Effects of Acute Citrulline Malate Supplementation on CrossFit® Exercise Performance: A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Study.

Given the increasing popularity of CrossFit® as a high-intensity functional training program and the potential benefits of citrulline malate (CM) in enhancing exercise performance through its role as a precursor to L-arginine and nitric oxide production, this study aimed to investigate the acute effects of CM supplementation on CrossFit® performance and cardiovascular function. Using a randomized, double-blind, placebo-controlled, cross-over design, 21 recreationally active participants (mean age 22.2 ± 2.6 years, mean body weight 75.9 ± 10.4 kg) with CrossFit® experience completed the "Cindy" workout under CM and placebo conditions. Participants consumed 4.4 g of CM or a placebo 60 min before the workout, and the performance was measured by the number of rounds completed. Secondary outcomes included heart rate response, time spent in different heart rate intensity zones, and post-exercise recovery time. The results indicated no significant difference in the number of rounds completed between the CM and placebo conditions (13.5 ± 5.2 vs. 13.8 ± 6.7 rounds, respectively; p = 0.587). However, the time spent in zone 4 (80-90% of HR max) was significantly increased in the CM condition (527 ± 395 s vs. 453 ± 334 s; p = 0.017), suggesting a potential benefit for aerobic capacity and anaerobic threshold. No significant differences in post-exercise recovery time were observed (6.6 ± 4.7 h vs. 6.9 ± 4.7 h; p = 0.475). This study highlights the need for further research with larger sample sizes, both genders, and different CM dosages to clarify these findings and better understand CM's role in enhancing athletic performance.

Safety and effectiveness of acute intermittent hypoxia during a single treatment at different hypoxic severities.

PURPOSE: Examine the cardiovascular, muscular function, cognitive, and neural plastic responses to determine the safety and effectiveness of acute Intermittent hypoxia (AIH) at a low, high, and control fractional inspired oxygen (FiO2) dosage METHODS: Thirteen human participants performed 30-min of AIH in 60-s intervals at FiO2's of 0.21 (AIH21), 0.15 (AIH15), and 0.09 (AIH9). Heart rate variability (root mean squared of successive differences; RMSSD), heart rate, oxygen saturation (SpO2), blood pressure, muscular strength, neuromuscular activation, cerebral hemodynamic responses, cognition, symptomology, and brain-derived neurotrophic factor (BDNF) responses were measured before (Pre-AIH), after (post-AIH), and at 20-min of recovery (Recovery-AIH) RESULTS: There were no differences between AIH protocols for heart rate, RMSSD, blood pressure, or SpO2. Muscular strength improved Post-AIH for AIH15 (10 %) and AIH9 (14 %) and remained elevated (6 %) at Recovery-AIH. Neuromuscular activation increased Pre-AIH to Post-AIH for AIH15 (10 %) and AIH9 (11 %). Cerebral hemodynamic responses were not impacted between conditions. Both AIH15 and AIH9 increased BDNF Post-AIH (62 %) and Recovery-AIH (63 %) CONCLUSION: Acute intermittent hypoxia is generally safe and effective at producing neural plastic responses, but further examination of co-occurring cardiovascular diseases is needed. This study provides safety focused findings which will widen the adoption and refinement of AIH protocols.

The Effects of Blood Flow Restriction Aerobic Exercise on Body Composition, Muscle Strength, Blood Biomarkers, and Cardiovascular Function: A Narrative Review.

Blood flow restriction exercise has emerged as a promising alternative, particularly for elderly individuals and those unable to participate in high-intensity exercise. However, existing research has predominantly focused on blood flow restriction resistance exercise. There remains a notable gap in understanding the comprehensive effects of blood flow restriction aerobic exercise (BFRAE) on body composition, lipid profiles, glycemic metabolism, and cardiovascular function. This review aims to explore the physiological effects induced by chronic BFRAE. Chronic BFRAE has been shown to decrease fat mass, increase muscle mass, and enhance muscular strength, potentially benefiting lipid profiles, glycemic metabolism, and overall function. Thus, the BFRAE offers additional benefits beyond traditional aerobic exercise effects. Notably, the BFRAE approach may be particularly suitable for individuals with low fitness levels, those prone to injury, the elderly, obese individuals, and those with metabolic disorders.

Efficacy and safety of novel freeze-dried plasma products in a porcine combat casualty model.

