American Journal Of Physiology. Heart And Circulatory Physiology[JOURNAL]
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200 papers
ERBB4 activation prevents microvascular dysfunction in a large animal model of hypertensive heart disease.
Tubeeckx MRL, Bringmans T, Goovaerts B … +10 more , Van den Bogaert S, Grootaert MOJ, Jones EAV, Korpisalo P, Juusola G, Wirth G, Murphy SL, Heidbuchel H, De Keulenaer GW, Segers VFM
Am J Physiol Heart Circ Physiol · 2026 Jun · PMID 42154729 · Publisher ↗
Coronary microvascular dysfunction (CMD) participates in the pathophysiology of multiple cardiovascular diseases, but treatment options are limited. A new treatment option may include V-erb-b avian erythroblastic viral o...
Coronary microvascular dysfunction (CMD) participates in the pathophysiology of multiple cardiovascular diseases, but treatment options are limited. A new treatment option may include V-erb-b avian erythroblastic viral oncogene homology-type 4 (ERBB4) stimulation by neuregulin-1 (NRG1), which has anti-inflammatory, antifibrotic, and cardioprotective effects in models of heart failure. This work assess the effect of NRG1/ERBB4 stimulation on CMD in hypertensive heart disease. Hypertensive heart disease was induced in 12 Aachen minipigs by implantation of deoxycorticosterone acetate (DOCA) pellets for 8 wk and compared with six controls. The DOCA pigs were randomized to a weekly infusion of JK07, a NRG1 fusion protein with improved pharmacokinetic and pharmacodynamic properties, or vehicle. Microvascular resistance was measured using the bolus thermodilution method. DOCA significantly increased microvascular resistance compared with controls (from 14.5 to 19.9 mmHg·s, = 0.028). This increase was abrogated by JK07 (11.3 mmHg·s, = 0.018 vs. DOCA). P/ increased by DOCA compared with controls (from 2,415.5 to 4,455.5 mmHg/s, = 0.011), which was also abrogated by JK07 (3,107.3 mmHg/s, = 0.055 vs. DOCA). Interstitial left ventricular fibrosis was significantly lower in JK07-treated pigs compared with DOCA only (2.1 vs. 5.4%, = 0.026), but without a difference in perivascular fibrosis ( = 0.48). JK07 did not affect myocyte cross-sectional area, capillary density, pericyte coverage, microvascular vessel thickness, inflammatory cytokines, or endothelial activation. ERBB4 activation by JK07 can prevent CMD in a DOCA hypertensive pig model. The exact mechanism of the protective effects of JK07 on microvascular resistance remains elusive however. CMD is implicated in numerous cardiac diseases, for which only a few therapeutic options are available. Stimulation of the ERBB4/NRG1 pathway has shown beneficial effects in preclinical models of heart failure. JK07 is a selective ERBB4 agonist of interest. JK07 was able to prevent the increase in microvascular resistance in a DOCA-induced hypertensive pig model, as measured by the bolus thermodilution method.
Myocardial YBX1 is dispensable for cardiac development and function.
Stanley EV, Han Z, Sassower R … +3 more , Gao C, Kessinger CW, Wu T
Am J Physiol Heart Circ Physiol · 2026 Jun · PMID 42154661 · Publisher ↗
The Y-box-binding protein 1 (YBX1) is a DNA- and RNA-binding protein with multifaceted roles in transcriptional, posttranscriptional, and translational regulation. Consequently, YBX1 controls many aspects of cellular fun...
