Human Cardiovascular Function Research Articles

Influence of Age and Sex on Stability Indicators of the Right-Left Hemodynamic Balance of Skin Microcirculation in Symmetrical Areas of the Human Head.

Indicators (markers) of microcirculation stability (MCR) of the skin in symmetric areas of the head were studied in young (18-19-years-old) and elderly (60-80-years-old) male and female subjects. We performed synchronous MCR measurements of symmetrical areas of the head using laser Doppler flowmetry in 40 healthy volunteers (10 men and 10 women in each age group). Numerical values of stability markers (T1, T2, and ζ) and indicators of the right-left hemodynamic balance of the MCR (regression coefficients a1, a2, b1, b2) were obtained using the previously developed computational and experimental methods. The coefficients a2 and b2 that determine the contribution of the right MCR bed to the right-left hemodynamic balance were higher in elderly men than in young men, while in young and elderly women, no significant differences in the values of these coefficients were revealed. In young men, coefficients a2 and b2 were lower than in young women, while in elderly subjects, the sex differences in these coefficients were leveled. Young men have lower stability markers than women, while in elderly subjects, these stability markers were similar in men and women. No significant age and sex differences in the level of perfusion of the symmetrical temporal regions were found. The results attest to low stability of MCR in young men in comparison with young women and similar stability in old age, which, apparently, can be explained by the influence of sex hormones on the regulation of human cardiovascular functions.

Analysis of cardiovascular function in diabetic patients using EEMD-ICA fusion multi-scale percussion entropy.

Diabetes is a chronic disease that can lead to a variety of complications and even cause death. The signal characteristics of the photoplethysmography signals (PPG) and electrocardiogram signals (ECG) can reflect the autonomic and vascular aspects of the effects of diabetes on the body. Based on the complex mechanism of interaction between PPG and ECG, a set of ensemble empirical mode decomposition-independent component analysis (EEMD-ICA) fusion multi-scale percussion entropy index (MSPEI) method was proposed to analyze cardiovascular function in diabetic patients. Firstly, the original signal was decomposed into multiple Intrinsic Mode Function (IMFs) by ensemble empirical mode decomposition EEMD, principal components of IMF were extracted by independent component analysis (ICA), then the extracted principal components were reconstructed to eliminate the complex high and low frequency noise of physiological signals. In addition, the MSPEI was calculated for the ECG R-R interval and PPG amplitude sequence.(RRI and Amp) The results showed that, compared with EEMD method, the SNR of EEMD-ICA method increases from 2.1551 to 11.3642, and the root mean square error (RMSE) decreases from 0.0556 to 0.0067. This algorithm can improve the performance of denoising and retain more feature information. The large and small scale entropy of MSPEI (RRI,Amp) was significantly different between healthy and diabetic patients (p< 0.01). Compared with arteriosclerosis index (AI) and multi-scale cross-approximate entropy (MCAE): MSPEISS (RRI,Amp) indicated that diabetes can affect the activity of human autonomic nervous system, while MSPEILS (RRI,Amp) indicated that diabetes can cause or worsen arteriosclerosis. Multi-scale Percussion Entropy algorithm has more advantages in analyzing the influence of diabetes on human cardiovascular and autonomic nervous function.

Muscarinic control of cardiovascular function in humans: a review of current clinical evidence.

To review the available evidence on the impact of muscarinic receptor modulation on cardiovascular control in humans. In this narrative Review we summarize data on cardiovascular endpoints from clinical trials of novel subtype-selective or quasi-selective muscarinic modulators, mostly PAMs, performed in the last decade. We also review the cardiovascular phenotype in recently described human genetic and autoimmune disorders affecting muscarinic receptors. Recent advancements in the development of compounds that selectively target muscarinic acetylcholine receptors are expanding our knowledge about the physiological function of each muscarinic receptor subtype (M1, M2, M3, M4, M5). Among these novel compounds, positive allosteric modulators (PAMs) have emerged as the preferred therapeutic to regulate muscarinic receptor subtype function. Many muscarinic allosteric and orthosteric modulators (including but not limited to xanomeline-trospium and emraclidine) are now in clinical development and approaching regulatory approval for multiple indications, including the treatment of cognitive and psychiatric symptoms in patients with schizophrenia as well as Alzheimer's disease and other dementias. The results of these clinical trials provide an opportunity to understand the influence of muscarinic modulation on cardiovascular autonomic control in humans. While the results and the impact of each of these therapies on heart rate and blood pressure control have been variable, in part because the clinical trials were not specifically designed to measure cardiovascular endpoints, the emerging data is valuable to elucidate the relative cardiovascular contributions of each muscarinic receptor subtype. Understanding the muscarinic control of cardiovascular function is of paramount importance and may contribute to the development of novel therapeutic strategies for treating cardiovascular disease.

