Background: The blockade of the progression or onset of pathological events is essential for the homeostasis of an organism. Some common pathological mechanisms involving a wide range of diseases are the uncontrolled inflammatory reactions that promote fibrosis, oxidative reactions, and other alterations. Natural plant compounds (NPCs) are bioactive elements obtained from natural sources that can regulate physiological processes. Inflammation is recognized as an important factor in the development and evolution of chronic renal damage. Consequently, any compound able to modulate inflammation or inflammation-related processes can be thought of as a renal protective agent and/or a potential treatment tool for controlling renal damage. The objective of this research was to review the beneficial effects of bioactive natural compounds on kidney damage to reveal their efficacy as demonstrated in clinical studies. Methods: This systematic review is based on relevant studies focused on the impact of NPCs with therapeutic potential for kidney disease treatment in humans. Results: Clinical studies have evaluated NPCs as a different way to treat or prevent renal damage and appear to show some benefits in improving OS, inflammation, and antioxidant capacity, therefore making them promising therapeutic tools to reduce or prevent the onset and progression of KD pathogenesis. Conclusions: This review shows the promising clinical properties of NPC in KD therapy. However, more robust clinical trials are needed to establish their safety and therapeutic effects in the area of renal damage. Historically, natural plant compounds (NPCs) have been used as treatments and their chemical structures could give rise to new therapeutic options . NPCs arThis systematic review is based on pertinent papers revealed by a selective search using relevant keywords that were collected from databases such as Science Direct, EBSCO, Scopus, and PubMed to analyze clinical trials focused on the potential impact of natural bioactive compounds regarding their therapeutic efficacy as a treatment for renal diseases. The principal objective of this review of the effects of bioactive natural compounds on kidney damage was to reveal the efficacy demonstrated in clinical studies.2) for more than 3 months, and progressive glomerular, tubular, and interstitial damage [Kidney damage is a global public health problem that has been growing worldwide. Renal diseases involve acute kidney injury (AKI) and CKD, which can lead to ESRD. Consequently, patients needing renal replacement therapy are estimated to number between 4.902 and 7.083 million . CKD is l damage ,33,34. Tl damage . 2O2). In addition, TGF-β has been demonstrated to increase ROS production and to decrease the antioxidant system, thus inducing OS and/or redox imbalance. Essentially, redox imbalance significantly helps TGF-β’s pathophysiologic properties such as fibrosis [Numerous molecular signaling pathways are implicated in the onset and progression of renal damage, including the renin–angiotensin system (RAS), which is the central regulator of kidney fibrosis. Together, tissue and circulatory RAS are believed to be overstimulated in the progress of kidney fibrosis stimulation. RAS increases levels of angiotensin II (Ang II), which play a dominant role in kidney fibrosis by mediating the liberation of transforming growth factor-β (TGF-β) and starting inflammatory processes ,37,38,39fibrosis ,47. TGF-fibrosis ,49,50,51fibrosis ,53. Essefibrosis ,55,56. Rfibrosis ,49,57. Rfibrosis ,59. ThesAllium sativum L.) are organosulfur compounds (OSCs). Among these compounds, the most plentiful sulfur composite contained in fresh and dry garlic is alliin  [The main bioactive constituents of garlic (lfoxide) ,61. Allilfoxide) , antioxilfoxide) , and othlfoxide) .A randomized double-blind clinical trial study evaluated the effect of garlic extract on the serum inflammatory markers of 42 subjects undergoing peritoneal dialysis (PD), a renal failure therapy. The patients received a dose of 400 mg of a standardized garlic extract, which was made in the shape of tablets including 1 mg (1000 mcg) of alliin. The dosing scheme in the cases group (garlic extract group) was twice a day for 8 weeks, while the control group received standard treatments plus a placebo during the same period. The results showed that in the patients who received the garlic extract, the inflammatory markers IL-6, C reactive protein (CRP), and the erythrocyte sedimentation rate (ESR) were all significantly reduced, while in the placebo group, a significant decrease was only observed in IL-6. However, the assessment of these effects in larger trials is strongly recommended [Haematococcus alga [Helicobacter pylori (H. pylori) treated with 40 mg of astaxanthin daily and 23 patients were administered a placebo, so the authors suggested that these differences indicated a greater change to a humoral immune response instead of a cytotoxic response [H. pylori [Xanthophyll carotenoid colorant that has beneficial properties, including anticancer, antioxidant, and anti-inflammatory properties. The most common source of astaxanthin  as used in nutritional