Search

Cardiac fibroblasts play a pivotal role in maintaining heart homeostasis by depositing extracellular matrix (ECM) to provide structural support for the myocardium, vasculature, and neuronal network and by contributing to essential physiological processes. In response to injury such as myocardial infarction or pressure overload, fibroblasts become activated, leading to increased ECM production that can ultimately drive left ventricular remodeling and progress to heart failure. Recently, the American Journal of Physiology-Heart and Circulatory Physiology issued a call for papers on cardiac fibroblasts that yielded articles with topics spanning fibroblast physiology, technical considerations, signaling pathways, and interactions with other cell types. This mini-review summarizes those articles and places the new findings in the context of what is currently known for cardiac fibroblasts and what future directions remain. [ABSTRACT FROM AUTHOR]

The maternal cardiovascular system undergoes functional and structural adaptations during pregnancy and postpartum to support increased metabolic demands of offspring and placental growth, labor, and delivery, as well as recovery from childbirth. Thus, pregnancy imposes physiological stress upon the maternal cardiovascular system, and in the absence of an appropriate response it imparts potential risks for cardiovascular complications and adverse outcomes. The proportion of pregnancy-related maternal deaths from cardiovascular events has been steadily increasing, contributing to high rates of maternal mortality. Despite advances in cardiovascular physiology research, there is still no comprehensive understanding of maternal cardiovascular adaptations in healthy pregnancies. Furthermore, current approaches for the prognosis of cardiovascular complications during pregnancy are limited. Machine learning (ML) offers new and effective tools for investigating mechanisms involved in pregnancy-related cardiovascular complications as well as the development of potential therapies. The main goal of this review is to summarize existing research that uses ML to understand mechanisms of cardiovascular physiology during pregnancy and develop prediction models for clinical application in pregnant patients. We also provide an overview of ML platforms that can be used to comprehensively understand cardiovascular adaptations to pregnancy and discuss the interpretability of ML outcomes, the consequences of model bias, and the importance of ethical consideration in ML use. [ABSTRACT FROM AUTHOR]

Maternal mortality rates are at an all-time high across the world and are set to increase in subsequent years. Cardiovascular disease is the leading cause of death during pregnancy and postpartum, especially in the United States. Therefore, understanding the physiological changes in the cardiovascular system during normal pregnancy is necessary to understand disease-related pathology. Significant systemic and cardiovascular physiological changes occur during pregnancy that are essential for supporting the maternal-fetal dyad. The physiological impact of pregnancy on the cardiovascular system has been examined in both experimental animal models and in humans. However, there is a continued need in this field of study to provide increased rigor and reproducibility. Therefore, these guidelines aim to provide information regarding best practices and recommendations to accurately and rigorously measure cardiovascular physiology during normal and cardiovascular disease-complicated pregnancies in human and animal models. [ABSTRACT FROM AUTHOR]

Pressure overload-induced hypertrophy compromises cardiac stretch-induced compliance (SIC) after acute volume overload (AVO). We hypothesized that SIC could be enhanced by physiological hypertrophy induced by pregnancy's chronic volume overload. This study evaluated SIC-cardiac adaptation in pregnant women with or without cardiovascular risk (CVR) factors. Thirty-seven women (1st trimester, 1stT) and a separate group of 31 (3rd trimester, 3rdT) women [healthy or with CVR factors (obesity and/or hypertension and/or with gestational diabetes)] underwent echocardiography determination of left ventricular end-diastolic volume (LVEDV) and E/e' before (T0), immediately after (T1), and 15 min after (T2; SIC) AVO induced by passive leg elevation. Blood samples for NT-proBNP quantification were collected before and after the AVO. Acute leg elevation significantly increased inferior vena cava diameter and stroke volume from T0 to T1 in both 1stT and 3rdT, confirming AVO. LVEDV and E/e' also increased immediately after AVO (T1) in both 1stT and 3rdT. SIC adaptation (T2, 15 min after AVO) significantly decreased E/e' in both trimesters, with additional expansion of LVEDV only in the 1stT. NT-pro-BNP increased slightly after AVO but only in the 1stT. CVR factors, but not parity or age, significantly impacted SIC cardiac adaptation. A distinct functional response to SIC was observed between 1stT and 3rdT, which was influenced by CVR factors. The LV of 3rdT pregnant women was hypertrophied, showing a structural limitation to dilate with AVO, whereas the lower LV filling pressure values suggest increased diastolic compliance. NEW & NOTEWORTHY The sudden increase of volume overload triggers an acute myocardial stretch characterized by an immediate rise in contractility by the Frank-Starling mechanism, followed by a progressive increase known as the slow force response. The present study is the first to characterize echocardiographically the stretch-induced compliance (SIC) mechanism in the context of physiological hypertrophy induced by pregnancy. A distinct functional adaptation to SIC was observed between first and third trimesters, which was influenced by cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