Non-Alcoholic Functional Drinks Containing Natural Raw Materials

The purpose of research was comprehensive research to clarify the feasibility and possibility of using non-traditional raw materials and metal complexes in functional food products.The realization of the possibilities of using collagen base in food products as a carrier of biologically active substances is of great interest. The joint use of collagen in the design of functional products with components of plant raw materials and biocomplexes seems rational for people suffering from a deficiency of minerals, dietary fiber, vitamins, etc. and contributes to an increase in shelf life.Methods. The objects of the study were: succinic, ascorbic and nicotinic acids; biologically active medicinal substances; salts of 3D-metals, coordination compounds of metals; extracts of St. John's wort herb (Hyperici herba), inflorescences of marigolds prostrate (Tagets patula L), Calendula officinalis and fruits of common cherry (Prúnus pádus). Compositions of functional soft drinks with collagen.Results. It has been established that biocomplexes have pronounced antimicrobial and anti-inflammatory activity, exhibit an antihypoxic effect comparable to comparison drugs in collagen-based polymer systems, which opens up broad prospects for their use as biologically active compounds in the food industry. One of the objectives of the study was to develop the composition and technology for producing a functional jelly-like drink using biocomplexes and herbal medicinal raw materials, which made it possible to obtain soft drinks with a high content of biologically active substances: esters, minerals, trace elements, alkaloids, biogenic amines and other biologically active substances.Conclusion. Drinks with high organoleptic characteristics that persist for a long time, high nutritional and biological value and reduced contamination, contributing to the improvement of metabolic processes, were obtained. The proposed soft drinks can be recommended for dietary and therapeutic and preventive nutrition to various groups of people suffering from a deficiency of minerals, dietary fiber, which manifests itself in diseases of the digestive and musculoskeletal systems, violation of human cardiovascular functions.

Greater aortic perivascular adipose tissue density is associated with aging, aortic stiffness, and central blood pressure in humans.

Aging results in aortic perivascular adipose tissue (aPVAT)-mediated aortic stiffening in preclinical animal models to promote cardiovascular dysfunction. We hypothesized that greater human aPVAT density will be associated with aging, higher aortic stiffness, and blood pressure (BP). Fourteen apparently healthy adults (6 M/8 F, age range 20-79 yr) were recruited for this study. Aortic stiffness, assessed by carotid-femoral pulse wave velocity (cfPWV), resting aortic BP via pulse wave analysis, and aPVAT and abdominal visceral adipose tissue (VAT) density by computed tomography attenuation were acquired. aPVAT and epididymal (visceral) fat from young (4-6 mo) and old (27-29 mo) mice were used for ex vivo-conditioned media intrinsic mechanical stiffness experiments. Compared with younger adults, older adults had higher cfPWV (8.6 ± 0.4 vs. 6.2 ± 0.6 m/s, P < 0.05) and greater aPVAT attenuation (-80.2 ± 2.0 vs. -95.9 ± 1.5 HU, P < 0.05), but not VAT attenuation (P > 0.05). aPVAT-conditioned media from old mice compared with young mice increased intrinsic mechanical stiffness of the aorta (4,519 ± 510 vs. 2,325 ± 563 kPa, P < 0.05), which was not observed with epididymal fat-conditioned media from old mice (P > 0.05). aPVAT, but not VAT density, was positively associated with age (r = 0.89), cfPWV (r = 0.56), resting augmentation index normalized to heart rate 75 (AIxHR75; r = 0.67), aortic systolic BP (r = 0.58), and aortic pulse pressure (PP; r = 0.59; P < 0.05, all) and were independent of VAT density (P < 0.05, all). These data herein provide evidence for aPVAT as a novel fat depot and therapeutic target to lower aortic stiffness and future cardiovascular disease risk with aging in humans.NEW & NOTEWORTHY Aortic perivascular adipose tissue (aPVAT) promotes age-related aortic stiffening in preclinical animal models, but the relation between aPVAT density and cardiovascular function in adults is unknown. We demonstrate that aPVAT, but not abdominal visceral adipose tissue density, is positively associated with aging, aortic stiffness, and higher resting aortic blood pressure in apparently healthy adults. These findings provide novel evidence for aPVAT as a viable therapeutic target for improving cardiovascular function in humans.