The Y-box-binding protein 1 (YBX1) is a DNA- and RNA-binding protein with multifaceted roles in transcriptional, posttranscriptional, and translational regulation. Consequently, YBX1 controls many aspects of cellular function, including proliferation, differentiation, and apoptosis. In recent years, YBX1 emerged as an important player in the cardiovascular system, whose dysregulation underlies many forms of heart disease. Intriguingly, although reducing YBX1 levels in the myocardium confers protection against pathological cardiac remodeling, YBX1 knockdown in the heart also induces cardiac hypertrophy and fibrosis, raising safety concerns about targeting YBX1 therapeutically. Nevertheless, prior YBX1 loss-of-function studies used RNA interference (RNAi), which is susceptible to off-target effects and likely affected multiple cardiac cell types. Therefore, "clean" YBX1 cardiac-specific loss-of-function genetic models are required to delineate YBX1's precise role in the heart. To that end, we constructed both global and cardiomyocyte (CM)-specific knockout (KO) mouse models. Although global KO mice died in utero and exhibited severe cardiac defects, including noncompaction and delayed septal development, cardiomyocytes-specific KO mice () did not exhibit obvious morphological anomaly or cardiac dysfunction, suggesting that the myocardial YBX1 is dispensable for heart development and function. Although RNA sequencing (RNA-Seq) analysis revealed the upregulation of a few fibrosis-related genes, they did not drive cardiac fibrosis in hearts. Our study provides compelling evidence that deleting YBX1 specifically in CMs would not cause unwanted adverse effects. However, caution is required to ensure the YBX1 ablation is restricted to CMs, as loss of YBX1 in other cell types may lead to cardiac defects. This study presents a genetic, cardiomyocyte-specific loss-of-function mouse model, addressing limitations of prior RNA interference (RNAi) approaches. Global YBX1 deletion causes embryonic lethality with severe cardiac malformations, whereas cardiomyocyte-specific deletion results in only transient embryonic noncompaction that resolves with normal adult heart structure and function. Cardiac function remained preserved for up to 11 mo, and although fibrosis-related genes were upregulated, no overt fibrotic phenotype was observed, supporting cardiomyocyte-targeted YBX1 reduction as a potentially safe therapeutic strategy.
Modes of onset of ventricular arrhythmias in J-wave syndromes: mechanistic insights from computational modeling.
Zhang Z, Qu Z
Am J Physiol Heart Circ Physiol · 2026 Jun · PMID 42141763 · Full text
Different modes of onset of ventricular arrhythmias (VA), preceded by characteristic electrocardiogram patterns, have been observed in patients with J-wave syndromes (JWS), including Brugada syndrome, early repolarizatio...
Different modes of onset of ventricular arrhythmias (VA), preceded by characteristic electrocardiogram patterns, have been observed in patients with J-wave syndromes (JWS), including Brugada syndrome, early repolarization syndrome, and idiopathic ventricular fibrillation. However, the underlying mechanisms remain unclear. The goal of this study is to use computational modeling to elucidate the mechanisms for spontaneous initiation of VA in JWS, particularly the characteristic modes of onset shown in clinical settings. Phase-2 reentry (P2R) was induced by transient outward potassium currents () or loss-of-function sodium channel () mutations in heterogeneous tissue. The computational models replicated the characteristic electrocardiogram patterns and modes of VA onset observed in human patients, including ) fast heart rate-dependent or "short-long-normal-short" sequence to VA; ) pause-dependent or "short-long-short" sequence to VA; and ) sudden onset of VA. Fast heart rate-dependent arrhythmogenesis was driven by either fast or mutations-induced P2R with the rate dependence caused by delayed rectifier potassium current recovery. Pause-dependent arrhythmogenesis was driven by slow or by fast combined with calcium transient restitution. P2Rs could manifest as short-coupled premature ventricular complexes or degenerate into reentrant arrhythmias, depending on the size of the all-or-none repolarization region caused by the spike-and-dome action potential morphology. In conclusion, VA in JWS can be initiated via P2R following a "short-long-normal-short" sequence, a "short-long-short" sequence, or suddenly. P2R and its rate-dependence via the recovery of slow , delayed rectifier potassium current, or calcium transient underlie different modes of onset of VA. Computational models replicated the characteristic electrocardiogram patterns and modes of VA onset observed in human patients with JWS, including "short-long-normal-short" sequence to VA, "short-long-short" sequence to VA, and sudden onset of VA. Mechanisms of these rate-dependent onset of VA and the potential ionic causes were revealed by the computer simulations. This study not only provides mechanistic insights into spontaneous genesis of VA in JWS but also important information for identifying therapeutic targets.
Late-gestation mineralocorticoid receptor antagonism lowers maternal blood pressure and attenuates placental insufficiency induced by leptin in pregnant mice.
Sones JL
Am J Physiol Heart Circ Physiol · 2026 Jun · PMID 42133051 · Full text
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Heart rate and vascular responses to spontaneous arousals following experimental sleep restriction.
Greenlund IM, Covassin N, Bukartyk J … +3 more , St Louis EK, Calvin AD, Somers VK
Am J Physiol Heart Circ Physiol · 2026 Jun · PMID 42133047 · Publisher ↗
Chronic short sleep duration is associated with cardiovascular disease (CVD) risk, especially in females. The impact of biological sex on hemodynamic reactivity to spontaneous nocturnal arousals following experimental sl...