BACKGROUND: Hemorrhagic shock is well documented as a leading cause of preventable fatalities among military casualties. During military operations plasma can be transfused while waiting for whole blood. This study was conducted to assess the safety and efficacy of two new freeze-dried plasma formulations in a porcine model of traumatic hemorrhagic shock. STUDY DESIGN AND METHODS: In the face of species-specific transfusion, transfusible blood products were derived from porcine sources. The efficacy of three lyophilized plasma (LP) formulations was evaluated: lyophilized plasma (LP), concentrated lyophilized plasma (CLP), and platelet-rich concentrated lyophilized plasma (PCLP). Pigs were subjected to multi-trauma and hemorrhagic shock. Ninety minutes post-shock induction, the animals were treated with one of the three lyophilized products. Monitoring included systolic blood pressure and cardiac output. Point-of-care and laboratory diagnostic tests were used to assess renal function, real-time hemostasis (ROTEM), and coagulation. Histological examinations of kidney, lung, and muscle tissues were conducted 4 h after shock induction. RESULTS: CLP and PCLP significantly improved systolic blood pressure and cardiac output and positively influenced base excess, creatinine, various ROTEM, and coagulation markers compared with standard LP without histologic modification. No adverse effect was associated with the transfusion of any of the plasma products throughout the experimental procedures. CONCLUSION: Both CLP and PCLP exhibit promising therapeutic potential for managing hemorrhagic shock in scenario where whole blood supplies are limited. However, the distinct physiological and coagulation characteristics of the swine model necessitate further investigation using humanized preclinical models to fully understand their clinical applicability and constraints.

Dimethyl Fumarate Prevents the Development of Chronic Social Stress-Induced Hypertension in Borderline Hypertensive Rats.

This study investigated the effects of chronic crowding-induced social stress and dimethyl fumarate (DMF) on borderline hypertensive rats, focusing on the transcription nuclear factor (erythroid-derived 2)-like 2 (NRF2) gene Nfe2l2, on the expression of selected NFR2-mediated gene expressions in the heart, and on vascular function. Rats were exposed to chronic crowding, DMF treatment (30 mg/kg/day, p.o.), or a combination of both for six weeks. Blood pressure (BP) was measured non-invasively, gene expressions were analysed using RT-qPCR, and vascular function was assessed by measuring noradrenaline (NA)-induced vasoconstriction and endothelium-dependent and -independent relaxations in the femoral arteries using a wire myograph. Chronic stress increased BP, Nfe2l2 expression, and NA-induced vasoconstriction, though it did not affect relaxation responses nor the left heart ventricle-to-body weight (LHV/BW) ratio. DMF elevated Nfe2l2 expression (as the main effect) in the heart but did not alter BP and vascular functions vs. control when administered alone. Interestingly, DMF increased the LHV/BW ratio, supposedly due to reductive stress induced by continuous NRF2 activation. When combined with stress, DMF treatment prevented stress-induced hypertension and mitigated NA-induced vasoconstriction without altering relaxation functions. In addition, the combination of stress and DMF increased Tnf and Nos2 expression and the expressions of several genes involved in iron metabolism. In conclusion, these findings suggest that DMF can prevent chronic stress-induced hypertension by reducing vascular contractility. Moreover, DMF itself may produce reductive stress in the heart and induce inflammation when combined with stress. This indicates a need for the careful consideration of long-term DMF treatment considering its impact on the heart.

Effects of Acute Beetroot Juice Supplementation and Exercise on Cardiovascular Function in Healthy Men in Preliminary Study: A Randomized, Double-Blinded, Placebo-Controlled, and Crossover Trial.

Nitrate-rich beetroot juice (NRBRJ) can potentially enhance exercise performance and improve cardiovascular function, leading to an increased use of NRBRJ over the years. However, the combined effects of NRBRJ supplementation and exercise on cardiovascular function remain unclear. Therefore, this study compared cardiovascular function responses to submaximal exercise with either placebo (PLA) or NRBRJ supplementation in healthy men. Twelve healthy men (aged 25.2 ± 2.3 years) completed the 30-min submaximal cycle ergometer exercise trials corresponding to 70% maximal heart rate (HRmax) with either PLA or NRBRJ supplementation in a random order. The mean exercise load, heart rate (HR), stroke volume (SV), cardiac output (CO), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and total peripheral resistance (TPR) were measured during exercise. The brachial-ankle pulse wave velocity (baPWV) and flow-mediated dilation (FMD) were measured before and after exercise. NRBRJ supplementation was more effective than PLA in increasing the mean exercise load and decreasing DBP and MAP during submaximal exercise. Furthermore, baPWV decreased in the NRBRJ trial and was considerably lower after exercise in the NRBRJ-supplemented group than in the PLA-supplemented group. FMD significantly increased in the PLA and NRBRJ trials; however, NRBRJ supplementation demonstrated a significantly higher FMD before and after exercise than PLA supplementation. In conclusion, acute NRBRJ supplementation and exercise were more effective than PLA supplementation and exercise in improving aerobic exercise capacity and cardiovascular function in healthy men.

