American journal of physiology. Heart and circulatory physiology最新文献

Hypertensive disorders of pregnancy, particularly early-onset preeclampsia (EOPE), are major causes of perinatal morbidity and mortality. Although impaired placentation has long been recognized as a key mechanism, increasing evidence highlights the contribution of maternal cardiovascular dysfunction. However, how maternal hemodynamics influences neonatal circulatory transition remains poorly understood. In this prospective study, mother-infant pairs from pregnancies complicated by EOPE were enrolled if the mother had undergone echocardiographic assessment within 3 wk before delivery and the neonate had received continuous hemodynamic monitoring by electrical cardiometry for at least 72 h after birth. Associations between maternal and neonatal hemodynamic parameters were explored using correlation analysis, and generalized linear mixed-effects models (GLMMs) accounted for repeated neonatal measurements, neonatal exposure to dopamine or dobutamine, and patent ductus arteriosus (PDA). Maternal systolic function indices [cardiac output (CO), ejection fraction (EF), and tissue Doppler s' velocities] inversely correlated with neonatal CO in fully adjusted GLMM models. EF was positively associated with neonatal systemic vascular resistance when adjusted for inotropic support (P = 0.010), with attenuation after additional adjustment for PDA (P = 0.052). Overall, maternal systolic impairment in EOPE was associated with higher neonatal CO, indicating a compensatory increase in neonatal cardiac performance, whereas changes in neonatal vascular tone were minimal. These findings provide the first quantitative evidence of maternal-neonatal hemodynamic coupling and support the value of integrated cardiovascular assessment of both mother and newborn in hypertensive pregnancies.NEW & NOTEWORTHY This study provides the first evidence that maternal cardiovascular maladaptation in preeclampsia is directly mirrored in neonatal hemodynamics. Newborns displayed a compensatory rise in cardiac output in response to maternal systolic dysfunction, whereas changes in neonatal vascular tone remained minimal. Although maternal and neonatal circulations are traditionally examined independently, these findings underscore a tightly linked maternal-fetal hemodynamic dyad, offering new insight into the physiological continuity that spans the perinatal transition.

The search for effective adjuncts to procedural revascularization for patients with coronary artery disease (CAD) has revealed, after several successful outcomes trials, the substantial potential of glucagon-like peptide 1 (GLP-1) analogs such as semaglutide. Because this potential has not been mechanistically illuminated in the setting of CAD and metabolic syndrome, we used a large animal model to evaluate the cardiac consequences of GLP-1 receptor (GLP-1R) agonism. Sixteen Yorkshire swine, after provision of a high-fat diet for 5 wk to induce metabolic syndrome, underwent ameroid constrictor-mediated induction of focal CAD. Animals were then either randomized to receive semaglutide (SEM, n = 8, 4 males, 4 females) or no drug (CON, n = 8, 4 males, 4 females) for 5 wk, followed by a terminal sternotomy for left ventricular pressure-volume catheterization, coronary collateral characterization, and myocardial resection and sectioning. Coronary arterioles from the peri-ischemic myocardium were mounted and suffused to assess vasoactivity, and molecular changes within the most ischemic territory were assayed using immunoblotting, immunofluorescence, and proteomics. Treated animals exhibited enhanced left ventricular filling, end diastolic volume, stroke volume, and cardiac index (all P < 0.05); increased arteriolar density (P < 0.001); improved microvascular endothelium-dependent vasodilation (P < 0.01); and, as indicated by increases in fibroblast growth factor, angiostatin, endostatin, and endothelial nitric oxide synthase (eNOS) (all P < 0.01) augmented vascular remodeling and endothelial function. In a large animal model that recapitulates the clinical comorbidities of CAD, improved left ventricular arteriolar density, vascular reactivity, and performance throughout the cardiac cycle position semaglutide as a highly promising addition to the adjunctive armamentarium against CAD.NEW & NOTEWORTHY In a clinically relevant swine model of chronic ischemic cardiomyopathy, oral semaglutide improved ventricular performance, likely through enhanced coronary collateralization. This benefit holds particular promise for patients with obesity and type 2 diabetes-populations already eligible for GLP-1 analog therapy. These findings support the initiation of randomized clinical trials of early GLP-1R agonist use at the time of CAD diagnosis to assess long-term outcomes and potential incorporation into standard ischemic heart disease management.