Chronic short sleep duration is associated with cardiovascular disease (CVD) risk, especially in females. The impact of biological sex on hemodynamic reactivity to spontaneous nocturnal arousals following experimental sleep restriction remains largely unknown. We therefore investigated the effect of 9-day 4-h sleep restriction on heart rate (HR) and pulse transit time (PTT) changes following spontaneous arousals in healthy males and females. We hypothesized that HR and PTT reactivity would be augmented following sleep restriction, and these responses would be more robust in females. Nineteen participants (8 females; 23 ± 5 yr) were enrolled into this study, which included two 16-day in-patient studies comprised of sleep restriction (4-h sleep opportunity) and normal sleep (9-h sleep opportunity) study arms. Overnight polysomnography on (acclimation), (early experimental), (late experimental), and (recovery) of each sleep intervention was used to analyze HR and PTT responses to spontaneous arousals. Sleep restriction did not alter HR or PTT reactivity in males or females during the early experimental phase (; interaction: > 0.05). The HR response to arousal was altered in a sex-dependent manner following sleep restriction during the late experimental phase (, interaction: = 0.013). Continued sleep loss resulted in greater PTT reduction following spontaneous arousals in females, but not in males (, interaction: = 0.007). Sustained sleep curtailment disrupts nocturnal vascular responsiveness to spontaneous arousals, more evident in females than in males. These findings provide mechanistic insight into the sex-specific relationship between shortened sleep duration and CVD risk in females. Clinical Trials Registration: Physiologic Effects of Sleep Restriction, https://clinicaltrials.gov/study/NCT01433315?term=NCT01433315&rank=1, NCT01433315. Augmented cardiovascular responses to spontaneous nocturnal arousals were previously shown in chronic short-sleeping adults, without known sex differences. Sustained 4-h sleep restriction produced a sex-dependent alteration in heart rate responses to arousals and resulted in a prolonged reduction in postarousal pulse transit time in females only. These findings yield the first sex-specific characterization of nocturnal cardiovascular responses to spontaneous arousals following sleep restriction, and may place females at greater sleep truncation-related cardiovascular disease risk.
Lipidomic remodeling is associated with hemodynamic severity in calcific aortic valve stenosis.
Surendran A, Stamenkovic A, Jassal DS … +2 more , Shah A, Ravandi A
Am J Physiol Heart Circ Physiol · 2026 Jun · PMID 42126129 · Publisher ↗
Calcific aortic valve stenosis (CAVS) is characterized by progressive leaflet calcification driven in part by lipid dysregulation, yet the metabolic pathways underlying disease advancement remain poorly understood. LC/MS...
Calcific aortic valve stenosis (CAVS) is characterized by progressive leaflet calcification driven in part by lipid dysregulation, yet the metabolic pathways underlying disease advancement remain poorly understood. LC/MS-based lipidomics was performed on aortic valve tissue from 99 patients undergoing surgical replacement and on plasma from an independent cohort of 107 individuals (58 severe AS; 49 controls). Unsupervised k-means clustering defined lipid-based phenotypes that were compared with echocardiographic markers of severity. Plasma-tissue concordance was assessed in an overlap subset ( = 17), and the discriminatory performance of plasma lipids was examined using ROC analysis. Tissue lipidomics identified three molecular clusters associated with differing hemodynamic profiles. The most pronounced metabolic remodeling was observed between cluster 3 and the other clusters, which exhibited higher hemodynamic burden, and was marked by increases in diacylglycerols (DG), alkyl lysophosphatidylcholines [LPC(O)], and dihexosylceramides (Hex2Cer). DG and LPC(O) species also showed strong associations with valve stiffness and calcification burden. In plasma, several DG species were positively associated with AS status, whereas selected triglycerides demonstrated inverse associations. In exploratory ROC analyses, TG 52:4 and TG 54:4 showed discriminatory potential (AUC 0.831 and 0.880, respectively). These triglycerides also demonstrated strong plasma-tissue concordance (r > 0.7). Comprehensive lipidomic profiling reveals early, pathway-specific lipid remodeling that parallels clinical severity in CAVS. DG and LPC(O) species associate with valvular stiffening, while circulating TG 52:4 and TG 54:4 emerge as candidate noninvasive biomarkers requiring independent validation. Our study delivers the largest lipidomic analysis of human aortic valves, revealing early metabolic shifts, especially in diacylglycerols and alkyl-lysophosphatidylcholines that closely track hemodynamic severity. By integrating valve tissue and plasma profiles, we identify triglycerides TG 52:4 and TG 54:4 as promising noninvasive candidate biomarkers. These findings clarify lipid-driven mechanisms of calcific aortic stenosis and highlight new opportunities for earlier detection and risk stratification.