A soft and ultrasensitive force sensing diaphragm for probing cardiac organoids instantaneously and wirelessly

Time-lapse mechanical properties of stem cell derived cardiac organoids are important biological cues for understanding contraction dynamics of human heart tissues, cardiovascular functions and diseases. However, it remains difficult to directly, instantaneously and accurately characterize such mechanical properties in real-time and in situ because cardiac organoids are topologically complex, three-dimensional soft tissues suspended in biological media, which creates a mismatch in mechanics and topology with state-of-the-art force sensors that are typically rigid, planar and bulky. Here, we present a soft resistive force-sensing diaphragm based on ultrasensitive resistive nanocracked platinum film, which can be integrated into an all-soft culture well via an oxygen plasma-enabled bonding process. We show that a reliable organoid-diaphragm contact can be established by an ‘Atomic Force Microscope-like’ engaging process. This allows for instantaneous detection of the organoids’ minute contractile forces and beating patterns during electrical stimulation, resuscitation, drug dosing, tissue culture, and disease modelling.

Sleep Loss Influences the Interconnected Brain-Body Regulation of Cardiovascular Function in Humans.

Poor sleep is associated with hypertension, a major risk factor for cardiovascular disease. However, the mechanism(s) through which sleep loss affects cardiovascular health remains largely unknown, including the brain and body systems that regulate vascular function. Sixty-six healthy adults participated in a repeated-measures, crossover, experimental study involving assessments of cardiovascular function and brain connectivity after a night of sleep and a night of sleep deprivation. First, sleep deprivation significantly increased blood pressure-both systolic and diastolic. Interestingly, this change was independent of any increase in heart rate, inferring a vasculature-specific rather than direct cardiac pathway. Second, sleep loss compromised functional brain connectivity within the vascular control network, specifically the insula, anterior cingulate, amygdala, and ventral and medial prefrontal cortices. Third, sleep loss-related changes in brain connectivity and vascular tone were not independent, but significantly interdependent, with changes within the vascular control brain network predicting the sleep-loss shift toward hypertension. These findings establish an embodied framework in which sleep loss confers increased risk of cardiovascular disease through an impact upon central brain control of vascular tone, rather than a direct impact on accelerated heart rate itself.

Nexus Between Human Thermoregulation and Cardiovascular Functions—A Preliminary Simulation for a Moderate Variation of Temperature

AbstractThough the interaction between cardiovascular functions and thermoregulation is enormously complex yet immensely important, very little effort to date has been spent to simulate it from a system point of view. The present work aims at simulating the mutual interaction of human thermoregulation and cardiovascular functions by combining simple models of these two systems. While for thermoregulation, a lumped parameter multi-node model has been developed, a SIMULINK-based approach of electrical analogy has been taken for the cardiovascular system. These two models are coupled by different physiological and control actions, represented by well-established correlations. Three case studies have been conducted. In the first case, thermoregulation of a healthy human being is considered for a prescribed temperature cycle of moderate variation. Under heat stress, cardiac output increases by a joint effect of heart rate and stroke volume while under the cold condition, the variation of the cardiac output is less and is primarily governed by the heart rate. For the case of a reduced ejection fraction of the left ventricle, though there is a notable decrease in skin blood flow, negligible variation in skin and core temperature is observed. In the case of acute aortic stenosis, it is found that the blood pressure falls severely from its normal level causing hypotension and is further aggravated even under moderate heat stress. Such a situation might have further consequences like heat stroke. Finally, the limitations of the present study have been highlighted and suggestions have been made for further improvement.

