Promoted coagulant activity and disrupted blood-brain barrier depending on phosphatidylserine externalization of red blood cells exposed to ZnO nanoparticles.

Zinc oxide nanoparticles (ZnO-NPs) are nanomaterials mainly produced and used worldwide. They translocate to circulatory systems from various exposure routes. While blood and endothelial cells are persistently exposed to circulating ZnO-NPs, the potential risks posed by ZnO-NPs to the cardiovascular system are largely unknown. Our study identified the potential risk of thrombosis and disturbance of the blood-brain barrier (BBB) by coagulant activity on red blood cells (RBCs) caused by ZnO-NPs. ZnO-NPs promoted the externalization of phosphatidylserine and the generation of microvesicles through an imbalance of intracellular mechanisms regulating procoagulant activity in human RBCs. The coagulation cascade leading to thrombin generation was promoted in ZnO-NPs-treated human RBCs. Combined with human RBCs, ZnO-NPs caused coagulant activity on isolated rat RBCs and rat venous thrombosis models. We identified the erythrophagocytosis of RBCs into brain endothelial cells via increased PS exposure induced by ZnO-NPs. Excessive erythrophagocytosis contributes to disrupting the BBB function of endothelial cells. ZnO-NPs increased the procoagulant activity of RBCs, causing venous thrombosis. Excessive erythrophagocytosis through ZnO-NPs-treated RBCs resulted in the dysfunction of BBB. Our study will help elucidate the potential risk ZnO-NPs exert on the cardiovascular system.

Ventricular Tachyarrhythmia in a Newborn Baby.

Supraventricular tachycardia (SVT) is a narrow QRS complex tachyarrhythmia with a heart rate above 220 beats per minute in infants and children. Ventricular tachycardia can be due to electrolyte abnormalities, cardiomyopathies, congenital heart disease, myocarditis or drug toxicity. Incidence has been estimated to be 1 in 250 to 1 in 1000 with spontaneous resolution in infants by one year of life. We present a full-term neonate who started experiencing a tachyarrhythmia on day zero of life until she reverted to sinus rhythm on day nine of life. The rhythm was most likely a ventricular tachyarrhythmia rather than supraventricular tachycardia due to its unresponsiveness to adenosine, wide QRS complexes, and lack of association with hemodynamic instability. This is a unique case presentation of a ventricular tachyarrhythmia for its diagnostic and therapeutic challenges, it's idiopathic nature and lack of association with any cardiac compromise, congenital heart disease or electrolyte imbalance.

Septic cardioembolic stroke secondary to infective endocarditis in a young patient with rheumatic heart disease: a case report.

The risk of stroke due to infective endocarditis is particularly high during the first week. Moreover, in low-resource settings where imaging access is limited, and diagnostic pathways are inaccurate the risk further increases. In addition to antibiotic therapy, treatment may include intravenous thrombolysis, with high risk of hemorrhagic complications in patients with infective endocarditis or mechanical thrombectomy. We report here a case of a 24-year-old male with rheumatic heart disease presenting a septic cardioembolic stroke secondary to infective endocarditis that was successfully treated in a low-resource setting.

Acute ST-elevation myocardial infarction (STEMI) in a young man with unknown multiple and mixed Valvular heart diseases: case report.

Although the incidence of systemic thromboembolism in valvular heart disease has been reported to be as high as 10% to 35%, embolization to the coronary arteries is uncommon. We present a case of a patient with acute myocardial infarction caused by coronary thromboemboli associated with combined valvular heart disease and atrial fibrillation. The thromboemboli were documented in the left descending artery. Coronary interventions including thromboaspiration and percutaneous coronary balloon angioplasty were attempted.

Right ventricular papillary muscle crossing the moderator band mimicked infective endocarditis: the utility of multimodal imaging.

Right-sided infective endocarditis (RSIE) generally carries a positive prognosis; however, it can result in complications such as heart failure, underscoring the importance of prompt diagnosis. While echocardiography serves as the standard diagnostic tool, it may occasionally face challenges in distinguishing between normal structures and vegetations. In this report, we present the case of a 60-year-old man diagnosed with pyogenic vertebral osteomyelitis, alongside suspected coexisting RSIE. During both transthoracic and transesophageal echocardiography, a rod-like mobile structure was observed adjacent to the right ventricular moderator band. However, confirming its nature as an infective vegetation proved challenging. Despite the inconclusive diagnosis of IE by echocardiography, the positron emission tomography/computed tomography (PET/CT) scan and cardiac magnetic resonance imaging (MRI) played a pivotal role in distinguishing between normal structures and vegetations. Since IE could develop life-threatening events, the role of multimodal imaging is of paramount importance. This case serves as a compelling example of the diagnostic value through the integration of PET/CT and MRI in ruling out IE.

