT, epicardial adipose tissue (EAT), and subcutaneous adipose tissue (SAT) were obtained. RNA sequencing, histological analysis, quantitative reverse transcription polymerase chain reaction and western blot studies were performed on those samples. RESULTS: Human AA-PVAT exhibited smaller adipocyte morphology and high expression of brown adipocyte marker. Transcriptome analysis revealed that AA-PVAT showed unique transcriptome characteristics compared with EAT and SAT. While comparing CAD and AVD patients, AA-PVAT exhibited a decreasing brown phenotype and higher inflammatory response in AVD patients. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis suggested that the differentially expressed genes in AA-PVAT between CAD and AVD patients were involved mainly in the processes of inflammation and metabolism regulation. CONCLUSIONS: Human AA-PVAT is a BAT-like adipose tissue with unique transcriptome characteristics, and exhibits a weakened brown phenotype and an enhanced inflammation response in AVD patients.
Subject(s)
Aortic Valve Disease , Coronary Artery Disease , Adipose Tissue/metabolism , Animals , Aorta/metabolism , Humans , Inflammation , Mice , Pericardium/metabolismABSTRACT
INTRODUCTION: Coronary CT angiography (CCTA)-derived quantitative flow ratio (CT-QFR) is a novel non-invasive technology to assess the physiological significance of coronary stenoses, which enables fast and on-site computation of fractional flow reserve (FFR) from CCTA images. The objective of this investigator-initiated, prospective, single-centre clinical trial is to evaluate the diagnostic performance of CT-QFR with respect to angiography-derived QFR, using FFR as the reference standard. METHODS AND ANALYSIS: A total of 216 patients who have at least one lesion with a diameter stenosis of 30%-90% in an artery with ≥2.0 mm reference diameter will be enrolled in the study. FFR will be measured during invasive coronary angiography. CT-QFR and QFR will be assessed in two independent core laboratories in a blinded fashion. The primary endpoint is the diagnostic accuracy of CT-QFR in identifying haemodynamically significant coronary stenosis with FFR as the reference standard. The major secondary endpoint is the non-inferiority of CT-QFR compared with QFR in the patients without extensively calcified lesions. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of Huadong Hospital Affiliated to Fudan University (2020K192). Outcomes will be disseminated through publications in peer-reviewed journals and presentations at scientific conferences. TRIAL REGISTRATION NUMBER: NCT04665817.
Subject(s)
Coronary Artery Disease , Coronary Stenosis , Fractional Flow Reserve, Myocardial , Computed Tomography Angiography , Coronary Angiography/methods , Coronary Artery Disease/complications , Coronary Artery Disease/diagnostic imaging , Coronary Stenosis/complications , Coronary Stenosis/diagnostic imaging , Coronary Vessels , Fractional Flow Reserve, Myocardial/physiology , Humans , Predictive Value of Tests , Prospective Studies , Severity of Illness Index , Tomography, X-Ray ComputedABSTRACT
Background Coronary physiology measurement in serial coronary lesions with multiple stenoses is challenging. Therefore, we evaluated the feasibility of Murray fractal law-based quantitative flow ratio (µQFR) virtual stenting for guidance of serial coronary lesions intervention. Methods and Results Patients who underwent elective coronary angiography and had 2 serial de novo coronary lesions of 30% to 90% diameter stenosis by visual estimation were prospectively enrolled. µQFR and fractional flow reserve (FFR) were assessed after coronary angiography. In vessels with an FFR ≤0.80, the lesion with the larger pressure gradient was considered to be the primary lesion and treated firstly, followed by FFR measurement. The second lesion was stented when FFR ≤0.80. All µQFR and predicted µQFR after stenting were calculated from diagnostic coronary angiography before interventions, with the analysts masked to the FFR data. A total of 54 patients with 61 target vessels were interrogated. Percutaneous coronary intervention was performed in 44 vessels with FFR ≤0.80. After stenting the primary lesions, 14 nonprimary lesions had FFR ≤0.80 and a second drug-eluting stent was implanted. There was excellent correlation (r=0.97, P<0.001) and good agreement (mean difference: 0.00±0.03) between baseline µQFR and FFR in identifying flow-limiting lesions. Per-vessel diagnostic accuracy of µQFR on de novo lesions was 96.7% (95% CI, 88.7%-99.6%). µQFR and FFR are highly consistent (93.2%) in identifying the primary lesion requiring revascularization. After stenting the primary lesions, per-vessel diagnostic accuracy of predicted µQFR for identifying the significance of the nonprimary lesion was 90.9%. Predicted residual µQFR with virtual stenting was higher than final FFR (mean difference: 0.05±0.06). Conclusions In vessels with serial coronary lesions, virtual stenting by µQFR can identify the primary flow-limiting lesion for revascularization.