On the haemodynamic consequence of the chemoreflex and muscle mechanoreflex interaction in women and men: two tales, one story.

The cardiovascular response resulting from the individual activation of the muscle mechanoreflex (MMR) or the chemoreflex (CR) is different between men and women. Whether the haemodynamic consequence resulting from the interaction of these sympathoexcitatory reflexes is also sex-dependent remains unknown. MMR and CR were activated by passive leg movement (LM) and exposure to hypoxia (O2 -CR) or hypercapnia (CO2 -CR), respectively. Twelve young men and 12 young women completed two experimental protocols: (1) resting in normoxia (PET O2 : ∼83mmHg, PET CO2 : ∼34mmHg), normocapnic hypoxia (PET O2 : ∼48mmHg, PET CO2 : ∼34mmHg) and hyperoxic hypercapnia (PET O2 : ∼524mmHg, PET CO2 : ∼44mmHg); (2) LM under the same gas conditions. During the MMR:O2 -CR coactivation, in men, the observed mean arterial pressure (MAP) and cardiac output (CO) were not different (additive effect), while the observed leg blood flow (LBF) and vascular conductance (LVC) were significantly lower (hypo-additive), compared with the sum of the responses elicited by each reflex alone. In women, the observed MAP was not different (additive) while the observed CO, LBF and LVC were significantly greater (hyper-additive), compared with the summated responses. During the MMR:CO2 -CR coactivation, in men, the observed MAP, CO and LBF were not different (additive), while the observed LVC was significantly lower (hypo-additive), compared with the summated responses. In women, the observed MAP was significantly higher (hyper-additive), while the observed CO, LBF and LVC were not different (additive), compared with the summated responses. The interaction of the MMR and CR has a pronounced influence on the autonomic cardiovascular control, with the haemodynamic consequences differing between men and women. KEY POINTS: The cardiovascular response resulting from the activation of the muscle mechanoreflex (MMR) or the chemoreflex (CR) was previously shown to be different between women and men; this study focused on the haemodynamic consequence of the interaction of these two sympathoexcitatory reflexes. MMR and CR were activated by passive leg movement and exposure to hypoxia (O2 -CR) or hypercapnia (CO2 -CR), respectively. Individual and interactive reflex effects on central and peripheral haemodynamics were quantified in healthy young women and men. In men, the MMR:O2 -CR and MMR:CO2 -CR interactions restricted peripheral haemodynamics, likely by potentiating sympathetic vasoconstriction. In women, the MMR:O2 -CR interaction facilitated central and peripheral haemodynamics, likely by potentiating sympathetic vasodilatation; however, the MMR:CO2 -CR interaction was simply additive for the central and peripheral haemodynamics. The interaction between the MMR and the CR exerts a profound influence on the autonomic control of cardiovascular function in humans, with the haemodynamic consequences differing between women and men.

P-778 High altitude significantly affects pregnancy, implantation, live birth, and miscarriage rates in patients subjected to in vitro fertilization procedures with donated oocytes