There have been ongoing efforts by federal agencies and scientific communities since the early 1990s to incorporate sex and/or gender in all aspects of cardiovascular research. Scientific journals provide a critical function as change agents to influence transformation by encouraging submissions for topic areas, and by setting standards and expectations for articles submitted to the journal. As part of ongoing efforts to advance sex and gender in cardiovascular physiology research, the American Journal of Physiology-Heart and Circulatory Physiology recently launched a call for papers on Considering Sex as a Biological Variable. This call was an overwhelming success, resulting in 78 articles published in this collection. This review summarizes the major themes of the collection, including Sex as a Biological Variable Within: Endothelial Cell and Vascular Physiology, Cardiovascular Immunity and Inflammation, Metabolism and Mitochondrial Energy, Extracellular Matrix Turnover and Fibrosis, Neurohormonal Signaling, and Cardiovascular Clinical and Epidemiology Assessments. Several articles also focused on establishing rigor and reproducibility of key physiological measurements involved in cardiovascular health and disease, as well as recommendations and considerations for study design. Combined, these articles summarize our current understanding of sex and gender influences on cardiovascular physiology and pathophysiology and provide insight into future directions needed to further expand our knowledge. [ABSTRACT FROM AUTHOR]

The baroreflex is a powerful physiological mechanism for rapidly adjusting heart rate in response to changes in blood pressure. Spontaneous baroreflex sensitivity (BRS) has been shown to decrease with age. However, studies of sex differences in these age-related changes are rare. Here we investigated several markers of spontaneous baroreflex function in a large sample of healthy individuals. Cardiovascular signals were recorded in the supine position under carefully controlled resting conditions. After quality control, n = 980 subjects were divided into five age groups [age < 30 yr (n = 612), 30-39 yr (n = 140), 40-49 yr (n = 95), 50-59 yr (n = 61), and >60 yr (n = 72)]. Spontaneous baroreflex function was assessed in the time domain (bradycardic and tachycardic slope) and in the frequency domain in the low- and high-frequency band (LF-a, HF-a) applying the transfer function. General linear models showed a significant effect of factor age (P < 0.001) and an age - sex interaction effect (P < 0.05) on each indicator of the baroreflex function. Simple main effects showed a significantly higher BRS as indicated by tachycardic slope, LF-a and HF-a in middle-aged women compared with men (30-39 yr) and higher LF-a, bradycardic and tachycardic slope in men compared with women of the oldest age group (>60 yr). Changes in BRS over the lifespan suggest that baroreflex function declines more slowly but earlier in life in men than in women. Our findings could be linked to age-related changes in major sex hormone levels, suggesting significant implications for diverse cardiovascular outcomes and the implementation of targeted preventive strategies. [ABSTRACT FROM AUTHOR]