supplements is obtained from cus alga . The Foocus alga . Studiesresponse . Moreove. pylori .p < 0.01), serum triglycerides, very-low-density lipoprotein cholesterol (VLDLc) levels, and systolic blood pressure [Likewise, a randomized placebo-controlled trial was conducted to investigate the possible action of astaxanthin administration on lipid peroxidation, adiponectin levels, glycemic control, anthropometric indices, and insulin sensitivity in subjects with T2DM, which is a common cause and driver of kidney damage. In the study group, after 8 weeks of 8 mg of astaxanthin administration, the serum adiponectin concentration increased and there was a reduction in visceral body fat mass  nor the serum creatinine concentrations of the control group changed significantly after basic therapy, but they decreased considerably in the baicalin adjunctive therapy group. It can be assumed, based on these two indices, that the renal function of the baicalin group improved, probably due to the baicalin adjunctive therapy. Therefore, baicalin may decrease AKI in pediatric patients with sepsis. Although this study demonstrated the protective effect of baicalin against AKI in this study group, shown as a decrease in BUN and creatinine levels, the authors did not report the dose administered and therefore the appropriate dosage and probable complications need to be evaluated in subsequent studies .Opuntia stricta fruits had the ability to modulate genes/protein expression in coronary artery disease (CAD) patients. CKD is a major risk factor for CAD. Patients with CKD display a high prevalence of hypertension, and cardiovascular disease (CVD) is the leading cause of morbidity and mortality in these patients. The high prevalence of traditional CAD risk factors, such as diabetes and hypertension, mean that such patients are also exposed to other non-traditional uremia-related CVD risk factors, including inflammation, oxidative stress, and abnormal calcium–phosphorus metabolism [Another NPC with interesting properties in renal disease is betalain. Betalains are divided into two groups: betacyanins, which produce red tones and are formed by condensation of a cyclo-DOPA  structure with betalamic acid, and betaxanthines, which produce yellow coloration and are synthesized from different amino compounds and betalamic acid . A pilottabolism .Beta vulgaris), a betacyanin-rich supplement of prickly pear cactus (Opuntia stricta), and a placebo. The results showed that betalain increased sirtuin-1 (SIRT1) and reduced lectin-like oxidized LDL receptor 1 (LOX1) and highly sensitive C reactive protein (hs-CRP) in the peripheral blood mononuclear cells (PBMCs) of patients. These results may be due to the reduction in OS and inflammation via the antioxidant and anti-inflammatory properties of betalains. Thus, betalains may be promising alternatives for supplementing therapies in OS, inflammation, and aging-associated diseases. However, additional analyses are necessary to gain a deeper understanding of their specific physiological functions [In a pilot randomized crossover trial, 48 male coronary artery disease patients received about 50 mg of betalain or betacyanin daily for 2 weeks on three occasions separated by washout periods. Patients were divided into three groups depending on the supplement: a betalain-rich supplement of red beetroot  guidelines) by Kemmner et al. suggested that the administration of beetroot juice with a nitrate load of 300 mg to nine patients increased nitric oxide (NO) concentrations and reduced the renal resistive index (RRI), which are prognostic markers for cardiovascular mortality, compared with a placebo . This rehropathy .Rhizoma coptidis and Cortex phellodendri. New analyses have demonstrated that berberine has numerous pharmacological benefits, such as lowering blood glucose, antioxidant activity, blood lipid regulation, reduced inflammation, and elevated insulin sensitivity, thus improving insulin resistance [It is an isoquinoline alkaloid and is the main active compound isolated from sistance ,82. Recesistance . The urisistance . Berberisistance .Cordyceps militaris, belonging to the Clavicipitaceae family. It is a fungus with a long history of common use in traditional medicine and its specific compound, cordycepin, has several health-promoting properties, including anticancer, anti-inflammatory, immunomodulatory, antidiabetic, and antiobesity effects [Cordyceps militaris was administered at 100 mg daily and compared with a placebo (control group). Cordyceps militaris decreased the protein concentration of TLR4, NF-κB p65, COX2, IL-1β, and TNF-α. Their results showed that eGFR was considerably improved compared with the control group after 3 months of treatment. This showed that Cordyceps militaris improved the eGFR of CKD patients, and the outcomes suggested that Cordyceps militaris ameliorated kidney function and controlled blood levels of urinal protein, BUN, and creatinine. This study provided support for the possibility that Cordyceps militaris controlled CKD evolution by controlling the TLR4/NF-κB redox signaling pathway [It is a naturally derived active compound produced by  effects ,86,87. F