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

Fetal echocardiography in twin-to-twin transfusion pregnancies treated with photocoagulation noted impaired cardiac function. Systematic information about cardiac structure or function and arterial distensibility after birth is not available. This study evaluated cardiovascular function and arterial dynamic properties in survivors of twin-to-twin transfusion syndrome (TTTS). Eleven pairs of donor-recipient twins were compared with each other and with 20 singletons of comparable gestational age. The twin cohort was born at 31.5 ± 2 wk gestational age; birthweights of donors-recipients were comparable (donors: 1,358 ± 421 g vs. recipients: 1,617 ± 460 g, P = 0.2). Significant intertwin differences were noted for cardiac function parameters. Recipients had greater septal thickness (donors: 2.3 ± 0.15 vs. recipients: 2.7 ± 0.36 mm, P = 0.01) and globularity [lower sphericity index (donors: 1.76 ± 0.1 vs. recipients: 1.62 ± 0.12, P = 0.009)]. They also had lower cardiac function [tricuspid annular plane systolic excursion (donors: 4.6 ± 0.5 vs. recipients: 4.1 ± 0.4 mm, P = 0.02) and right ventricular fractional area change (donors: 30 ± 1 vs. recipients: 27.7 ± 1.3%, P = 0.0001)]. Compared with singletons, differences were statistically more significant for recipients. Arterial distensibility however was more affected in donors [higher arterial wall stiffness index (donors: 2.5 ± 0.2 vs. recipients: 2.2 ± 0.2, P = 0.008) and lower pulsatile diameter (donors: 51 ± 5 vs. recipients: 63 ± 10 µm, P < 0.0001)]. Compared with singletons, the differences were statistically more significant for donors. Evaluation in the neonatal period noted that cardiac function and arterial distensibility are affected in TTTS twins. These cohorts will benefit from close postnatal follow-up for the evolution of cardiac and arterial impairments.NEW & NOTEWORTHY Evaluation for fetuses with twin-to-twin transfusion syndrome noted impaired cardiac function in recipients. Systematic data after birth are lacking. We noted greater ventricular dilatation, globularity, and hypertrophied interventricular septum in the recipient. Right ventricular contractility was reduced; differences between recipients-singletons had greater statistical significance compared with donors-singletons. The aorta had greater stiffness and lower distensibility in donors compared with recipients; the differences for arterial indices were statistically more significant with donors-singletons.

Diversity in academic medicine and research enhances the quality of the science produced and the efficacy of patient care. Diversity, equity, inclusion, and accessibility (DEIA) statements have recently been suggested or required by academic job postings as a way to measure candidate's commitments to fostering DEIA in their role. In this perspective, we discuss steps to craft effective DEIA statements that convey your actions in, and commitment to, DEIA. We recognize that mandating DEIA statements may actually result in inauthentic or disingenuous statements and offer solutions to encouraging academics to arrive at a meaningful statement that represents their own perspectives on diversity. Last, we provide examples of DEIA statements from three academics at different career points.

Preeclampsia, a hypertensive disorder of pregnancy, results in increased lifetime cardiovascular disease (CVD) risk. Total aortic stiffness, a robust risk factor for CVD, is composed of load-dependent (blood pressure load on arterial wall) and structural (intrinsic changes in arterial wall) mechanisms. Total aortic stiffness is also associated with reduced cardiovagal baroreflex sensitivity (BRS). We sought to determine 1) whether elevated total aortic stiffness among women with a history of preeclampsia (hxPE) is attributed to load-dependent or structural stiffness, and 2) whether either mechanism is associated with lower BRS. Total aortic stiffness (carotid-femoral pulse wave velocity) and spontaneous cardiovagal BRS (sequence technique) were measured among women 1-5 yr postpartum (n = 115; age 34 ± 4 yr; hxPE n = 51; controls n = 64). Structural aortic stiffness was calculated from participant-specific exponential models by standardizing aortic stiffness to a "reference" blood pressure. Load-dependent stiffness was calculated as total minus structural stiffness. Total [+0.8 m/s, 95% confidence interval (CI) (-0.99, -0.23), P = 0.002] and load-dependent [+0.4 m/s, 95% CI (-0.56, -0.22), P < 0.001], but not structural [95% CI (-0.52, 0.08), P = 0.16] aortic stiffness were higher among women with a hxPE compared with controls. Women with a hxPE had lower BRS (P = 0.042) that was negatively associated with total [B = -3.24 ms/mmHg, 95% CI (-6.35, -0.13), P = 0.042] and load-dependent [B = -5.91 ms/mmHg, 95% CI (-11.31, -0.51), P = 0.033] aortic stiffness. Load-dependent, not structural, aortic stiffness mechanisms contribute to higher total aortic stiffness among women with a hxPE and are associated with lower cardiovagal BRS. Postpartum monitoring for high BP is critical to reduce increased CVD risk after preeclampsia.NEW & NOTEWORTHY The novel finding is that load-dependent stiffness, not structural stiffness, is the primary mechanism of aortic stiffness, and is associated with reduced baroreflex sensitivity in women with a history of preeclampsia. These findings may help tailor high blood pressure prevention and management strategies in this population to prevent structural aortic stiffening, altered baroreflex control, and increased lifetime cardiovascular disease (CVD) risk.