Amine-modified nanoplastics promote the procoagulant activation of isolated human red blood cells and thrombus formation in rats.

BACKGROUND: Microplastics (MPs) and nanoplastics (NPs) formed from decomposed plastic are increasing environmental threats. Although MPs and NPs exposed through various routes enter the systemic circulation, the potential toxicity of those is largely unknown. We investigated whether polystyrene NPs (PS-NPs) promote the coagulation activity of red blood cells (RBCs). RESULTS: We tested several types of PS-NPs using human RBCs and found that amine-modified 100 nm PS-NPs were the most potent. We measured the uptake of PS-NPs using flow cytometry and confocal microscopy. Electron microscopy revealed morphological changes of RBCs by PS-NPs. PS-NPs induced the externalization of phosphatidylserine, generation of microvesicles in RBCs, and perturbations in the intracellular microenvironment. PS-NPs increased the activity of scramblases responsible for phospholipid translocation in RBCs. PS-NPs modulated the functional interaction to adjacent tissues and coagulation cascade, enhancing RBC adhesion and thrombin generation. Our observations in human RBCs were consistent with those in isolated rat RBCs, showing no inter-species differences. In rat venous thrombosis models, the intravenous administration of PS-NPs enhanced thrombus formation. CONCLUSION: Amine-modified PS-NPs induce the prothrombotic activation of RBCs causing thrombus formation. We believe that our study will contribute to understanding the potential toxicity of amine-modified polystyrene particles in blood cells and cardiovascular systems.

Time of day as a critical variable in biology.

BACKGROUND: Circadian rhythms are important for all aspects of biology; virtually every aspect of biological function varies according to time of day. Although this is well known, variation across the day is also often ignored in the design and reporting of research. For this review, we analyzed the top 50 cited papers across 10 major domains of the biological sciences in the calendar year 2015. We repeated this analysis for the year 2019, hypothesizing that the awarding of a Nobel Prize in 2017 for achievements in the field of circadian biology would highlight the importance of circadian rhythms for scientists across many disciplines, and improve time-of-day reporting. RESULTS: Our analyses of these 1000 empirical papers, however, revealed that most failed to include sufficient temporal details when describing experimental methods and that few systematic differences in time-of-day reporting existed between 2015 and 2019. Overall, only 6.1% of reports included time-of-day information about experimental measures and manipulations sufficient to permit replication. CONCLUSIONS: Circadian rhythms are a defining feature of biological systems, and knowing when in the circadian day these systems are evaluated is fundamentally important information. Failing to account for time of day hampers reproducibility across laboratories, complicates interpretation of results, and reduces the value of data based predominantly on nocturnal animals when extrapolating to diurnal humans.

Cardiovascular Effects of Whole-Body Cryotherapy in Non-professional Athletes.

Objectives: The study aimed to investigate changes in heart rate, blood pressure, respiratory rate, oxygen saturation, and body temperature in non-professional trained runners during whole body cryotherapy (WBC). Methods: Ten middle-distance runners received 3 once-a-day sessions of WBC. Subjects underwent BP measurements and ECG recorded before and immediately after the daily WBC session. During WBC we recorded a single lead trace (D1) for heart rhythm control. In addition, the 5 vital signs Blood pressure, heart rate, respiratory rate, oxygen saturation, and body temperature were monitored before, during, and after all WBC session. Results: We did not report significant changes in ECG main intervals (PR, QT, and QTc). Mean heart rate changed from 50.98 ± 4.43 bpm (before) to 56.83 ± 4.26 bpm after WBC session (p < 0.05). The mean systolic blood pressure did not change significantly during and after WBC [b baseline: 118 ± 5 mmHg, changed to 120 ± 3 mmHg during WBC, and to 121 ± 2 mmHg after session (p < 0.05 vs. baseline)]. Mean respiratory rate did not change during WBC as well as oxygen saturations (98 vs. 99%). Body temperature was slightly increased after WBC, however it remains within physiological values. Conclusion: In non-professional athletes WBC did not affect cardiovascular response and can be safely used. However, further studies are required to confirm these promising results of safety in elderly non-athlete subjects.