effects . In a cl pathway . Curcuma longa). Curcumin (diferuloylmethane) has been shown to be a TNF blocker in vitro and in vivo; nevertheless, only a limited number of analyses have confirmed that curcumin is efficient at reducing TGF- β, IL-8, and TNF-α levels in preclinical [n = 20) and a control group (n = 20). Individually, the test group subjects were given one capsule containing 500 mg turmeric, 22.1 mg of which was the active component curcumin, administered with each meal (three capsules daily) for 2 months. Their results demonstrated that serum TGF-β and IL-8 values were considerably lower post-turmeric administration, and that short-term turmeric supplementation can reduce proteinuria. Furthermore, they did not report any adverse effects associated with turmeric intake during the 2-month trial duration [It is a component of turmeric  and hs-CRP in ESRD patients. Nevertheless, the authors described that a larger sample size and a longer therapy period would be required to additionally confirm the long-term efficacy and safety of adding turmeric in the hemodialysis (HD) population . A revieOther studies have also shown that curcumin was an effective adjuvant therapy for decreasing macroscopic proteinuria, as was shown in a randomized double-blind clinical trial performed on 46 patients with T2DM. In this study, the patients received 500 mg (one capsule) of curcumin three times/day after meals for 16 weeks. . The resAdditionally, a randomized placebo-controlled trial examined the effects of curcumin and quercetin on early graft function in 43 dialysis-dependent cadaveric renal recipients. A single capsule of curcumin (480 mg) and quercetin (20 mg) was administered to patients for 1 month after the transplant operation. The instigators of this report concluded that curcumin and quercetin may restore early outcomes in cadaveric kidney transplantation, possibly through activation of heme oxygenase-1 (HO-1) . A likelIn the same way, short-term turmeric administration may decrease hematuria, proteinuria, and systolic blood pressure in subjects with relapsed or refractory lupus nephritis, as established in a randomized and placebo-controlled trial of 24 patients with this biopsy-proven pathology. Each patient in the test group was given one capsule for 3 months, providing 500 mg turmeric, 22.1 mg of which was the active element curcumin (three capsules daily). Nevertheless, long-term tests with higher doses of turmeric are required to elucidate its outcomes on the renal function of such patients and the rate of development of CKD of different origins . HoweverCamellia sinensis) have high anti-inflammatory, antioxidant, and antimutagenic properties in various biological systems. Polyphenols display potential beneficial health properties for chronic diseases, including CKD [Camellia sinensis), which is high in catechin (flavonoid subtype). Three major catechins found in green tea have been described: epicatechin, epigallocatechin, and epicatechin-3-gallate (EGCG). The most abundant and extensively investigated catechin is EGCG [Polyphenolic constituents  inside the promoter region of the cytoprotective genes and those encoding antioxidant enzymes, which are likewise modulated by NF-κB signaling pathways. Nevertheless, the majority of all studies using EGCG or green tea in kidney diseases have been in animal models or cell cultures. Therefore, clinical studies are needed to obtain scientific support for the renoprotective properties of EGCG on renal pathologies ,102.Emblica officinalis, an Indian gooseberry, in the treatment of uremic subjects with T2DM. An EGCG/AE tablet was administered orally (one tablet three times a day) to uremic diabetic patients for 3 months, using a total daily dose of 300 mg of EGCG and 300 mg of AE/day. The results showed that 1:1 EGCG/AE improved diabetic biomarkers, antioxidant protection, and the atherogenic index in uremic diabetic subjects. Based on these results, the researchers concluded that EGCG and AE has the potential for adjuvant use in the treatment of diabetic patients in a uremic state [In other research, the authors evaluated the possibility of using a mixture of EGCG and amla extract (AE) obtained from ic state ,103.A fruit designated as “a medicine in itself” that has long been included in traditional remedies for preventive and therapeutic purposes . It has It is a phenolic substance (a non-flavonoid stilbene polyphenol), and the trans-isomer is considered to be the most biologically active form. Numerous preclinical and clinical analyses have recognized the anti-inflammatory, antidiabetic, hepatoprotective, neuroprotective, anticancer, and antioxidant properties of resveratrol . Likewise, supporting in vivo and in vitro tests of RSV in renal damage indicated that it can decrease fibrosis, mesangial expansion, OS, and inflammatory cytokine levels, while improving renal structure and function . FurtherLikewise, an analysis was conducted of 24 patients diagnosed with hypertension between 45 and 65 years of age and with underlying endothelial damage who participated in a randomized double-blind placebo-controlled crossover trial. Each patient was administered a