Subject(s)
Coronary Artery Disease , Coronary Stenosis , Drug-Eluting Stents , Fractional Flow Reserve, Myocardial , Percutaneous Coronary Intervention , Coronary Angiography/methods , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/surgery , Coronary Stenosis/diagnostic imaging , Coronary Stenosis/therapy , Coronary Vessels/diagnostic imaging , Coronary Vessels/surgery , Feasibility Studies , Humans , StentsABSTRACT
OBJECTIVE: To prove the effectiveness and safety of multi-electrode ablation catheter in renal denervation (RDN) by optical coherence tomography (OCT). METHODS: Sixteen renal arteries were enrolled from 8 pigs. Angiography and OCT were performed to analyze the morphological changes before RDN and at 1-month follow-up. Blood pressure and creatinine were measured to prove the effectiveness and safety of the catheter. RESULTS: One renal artery was excluded because of the small diameter. Fifteen renal arteries successfully underwent renal denervation and OCT. Mean blood pressure was significantly reduced at 1 month after RDN (122.40 ± 3.54 mmHg vs. 106.50 ± 2.06 mmHg, n = 8, P < .001). Creatinine follow-up after 1 month showed no significant change (45.37 ± 7.44 vs. 65.87 ± 49.20 µmol/L, n = 8, P = 0.275). The minimal lumen diameter showed that the renal artery immediately narrowed after the procedure (7.17 ± 0.60 mm vs. 5.93 ± 0.97 mm, n = 15, P < .001). Vasospasm, vascular wall edemas, and thrombus formations all showed significant changes after the procedure except renal artery dissection (0% vs. 21.4%, P = 0.067) under the OCT. Adverse event as renal artery occluded showed no significant difference (0% vs. 6.7%, P > .05). OCT results showed no significant difference in vasospasm, dissections, wall edemas, and thrombus formations (P > .05) at 1 month after the procedure. CONCLUSION: This multi-electrode ablation catheter could cause minor injury to renal artery instantly after RDN, but it is found to be safe in the animal model at 1-month follow-up.
Subject(s)
Animal Experimentation , Catheter Ablation , Hypertension , Animals , Blood Pressure , Catheter Ablation/adverse effects , Catheters , Denervation , Electrodes , Hypertension/surgery , Kidney/diagnostic imaging , Kidney/surgery , Swine , Sympathectomy/adverse effects , Tomography, Optical Coherence , Treatment OutcomeABSTRACT
We report an interesting case of coronary arteritis and periaortitis in a 62-year-old man with a history of biopsy-proven IgG4-related pulmonary disease. After 2 years of immune-suppressive therapy, the perivascular tissue surrounding all coronary arteries and the abdominal aorta was significantly attenuated, except that the luminal stenosis was aggravated to 70% in the left anterior descending coronary artery. Treatment with aspirin, atorvastatin, and ezetimibe was added. The patient was discharged under strict lesion surveillance at follow-up.
Subject(s)
Aortitis/immunology , Arteritis/immunology , Coronary Artery Disease/immunology , Immunoglobulin G4-Related Disease/complications , Humans , Male , Middle AgedABSTRACT
Acute myocardial infarction is one of the leading causes of deaths worldwide. Although ameliorative therapies against ischemic injury have remarkably reduced death rates among patients, they are inevitably complicated by reperfusion injury. Therefore, it is essential to explore other approaches to reduce ischemia/reperfusion injury (IRI). Modulating the levels of nicotinamide adenine dinucleotide (NAD+) is a promising therapeutic strategy against some aging-related diseases. The aim of this study was to determine the role of NAD+ in a swine model of myocardial IRI. Fourteen Bama miniature pigs were subjected to 90 min transluminal balloon occlusion, and then randomly administrated with 20 mg/kg NAD+ or saline before reperfusion. Emission computerized tomography (ECT) was performed immediately and 4 weeks after reperfusion, and the cardiac tissues were analyzed histologically. In addition, the levels of cardiac function markers and the pro-inflammatory cytokines IL-1ß and TNF-α were also measured. NAD+ administration markedly reduced myocardial necrosis, enhanced glucose metabolism, and promoted cardiac function recovery. The extent of inflammation was also reduced in the NAD+ treated animals, and corresponded to less cardiac fibrosis and better ventricular compliance. Thus, NAD+ supplementation protected the myocardium from IRI, making it a promising therapeutic agent against acute myocardial ischemic disease.