Abstract Study question Is high altitude an important factor that affects the clinical outcomes in patients subjected toin vitrofertilization with donated oocytes? Summary answer Pregnancy, implantation, and live birth rates are significantly impacted by paternal chronic hypoxia in IVF procedures involving egg donors. What is known already High altitude is characterized by low temperatures, high UV radiation, and a hypoxic environment that significantly affect human physiology, including endocrine, cardiovascular, metabolic, and reproductive functions. Hypoxia can affect male reproduction differently, such as at the hormonal level, during spermatogenesis and gene expression. More importantly, hypoxia can affect key events during early embryo development, with time of exposure being the determining factor in the stage of fertilization and embryonic development in mammals. Study design, size, duration The following work is a retrospective nonrandomized study based on data from 85 IVF donor egg cycles performed at high altitude (Huancayo-Peru, 3,300 meter above sea level;n = 42) and at sea level (Guayaquil-Ecuador;n = 43) between July 2019 and December 2020. The same protocols of culture and embryo classification were used in both assisted reproduction laboratories. Participants/materials, setting, methods Anonymous oocytes donors (18-29 years old) underwent physical, gynecological and psychological examinations, with no family histories of hereditary or chromosomal diseases reported. According to seminal samples, IVF or ICSI was elected as the insemination procedure. Extended embryo culture until blastocyst stage was done in all procedures. Pregnancy, implantation, live birth, and miscarriage rates were compared between groups. Main results and the role of chance Out of a total of 983 included oocytes, 529 corresponded to high level patients; and 454, to sea level patients. Fertilization rates (95.1% vs 92.1%) and good-quality embryos at day 3 (79.7% vs 83.8%) were similar between high altitude and sea level groups (P &amp;gt; 0.05). The number of transferred embryos in recipients at high altitude was significantly higher compared to those transferred in recipients at sea level (1.90±0.29 vs 1.62±0.49) (P &amp;lt; 0.05). Blastocyst formation rates (39.3% vs 44.3%), pregnancy rates (61.9% vs 71.4%), implantation rates (48.8% vs 64.7%) and live birth rates per embryo transfer (46.3% vs 65.7%) were significantly lower in the patients at high altitude compared to those from sea level (P &amp;lt; 0.05). Significantly more miscarriages were observed at high altitude (23.1% vs 6.5%) (P &amp;lt; 0.05). Seminal parameters were similar between both evaluated groups. Limitations, reasons for caution The retrospective nature of this study and the small sample size may be reason for caution. Wider implications of the findings The negative effect of high altitude on reproduction has been shown previously in men, hypoxia could cause a degeneration in the germinal epithelium that affects spermatogenesis. We show that paternal chronic hypoxia affects preimplantation embryonic development, pregnancy, implantation, live birth, and miscarriage rates in IVF procedures using donated oocytes. Trial registration number not applicable

The Relationship Between Caffeinated Coffee and CVD Risk as well as Blood Pressure

Aspects around cardiovascular disease (CVD), especially its predisposing factors, have been studied for a long period. Recent studies have largely concentrated on coffee intake by elderly individuals with type 2 diabetes and its association with CVDs. Others have looked at the potential of coffee and tea in preventing CVD. The association between intake of caffeinated coffee with heart valve disease among the elderly has been another area of interest. However, there is still a gap in research in this area, explaining why this review was conducted to explore the effects of caffeinated coffee on human cardiovascular function as well as the association between coffee consumption and the blood pressure level. The review concludes that Caffeinated coffee consumption is associated with a lower risk of CVD. However, the association between caffeinated coffee intake and blood pressure needs further study.

A humanized anti‐cocaine mAb blocks the cardiovascular effects of cocaine in rats

Cocaine use and abuse is associated with significant morbidity and mortality. Further, its use has significant effects on cardiovascular function in humans and has been associated with development of chest pain, myocardial ischemia and in rare cases cardiac death. Currently, the FDA has no approved pharmacotherapy for cocaine abuse. We have developed and generated a humanized anti‐cocaine monoclonal antibody (mAb), h2E2, which dramatically decreases brain cocaine concentrations by sequestering cocaine in the plasma. As h2E2 proceeds into clinical trials, a significant question remains as to whether the increased plasma cocaine concentrations, increased circulation time of cocaine, and the decrease in cocaine excretion into the urine affects cardiac function. Therefore, the objective of this study was to determine the dose, duration and effects of cocaine administration in the presence and absence of mAb h2E2 on echocardiographic variables in an in vivo rat model.Echocardiography was performed on Sprague‐Dawley rats with indwelling catheters using the Vevo 2100 ultrasound machine with a 20mHz probe. Baseline echocardiographic long axis M‐mode images were collected prior to an i.v. cocaine push and at subsequent time points thereafter. Initial studies determined the dose‐dependent effect of cocaine on cardiac parameters including ejection fraction (EF), heart rate (HR) and cardiac output (CO). The most significant increase in EF was observed with 1.68mg/kg cocaineHCl, which was then used in the subsequent experiments.As noted, cocaine administration increased EF, with inversely proportional changes in left ventricular systolic volume. In addition, cocaine produced an immediate decrease in HR, which did not fully return to baseline over the 45 minute time course, likely due to the anesthesia, as the saline control group demonstrated comparable effects. Similarly, cocaine caused an immediate decrease in CO, which normalized over time.Pre‐administration of a single equimolar dose of h2E2 significantly blunted the effect of cocaine on EF, including both the initial drop as well as the subsequent increase. At one week and one month post h2E2, there was no significant blunting of the increased in cocaine‐induced inotropy. However, the initial decrease in EF was still blocked after one week. The initial cocaine‐induced drop in HR was blocked by h2E2, even at 1 week post‐injection. h2E2 similarly blocked the increase in CO, however this effect was not detectable after 1 week or 1 month.In conclusion, there were no significant adverse cardiac effects noted with h2E2 administration and co‐administration with cocaine resulted in significant blunting of both cocaine’s inotropic and chronotropic effects. Elevated plasma cocaine concentrations are pharmacologically inert in the presence of h2E2.