The effect of maternal hypercholesterolemia on neonatal indole metabolism and growth.
Hula N
Am J Physiol Heart Circ Physiol · 2026 Jun · PMID 42126104 · Publisher ↗
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Low-dose aspirin reduces placental inflammation and restores angiogenic balance in a rat model of excessive hypercholesterolemia in pregnancy.
de Oliveira AA, Quon A, Stokes A … +4 more , Spaans F, Graton ME, Cooke CM, Davidge ST
Am J Physiol Heart Circ Physiol · 2026 Jun · PMID 42126080 · Publisher ↗
Low-dose aspirin is recommended to pregnant individuals at increased risk of preeclampsia to improve outcomes. We recently showed that low-dose aspirin improves uterine artery function in a rat model of excessive hyperch...
Low-dose aspirin is recommended to pregnant individuals at increased risk of preeclampsia to improve outcomes. We recently showed that low-dose aspirin improves uterine artery function in a rat model of excessive hypercholesterolemia (eHC) in pregnancy, a known risk factor for preeclampsia. However, its effects on placentas from male and female offspring remain unclear. Here, we examined how low-dose aspirin affects various placental inflammatory and angiogenic markers, as well as the maternal soluble fms-like tyrosine kinase receptor-1 (sFlt-1)/placental growth factor (PlGF) ratio, in eHC pregnancies. We hypothesized that low-dose aspirin reduces placental inflammation, leading to angiogenic balance in these pregnancies. Sprague-Dawley rats were fed a control diet or a high cholesterol diet (to model eHC) from (GD) to , with placebo or low-dose aspirin administered from GD10 to 20. On GD20, placentas were collected and separated based on the fetal sex. eHC in pregnancy elevated maternal plasma sFlt-1 without altering PlGF, resulting in an increased sFlt-1/PlGF ratio; that did not occur with low-dose aspirin treatment. Moreover, placental was increased in male, but not in female, fetuses, and was reduced by low-dose aspirin. Placental PlGF was reduced in males, but increased in females, of eHC pregnancies; low-dose aspirin restored placental PlGF in only the female placentas. NLRP3 (a major placental inflammatory pathway) levels were increased in only eHC male placentas and normalized by low-dose aspirin. These findings reveal that low-dose aspirin restores the maternal plasma sFlt-1/PlGF ratio and suppresses placental inflammation through sex-specific mechanisms in eHC pregnancies. This study demonstrates that pregnancies complicated by excessive hypercholesterolemia have a higher maternal plasma sFlt-1/PlGF ratio driven by increased sFlt-1 levels, indicating an angiogenic imbalance. Importantly, this imbalance can be prevented with low-dose aspirin, an actionable therapeutic option during pregnancy. Low-dose aspirin suppressed placental inflammation (evidenced by decreased NLRP3 levels) and lowered placental-derived via sex-specific mechanisms.
Rethinking cell death in pressure-overload heart failure: a sex-specific necroptosis paradigm.
Al Rimon R, Krishnan V, Kassiri Z
Am J Physiol Heart Circ Physiol · 2026 Jun · PMID 42126074 · Publisher ↗
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The angles of physiology: how posture affects cardiopulmonary response to exercise testing.
Manferdelli G, Barton GP
Am J Physiol Heart Circ Physiol · 2026 Jun · PMID 42113626 · Publisher ↗
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What men's vessels can learn from women's: redefining vascular homeostasis through the lens of female reproductive history.
Goulopoulou S, Tucker SM
Am J Physiol Heart Circ Physiol · 2026 Jun · PMID 42113547 · Publisher ↗
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Myocardial relaxation, left ventricular filling, and exercise capacity in older subjects with dyspnea.
Sunderji ID, Erdei T, Bijnens B … +3 more , Marino P, Lloyd G, Fraser AG
Am J Physiol Heart Circ Physiol · 2026 Jun · PMID 42113527 · Publisher ↗
With aging, left ventricular (LV) early diastolic lengthening declines. Delayed or dyssynchronous untwisting and relaxation may slow and reduce filling and contribute to elevated diastolic pressures. Segmental variations...