Phenotyping heart failure using model-based analysis and physiology-informed machine learning.

To phenotype mechanistic differences between heart failure with reduced (HFrEF) and preserved (HFpEF) ejection fraction, a closed-loop model of the cardiovascular system coupled with patient-specific transthoracic echocardiography (TTE) and right heart catheterization (RHC) data was used to identify key parameters representing haemodynamics. Thirty-one patient records (10 HFrEF, 21 HFpEF) were obtained from the Cardiovascular Health Improvement Project database at the University of Michigan. Model simulations were tuned to match RHC and TTE pressure, volume, and cardiac output measurements in each patient. The underlying physiological model parameters were plotted against model-based norms and compared between HFrEF and HFpEF. Our results confirm the main mechanistic parameter driving HFrEF is reduced left ventricular (LV) contractility, whereas HFpEF exhibits a heterogeneous phenotype. Conducting principal component analysis, k -means clustering, and hierarchical clustering on the optimized parameters reveal (i) a group of HFrEF-like HFpEF patients (HFpEF1), (ii) a classic HFpEF group (HFpEF2), and (iii) a group of HFpEF patients that do not consistently cluster (NCC). These subgroups cannot be distinguished from the clinical data alone. Increased LV active contractility ( p<0.001 ) and LV passive stiffness ( p<0.001 ) at rest are observed when comparing HFpEF2 to HFpEF1. Analysing the clinical data of each subgroup reveals that elevated systolic and diastolic LV volumes seen in both HFrEF and HFpEF1 may be used as a biomarker to identify HFrEF-like HFpEF patients. These results suggest that modelling of the cardiovascular system and optimizing to standard clinical data can designate subgroups of HFpEF as separate phenotypes, possibly elucidating patient-specific treatment strategies. KEY POINTS: Analysis of data from right heart catheterization (RHC) and transthoracic echocardiography (TTE) of heart failure (HF) patients using a closed-loop model of the cardiovascular system identifies key parameters representing haemodynamic cardiovascular function in patients with heart failure with reduced and preserved ejection fraction (HFrEF and HFpEF). Analysing optimized parameters representing cardiovascular function using machine learning shows mechanistic differences between HFpEF groups that are not seen analysing clinical data alone. HFpEF groups presented here can be subdivided into three subgroups: HFpEF1 described as 'HFrEF-like HFpEF', HFpEF2 as 'classic HFpEF', and a third group of HFpEF patients that do not consistently cluster. Focusing purely on cardiac function consistently captures the underlying dysfunction in HFrEF, whereas HFpEF is better characterized by dysfunction in the entire cardiovascular system. Our methodology reveals that elevated left ventricular systolic and diastolic volumes are potential biomarkers for identifying HFrEF-like HFpEF patients.

Regulation of energy metabolism by combination therapy attenuates cardiac metabolic remodeling in heart failure.

Cardiac metabolic remodeling is recognized as an important hallmark of heart failure (HF), while strategies that target energy metabolism have therapeutic potential in treating HF. Shen-Fu formula (S-F) is a standardized herbal preparation frequently used in clinical practice and is a promising combinatorial therapy for HF-related metabolic remodeling. Herein, we performed an untargeted multi-omics analysis using transcriptomics, proteomics, and metabolomics on HF mice induced by transverse aortic constriction (TAC). Integrated and pathway-driven analyses were used to reveal the therapeutic targets associated with S-F treatment. The cardioprotective effect and potential mechanism of S-F were verified by the results from echocardiography, hemodynamics, histopathology, and biochemical assays. As a result, S-F significantly alleviated myocardial fibrosis and hypertrophy, thus reducing the loss of heart function during adverse cardiac remodeling in TAC mice. Integrated omics analysis showed that S-F synergistically mediated the metabolic flexibility of fatty acids and glucose in cardiac energy metabolism. These effects of S-F were confirmed by the activation of AMP-activated protein kinase (AMPK) and its downstream targets in the failing heart. Collectively, our results demonstrated that S-F suppressed cardiac metabolic remodeling through activating AMPK-related pathways via energy-dependent mechanisms.