Thoroughly Calibrated Modular Agent-Based Model of the Human Cardiovascular and Renal Systems for Blood Pressure Regulation in Health and Disease.

Here we present a modular agent-based mathematical model of the human cardiovascular and renal systems. It integrates the previous models primarily developed by A. C. Guyton, F. Karaaslan, K. M. Hallow, and Y. V. Solodyannikov. We performed the model calibration to find an equilibrium state within the normal vital sign ranges for a healthy adult. We verified the model’s abilities to reproduce equilibrium states with abnormal physiological values related to different combinations of cardiovascular diseases (such as systemic hypertension, chronic heart failure, pulmonary hypertension, etc.). For the model creation and validation, we involved over 200 scientific studies covering known models of the human cardiovascular and renal functions, biosimulation platforms, and clinical measurements of physiological quantities in normal and pathological conditions. We compiled detailed documentation describing all equations, parameters and variables of the model with justification of all formulas and values. The model is implemented in BioUML and available in the web-version of the software.

A Protective Strategy to Counteract the Oxidative Stress Induced by Simulated Microgravity on H9C2 Cardiomyocytes.

Microgravity affects human cardiovascular function inducing heart rhythm disturbances and even cardiac atrophy. The mechanisms triggered by microgravity and the search for protection strategies are difficult to be investigated in vivo. This study is aimed at investigating the effects induced by simulated microgravity on a cardiomyocyte-like phenotype. The Random Positioning Machine (RPM), set in a CO2 incubator, was used to simulate microgravity, and H9C2 cell line was used as the cardiomyocyte-like model. H9C2 cells were exposed to simulated microgravity up to 96 h, showing a slower cell proliferation rate and lower metabolic activity in comparison to cell grown at earth gravity. In exposed cells, these effects were accompanied by increased levels of intracellular reactive oxygen species (ROS), cytosolic Ca2+, and mitochondrial superoxide anion. Protein carbonyls, markers of protein oxidation, were significantly increased after the first 48 h of exposition in the RPM. In these conditions, the presence of an antioxidant, the N-acetylcysteine (NAC), counteracted the effects induced by the simulated microgravity. In conclusion, these data suggest that simulated microgravity triggers a concomitant increase of intracellular ROS and Ca2+ levels and affects cell metabolic activity which in turn could be responsible for the slower proliferative rate. Nevertheless, the very low number of detectable dead cells and, more interestingly, the protective effect of NA, demonstrate that simulated microgravity does not have “an irreversible toxic effect” but, affecting the oxidative balance, results in a transient slowdown of proliferation.