single dose of trans-resveratrol (300 mg) or a placebo. Measurements of blood pressure (BP), aortic systolic blood pressure (SBP), and brachial flow-mediated dilation (FMD) were monitored before and 1.5 h after the intervention. The key results reported were that FMD was considerably augmented in female but not male patients administered trans-resveratrol. These results suggest that hypertensive patients with endothelial dysfunction, mainly women and those with high LDL-c, showed an improvement in endothelial function with a single dose of trans-resveratrol, although there were no significant improvements in peripheral and central BP ranges ,109. Furthermore, in another randomized double-blind placebo-controlled clinical trial conducted in 60 patients with a diagnosis of T2DM and albuminuria, resveratrol was randomly administered at a dose of 500 mg per day or a placebo for a period of 90 days, and losartan was additionally supplemented at dose of 12.5 mg per day to all research subjects. Their results showed that the mean urine albumin/creatinine concentrations were significantly reduced in the RSV group, and urinary albumin clearance, fasting plasma glucose (FPG), insulin, homoeostasis model evaluation of insulin resistance (HOMA-IR), and glycosylated hemoglobin (HbA1c) all decreased considerably in the RSV group compared with the placebo group, while the antioxidant effect of RSV was estimated by measuring serum levels of SOD1, glutathione peroxidase (GSH-Px), and catalase (CAT). Patients treated with RSV showed significant increases in serum levels of SOD1, GSH-Px, CAT, and NO compared with the placebo, confirming its antioxidant actions. The authors concluded that RSV could be effective as an adjunct to angiotensin receptor blockers (ARBs) to diminish urinary albumin excretion in subjects with diabetic nephropathy .As indicated, the health benefits of RSV seem to be extensive, with the reduced side effects of RSV making it an interesting option for therapeutic use targeting renal damage. However, further research and clinical trials are indispensable for completely comprehending the actions of RSV on renal injury ,110.It is a bioactive component that is a precursor of glucosinolate in cruciferous vegetables, particularly in young broccoli sprouts (BS) ,112. Then = 27), 5 g/d BSP (n = 29), or a placebo (n = 25). The results showed that serum high-sensitive C reactive protein (hs-CRP) and interleukin-6 (IL-6) were lower in Group A (10 g/d dose) compared with the control group post-intervention. This indicated that sulforaphane-rich BSP had positive effects on inflammatory biomarkers in patients with T2DM [GSTM1-null genotypes [In the same way, BS supplements have long been commercialized for the promising health benefits of SFN, which induces the NrF2 pathway and the downstream chemoprotective genes, including Phase 2 enzymes. Most commercially available BS supplements contain BS packaged as glucoraphanin (GR), which is hydrolyzed to SFN by the intestinal microbiota, which synchronously augments the serum activities of Phase 2 enzymes such as NQO1 and glutathione S-transferase (GST), and also Nrf2 signaling, in several human tissues. The researchers suggested that low doses (30 mg per day) of GF have favorable chemoprotective actions in humans . Likewisith T2DM . On the ith T2DM . Additioenotypes .Renal disease usually develops over time, so it is not often diagnosed until significantly later, when renal function is severely impaired. Pathophysiologically, CKD is a consequence of numerous pathological lesions that abolish some of the nephrons; subsequently, the nephrons overcompensate with hyperfiltration. Over time, glomerular hypertension, albuminuria, and loss of renal activity are established. The increased glomerular capillary pressure triggers damage to the glomerular capillary endothelium, impairment of the podocytes lining the capillaries, and increased permeability of the macromolecules. ,119. AddResearch has recommended that diets rich in vegetables and fruits help to control body weight and defend against chronic disorders, including metabolic and cardiovascular disease, cancer, and CKD ,122,123.This review highlights the beneficial function of bioactive medicinal plant compounds on improving renal function. All natural compounds explained in this report appear to have some benefits in improving OS, inflammation, and antioxidant capacity. Several NPCs reduce fibrosis due to hyperglycemia-induced OS, attenuate proteinuria, decrease hematuria and systolic blood pressure, and exert anti-nephrotoxic effects, and thus they are promising therapeutic tools to reduce or prevent the onset and progress of KD pathogenesis. Natural bioactive compounds are considered to exert important actions within the mechanistic pathways and to possess promising clinical properties; however, additional investigations are necessary to obtain a deeper comprehension of their specific pathophysiological functions, and the evaluation of these effects in larger trials is strongly suggested.