Mechanisms of enhanced cardiorespiratory performance under hyperoxia differ with exposure duration in yellowtail kingfish.

Hyperoxia has been shown to expand the aerobic capacity of some fishes, although there have been very few studies examining the underlying mechanisms and how they vary across different exposure durations. Here, we investigated the cardiorespiratory function of yellowtail kingfish (Seriola lalandi) acutely (~20 h) and chronically (3-5 weeks) acclimated to hyperoxia (~200% air saturation). Our results show that the aerobic performance of kingfish is limited in normoxia and increases with environmental hyperoxia. The aerobic scope was elevated in both hyperoxia treatments driven by a ~33% increase in maximum O2 uptake (MO2max), although the mechanisms differed across treatments. Fish acutely transferred to hyperoxia primarily elevated tissue O2 extraction, while increased stroke volume-mediated maximum cardiac output was the main driving factor in chronically acclimated fish. Still, an improved O2 delivery to the heart in chronic hyperoxia was not the only explanatory factor as such. Here, maximum cardiac output only increased in chronic hyperoxia compared with normoxia when plastic ventricular growth occurred, as increased stroke volume was partly enabled by an ~8%-12% larger relative ventricular mass. Our findings suggest that hyperoxia may be used long term to boost cardiorespiratory function potentially rendering fish more resilient to metabolically challenging events and stages in their life cycle.

Adipocyte-specific disruption of the BBSome causes metabolic and autonomic dysfunction.

Obesity is a major public health issue due to its association with type 2 diabetes, hypertension, and other cardiovascular risks. The BBSome, a complex of eight conserved Bardet-Biedl syndrome (BBS) proteins, has emerged as a key regulator of energy and glucose homeostasis as well as cardiovascular function. However, the importance of adipocyte BBSome in controlling these physiological processes is not clear. Here, we show that adipocyte-specific constitutive disruption of the BBSome through selective deletion of the Bbs1 gene adiponectin (AdipoCre/Bbs1fl/fl mice) does not affect body weight under normal chow or high-fat and high-sucrose diet (HFHSD). However, constitutive BBSome deficiency caused impairment in glucose tolerance and insulin sensitivity. Similar phenotypes were observed after inducible adipocyte-specific disruption of the BBSome (AdipoCreERT2/Bbs1fl/fl mice). Interestingly, a significant increase in renal sympathetic nerve activity, measured using multifiber recording in the conscious state, was observed in AdipoCre/Bbs1fl/fl mice on both chow and HFHSD. A significant increase in tail-cuff arterial pressure was also observed in chow-fed AdipoCre/Bbs1fl/fl mice, but this was not reproduced when arterial pressure was measured by radiotelemetry. Moreover, AdipoCre/Bbs1fl/fl mice had no significant alterations in vascular reactivity. On the other hand, AdipoCre/Bbs1fl/fl mice displayed impaired baroreceptor reflex sensitivity when fed HFHSD, but not on normal chow. Taken together, these data highlight the relevance of the adipocyte BBSome for the regulation of glucose homeostasis and sympathetic traffic. The BBSome also contributes to baroreflex sensitivity under HFHSD, but not normal chow.NEW & NOTEWORTHY The current study show how genetic manipulation of fat cells impacts various functions of the body including sensitivity to the hormone insulin.

Heart rate variability helps classify phenotype in systemic sclerosis.