Heart failure with preserved ejection fraction (HFpEF) constitutes more than half of all HF cases, yet evidence-based therapies remain lacking due to limited understanding of its underlying pathological mechanisms. Our study aimed to uncover early pathological mechanisms in HFpEF by exposing mice to dietary conditions resembling a Western diet-rich in fats, salt, and low in fiber-alongside excess mineralocorticoids to replicate significant aspects of human HFpEF. Echocardiography was performed at both 3-wk and 6-wk intervals postchallenge, revealing cardiac alterations as early as 3 wk. While ejection fraction remained preserved, mice exhibited signs of diastolic dysfunction, reduced stroke volume, and left atrial enlargement. In addition, changes in pulmonary flow velocities were noted by the 3-wk mark, suggesting elevated pulmonary pressure. Extracardiac comorbidities included organ congestion, increased adiposity, impaired glucose tolerance, and hypercholesterolemia. Molecular analyses unveiled evidence of low-grade inflammation, oxidative stress, and impaired NO-cGMP-PKG signaling, contributing to the observed decrease in titin phosphorylation, thereby impacting myocardial stiffness. In addition, impaired nitric oxide (NO) signaling might have influenced the alterations observed in coronary flow reserve. Moreover, dysregulation of calcium signaling in cardiomyocytes and reduced sarcoplasmic reticulum (SR) load were observed. Interestingly, elevated phosphorylation of cMyBP-C was linked to preserved ejection fraction despite reduced SR load. We also observed intestinal atrophy, possibly due to a high-fat diet, low dietary fiber intake, and diminished gut perfusion, potentially contributing to systemic low-grade inflammation. These findings reveal how excess mineralocorticoid salt-induced hypertension and dietary factors, like high-fat and low-fiber intake, contribute to cardiac dysfunction and metabolic disturbances, offering insights into early HFpEF pathology in this model.NEW & NOTEWORTHY Our study demonstrates that feeding mice a Western diet rich in fat and salt and low in fiber alongside excess mineralocorticoids replicates aspects of human HFpEF. Cardiac alterations including diastolic dysfunction and decreased stroke volume with preserved ejection fraction were observed. Extracardiac effects included organ congestion, adiposity, glucose intolerance, and intestinal atrophy. Molecular analysis revealed inflammation, oxidative stress, impaired NO-cGMP-PKG signaling pathways, and altered calcium signaling in cardiomyocytes, shedding light on early pathological changes in HFpEF.