Acute blood pressure lowering after exercise seems to predict the extent of blood pressure reduction after chronic exercise training interventions. Based on that, the same weekly amount of exercise performed more frequently could be more beneficial for controlling blood pressure.To compare the effects of a combined training program (resistance plus aerobic exercise) performed four or two times per week on 24-h ambulatory blood pressure and other health-related outcomes in middle-aged and older individuals with hypertension.This study will be a randomized, parallel group, two-arm, superiority trial. Ninety-eight participants aged 50–80 years with a previous physician diagnosis of hypertension will be randomized to perform two or four sessions per week of combined training using the same total weekly overload. Primary outcomes will be 24-h ambulatory blood pressure and glycosylated hemoglobin; secondary outcomes will be endothelial function, physical fitness and quality of life. The outcomes will be assessed at baseline and at the end of 12 weeks period.Our conceptual hypothesis is that a combined exercise program performed four or two times per week with equalized weekly volume/overload will improve all outcomes in comparison to the baseline values, and that reductions in 24-h blood pressure and glycosylated hemoglobin will be more pronounced in the group that trained four times a week than twice. The results of this trial are expected to provide evidences to support that higher weekly frequency of combined training should be emphasized in aging adults with hypertension. Hypertension is one of the most important modifiable risk factors for developing cardiovascular disease, premature mortality , and typThe chronic reduction in blood pressure due to regular exercise seems to result from the sum of the acute decreases that follow each exercise bout  , 14. ThiTo the best of our knowledge, no studies have compared the effect of using different weekly combined training frequencies on 24-h ambulatory blood pressure. The aim of the present study is to compare the effects of a combined exercise program performed four versus two times per week on 24-h ambulatory blood pressure, glycosylated hemoglobin and other important health-related outcomes in middle-aged and older individuals with hypertension. The main outcome is the change from baseline to 12 weeks of follow-up in 24-h, daytime, nighttime systolic and diastolic ambulatory blood pressure, and glycosylated hemoglobin between the intervention groups. Secondary outcomes are the difference between mean change in office blood pressure, ambulatory blood pressure variability, endothelial function, as well as cardiorespiratory fitness, muscular strength and quality of life. We anticipate that at 12 weeks, combined exercise program, performed four or two times per week with equalized weekly volume/overload, will improve all outcomes in comparison to the baseline values and these improvements in blood pressure and glycosylated hemoglobin will be more pronounced in the group that trained four times per a week than twice.This is a single-center randomized controlled trial with concealed allocation, blinded measurers assessment, with 12 weeks of follow-up analyzed using an intention-to-treat approach. The recruitment will take place between March 2021 and December 2021 through social media and banners. The protocol followed the recommendations for interventional trials (SPIRIT) 2013 guidelines .The study will be conducted in the Clinical Research Center at the Hospital de Clínicas de Porto Alegre . The training setting is located outside of the center .Men and women aged 50–80 years will be eligible for this trial if they have:Previous physician diagnosis of primary hypertension or taking at least one antihypertensive medication;Not engaged in regular exercise programs (3 or more times per week) in the last 3 months before the study.Among eligible participants, those who fulfill the following criteria will be excluded:Physical and muscular injuries that limit to accomplishment of the different training proposed in the study;Underlying cardiovascular disease such as acute myocardial infarction, angina, stroke within the last 24 months;Presence of heart failure with NYHA classes III or IV;Chronic diseases such as cancer, kidney disease requiring dialysis, multiple sclerosis, Parkinson’s disease, among others;2;Body Mass Index ≥ 40 kg/mDiabetes Mellitus with target organs damage;Those who did not sign a consent form.2peak). CT2 will perform two combined training sessions per week composed of 20–30 minutes of resistance exercise  followed by 40–50 minutes of aerobic exercise . As an objective measure of aerobic exercise intensity, heart rate will be continuously recorded with a Polar HR monitor . Rating of perceived exertion will be used for determining the intensity of resistance exercises through the Borg scale (CR-10) [Participants will be randomly enrolled into one of two intervention groups: a combined resistance and aerobic training program performed four times per week (CT4) or two times per week (CT2) throughout 12 weeks. Participants will perform in sequence both resistance and aerobic training on the same session, starting with the resistance exercises immediately followed by the aerobic exercise . Both gr (CR-10) . The whoA blinded member of the research team, unaware of the study-group allocation, will handle the 24-h ambulatory blood pressure data. The primary hypothesis is that CT4 will lower 24-h systolic blood pressure as compared with CT2 and/or reduce glycosylated hemoglobin at a clinically meaningful amount. The outcomes will be measured at baseline and after 12 weeks period.The primary outcome will be 24-h, daytime and nighttime systolic blood pressure and glycosylated hemoglobin.Secondary outcomes will include office blood pressure, ambulatory blood pressure variability, endothelial function, quality of life, cardiorespiratory fitness and muscular strength.Outcomes will be assessed before and after the intervention period, irrespective of attendance or completion status. For participants who dropout of the study at any time after randomization, researchers will use contact information to invite such participants to undergo the end-study outcome assessments (12 weeks after the randomization). International Physical Activity Questionnaire  will be Participants will be recruited from electronic medical records, phone calls, e-flyers in social media, word of mouth, and personal references. Patients potentially eligible for the study will be contacted by telephone by the trial investigator, who will explain the study and ascertain the patient’s interest to participate. Those who accept to participate will attend the Clinical Research Center of Hospital de Clínicas de Porto Alegre, where the consent form will be signed, and the study assessments will be performed. The schedule of enrollment, interventions, and assessments is presented in Those who signed the consent will undergo to anamnesis and clinical screening, with sociodemographic, anthropometric and clinic data assessment, endothelial function evaluation, resting electrocardiogram and questionnaire to evaluate quality of life. After that, participants will perform a familiarization with strength and power muscle tests and with the mask that will be used in the cardiopulmonary test. In the second visit to the clinic, the equipment of ambulatory blood pressure monitoring will be installed. Participants will return to the laboratory to remove the equipment after 24-h and perform evaluations of the cardiorespiratory fitness, muscular strength and power. After that, a venous blood sample will be collected to measure glycosylated hemoglobin in A1C percentage. All variables will be assessed at baseline and at study completion. Participants will be asked to maintain their habitual activities and dietary habits at the time of recruitment and not starting new exercise regimens during the next 12 weeks.Ambulatory blood pressure monitoring will be assessed throughout 24-h in intervals of 15 minutes in daytime and 20 minutes in nighttime periods. Daytime period starts at 7 AM and nighttime starts at 11 PM, except in case that the participant describes a different sleep time and wake-up time. Participants will receive a diary to note daily activities, symptoms, sleep time and wake-up time, and will be instructed to avoid strenuous physical exercises and alcohol ingestion 24-h prior to exam. Each exam is considered valid when at least 14 measurements during the day and seven measurements at night [at night  were sucGlycosylated hemoglobin will be assessed through a blood sample with high-performance liquid chromatography technique .Ambulatory blood pressure variability will be calculated using the same data recorded in the ambulatory blood pressure device . The computer software is programed to calculate the average real variability [iability , and theiability .Office blood pressure will be measured after 10–20 minutes of rest, with the participant sitting quietly in a chair, according to standardized guidelines [idelines . Three mEndothelial function will be assessed using the flow-mediated dilatation technique [echnique . Baselinechnique .Cardiorespiratory fitness will be assessed using an incremental exercise test on a treadmill in order to determine peak oxygen consumption. The protocol consisted of an initial velocity of 3.5 km/h with 1% inclination for the first 2 minutes. Thereafter, velocity and grade will be incremented by 0.4–0.6 km/h and 0.5–1.0% inclination, respectively, every 1 minute until the participants achieve their volitional exhaustion [haustion . The expMuscular strength will be assessed through chair-stand test (lower-limbs) and isometric handgrip strength test (upper-limbs). Chair-stand test will be conducted using a folding chair without arms, with a seat height of 43.2 cm. The test will begin with the participant seated in the middle of the chair, back straight, feet approximately shoulder-width apart and placed on the floor at an angle slightly back from the knees. Arms should be crossed at the wrists and held against the chest. At the signal "go", the participant will stand up (body erect and straight) and then return to the initial seated position. The total number of stands executed correctly within 30-s and time to perform the first five repetitions will be used during the analyses [analyses . IsometrQuality of life