A Literature Review of the Effects of Self-Myofascial Release with a Foam Roller on Human Fascial System and Cardiovascular Function

PURPOSE: Self-myofascial release (SMR) using a foam roller is a popular intervention used to improve flexibility and restore skeletal muscles, fascia, tendons, ligaments and soft-tissue extensibility. However, the mechanism about the effects of SMR on flexibility, delayed onset of muscle soreness and arterial stiffness has not been elucidated. The purpose of this review is to provide basic knowledge for the mechanism about the effects of SMR from a functional and anatomical perspective.METHODS: In this review, we summarized previous studies investigating the effects of SMR which were associated with the human fascial system on flexibility, delayed onset of muscle soreness, arterial stiffness and autonomic nervous system (ANS).RESULTS: SMR with a foam roller can improve flexibility by increasing blood flow and circulation to the soft tissues. Foam rollingrelated mechanisms to increase range of motion or reduce pain include the activation of cutaneous and fascial mechanoreceptors and interstitial afferent nerves that modulate sympathetic/parasympathetic activation as well as the activation of global pain modulatory systems and reflex-induced reductions in muscle and myofascial tone. In addition, SMR with a foam roller may improve arterial stiffness, which was associated with increased circulating level of nitric oxide induced by elevated shear stress on the walls of the blood vessel.CONCLUSIONS: SMR using a foam roller improves flexibility by relaxing tension in skeletal muscles or fascia and may help to improve arterial stiffness and the function of the ANS. We suggest that SMR using a foam roller may help to reduce the risks of cardiovascular disease as a new alternative method.

Nitric oxide synthase inhibition with N(G)-monomethyl-l-arginine: Determining the window of effect in the human vasculature

Nitric oxide synthase (NOS) inhibition with N(G)-monomethyl-l-arginine (L-NMMA) is often used to assess the role of NO in human cardiovascular function. However, the window of effect for L-NMMA on human vascular function is unknown, which is critical for designing and interpreting human-based studies. This study utilized the passive leg movement (PLM) assessment of vascular function, which is predominantly NO-mediated, in 7 young male subjects under control conditions, immediately following intra-arterial L-NMMA infusion (0.24 mg⋅dl−1⋅min−1), and at 45–60 and 90–105 min post L-NMMA infusion. The leg blood flow (LBF) and leg vascular conductance (LVC) responses to PLM, measured with Doppler ultrasound and expressed as the change from baseline to peak (ΔLBFpeak and ΔLVCpeak) and area under the curve (LBFAUC and LVCACU), were assessed. PLM-induced robust control ΔLBFpeak (1135 ± 324 ml⋅min−1) and ΔLVCpeak (10.7 ± 3.6 ml⋅min−1⋅mmHg−1) responses that were significantly attenuated (704 ± 196 ml⋅min−1 and 6.7 ± 2 ml⋅min−1⋅mmHg−1) immediately following L-NMMA infusion. Likewise, control condition PLM ΔLBFAUC (455 ± 202 ml) and ΔLVCAUC (4.0 ± 1.4 ml⋅mmHg−1) were significantly attenuated (141 ± 130 ml and 1.3 ± 1.2 ml⋅mmHg−1) immediately following L-NMMA infusion. However, by 45–60 min post L-NMMA infusion all PLM variables were not significantly different from control, and this was still the case at 90–105 min post L-NMMA infusion. These findings reveal that the potent reduction in NO bioavailability afforded by NOS inhibition with L-NMMA has a window of effect of less than 45–60 min in the human vasculature. These data are particularly important for the commonly employed approach of pharmacologically inhibiting NOS with L-NMMA in the human vasculature.

Potential Therapeutic Effects of Exogenous Ketone Supplementation for Type 2 Diabetes: A Review.

Type 2 diabetes (T2D) is among the most prevalent non-communicable lifestyle diseases. We propose that overnutrition and low levels of physical activity can contribute to a vicious cycle of hyperglycemia, inflammation and oxidative stress, insulin resistance, and pancreatic β-cell dysfunction. The pathophysiological manifestations of T2D have a particular impact on the vasculature and individuals with T2D are at high risk of cardiovascular disease. Targeting aspects of the vicious cycle represent therapeutic approaches for improving T2D and protecting against cardiovascular complications. The recent advent of exogenous oral ketone supplements represents a novel, non-pharmacological approach to improving T2D pathophysiology and potentially protecting against cardiovascular disease risk. Herein, we review the emerging literature regarding the effects of exogenous ketone supplementation on metabolic control, inflammation, oxidative stress, and cardiovascular function in humans and highlight the potential application for breaking the vicious cycle of T2D pathophysiology.