With aging, left ventricular (LV) early diastolic lengthening declines. Delayed or dyssynchronous untwisting and relaxation may slow and reduce filling and contribute to elevated diastolic pressures. Segmental variations in the timing of early diastolic relaxation may impair LV suction during exercise and impact LV stroke volume reserve, especially in heart failure with preserved ejection fraction (HFpEF). To determine possible mechanisms causing dyspnea, we investigated 106 subjects aged ≥ 60 yr, including 38 patients with HFpEF, 26 breathless, 19 hypertensive, and 23 healthy controls, at rest and during submaximal exercise stress echocardiography. Global and regional early diastolic function were assessed by LV isovolumic relaxation time (IVRT), the deceleration time (DT) and propagation velocity of mitral inflow, and segmental variations in times-to-peak early diastolic myocardial velocity (e'). Global IVRT and DT were similar between groups at rest and during stress. During exercise, increments in mean segmental e' were similar between groups, whereas times-to-peak e' shortened variably, being 13%-20% longer in the midseptal and 30%-35% longer in the midlateral segments in HFpEF than in healthy or hypertensive subjects ( < 0.001). There were moderate inverse correlations between time-to-peak e' and LV inflow velocity, cardiac output on exercise, and 6-min walk distance (ρ -0.42, < 0.001). Slower early diastolic relaxation on exercise is associated with less stroke volume reserve and reduced exercise capacity. Machine learning might be able to identify subtle changes in timing of relaxation as a diagnostic or therapeutic target in subjects with HFpEF. Dyspnea in older subjects and patients with HFpEF is usually attributed to elevated LV filling pressures caused by reduced end-diastolic compliance. This study demonstrates that during exercise, slow early diastolic relaxation and reduced ventricular suction limit increments in early diastolic filling and impair stroke volume reserve, thereby reducing exercise capacity. Lowering late systolic pressure and augmenting early diastolic filling may be important targets for pharmacologic therapy to reduce dyspnea.
Relative contributions of mitochondrial and nonmitochondrial oxidative stress in age-related cutaneous microvascular endothelial dysfunction.
Jennings WE, Bangle JF, Davila GR … +1 more , Wolf ST
Am J Physiol Heart Circ Physiol · 2026 Jun · PMID 42113504 · Publisher ↗
Aging is associated with oxidative-stress-induced endothelial dysfunction, characterized by reduced nitric oxide (NO) signaling. The present study evaluated the contributions of mitochondrial- and nonmitochondrial oxidat...
Aging is associated with oxidative-stress-induced endothelial dysfunction, characterized by reduced nitric oxide (NO) signaling. The present study evaluated the contributions of mitochondrial- and nonmitochondrial oxidative stress in age-related endothelial dysfunction. Three intradermal microdialysis fibers were placed in the forearm for local delivery of pharmacological agents (10 mM Tempol, 1 mM MitoTempo, Ringer's vehicle control) to the cutaneous microvasculature in 15 older (67 ± 3 yr; 7 M and 8 F) adults. After ∼20 min baseline, local heating (42°C) induced cutaneous vasodilation, and perfusion of a NO synthase inhibitor (15 mM -nitro-l-arginine-methyl ester hydrochloride) allowed quantification of the NO- and non-NO contributions to the local heating response. Red cell flux was measured at each site by laser-Doppler flowmetry (LDF), and cutaneous vascular conductance (CVC = LDF/mean arterial pressure) was expressed as a percentage of maximum (%CVC; 28 mM sodium nitroprusside + 43°C). Tempol improved the local heating response compared with Ringer's (76.37 ± 18.99 vs. 51.07 ± 23.36, = 0.02), but MitoTempo ( = 0.25) did not. Likewise, Tempol improved the NO contribution to the response compared with Ringer's (61.40 ± 15.92 vs. 37.02 ± 20.64, = 0.01), but MitoTempo ( = 0.69) did not. Conversely, MitoTempo increased the non-NO-mediated component of the response compared with Ringer's (13.95 ± 16.43 vs. 4.04 ± 6.14; < 0.01), but Tempol did not ( = 0.41). There were no differences between Tempol and MitoTempo ( ≥ 0.14). These data suggest that, although mitochondrial oxidative stress may contribute, a considerable portion of the oxidative stress underlying age-related endothelial dysfunction is derived outside of the mitochondria. Age-related declines in nitric oxide-mediated cutaneous microvascular function are due, at least in part, to increased oxidative stress. However, the specific sources of oxidative stress that contribute to microvascular endothelial dysfunction with aging remain unclear. Here, we demonstrate that, although mitochondrial oxidative stress may contribute, a considerable portion of the oxidative stress underlying age-related endothelial dysfunction is derived outside of the mitochondria.
Successful careers in STEMM through leadership and professional development training.
Rigos AA, Alsharqi M, Frebel A
Am J Physiol Heart Circ Physiol · 2026 Jun · PMID 42113475 · Publisher ↗
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Acute effects of passive heat exposure on vascular function and exercise capacity in patients with chronic kidney disease.