We aimed to develop a systemic sclerosis (SSc) subtypes classifier tool to be used at the patient's bedside. We compared the heart rate variability (HRV) at rest (5-min) and in response to orthostatism (5-min) of patients (n = 58) having diffuse (n = 16, dcSSc) and limited (n = 38, lcSSc) cutaneous forms. The HRV was evaluated from the beat-to-beat RR intervals in time-, frequency-, and nonlinear-domains. The dcSSc group differed from the lcSSc group mainly by a higher heart rate (HR) and a lower HRV, in decubitus and orthostatism conditions. Stand-up maneuver lowered HR standard deviation (sd_HR), the major axis length of the fitted ellipse of Poincaré plot of RR intervals (SD2), and the correlation dimension (CorDim) in the dcSSc group while increased these HRV indexes in the lcSSc group (p = 0.004, p = 0.002, and p = 0.004, respectively). We identified the 5 most informative and discriminant HRV variables. We then compared 341 classifying models (1 to 5 variables combinations × 11 classifier algorithms) according to mean squared error, logloss, sensitivity, specificity, precision, accuracy, area under curve of the ROC-curves and F1-score. F1-score ranged from 0.823 for the best 1-variable model to a maximum of 0.947 for the 4-variables best model. Most specific and precise models included sd_HR, SD2, and CorDim. In conclusion, we provided high performance classifying models able to distinguish diffuse from limited cutaneous SSc subtypes easy to perform at the bedside from ECG recording. Models were based on 1 to 5 HRV indexes used as nonlinear markers of autonomic integrated influences on cardiac activity.

Effect of Mat Pilates Training on Blood Pressure, Inflammatory, and Oxidative Profiles in Hypertensive Elderly.

To determine the effects of mat Pilates training on blood pressure, inflammatory, and antioxidative markers in hypertensive elderly people, 34 hypertensive subjects aged 60-75 years were randomly divided into a control group (CON; n = 17) and a mat Pilates training group (MP; n = 17). The CON participants conducted normal daily activities and participated in neither organized exercises nor sports training, while those in the MP group received mat Pilates training for 60 min three times/week for 12 weeks. Parameters including blood pressure, cardiovascular function, nitric oxide (NO), tumor necrotic factor-alpha (TNF-α), superoxide dismutase (SOD), and malonaldehyde (MDA) were collected at baseline and the end of 12 weeks. The MP group had significantly decreased blood pressure, improved cardiovascular variables, decreased MDA and TNF-α, and increased NO and SOD compared with the CON group and the pre-training period (p < 0.05). In conclusion, these findings demonstrate the positive effects of 12 weeks of mat Pilates training in terms of reducing blood pressure and increasing blood flow related to improvements in anti-inflammatory and antioxidative markers in hypertensive elderly people. Mat Pilates training might be integrated as an alternative therapeutic exercise modality in clinical practice for hypertensive elderly individuals.

Subclinical Metabolic and Cardiovascular Factors and Brain White Matter Microstructural Integrity in Young Women.

Women who have experienced pregnancy complications, specifically preeclampsia and gestational diabetes, have well documented increased risks of cardiovascular, metabolic, and neurological disease later in life. This study examined how specific cardiovascular and metabolic risk factors for preeclampsia assessed in a non-pregnant state were associated with brain white matter microstructural integrity. This study examined sixty-two healthy women (mean age 31 ± 5 years) who received metabolic and cardiovascular assessments as well as multiple modality MRI imaging. Participants were either nulliparous (n = 31) or had a history of preterm preeclampsia (n = 31). Imaging included acquisition Diffusion Tensor Imaging (DTI) to assess white matter integrity within the brain. We hypothesized that healthy, young, non-pregnant women with cardiovascular and metabolic profiles suggesting elevated risk would have decreased white matter integrity, represented by lower Fractional Anisotropy (FA) and increased Mean Diffusivity (MD) estimates in the posterior cortical areas of the brain. We observed increased white matter degradation (lower FA and increased MD) in posterior and occipital tracts, commissural fibers, and subcortical structures in women with increased adiposity, worse measures of cardiovascular and metabolic function, including greater insulin resistance (HOMA-IR), hyperlipidemia, elevated blood pressure, and increased arterial stiffness. The relationships detected between subclinical cardiovascular and metabolic phenotypes and increased white matter disruption at a young age, outside of pregnancy, are indicative that adverse changes are detectable long before cognitive clinical presentation. This may suggest that many of the long-term cardiovascular and metabolic risks of aging are influenced by physiologic aging trajectories rather than damage caused by pregnancy complications.

Functional lateralization in the medial prefrontal cortex control of contextual conditioned emotional responses in rats.