Traumatic brain injury (TBI) is a prevalent neurological condition with long-term consequences that extend beyond the brain. Individuals with a history of TBI are at increased risk for cardiovascular complications, but the mechanisms remain poorly understood. Here, we tested the hypothesis that mild-to-moderate chronic cerebral hypoperfusion, modeled via bilateral carotid artery stenosis (BCAS), exacerbates cardiac dysfunction following TBI. Male and female Swiss Webster mice (8-10 wk old) were randomly assigned to Sham, BCAS, TBI, and BCAS + TBI groups. Cerebral blood flow (CBF) was evaluated at rest and after acetazolamide challenge to evaluate cerebrovascular reserve. Neuroinflammation was assessed in the insular cortex, using ionized calcium-binding adapter molecule 1 (IBA-1) and glial fibrillary acidic protein (GFAP) immunostaining. Cardiac function was evaluated using transthoracic echocardiography, and myocardial morphology was detected by hematoxylin and eosin staining. TBI significantly reduced cardiac function in both sexes, whereas BCAS had no effect by itself. Similar structural changes in cardiomyocytes, such as decreased nuclear density and increased nuclear size, were observed in both TBI and BCAS + TBI mice. BCAS alone robustly elicited gliosis in the insular cortex in the absence of cardiac dysfunction. BCAS + TBI also decreased CBF and cerebrovascular reactivity, along with enhanced glial activation in the insula. These results indicate that TBI-elicited cardiac injury is accompanied by neuroinflammation in central autonomic centers, and preexisting cerebral hypoperfusion does not increase cardiac vulnerability. This study highlights the role of the brain-heart axis as a key driving force in post-TBI morbidity and raises the possibility that cerebrovascular health may serve as a mediator of cardiac outcomes following brain injury.NEW & NOTEWORTHY TBI impairs cardiac function and induces glial activation in the insular cortex, a key autonomic region. Although mild-to-moderate chronic cerebral hypoperfusion (BCAS) induces gliosis and reduces cerebrovascular reserve, it does not exacerbate TBI-related cardiac dysfunction. Our findings demonstrate that TBI-driven neuroinflammatory signaling, rather than chronic hypoperfusion, underlies cardiac vulnerability after brain injury, highlighting the brain-heart axis as a key contributor to cardiovascular morbidity.

Sex differences are evident in vascular mitochondrial function; however, the impact of sex on microvascular bioenergetics has never been studied. We investigated the bioenergetics of freshly isolated mouse brain microvessels (BMVs) from young mice (6-8 wk). Oxygen consumption rate and extracellular acidification rates of BMVs were measured using Agilent Seahorse XFe24 analyzer. The real-time ATP rate assay showed reduced total ATP production with contributions from both glycolysis and oxidative phosphorylation (OxPhos) in BMVs from females compared with males. The mitochondrial stress test revealed lower basal respiration and ATP production in BMVs of females versus males. The glycolytic rate assay indicated reduced basal glycolysis and proton efflux rate (PER) in females, with no sex differences in basal PER and post-2-DG acidification. Mito fuel flex test found no differences in fuel substrate utilization. Measurements using homogenates of BMVs confirmed lower ATP levels in females, with no sex differences in citrate synthase activity or key mitochondrial protein/mRNA levels. Ex vivo oxygen-glucose deprivation followed by reoxygenation (OGD/R) of mouse BMVs displayed significantly reduced mitochondrial respiratory function as well as glycolytic activity in females versus males. However, OGD/R paradoxically increased lactate dehydrogenase release, a marker of cellular injury, from male BMVs but has no effect on female BMVs. Thus, female BMVs exhibited decreased mitochondrial respiratory and glycolytic function compared with males, despite similar substrate utilization for energy production. In young mice, the sex-dependent differences in OxPhos and glycolysis may increase the vulnerability of the microvasculature to OGD/R injury in males and vasoprotection in females.NEW & NOTEWORTHY Impact of sex on microvascular bioenergetics has never been studied. We measured oxygen consumption rates and extracellular acidification rates in mouse brain microvessels using Agilent Seahorse XFe24 analyzer. For the first time, we observed decreased mitochondrial respiratory and glycolytic function in brain microvessels of female mice compared with male mice. These sex-dependent differences in glycolysis and oxidative phosphorylation may increase the vulnerability/protection of the microvasculature to vascular cell injury.