Chavez DA, Garten RS, Rodriguez-Miguelez P … +5 more , Kim Y, Gagnon D, Romero SA, Kidd JM, Kirkman DL
Am J Physiol Heart Circ Physiol · 2026 Jun · PMID 42113470 · Publisher ↗
Vascular dysfunction and exercise intolerance contribute to chronic kidney disease (CKD)-related cardiovascular disease. Passive heat exposure provides a physiological stimulus for beneficial vascular adaptations and imp...
Vascular dysfunction and exercise intolerance contribute to chronic kidney disease (CKD)-related cardiovascular disease. Passive heat exposure provides a physiological stimulus for beneficial vascular adaptations and improvements in exercise capacity but has not yet been investigated in CKD. The purpose of this pilot study was to examine the physiological response to an acute bout of passive heat exposure in patients with CKD. In this randomized, crossover trial, 10 participants with Stage G2-G4 CKD were enrolled (means ± SE; age, 41 ± 4 yr; 6 females; estimated glomerular filtration rate, 55 ± 7 mL/min/1.73 m). After completing a baseline visit, participants completed two experimental visits: passive heat exposure via far-infrared sauna (HT; 25 min, 60°C) and thermoneutral control (CON; 25 min, 22°C). Macrovascular function, assessed by flow-mediated dilation (FMD), and microvascular function, assessed by the blood flow response to passive limb movement, were measured after a 60-min recovery period following exposure on each experimental visit. Exercise capacity was assessed with the 6-min walk test. Urinary markers of kidney function and injury were collected immediately and over 24 h following visits. FMD (3.84 ± 0.61 vs. 6.68 ± 0.76%, < 0.01) and leg blood flow response to passive limb movement (area under the curve, 179 ± 29 vs. 243 ± 23 arbitrary units, = 0.01) were greater following HT compared with CON. There was a clinically meaningful difference in 6-min walk distance between CON (632 ± 29 yards) and HT (670 ± 30 yards, < 0.01). There were no significant changes in kidney function or biomarkers of acute kidney injury following HT. In this pilot study, a single bout of passive heat exposure acutely improved vascular function and exercise capacity in patients with CKD. This is the first known study to examine the acute vascular, renal, and exercise response to a single bout of passive heat exposure in chronic kidney disease (CKD). Macrovascular function, microvascular function, and exercise capacity were acutely greater after a single session of passive heating, without any effect on kidney function or markers of kidney injury. These preliminary pilot findings could inform future clinical trials of chronic heat therapy for cardiovascular health in CKD.
Etiology-directed antihypertensive management: cashing in on what we know from the classical literature.
Moreira-Bouchard JD
Am J Physiol Heart Circ Physiol · 2026 Jun · PMID 42113469 · Publisher ↗
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Left ventricular flow dynamics in preterm infants assessed with high frame rate echocardiography with blood speckle tracking.
de Waal K, Crendal E, Fadnes S … +2 more , Sorensen K, Nyrnes SA
Am J Physiol Heart Circ Physiol · 2026 Jun · PMID 42095476 · Publisher ↗
The typical intracardiac blood flow pattern of a healthy left ventricle includes vortex formations to help store energy, facilitate valve closure, and propagation of blood flow toward the outflow tract. Intracardiac bloo...
The typical intracardiac blood flow pattern of a healthy left ventricle includes vortex formations to help store energy, facilitate valve closure, and propagation of blood flow toward the outflow tract. Intracardiac blood flow patterns can be visualized with high frame rate echocardiography with blood speckle tracking (BST) and analyzed for measures of cardiac efficiency such as kinetic energy (KE), energy loss (EL), vorticity (VO), and vortex complexity (VC). Preterm infants are at high risk of cardiac compromise, but mechanistic pathways are unclear. The aim of this study is to gather BST reference values in stable preterm infants. Stable low-risk preterm infants < 30 wk' gestation underwent echocardiography with BST early and late in the neonatal admission period. PyUSview software was used for intracardiac flow analysis. We included 55 stable preterm infants. KE, EL, VO, and VC were significantly higher in diastole when compared with systole, and most BST parameters increased during the admission period. EL/KE as a measure of cardiac efficiency remained stable around 3% during systole, but EL/KE during diastole increased from 4.9% to 9.2% along with increasing E and A velocities, which is higher than reported in healthy term infants. Reference ranges of BST intracardiac flow parameters in stable low-risk preterm infants suggest relatively poor cardiac inflow efficiency due to high EL. This data can assist in the development of further clinical applications for BST in preterm infants, such as predicting disease progression, monitoring treatments, and early diagnosis of adverse left ventricular remodeling. In this study, we explored a subgroup of newborns with high risk of cardiac failure during their intensive care stay, the very preterm infant. We present reference values for blood speckle-tracking-derived measures of cardiac efficiency. This data can assist in the development of further clinical applications for echo blood speckle tracking in preterm infants, such as predicting disease progression, monitoring treatments, and early diagnosis of adverse left ventricular (LV) remodeling.