The influence of climate change on human cardiovascular function

Climate change is considered to have great impact on human health. The heat waves have been associated with excess morbidity and mortality of cardiovascular diseases (CVD) across various populations and geographic locations. Important role in the heat-induced cardiovascular damage has endothelial dysfunction. It has been noticed that hot weather can impair tone and structure of the blood vessels via interfering with variety of biological factors such as nitric oxide synthesize, cytokine production and systemic inflammation. Also, due to dehydration and increased blood viscosity, by promoting thrombogenesis, heat has important impact on patients with atherosclerosis. During chronic exposure to the cold or hot weather cardiovascular function can be decreased, leading to a higher risk of developing heart attack, malignant cardiac arrhythmias, thromboembolic diseases and heat-induced sepsis like shock. It has been shown that changes in the ambient temperature through increasing blood pressure, blood viscosity, and heart rate, contribute to the cardiovascular mortality. The majority of deaths due to heat waves especially affect individuals with preexisting chronic CVD. This population can experience a decline in the health status, since extreme ambient temperature affects pharmacokinetic parameters of many cardiovascular drugs. Increased mortality from ischemic or hemorrhagic stroke can also be related to extreme temperature variations. On a cellular level, higher ambient temperature can limit storage of ATP and O2 increase amount of free radicals and toxic substances and induce neuronal apoptotic signal transduction, which all can lead to a stroke. Preserving cardiovascular function in context of extreme climate changing tends to be particularly challenging.

Impact of mental stress, the circadian system and their interaction on human cardiovascular function

The risk for adverse cardiovascular events (e.g., myocardial infarction, sudden cardiac death) peaks in the morning, possibly due to the effects of the endogenous circadian system on cardiovascular risk factors, or the occurrence in the morning of specific triggers, such as mental stress. To assess any interacting effects on cardiovascular function of mental stress and the circadian system, 12 healthy adults underwent a 240-h protocol with all measurements and behaviors scheduled evenly across the circadian cycle. Mental stress was repeatedly induced by performance-motivated serial addition tasks. Cardiovascular measures included hemodynamic function (heart rate, blood pressure), circulating catecholamines (epinephrine, norepinephrine), and estimates of sympathovagal balance and cardiac vagal modulation derived from heart rate variability analyses. Mental stress increased hemodynamic function, sympathovagal balance and epinephrine, and decreased cardiac vagal modulation. Endogenous circadian variation occurred in all cardiovascular measures: sympathovagal balance peaked in the circadian morning (∼9 AM), cardiac vagal modulation in the circadian night (∼4 AM), and heart rate and circulating catecholamines in the late circadian morning/early afternoon (∼12 PM). Importantly, the effects of mental stress and the endogenous circadian system on cardiovascular function occurred in conjunction, such that mental stress in the circadian morning caused greatest sympathovagal balance. This summation of effects could contribute to the increased morning cardiovascular vulnerability.

Biochemical, demographic, and self-reported tobacco-related predictors of the acute heart rate response to nicotine in smokers

Understanding the stimulatory effects of nicotine on cardiovascular function in humans is of great interest given the wide-spread use of different forms of combustible and smokeless products that deliver nicotine. An intravenous nicotine infusion procedure was used to evaluate factors associated with the acute heart rate (HR) response to nicotine (0.5 mg per 70 kg bodyweight) in a sample of 213 smokers. We tested for differential response to nicotine based on demographic characteristics (race [European American vs African America], sex, body mass index and age); a set of blood-based biomarkers (baseline nicotine, cotinine and cortisol levels and nicotine metabolite ratio); and a set of self-reported measures related to tobacco use. Nicotine infusion was first noted to increase HR approximately 10 beats per minute (95% CI: 7.8–12.3) one minute post-infusion, and 13 beats per minute (95% CI: 11.0–15.2) two minutes post-infusion. Higher cortisol, lower nicotine levels, higher nicotine metabolite ratio, being female and greater withdrawal symptoms were independently associated with a potentiated increase in HR 1 or 2 min after nicotine infusion. Factors associated with the acute HR effects of nicotine warrant further investigation given their potential to inform the development of nicotine delivery systems as tobacco harm reduction approaches for smokers.