Atrial dysfunction plays a critical role in cardiac disease, particularly during arrhythmias and in heart failure, where impaired atrial contraction can compromise cardiac output. Yet, models that allow direct assessment of human atrial biomechanics remain scarce. Living myocardial slices (LMS) have the potential to revolutionize preclinical cardiac studies by preserving native architecture and performance in near-physiological environments, offering a patient-specific platform to investigate atrial function. To address this gap, we present the first functional analysis of human atrial LMS across diverse disease phenotypes, including healthy tissue, heart failure (HF), rhythm disorders, and atrial dilatation. Using the largest human atrial LMS dataset to date, containing 250 slices from 48 patients, we assessed contractile force, kinetics, force-frequency relationships, and refractoriness during the acute culture phase. Atrial slices exhibited faster contractions than ventricular LMS. HF and dilated atria showed reduced contractile force and prolonged contraction and relaxation, whereas slices from patients with atrial fibrillation displayed preserved or enhanced kinetics with increased variability in refractoriness. Structural analyses confirmed elevated fibrosis in all disease groups, along with disease-specific alterations in cellular morphology and tissue organization. Together, these findings provide a reference framework for human atrial biomechanics, thereby positioning LMS as a promising model for studying atrial pathophysiology in vitro.NEW & NOTEWORTHY Human atrial living myocardial slices (LMS) bridge the gap between clinical disease and tissue-level mechanistic insight. Using the largest dataset of human atrial slices to date, this study maps the biomechanical landscape of the atrium and reveals preserved disease-specific signatures in vitro. These findings position LMS as a promising platform for studying atrial pathophysiology and therapeutic development.

Traditional echocardiographic metrics of right ventricular (RV) function, including tricuspid annular plane systolic excursion and two-dimensional (2-D) strain, are limited to the description of longitudinal systolic function. These metrics, however, fail to account for the complex, three-dimensional (3-D) deformation of the RV. 3-D echocardiograms (3DE) were obtained simultaneously during clinically indicated right heart catheterization (RHC). We determined the maximum principal surface strain (PS_Max) and angle (ϴ_Max) of RV surface deformation in pulmonary arterial hypertension (PAH) and control patients. We compared 22 control patients to 37 patients with PAH, of whom 11 met hemodynamic criteria for right heart (RH) failure. Compared with 2-D descriptors of RV function, PS_Max was significantly different between controls and patients with PAH and between PAH patients with and without RH failure. ϴ_Max was progressively oriented longitudinally in PAH patients without RH failure compared to PAH patients with RH failure [37.5° (34.3° to 40.8°) vs. 34.3° (32.1° to 36.2°), P = 0.042] and in PAH patients with worse New York Heart Association functional class. Thirty-day outcomes were significantly different with an optimal cutoff of PS_Max of -21.4%, with a hazard ratio of 6.8 (95% CI 1.3 to 35.2, P = 0.022). PS_Max is a robust marker of RH failure and provides prognostic value in PAH beyond conventional 2-D descriptors of RH function. Progressive longitudinal deformation of ϴ_Max is associated with worse RH function and functional class.NEW & NOTEWORTHY Impaired PS_Max is associated with worse RV systolic function and outcomes in PAH when compared with conventional 2-D metrics of RV systolic function, while ϴ_Max is progressively oriented longitudinally in PAH patients with RH failure compared to those without RH failure, potentially reflecting an echocardiographic representation of maladaptive RV myofiber reorientation. PS_Max and ϴ_Max represent a powerful and concise way to describe RV systolic function that may prove useful in the care of PAH patients.

Adults with Down syndrome (Ds) demonstrate unique cardiovascular features, including smaller left ventricular volumes and lower blood pressure. Ventricular-arterial coupling (VAC), a key measure of cardiovascular efficiency, has not been previously studied in this adult population. Understanding VAC in adults with Ds may reveal compensatory mechanisms that maintain cardiac output despite distinct cardiovascular characteristics. This study used echocardiographic parameters to compare the VAC ratio of adults with and without Ds. Baseline echocardiographic data were collected from 28 adults with Ds and 18 adults without Ds (aged 18-35 yr), all of whom had low physical activity levels. The VAC ratio was calculated using the single-beat method. Adults with Ds had lower VAC ratios and diastolic blood pressure, faster preejection times, shorter normalized systolic durations, and a higher ejection fraction than adults without Ds. Adults with Ds exhibit distinct cardiovascular adaptations, including a lower VAC ratio and a shorter systolic duration, suggesting increased cardiac workload. Higher ejection fraction and faster preejection period indicate potential compensatory mechanisms to maintain cardiac output, whereas lower diastolic blood pressure may reduce coronary perfusion and preload. These findings demonstrate differences in cardiac function and timing in adults with Ds in this study.NEW & NOTEWORTHY This study reveals, for the first time, that adults with Down syndrome exhibit significantly lower ventricular-arterial coupling ratios, reflecting distinct cardiac timing and functional adaptations. These findings could indicate a compensatory mechanism to maintain cardiac output despite reduced diastolic pressure and smaller cardiac chambers, providing novel insight into the integrated cardiovascular physiology of adults with Down syndrome and its potential implications for exercise tolerance and long-term cardiovascular health.