Wavelet analysis (WA) provides superior time-frequency decomposition of complex signals than conventional spectral analysis tools. To illustrate its usefulness in assessing transient phenomena, we applied a custom-developed WA algorithm to laser-Doppler (LD) signals of the cutaneous microcirculation measured at glabrous (finger pulp) and nonglabrous (forearm) sites during early recovery after dynamic exercise. This phase, importantly contributing to the establishment of thermal homeostasis after exercise cessation, has not been adequately explored because of its complex, transient form. Using WA, we decomposed the LD signals measured during the baseline and early recovery into power spectra of characteristic frequency intervals corresponding to endothelial nitric oxide (NO)-dependent, neurogenic, myogenic, respiratory, and cardiac physiological influence. Assessment of relative power (RP), defined as the ratio between the median power in the frequency interval and the median power of the total spectrum, revealed that endothelial NO-dependent (5.87 early recovery; 1.53 baseline; P = 0.005; Wilcoxon signed-rank test) and respiratory (0.71 early recovery; 0.40 baseline; P = 0.001) components were significantly increased, and myogenic component (1.35 early recovery; 1.83 baseline; P = 0.02) significantly decreased during early recovery in the finger pulp. In the forearm, only the RP of the endothelial NO-dependent (1.90 early recovery; 0.94 baseline; P = 0.009) component was significantly increased. WA presents an irreplaceable tool for the assessment of transient phenomena. The relative contribution of the physiological mechanisms controlling the microcirculatory response in the early recovery phase appears to differ in glabrous and nonglabrous skin when compared with baseline; moreover, the endothelial NO-dependent influence seems to play an important role. [ABSTRACT FROM AUTHOR]

Preeclampsia is a hypertensive disorder that affects pregnant women and can lead to complications and mortality. Women with a history of preeclampsia are at a higher risk of developing hypertension and cardiovascular events. A recent study investigated the cardiovascular responses to stress in women with and without a history of preeclampsia. The study found that women with a recent history of preeclampsia had exaggerated cardiovascular responses during static handgrip exercise, but not during other stressors such as apnea or mental stress. These findings raise new research questions about the mechanisms behind these responses and the potential long-term cardiovascular consequences of preeclampsia. [Extracted from the article]