A Statewide Assessment of Prehospital Electrocardiography Approaches of Acquisition and Interpretation for ST-Elevation Myocardial Infarction Based on Emergency Medical Services Characteristics.

Background: The American Heart Association recommends acquiring and interpreting prehospital electrocardiograms (ECG) for patients transported by Emergency Medical Services (EMS) to the emergency department with symptoms highly suspicious of acute coronary syndrome. If interpreted correctly, prehospital ECGs have the potential to improve early detection of ST-elevation myocardial infarction (STEMI) and inform prehospital activation of the cardiac catheterization laboratory, thus reducing total ischemic time and improving patient outcomes. Standardized protocols for prehospital ECG interpretation methods are lacking due to variations in EMS system design, training, and procedures. Objectives: We aimed to describe approaches for prehospital ECG interpretation in EMS systems across North Carolina (NC), and examine potential differences among systems. Methods: A 35-item internet survey was sent to all NC EMS systems (n = 99). Questions pertaining to prehospital ECG interpretation methods included: paramedic, computerized algorithm (i.e., software interpretation), combined approaches, and/or transmission for physician interpretation, transmission capability, cardiac catheterization laboratory activation, and EMS system characteristics (e.g. rural versus urban). Data were summarized and compared. Results: A total of 96 EMS systems across NC responded to the survey (97% response rate); of these, 69% were rural. EMS medical directors (53%) or EMS administrative directors (42%) completed the majority of surveys. While 91% of EMS systems had a prehospital ECG interpretation protocol in place, only 61% had a written cardiac catheterization laboratory activation policy. More than half (55%) of systems reported paramedic interpretation of prehospital ECGs, followed by a combined paramedic and software interpretation approach (39%), physician interpretation (4%), or software interpretation only approach (2%). Nearly 80% of EMS systems transmitted prehospital ECGs to receiving hospitals (always or sometimes), regardless of interpretation method. All EMS systems had some paid versus non-paid EMS personnel and the majority (86%) had both basic and advanced life support capabilities. Conclusions: Most NC EMS systems had a paramedic only ECG interpretation or paramedic in combination with a computerized algorithm approach. Very few used a physician read approach following transmission, even in rural service areas.

An unusual cause of lacunar infarcts: Lambl's excrescences on aortic valve shown in detail by 3D transesophageal echocardiography.

Lambl's excrescences (LE) are rare cardiac structures. They are associated with catastrophic thromboembolic and coronary events. Despite resulting in such important events, 2D echocardiographic imaging modalities may overlook LE owing to very thin cardiac structures. So, 3D echocardiographic imaging modalities may fully offer this cardiac mass and provide us to more accurately guess the complication rate related to LE due to the fact that 3D echocardiographic imaging techniques have higher spatial resolution and are not based on the geometric assumption. Indeed, another benefit of 3D echocardiographic imaging modalities in this population is that these imaging modalities clearly provide the relationship to adjacent structures of LE and its movement over a cardiac cycle in 3D space. In our case report, we aim to present the usefulness of 3D echocardiography as a modality to clearly offer all features of LE, furthermore to give valuable information about management in patients with thromboembolic events leading to LE.

Implantation of the Micra leadless pacemaker in a patient with a low body mass index of 16.

A 71-year-old female patient has a history of complete heart block and recurrent pacemaker site infection requiring multiple pacemaker explanations. A leadless pacemaker using passive fixation was inserted into the right ventricular apex via transvenous approach without complications. This case illustrates the feasibility of implanting a leadless pacemaker system in a small-sized adult with a low body mass index of 16 (weight: 33.7 kg, height: 145 cm) which may have potential application in elderly Asian subjects.

Arterial (Aortic) Stiffness in Patients with Resistant Hypertension: from Assessment to Treatment.

PURPOSE OF REVIEW: The purpose of the review is to examine whether measurement of aortic stiffness could be especially value-adding for risk stratification and treatment among patients with resistant hypertension (RH). RECENT FINDINGS: Adverse arterial remodeling and increased aortic stiffness is associated with RH, and it may be of additional clinical benefit to measure aortic stiffness in these patients. However, there is insufficient evidence to determine whether aortic stiffness is excessively high relative to the level of blood pressure (BP) among people with RH. This issue needs resolution as it could help refine management decisions guided by aortic stiffness. If conventional antihypertensive therapy fails to lower BP in patients with RH, there is good rationale for effectiveness of spironolactone as add on therapy, and this should also improve aortic stiffness. Lifestyle intervention with exercise and diet should be additionally efficacious towards improving BP and aortic stiffness in patients with RH, but there is limited data in this patient population. For better characterization on the effects of BP treatment on aortic stiffness, measures of central aortic BP may help refine management decisions above and beyond conventional arm cuff BP. There is strong evidence to support the use of aortic stiffness as a tool to aid risk stratification in hypertension management. Although there is a theoretical basis for special additional benefit of measuring aortic stiffness in patients with RH (as distinct from uncomplicated hypertension), at this time, there is inadequate data available to make definitive conclusions and is an area for future investigation.