Prepregnancy obesity, gestational weight gain, and their relationship with maternal lipid levels at delivery across racial and ethnic populations.
Laufer XX, Frolova AI, Raghuraman N … +4 more , Martin SL, England SK, Stout MJ, Garr Barry V
Am J Physiol Heart Circ Physiol · 2026 Jun · PMID 42095460 · Publisher ↗
Maternal dyslipidemia is associated with adverse pregnancy outcomes and long-term cardiovascular risk. Prepregnancy obesity and excessive gestational weight gain may exacerbate dysfunctional lipid profiles, particularly...
Maternal dyslipidemia is associated with adverse pregnancy outcomes and long-term cardiovascular risk. Prepregnancy obesity and excessive gestational weight gain may exacerbate dysfunctional lipid profiles, particularly at full term gestation when lipid burden peaks. However, studies on maternal lipids at delivery are lacking. This study aims to examine the associations of prepregnancy BMI (pBMI) and gestational weight gain (GWG) with maternal lipids at delivery across a cohort composed of two dominant ethnicities. This was a secondary analysis of a prospective study and comprised of 500 singleton pregnancies delivering at term (≥37 wk). The association of pBMI and GWG with total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) were examined by multivariate models. Analyses adjusted for potential confounders and stratified by race. Sensitivity analyses omitted gestational diabetes and hypertensive disorders. Participants had pBMI of 28.4 ± 7.5 kg/m and GWG of 26.5 ± 15.0 lbs. The pBMI was inversely associated with HDL-C only among White women ( < 0.01). GWG distribution varied by pBMI ( < 0.0001). Among women with obesity, GWG was positively associated with HDL-C in the full cohort and in Black women and inversely associated with TC and LDL-C in White women. Associations with GWG were attenuated after excluding those with gestational diabetes or hypertensive disorders. GWG and pBMI shape maternal lipid profiles at delivery with substantial differences between White and Black patients. One-size-fits-all guidelines for pBMI and GWG may not appropriately manage maternal dyslipidemia and address associated adverse pregnancy outcomes or long-term cardiovascular morbidity. Prepregnancy BMI (pBMI) and gestational weight gain (GWG) may modulate maternal dyslipidemia during pregnancy, which is associated with adverse pregnancy outcomes and long-term cardiovascular risks. Studies of maternal lipid levels at delivery, when lipid burden peaks, are lacking. Our findings suggest GWG may have a stronger impact than pBMI on delivery lipid levels, with significant differences between White and Black patients, challenging the one-size-fits-all approach to pBMI and GWG recommendations in managing maternal dyslipidemia.
Absolute and workload-indexed exercise blood pressure responses: associations with cardiac output, vascular resistance, and cardiorespiratory fitness in females.
Janssens K, Howden EJ, Mitchell AM … +6 more , Wright L, Climie RE, Parr EB, Haykowsky MJ, La Gerche A, Foulkes SJ
Am J Physiol Heart Circ Physiol · 2026 Jun · PMID 42090306 · Publisher ↗
During exercise, vascular resistance, the ratio of arterial pressure to blood flow [i.e., cardiac output (CO)], is an important component of the hemodynamic response determining peak oxygen uptake (V̇o). However, how sys...