Endothelial dysfunction is an early consequence of vascular inflammation and a driver of coronary atherosclerotic disease leading to myocardial infarction. The red blood cells (RBCs) mediate endothelial dysfunction in patients at cardiovascular risk, but their role in patients with acute myocardial infarction is unknown. This study aimed to investigate if RBCs from patients with ST-elevation myocardial infarction (STEMI) induced endothelial dysfunction and the role of systemic inflammation in this effect. RBCs from patients with STEMI and aged-matched healthy controls were coincubated with rat aortic segments for 18 h followed by evaluation of endothelium-dependent (EDR) and endothelium-independent relaxation (EIDR). RBCs and aortic segments were also analyzed for arginase and oxidative stress. The patients were divided into groups depending on C-reactive protein (CRP) levels at admission. RBCs from patients with STEMI and CRP levels ≥2 mg/L induced impairment of EDR, but not EIDR, compared with RBCs from STEMI and CRP <2 mg/L and healthy controls. Aortic expression of arginase 1 was increased following incubation with RBCs from patients with STEMI and CRP ≥2, and arginase inhibition prevented the RBC-induced endothelial dysfunction. RBCs from patients with STEMI and CRP ≥2 had increased reactive oxygen species compared with RBCs from patients with CRP <2 and healthy controls. Vascular inhibition of NADPH oxidases and increased dismutation of superoxide improved EDR. RBCs from patients with STEMI and low-grade inflammation induce endothelial dysfunction through a mechanism involving arginase 1 as well as increased RBC and vascular superoxide by NADPH oxidases.NEW & NOTEWORTHY Red blood cells from patients with STEMI and systemic inflammation induce endothelial dysfunction ex vivo. The RBC-induced endothelial dysfunction is mediated through increased arginase 1 and a shift in the redox balance toward oxidative stress. Inhibition of arginase or free radicals attenuates the impairment of endothelial function. The study suggests that red blood cells deserve attention as a key player in systemic inflammation and STEMI.

The accuracy of femoral artery blood flow measurements via Doppler ultrasound hinges on assumptions of laminar flow upstream of the femoral bifurcation. Existing scanning guidelines recommend a minimum proximity to the flow divider of 2-3 cm for avoiding multidirectional blood flow yet lack experimental evidence to support this recommendation. This study aimed to determine the minimum distance required to avoid multidirectional flow contamination near the femoral bifurcation and to assess the reliability of vector flow imaging (VFI) in these measurements. Twenty healthy adults (10 females, 25 ± 4 yr) participated in this study. Ultrasound VFI was used to visualize blood flow patterns and quantify flow uniformity via vector concentration coefficient (VCC), and multidirectional flow length was quantified at rest in triplicate (n = 20), postisometric contraction (n = 20), and during thigh cuffing (n = 10). At rest, the mean multidirectional flow length was 3.12 ± 0.59 cm, which decreased to 2.80 ± 0.66 cm postcontraction (P = 0.02). Thigh cuffing (80 mmHg) resulted in a multidirectional flow length of 2.75 ± 0.64 cm, not significantly different from rest (P = 0.69). Males exhibited a shorter multidirectional flow length compared with females (mean difference: 0.31 ± 0.71 cm, P = 0.05). The VCC increased from 0.39 ± 0.08 at rest to 0.57 ± 0.15 postcontraction (P < 0.01), indicating increased flow uniformity. Reliability metrics demonstrated good-to-excellent reproducibility at rest, with intraclass correlation coefficient [ICC(3,1)] = 0.85 and 0.84 and coefficient of variation (CV)% = 7.1 ± 6.2% and 7.5 ± 4.5% for multidirectional flow length and VCC, respectively. Our data suggest a minimum scanning proximity of 3.5 cm to the femoral bifurcation to ensure that blood flow assessments are free of multidirectional flow and invite further study in different body positions and arteries of interest to increase rigor in this area.NEW & NOTEWORTHY Current ultrasound scanning guidelines to avoid multidirectional flow contamination in the femoral artery of 2-3 cm lack supporting evidence. We used vector flow imaging to report the multidirectional flow length during rest and manipulation of downstream vessel resistance in males and females. We suggest measurements at least 3.5 cm upstream from the femoral bifurcation to minimize multidirectional flows. This study also supports reliability of vector flow imaging for femoral artery assessments, with good-to-excellent reproducibility of results.

Diabetes mellitus (DM) is characterized by chronic hyperglycemia, and despite intensive glycemic control, the risk of heart failure in patients with diabetes remains high. Diabetes-induced heart failure (DHF) presents a unique metabolic challenge, driven by significant alterations in cardiac substrate metabolism, including increased reliance on fatty acid oxidation, reduced glucose utilization, and impaired mitochondrial function. These metabolic alterations lead to oxidative stress, lipotoxicity, and energy deficits, contributing to the progression of heart failure. Emerging research has identified novel mechanisms involved in the metabolic remodeling of diabetic hearts, such as autophagy dysregulation, epigenetic modifications, polyamine regulation, and branched-chain amino acid (BCAA) metabolism. These processes exacerbate mitochondrial dysfunction and metabolic inflexibility, further impairing cardiac function. Therapeutic interventions targeting these pathways-such as enhancing glucose oxidation, modulating fatty acid metabolism, and optimizing ketone body utilization-show promise in restoring metabolic homeostasis and improving cardiac outcomes. This review explores the key molecular mechanisms driving metabolic remodeling in diabetic hearts, highlights advanced methodologies, and presents the latest therapeutic strategies for mitigating the progression of DHF. Understanding these emerging pathways offers new opportunities to develop targeted therapies that address the root metabolic causes of heart failure in diabetes.