Simulated annealing approach to vascular structure with application to the coronary arteries.

Do the complex processes of angiogenesis during organism development ultimately lead to a near optimal coronary vasculature in the organs of adult mammals? We examine this hypothesis using a powerful and universal method, built on physical and physiological principles, for the determination of globally energetically optimal arterial trees. The method is based on simulated annealing, and can be used to examine arteries in hollow organs with arbitrary tissue geometries. We demonstrate that the approach can generate in silico vasculatures which closely match porcine anatomical data for the coronary arteries on all length scales, and that the optimized arterial trees improve systematically as computational time increases. The method presented here is general, and could in principle be used to examine the arteries of other organs. Potential applications include improvement of medical imaging analysis and the design of vascular trees for artificial organs.

Oral L-Arginine Administration Improves Anthropometric and Biochemical Indices Associated With Cardiovascular Diseases in Obese Patients: A Randomized, Single Blind Placebo Controlled Clinical Trial.

BACKGROUND: Recently, the potential of L-arginine supplementation as a novel and effective strategy for weight loss and improving biochemical parameters in obese patients has been under consideration. OBJECTIVES: To evaluate the influence of 8-week oral L-arginine supplementation on body mass index (BMI), waist circumference (WC), triceps skinfold (TS), subscapular skinfold (SS), systolic blood pressure (SBP), diastolic blood pressure (DBP), plasma fasting blood sugar (FBS), glycated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and malondialdehyde (MDA) in patients with BMI values > 29.9 or visceral obesity (WC > 102 cm in men or > 88 cm in women). PATIENTS AND METHODS: Ninety obese patients were included in a single-blind randomized controlled trial. Patients were randomized to receive either L-arginine (3 or 6 g thrice daily) or placebo for 8 weeks. Anthropometric and biochemical indices, dietary intake, and blood pressure values were measured at the baseline and after the 8-week intervention. RESULTS: Significant decreases in anthropometric parameters, blood pressure (SBP, DBP), FBS, HbA1c, LDL, MDA (P < 0.001), TG (P = 0.02), and TC (P = 0.002) and a significant increase in HDL (P < 0.001) were observed in the intervention group, compared to the control group. In the control group, no significant differences were found between the baseline and end-of-intervention measurements. CONCLUSIONS: In conclusion, oral L-Arginine supplementation appears to improve anthropometric parameters, blood pressure values, and some blood biochemical indices associated with cardiovascular disease prevention.

On a sparse pressure-flow rate condensation of rigid circulation models.

Cardiovascular simulation has shown potential value in clinical decision-making, providing a framework to assess changes in hemodynamics produced by physiological and surgical alterations. State-of-the-art predictions are provided by deterministic multiscale numerical approaches coupling 3D finite element Navier Stokes simulations to lumped parameter circulation models governed by ODEs. Development of next-generation stochastic multiscale models whose parameters can be learned from available clinical data under uncertainty constitutes a research challenge made more difficult by the high computational cost typically associated with the solution of these models. We present a methodology for constructing reduced representations that condense the behavior of 3D anatomical models using outlet pressure-flow polynomial surrogates, based on multiscale model solutions spanning several heart cycles. Relevance vector machine regression is compared with maximum likelihood estimation, showing that sparse pressure/flow rate approximations offer superior performance in producing working surrogate models to be included in lumped circulation networks. Sensitivities of outlets flow rates are also quantified through a Sobol׳ decomposition of their total variance encoded in the orthogonal polynomial expansion. Finally, we show that augmented lumped parameter models including the proposed surrogates accurately reproduce the response of multiscale models they were derived from. In particular, results are presented for models of the coronary circulation with closed loop boundary conditions and the abdominal aorta with open loop boundary conditions.