During exercise, vascular resistance, the ratio of arterial pressure to blood flow [i.e., cardiac output (CO)], is an important component of the hemodynamic response determining peak oxygen uptake (V̇o). However, how systolic blood pressure (SBP) responses reflect this pressure-flow relationship, and their association with V̇o remain incompletely understood. We performed cardiopulmonary exercise testing in 135 females (51 ± 8 yr) across a broad fitness spectrum to evaluate V̇o and SBP responses. SBP responses were stratified by maximal SBP (SBP <190 mmHg or ≥190 mmHg) and workload-indexed SBP (SBP/W-slope; low vs. high based on sex- and age-specific median values). Peak CO (CO) was quantified from exercise cardiac magnetic resonance imaging. SBP ≥190 mmHg occurred in 74 participants (55%), high SBP/W-slope in 41 (30%), and 26 (19%) had both. A high SBP/W-slope was associated with lower V̇o (1.7 ± 0.4 vs. 2.1 ± 0.6 L/min; < 0.001) and CO (12.8 ± 2.3 vs. 15.7 ± 3.5 L/min; < 0.001) and higher total peripheral resistance (TPR; 11.2 ± 2.3 vs. 9.0 ± 2.0 mmHg·min/L; < 0.001). In contrast, a low SBP/W-slope despite SBP ≥190 mmHg had the highest V̇o and CO and larger reductions in TPR compared with high SBP/W-slope groups. SBP ≥190 mmHg in isolation was associated with higher V̇o and CO, although it also identified females with low fitness and CO. Thus, SBP/W-slope provides a framework for interpreting SBP relative to flow, with higher slopes indicating an unfavorable pressure-flow profile characterized by higher vascular resistance, lower CO, and reduced V̇o. In contrast, SBP reflects both flow and resistance. Incorporating SBP/W-slope may therefore improve identification of females with impaired pressure-flow regulation. In females, a higher workload-indexed systolic blood pressure (SBP/W)-slope during exercise was associated with greater peripheral vascular resistance, lower cardiac output, and lower cardiorespiratory fitness, irrespective of maximal systolic blood pressure (SBP). In contrast, an exaggerated SBP alone reflected differing contributions of increased flow (i.e., cardiac output) or increased vascular resistance across individuals. Evaluating the SBP/W-slope provides a more physiologically informed interpretation of exercise blood pressure and may improve identification of females with impaired pressure-flow regulation and reduced cardiovascular reserve.
Biological sex modulates dynamic cerebral autoregulation and its directional sensitivity.
Labrecque L, Roy MA, Dehnavi SS … +3 more , Taghizadeh M, Pagé F, Brassard P
Am J Physiol Heart Circ Physiol · 2026 Jun · PMID 42089907 · Publisher ↗
Dynamic cerebral autoregulation (dCA) exhibits directional sensitivity, characterized by greater buffering capacity of cerebral blood flow when mean arterial pressure (MAP) increases than when MAP decreases. Although dCA...
Dynamic cerebral autoregulation (dCA) exhibits directional sensitivity, characterized by greater buffering capacity of cerebral blood flow when mean arterial pressure (MAP) increases than when MAP decreases. Although dCA is known to differ between sexes, it remains unclear whether its hysteresis-like pattern is sex-dependent. In 35 healthy participants (17 females and 18 males; age: 29 ± 7 yr), we assessed the influence of sex on dCA and its directional sensitivity. Participants underwent 7 min of oscillatory lower body negative pressure (OLBNP) at ∼0.05 Hz (20-s cycles) and ∼0.10 Hz (10-s cycles) while middle cerebral artery mean blood velocity (MCAv) and MAP were recorded. dCA was quantified using transfer function analysis (TFA), and absolute and relative directional sensitivity was assessed using time-corrected ratios of MCAv to MAP changes (ΔMCAv/ΔMAP and RelMCAv/RelMAP). TFA metrics did not differ between sexes at either oscillation frequency except TFA phase at ∼0.10 Hz OLBNP, which was higher in females (1.14 ± 0.38 vs. 0.85 ± 0.35 rad; = 0.0431). At ∼0.05-Hz OLBNP, ΔMCAv/ΔMAP showed neither a MAP direction effect ( = 0.0714) nor a biological sex effect ( = 0.0629). RelMCAv/RelMAP showed a MAP direction effect ( = 0.0405) but no biological sex effect. At ∼0.10 Hz, ΔMCAv/ΔMAP demonstrated significant effects of MAP direction ( < 0.0001), biological sex ( = 0.0150), and their interaction ( = 0.0075). Post hoc analysis revealed that ΔMCAv/ΔMAP was lower than ΔMCAv/ΔMAP in females only. These findings indicate that females exhibit better dCA and greater directional sensitivity at ∼0.10-Hz OLBNP. The novel finding of this study is that females exhibit improved dynamic cerebral autoregulation and demonstrate greater directional sensitivity when assessed using ΔMCAv/ΔMAP, at ∼0.10-Hz OLBNP. We also provide evidence of a hysteresis-like pattern at ∼0.05-Hz OLBNP through the application of our RelMCAv/RelMAP metric. Together, these results underscore the importance of accounting for biological sex and employing a multimetric analytical approach when investigating dynamic cerebral autoregulation.
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