A functional lateralization has been reported in control of emotional responses by the medial prefrontal cortex (mPFC). However, a hemisphere asymmetry in involvement of the mPFC in expression of fear conditioning responses has never been reported. Therefore, we investigated whether control by mPFC of freezing and cardiovascular responses during re-exposure to an aversively conditioned context is lateralized. For this, rats had guide cannulas directed to the mPFC implanted bilaterally or unilaterally in the right or left hemispheres. Vehicle or the non-selective synaptic inhibitor CoCl2 was microinjected into the mPFC 10 min before re-exposure to a chamber where the animals had previously received footshocks. A catheter was implanted into the femoral artery before the fear retrieval test for cardiovascular recordings. We observed that bilateral microinjection of CoCl2 into the mPFC reduced both the freezing behavior (enhancing locomotion and rearing) and arterial pressure and heart rate increases during re-exposure to the aversively conditioned context. Unilateral microinjection of CoCl2 into the right hemisphere of the mPFC also decreased the freezing behavior (enhancing locomotion and rearing), but without affecting the cardiovascular changes. Conversely, unilateral synaptic inhibition in the left mPFC did not affect either behavioral or cardiovascular responses during fear retrieval test. Taken together, these results suggest that the right hemisphere of the mPFC is necessary and sufficient for expression of freezing behavior to contextual fear conditioning. However, the control of cardiovascular responses and freezing behavior during fear retrieval test is somehow dissociated in the mPFC, being the former bilaterally processed.

Exposure to emissions generated by 3-dimensional printing with polycarbonate: effects on peripheral vascular function, cardiac vascular morphology and expression of markers of oxidative stress in male rat cardiac tissue.

Three-dimensional (3D) printing with polycarbonate (PC) plastic occurs in manufacturing settings, homes, and schools. Emissions generated during printing with PC stock and bisphenol-A (BPA), an endocrine disrupter in PC, may induce adverse health effects. Inhalation of 3D printer emissions, and changes in endocrine function may lead to cardiovascular dysfunction. The goal of this study was to determine whether there were any changes in markers of peripheral or cardiovascular dysfunction in animals exposed to PC-emissions. Male Sprague Dawley rats were exposed to PC-emissions generated by 3D printing for 1, 4, 8, 15 or 30 d. Exposure induced a reduction in the expression of the antioxidant catalase (Cat) and endothelial nitric oxide synthase (eNos). Endothelin and hypoxia-induced factor 1α transcripts increased after 30 d. Alterations in transcription were associated with elevations in immunostaining for estrogen and androgen receptors, nitrotyrosine, and vascular endothelial growth factor in cardiac arteries of PC-emission exposed animals. There was also a reduction eNOS immunostaining in cardiac arteries from rats exposed to PC-emissions. Histological analyses of heart sections revealed that exposure to PC-emissions resulted in vasoconstriction of cardiac arteries and thickening of the vascular smooth muscle wall, suggesting there was a prolonged vasoconstriction. These findings are consistent with studies showing that inhalation 3D-printer emissions affect cardiovascular function. Although BPA levels in animals were relatively low, exposure-induced changes in immunostaining for estrogen and androgen receptors in cardiac arteries suggest that changes in the action of steroid hormones may have contributed to the alterations in morphology and markers of cardiac function.

Exposure to the antineoplastic ifosfamide alters molecular pathways related to cardiovascular function, increases heart rate, and induces hyperactivity in zebrafish (Danio rerio).

Ifosfamide is an alkylating antineoplastic drug used in chemotherapy, but it is also detected in wastewater. Here, the objectives were to (1) determine teratogenic, cardiotoxic, and mitochondrial toxicity potential of ifosfamide exposure; (2) elucidate mechanisms of toxicity; (3) characterize exposure effects on larval behavior. Survival rate, hatch rate, and morphological deformity incidence were not different amongst treatments following exposure levels up to 1000 µg/L ifosfamide over 7 days. RNA-seq reveled 231 and 93 differentially expressed transcripts in larvae exposed to 1 µg/L and 100 µg/L ifosfamide, respectively. Several gene networks related to vascular resistance, cardiovascular response, and heart rate were affected, consistent with tachycardia observed in exposed embryonic fish. Hyperactivity in larval zebrafish was observed with ifosfamide exposure, potentially associated with dopamine-related gene networks. This study improves ecological risk assessment of antineoplastics by elucidating molecular mechanisms related to ifosfamide toxicity, and to alkylating agents in general.