Coronavirus disease 2019 (COVID-19) is reported to have long-term effects on cardiovascular health and physical functioning, even in the nonhospitalized population. The physiological mechanisms underlying these long-term consequences are however less well described. We compared cardiovascular risk factors, arterial stiffness, and physical functioning in nonhospitalized patients with COVID-19, at a median of 6 mo postinfection, versus age- and sex-matched controls. Cardiovascular risk was assessed using blood pressure and biomarker concentrations (amino-terminal pro-B-type-natriuretic-peptide, high-sensitive cardiac troponin I, C-reactive protein), and arterial stiffness was assessed using carotid-femoral pulse wave velocity. Physical functioning was evaluated using accelerometry, handgrip strength, gait speed and questionnaires on fatigue, perceived general health status, and health-related quality of life (hrQoL). We included 101 former patients with COVID-19 (aged 59 [interquartile range, 55-65] yr, 58% male) and 101 controls. At 175 [126-235] days postinfection, 32% of the COVID-19 group reported residual symptoms, notably fatigue, and 7% required post-COVID-19 care. We found no differences in blood pressure, biomarker concentrations, or arterial stiffness between both groups. Former patients with COVID-19 showed a higher handgrip strength (43 [33-52] vs. 38 [30-48] kg, P = 0.004) and less sleeping time (8.8 [7.7-9.4] vs. 9.8 [8.9-10.3] h/day, P < 0.001) and reported fatigue more often than controls. Accelerometry-based habitual physical activity levels, gait speed, perception of general health status, and hrQoL were not different between groups. In conclusion, one in three nonhospitalized patients with COVID-19 reports residual symptoms at a median of 6 mo postinfection, but we were unable to relate these symptoms to increases in cardiovascular risk factors, arterial stiffness, or physical dysfunction. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is the leading cause of death in chronic kidney disease (CKD). Abnormal arterial hemodynamics contribute to CVD, a relationship that can be mediated by microvascular dysfunction. The purpose of this study was to investigate potential sex differences in arterial hemodynamics and microvascular dysfunction in patients with stages 3 to 4 CKD. Vascular function was assessed in 22 male (mean ± SD; age, 56 ± 13 yr) and 10 female (age, 63 ± 9 yr) patients. Arterial hemodynamics were acquired with combined tonometry and oscillometry. Skin blood flow was used as a model of microvascular function. Participants were instrumented with three microdialysis fibers for the delivery of 1) Ringer’s solution; 2) superoxide dismutase mimetic, Tempol; and 3) nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, apocynin. Blood flow was measured via laser-Doppler flowmetry during standardized local heating (42°C). Central pulse pressure (mean ± SE; 62 ± 9 vs. 46 ± 3 mmHg; P = 0.01) and augmentation index (36 ± 3 vs. 26 ± 3%; P = 0.03) were higher in females. There was a trend for higher central systolic pressures in females (146 ± 9 vs. 131 ± 3 mmHg; P = 0.06). Females reported higher forward (39 ± 4 vs. 29 ± 2 mmHg; P = 0.004) and reflected (27 ± 3 vs. 19 ± 1 mmHg; P < 0.001) wave amplitudes. Cutaneous vascular function was impaired in females compared with males (77 ± 3 vs. 89 ± 1%, P = 0.001). Microvascular function was improved following the delivery of Tempol and apocynin in females but not in males. Female patients with CKD had poorer central hemodynamics and reduced microvascular function compared with their male counterparts. Oxidative stress may contribute to lower microvascular function observed in females. NEW & NOTEWORTHY There are limited data regarding the physiological mechanisms of potential sex differences in central hemodynamics and vascular function in chronic kidney disease (CKD). We report that older female patients with nondialysis CKD have higher central pulse pressures compared with male patients with CKD. In addition, older females with CKD have lower microvascular function compared with their male counterparts, and oxidative stress contributes to the lower microvascular function in older female patients with CKD. [ABSTRACT FROM AUTHOR]

As opposed to arterial distension in the radial plane, longitudinal wall motion (LWM) is a multiphasic and bidirectional displacement of the arterial wall in the anterograde (i.e., in the direction of blood flow) and retrograde (i.e., opposing direction of blood flow) directions. Although initially disregarded as imaging artifact, LWM has been consistently reported in ultrasound investigations in the past decade and is reproducible beat-to-beat, albeit with large interindividual variability across healthy and diseased populations. Emerging literature has sought to examine the mechanistic control of LWM to explain the shape and variability of the motion pattern but lacks considerations for key foundational vascular principles at the level of the arterial wall ultrastructure. The purpose of this review is to summarize the potential factors that underpin the causes and control of arterial LWM, spanning considerations from the arterial extracellular matrix to systems-level integrative theories. First, an overview of LWM and relevant aspects wall composition will be discussed, including major features of the multiphasic pattern, arterial wall extracellular components, tunica fiber orientations, and arterial longitudinal prestretch. Second, current theories on the systems-level physiological mechanisms driving LWM will be discussed in the context of available evidence including experimental human research, porcine studies, and mathematical models. Throughout, we discuss implications of these observations with suggestions for future priority research areas. [ABSTRACT FROM AUTHOR]

The recent move to require sex as a biological variable (SABV), which includes gender, into the reporting of research published by the American Journal of Physiology-Heart and Circulatory Physiology follows a growing, and much-needed, trend by journals. Understandably, there is concern over how to do this without adding considerable work, especially if one's primary research focus is not on elucidating sex/gender differences. The purpose of this article is to provide additional guidance and examples on how to incorporate SABV into the conduct and reporting of basic and clinical research. Using examples from our research, which includes both studies focused and not focused on sex/gender differences, we offer suggestions for how to incorporate SABV into basic and clinical research studies. [ABSTRACT FROM AUTHOR]