ABSTRACT
Many robotic platforms can indeed reduce radiation exposure to clinicians during percutaneous coronary intervention (PCI), however, interventionalists' natural manipulations are rarely involved in robot-assisted PCI. This requires more attention to analyze interventionalists' natural behaviors during conventional PCI. In this study, four types of natural behavior (i.e., muscle activity, hand motion, proximal force, and finger motion) were synchronously acquired from ten subjects while performing six typical types of guidewire manipulation. These behaviors are evaluated by a hidden Markov model (HMM) based analysis framework for relevant behavior selection. Relevant behaviors are further used as the input of two HMM-based classification frameworks to recognize guidewire motion patterns. Experimental results show that under the basic classification framework (BCF), 91.01% and 93.32% recognition accuracies can be achieved by using all behaviors and relevant behaviors, respectively. Furthermore, the hierarchical classification framework can significantly enhance the recognition ability of relevant behaviors with an accuracy of 96.39%. These promising results demonstrate great potential of proposed methods for promoting the future design of human-robot interfaces in robot-assisted PCI.
Subject(s)
Behavior , Motion , Percutaneous Coronary Intervention , Algorithms , Electromyography , Humans , Markov Chains , Muscles/physiology , Reproducibility of ResultsABSTRACT
OBJECTIVE: To instigate the values of 64 row spiral CT in pre-operative assessment of the occlusion and intra-operative guidance in percutaneous coronary intervention for chronic total occlusion (CTO) in coronary heart disease. METHODS: Fifteen coronary disease patients planned to receive percutaneous coronary intervention underwent 64-row spiral CT-coronary angiography and coronary angiography (CAG). The diagnostic effects of these 2 techniques were compared. RESULTS: Seventeen CTO lesions were confirmed. MSCT succeeded to show the lengths of the 17 CTO lesions with a calcification identification rate of 76.4%, significantly higher than that of the CAG (41.5%). By cross-section examination, MSCT succeeded to detect the occlusion degree of the calcified lesions, and showed that 3 CTO lesions were occluded at a rate < 50%, and 10 lesions at a rate > or = 50%. Twelve complete occlusion lesions in 11 patients underwent PCT, success was seen in 6 of which and failure in the other 6. Univariate analysis showed that the length of lesion, branching at the proximal site, formation of bridging lateral branch, form of occlusion end, and calcification were all not significantly related to the success or failure of intervention. The percentage of the calcification area > or = 50% in the intervention failure group was 83.3%, significantly higher than that in the intervention success group (16.7%, P = 0.05). 3-D images of coronary artery could be obtained by MSCT to show all the complete occlusive lesions. CONCLUSION: 64-MSCT demonstrates a remarkable ability to identify silicified lesions, can re-establish 3-D images of coronary artery, and effectively guide the intervention therapy.
Subject(s)
Coronary Angiography/methods , Coronary Occlusion/diagnostic imaging , Tomography, Spiral Computed , Adult , Aged , Aged, 80 and over , Angioplasty, Balloon, Coronary/methods , Coronary Occlusion/surgery , Humans , Imaging, Three-Dimensional , Middle AgedABSTRACT
OBJECTIVE: To explore the effectiveness of renal denervation (RDN) on blood pressure with the appropriate dosage of phenol/ethanol solution in spontaneously hypertensive rats (SHRs). METHODS: RDN was performed on the bilateral renal artery. Forty SHRs were divided into four groups according on the dosage of phenol (10% phenol in absolute ethanol): sham group, 0.5 mL phenol group, 1 mL phenol group and 1.5 mL phenol group (n = 10 in each group). Blood pressure was measured by tail-cuff plethysmography. Plasma creatinine was determined four weeks after the treatment. The kidneys and renal arteries were collected and processed for histological examination. RESULTS: A sustained decrease in systolic blood pressure (SBP) was only observed after the application of 1 mL phenol for four weeks, while SBP was lowered during the first week after RDN and increased in the following three weeks in the 0.5 mL and 1.5 mL phenol groups compared with the sham group. Renal norepinephrine (NE) was significantly decreased four weeks after RDN in the 1 mL and 1.5 mL phenol group compared with the sham group, but not in the 0.5 ml group. RDN with 1 mL phenol obviously reduced glomerular fibrosis. Histopathological analysis showed that tyrosine hydroxylase immunoreactivity was lower in the 1 mL and 1.5 mL phenol groups compared with the sham group. Moderate renal artery damage occurred in the 1.5 mL phenol group. CONCLUSION: Chemical denervation with 1 ml phenol (10% phenol in absolute ethanol) effectively and safely damaged peripheral renal sympathetic nerves and contributed to the sustained reduction of blood pressure in SHRs.