Rheumatoid arthritis (RA) is characterized by deteriorated vascular health and increased cardiovascular risk. Physical activity (PA) is recommended for cardiovascular management in RA, but evidence on the associations between objectively measured PA and vascular health markers in RA is limited. In this cross-sectional study, 82 postmenopausal women with RA (62 ± 7 yr) undertook ultrasound assessments of vascular function and structure, including brachial and superficial femoral artery (BA and SFA) flow-mediated dilation; baseline and post-hyperemia peak diameters; and carotid intima-media thickness. Participants also performed a 7-day accelerometer-based assessment of PA and sedentary behavior (SB). Fitted regression models controlled for age, body mass index, and disease activity were conducted to examine associations between vascular and PA outcomes. Regression analyses revealed that prolonged SB (bouts >60 min) and total sedentary time were inversely associated with both baseline and peak BA diameters, with each additional hour of SB resulting in decreases of 0.08-0.1 mm in these diameters (P ≤ 0.01). Total sedentary time also showed similar negative associations with peak SFA diameters (β = -0.14 [-0.24 to -0.05], P < 0.01). Conversely, light-intensity PA and stepping time were positively associated with both baseline and peak BA diameters, with each additional hour increasing these diameters by 0.10-0.24 mm (P ≤ 0.02). Finally, standing time was positively associated with SFA peak diameter (β = 0.11 [0.01-0.20], P = 0.02). No associations were found between moderate-to-vigorous PA and vascular outcomes. In conclusion, in patients with RA, SB was negatively, whereas light PA was positively, associated with BA and SFA diameters. These findings suggest that reducing SB and increasing PA, even at light intensities, may improve vascular health in RA.NEW & NOTEWORTHY This was the first study to investigate associations between objectively measured physical activity and markers of vascular health in rheumatoid arthritis (RA). The findings suggest that reducing sedentary behavior and increasing light or total physical activity are associated with improved vascular outcomes in RA. These results support further investigation into interventions aimed at reducing sedentary time and replacing with any type of physical activity as a potential strategy for improving cardiovascular outcomes in individuals with RA.

Here we test the hypothesis that continuous nicotine exposure throughout pre- and postnatal development (developmental nicotine exposure, DNE) alters the cardiovascular structure and function in neonatal and juvenile rats. Echocardiography showed that DNE reduced left ventricular mass, left ventricular outflow tract (LVOT) diameter, and posterior wall thickness, but only in females. Both male and female DNE rats had a lower end-systolic volume, higher ejection fraction, and increased fractional shortening, with unchanged stroke volume and cardiac output. Left ventricular single cardiac myocytes from male and female DNE animals exhibited increased calcium-evoked maximal tension with no effect on EC₅₀. Tail-cuff plethysmography in awake rats showed that DNE males had lower systolic blood pressure and higher heart rate than control males. No significant changes in preload, afterload, or the in vitro renal artery response to vasodilators were observed. The results suggest that DNE enhances myocyte tension-generating capacity, possibly compensating for an unknown developmental insult, which may differ in males and females. Although this adaptation maintains normal resting cardiac function, it may lead to reduced cardiac reserve, increased energy demand, and elevated oxidative stress, potentially compromising both short- and long-term cardiovascular health in developing neonates.NEW & NOTEWORTHY Developmental nicotine exposure (DNE) induced cardiovascular changes in neonatal/juvenile rats. Relative to controls, females had reduced left ventricular mass and dimensions, while both sexes had increased ejection fraction and fractional shortening. DNE increased calcium-evoked tension in cardiac myocytes, suggesting an adaptive mechanism as resting cardiac output was preserved. Despite normal resting function, these changes may reduce cardiac reserve, potentially compromising long-term cardiovascular health. These novel findings highlight how DNE disrupts cardiovascular development and function.