Effect of supervised exercise training on cardiovascular function in patients with intermittent claudication: a systematic review and meta-analysis of randomized controlled trials.

This study aimed to determine the effect of supervised exercise training (SET) on cardiovascular function in patients with intermittent claudication (IC). A systematic search in MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases was conducted. Primary outcomes were systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), rate pressure product (RPP), cardiac output (CO), peak oxygen consumption (VO2peak), and heart rate variability (HRV). Secondary outcomes were maximum walking distance (MWD) and pain-free walking distance (PFWD). Outcomes were reported as weighted mean difference (WMD) between the SET group and the control group and synthesized by using the random-effects model. Seventeen RCTs with a total of 936 patients were included in this review. SET resulted in significant improvements of SBP (WMD = - 7.40, 95% CI - 10.69 ~ - 4.11, p < 0.001, I2 = 15.2%), DBP (WMD = - 1.92, 95% CI - 3.82 ~ - 0.02, p = 0.048, I2 = 0.0%), HR (WMD = - 3.38, 95% CI - 6.30 ~ - 0.46, p = 0.023, I2 = 0.0%), RPP (WMD = - 1072.82, 95% CI - 1977.05 ~ - 168.59, p = 0.020, I2 = 42.7%), and VO2peak with plantar flexion ergometer exercise (WMD = 5.57, 95% CI 1.66 ~ 9.49, p = 0.005, I2 = 62.4%), whereas CO and HRV remained statistically unaltered. SET also improved MWD (WMD = 139.04, 95% CI 48.64 ~ 229.44, p = 0.003, I2 = 79.3%) and PFWD (WMD = 40.02, 95% CI 23.85 ~ 56.18, p < 0.001, I2 = 0.0%). In conclusion, SET is effective in improving cardiovascular function in patients with IC, which was confirmed on outcomes of cardiovascular function associated with exercise ability. The findings hold out that the standard therapy of SET can improve not only walking distance but also cardiovascular function in patients with IC.

Acetic Acid: An Underestimated Metabolite in Ethanol-Induced Changes in Regulating Cardiovascular Function.

Acetic acid is a bioactive short-chain fatty acid produced in large quantities from ethanol metabolism. In this review, we describe how acetic acid/acetate generates oxidative stress, alters the function of pre-sympathetic neurons, and can potentially influence cardiovascular function in both humans and rodents after ethanol consumption. Our recent findings from in vivo and in vitro studies support the notion that administration of acetic acid/acetate generates oxidative stress and increases sympathetic outflow, leading to alterations in arterial blood pressure. Real-time investigation of how ethanol and acetic acid/acetate modulate neural control of cardiovascular function can be conducted by microinjecting compounds into autonomic control centers of the brain and measuring changes in peripheral sympathetic nerve activity and blood pressure in response to these compounds.

Phenotyping cardiopulmonary exercise testing measures in heart failure with reduced ejection fraction: A comparison between Italy and Brazil.

BACKGROUND: While patients with heart failure (HF) with reduced left ventricular ejection fraction (HFrEF) constitutes a global health crisis the incidence, prevalence and prognosis of the disease may differ depending on the continent and country. OBJECTIVE: To profile, analyze and compare cardiopulmonary exercise testing (CPET) data of patients with HFrEF between Italian and Brazilian cohorts. METHODS: In this observational study, a total of 630 patients with clinical and functional diagnosis of HFrEF (315 patients from Brazil and 315 patients from Italy) performed CPET. RESULTS: Although Brazilian patients were slightly younger (Brazil 60±10 vs Italy 64±11 p<0.001) with a better peak oxygen consumption (V̇O2), circulatory power and left ventricular ejection fraction (LVEF) (p<0.01), ventilatory inefficiency and oscillation ventilation was higher when compared to the Italian cohort. When stratifying patients with LVEF≤30 % and age≥60 years, Brazilian patients presented worse ventilatory efficiency, and lower peak V̇O2 compared to the Italian cohort. CONCLUSION: Patients with HFrEF from Brazil exhibited higher ventilatory inefficiency and a greater prevalence of oscillatory ventilation during CPET compared to patients with the same diagnosis from Italy.