ABSTRACT
This study was designed to explore the effects of long-term renal denervation (RDN) on blood pressure and renal function in spontaneously hypertensive rats (SHR). RDN was performed in bilateral renal arteries with 10% phenol in absolute ethanol in SHR and Wistar-Kyoto rats (WKY) at 13 weeks. Age-matched SHR and WKY served as controls. Blood pressure was measured. Plasma, urine and kidneys were collected 8 months after the RDN operation. Plasma renin activity (PRA), aldosterone levels, reactive oxidative stress, renal function and structural remodeling were assessed. RDN-treated SHR demonstrated a lower spontaneous rise in systolic blood pressure than rats in the SHR-Sham group (P < 0.01, at 20, 27, 34 and 41 weeks), except at 48 weeks (198.2 ± 12.9 vs 209.4 ± 11.9 mmHg, P = 0.145). WKY were not affected by RDN. Renal tissue norepinephrine was decreased by RDN in both SHR and WKY. Plasma PRA activity, aldosterone levels, and NAD(P)H oxidase activity were reduced by the RDN in SHR. Plasma eNOS and NO were increased by RDN only in SHR. The renal nerve was destroyed by RDN with no regeneration after 8 months. The progression of renal dysfunction associated with urinary protein excretion, glomerular sclerosis, and tubulointerstitial fibrosis was attenuated by RDN only in SHR through downregulation of the ACE/Ang II/AT1R axis and upregulation of the ACE2/Ang-(1-7)/MasR axis in the kidney. Thus, RDN delays the onset of hypertension and ameliorates glomerular sclerosis and tubulointerstitial fibrosis in SHR.
ABSTRACT
Recently, the effectiveness of renal sympathetic nerve denervation for treatment of hypertension has been doubted after SYMPLICITY HTN-3 trial. An ideal animal model is still unavailable for preclinical study about catheter-based renal sympathetic nerve denervation for treatment of hypertension. Traditional high-dose deoxycorticosterone acetate (DOCA)-induced hypertension pig model has some problems due to extensive end-organ damage. Based on the similarity in the anatomic characteristics of renal artery between pigs and humans, this study was undertaken to establish a low-dose sustained-release DOCA-induced hypertension model in pigs. A total of 14 pigs were subcutaneously implanted with low-dose DOCA in the abdomen and cannulated from the femoral artery for the measurement of blood pressure (BP). Plasma angiotensin I (Ang I), angiotensin II (Ang II), plasma renin activity (PRA), aldosterone (Ald), creatinine, epinephrine, and norepinephrine (NE) were determined before and after treatments. The kidneys were collected and processed for hematoxylin and eosin staining, Masson-Goldner trichromic, and periodic acid Schiff staining. Ten pigs survived for 1 month. Mean BP significantly increased after 2-week treatment (P < .001). The plasma Ang I, Ang II, PRA, and Ald significantly decreased (Ang I: 6.92 ± 6.06 vs. 2.22 ± 3.08, P = .002; Ang II: 768.85 ± 525.8 vs. 213.76 ± 148.63, P = .003; PRA: 1.68 ± 1.67 vs. 0.29 ± 0.39, P = .008; Ald: 0.37 ± 0.12 vs. 0.25 ± 0.09, P < .001), but norepinephrine significantly increased (7.59 ± 4.57 vs. 16.96 ± 10.38, P = .021). Plasma creatinine remained unchanged. Hisotological examination showed mild damage to the kidney. Low-dose sustained-release DOCA is able to induce hypertension in pigs. A femoral catheter is not only helpful for monitoring BP, but can be used to quickly exchange the renal sympathetic nerve denervation equipment.
Subject(s)
Disease Models, Animal , Hypertension/surgery , Kidney/innervation , Mineralocorticoids/pharmacology , Swine, Miniature/physiology , Sympathectomy , Animals , Blood Pressure/drug effects , Blood Pressure Determination/methods , Catheters , Delayed-Action Preparations/pharmacology , Desoxycorticosterone/pharmacology , Dose-Response Relationship, Drug , Drug Implants/pharmacology , Femoral Artery/surgery , Humans , Hypertension/blood , Hypertension/chemically induced , Kidney/pathology , Kidney Function Tests , Male , Renin-Angiotensin System/drug effects , SwineABSTRACT
An integration of virtual screening and kinase assay was reported to identify AMPK kinase inhibitors from various natural medicines.The activation of AMP-activated protein kinase (AMPK) signalling pathway plays a central role in the pathologic progression of atherosclerosis (AS). Targeting the AMPK is thus considered as a potential therapeutics to attenuate AS. Here, we report the establishment of a synthetic pipeline that integrates in silico virtual screening and in vitro kinase assay to discover new lead compounds of AMPK inhibitors. The screening is performed against a large-size pool of structurally diverse natural products, from which a number of compounds are inferred as promising candidates, and few of them are further tested in vitro by using a standard kinase assay protocol to determine their inhibitory potency against AMPK. With this scheme we successfully identify five potent AMPK inhibitors with IC50 values at micromolar level. We also examine the structural basis and molecular mechanism of nonbonded interaction network across the modelled complex interface of AMPK kinase domain with a newly identified natural medicine.