Immunotherapeutic Properties of Dexmedetomidine on Pain Management and Cardiovascular Function in Videolaparoscopic Cholecystectomies: A Randomized, Two-Arm, Double-Blinded, Placebo-Controlled Trial.

BACKGROUND: Laparoscopy represented one of the most innovative surgical techniques approached in the surgery field. Dexmedetomidine association with general anesthesia promotes the response control to trauma by altering the neuroinflammatory reflex, provides better clinical outcomes in the postoperative period and reduces the excessive use of drugs with risk for addiction. This trial aims to evaluate the potential drug treatment of dexmedetomidine on organic function, with the targets in neuroinflammation, perioperative pain control and blood pressure measurements in a medium-sized surgical model. METHODS: Fifty-two patients were randomized in two groups: Sevoflurane and Dexmedetomidine - A (dexmedetomidine infusion [1 µg/kg loading, .2-.5 µg/kg/h thereafter]) vs Sevoflurane and Saline .9% - B. Three blood samples were collected at three times: before surgery, 4 to 6 hours after surgery and 24 hours postoperatively. The primary outcome was inflammatory and endocrine mediators dosage analisys. Finally, we evaluated pain and opioid use as secondary outcomes, also the hemodynamic values. RESULTS: In Dexmedetomidine group A, a reduction of Interleukin 6 was found during 4-6 hours after surgery. A reduction of IL-10 was noted in the measurement of its values 24 hours after the procedure, with statistical significance. Also, systolic and diastolic blood pressure, as well heart rate were attenuated, and there was a lower incidence of pain and opioid consumption in the first postoperative hour (P < .0001) in the anesthetic recovery room. CONCLUSIONS: Dexmedetomidine provided anti-inflammatory activity, sympatholytic effect and analgesia with cardiovascular safety. It reinforces the therapeutic nature of highly selective α2-adrenergic agonists when combined within anesthetic interventions.

CVD phenotyping in oncologic disorders: cardio-miRNAs as a potential target to improve individual outcomes in revers cardio-oncology.

With the increase of aging population and prevalence of obesity, the incidence of cardiovascular disease (CVD) and cancer has also presented an increasing tendency. These two different diseases, which share some common risk factors. Relevant studies in the field of reversing Cardio-Oncology have shown that the phenotype of CVD has a significant adverse effect on tumor prognosis, which is mainly manifested by a positive correlation between CVD and malignant progression of concomitant tumors. This distal crosstalk and the link between different diseases makes us aware of the importance of diagnosis, prediction, management and personalized treatment of systemic diseases. The circulatory system bridges the interaction between CVD and cancer, which suggests that we need to fully consider the systemic and holistic characteristics of these two diseases in the process of clinical treatment. The circulating exosome-miRNAs has been intrinsically associated with CVD -related regulation, which has become one of the focuses on clinical and basic research (as biomarker). The changes in the expression profiles of cardiovascular disease-associated miRNAs (Cardio-miRNAs) may adversely affect concomitant tumors. In this article, we sorted and screened CVD and tumor-related miRNA data based on literature, then summarized their commonalities and characteristics (several important pathways), and further discussed the conclusions of Cardio-Oncology related experimental studies. We take a holistic approach to considering CVD as a risk factor for tumor malignancy, which provides an in-depth analysis of the various regulatory mechanisms or pathways involved in the dual attribute miRNAs (Cardio-/Onco-miRNAs). These mechanisms will be key to revealing the systemic effects of CVD on tumors and highlight the holistic nature of different diseases. Therefore, the Cardio-miRNAs should be given great attention from researchers in the field of CVD and tumors, which might become new targets for tumor treatment. Meanwhile, based on the principles of precision medicine (such as the predictive preventive personalized medicine, 3PM) and reverse Cardio-oncology to better improve individual outcomes, we should consider developing personalized medicine and systemic therapy for cancer from the perspective of protecting cardiovascular function.

The value of circular reasoning: what Harvey taught and we forgot.

William Harvey discovered that the cardiovascular system is a closed hydraulic circle. Since that discovery, many haemodynamic models have strayed by dividing the circulation into segments, which can be misleading. An alternative model is presented that both preserves circular hydraulics and provides a comprehensive picture of overall cardiovascular function using a novel cardiovascular vector graphic. The practical value of this approach resides in its ease of visualising critical physiological variables and ease of predicting and communicating how changes in those variables affect function.