will be evaluated through WHOQOL-BREF questionnaire [ionnaire . The queData will be collected on standardized forms identified by subject number and trial ID and containing instructions for standardized operational procedures. All data will be stored and managed through the use of Research Electronic Data Capture (REDCap) electronic data capture tools hosted at the center. A researcher will conduct audition for missing or inaccurate data. Data will be backed up daily by automated export procedures from secure servers of the Hospital de Clínicas de Porto Alegre.A sample size of 98 individuals with hypertension on 1:1 ratio  and  allowing a dropout rate of 10%, will be able to detect a difference of 4 ± 10 mmHg in systolic 24-h blood pressure among groups. Statistical power set at 80% including a type I error rate of 5%. WinPepi software calculator was used to estimate the sample size .www.random.org), with blocks of random sizes that will not be disclosed to ensure concealment. Groups will be generated by stratified randomization per sex, age (50–64 and 65–80 years), and baseline systolic ambulatory blood pressure in order to provide homogeneity on these prognostic factors. The epidemiologist will not participate in the recruitment or assignment to intervention sessions. The outcome assessors and data statistical analyses will be double masking to the endpoints of study. Participants and exercise instructors can’t be blinded for intervention because the nature of it, but they won’t know about randomization until the moment of assignment.The randomization list will be generated by an epidemiologist using web software . Adherence will be treated as the percent of intervention sessions fully accomplished without protocol deviations given the total number of scheduled sessions.Data on all adverse events will be collected and included in medical reports, which will be forwarded to the Ethics Committee of the institution. To ensure patient safety, we will monitor any adverse events occurred during the study, and all participants will be monitored throughout the study follow up and during four weeks after study finished.The endpoints will be analyzed using a full analysis set including all randomized participants, therefore allowing intention-to-treat analyses. A second set of per-protocol analysis will be performed including participants that completed the trial with adherence to at least 80% of the intervention sessions .Data distribution will be analyzed using Shapiro-wilk test with analysis of histogram and Q-Q plots in combination. The homogeneity of data will be checked using Levene test. Data will be expressed as means and standard error for variables with normal distribution or medians and interquartile range for non-normal distributions and 95% confidence intervals (95%CI). Ambulatory blood pressure monitoring will be analyzed as daytime, nighttime and 24-h systolic and diastolic blood pressure. Primary and secondary outcomes will be analyzed using generalized estimating equation model (GEE) for correlated measures. Adjustment for multiple comparisons will be accomplished using Sequential Bonferroni test. All analysis will be conducted using SPSS Statistics for Windows, version 22.0 .All participants will read and sign an informed consent form before enrollment. Participation will be voluntary, and all ethical principles of confidentiality and data protection will be maintained. The study protocol will be conducted according to the principles of the Declaration of Helsinki and in compliance with the Brazilian legal (number 466/2012) and regulatory framework for research involving human beings. The study protocol was approved by the Institutional Review Board of Hospital de Clinicas de Porto Alegre, Brazil (GPPG number 3.641.90), is registered in ClinicalTrials.gov under the identifier: NCT04218903. The expected date for the beginning of the study is March 2021 and anticipated date of completion is December 2021.We intend to disseminate the methods and findings of the study through individual explanation about the main findings and practical application of the study to each participant; press releases written by journalists and using our personal social media to the general public; and submit scientific manuscripts related to our main findings.To the best of our knowledge, this study will be the first randomized clinical trial comparing the effects of a combined training program, performed four or twice a week, on blood pressure over 24-h. Other important results related to the health of middle-aged and older individuals and hypertensive patients should be provided.Different physical activities can be effective to reduce blood pressure in middle-aged and older adults with hypertension . ChronicBased on the above-mentioned gaps related to the use of the same amount of exercise using different weekly training frequencies and the potential benefits of combined training in aging adults, this study will provide evidence on blood pressure reduction after a combined resistance and aerobic training program performed two and four times per week throughout 12-weeks in middle-aged and older patients with essential hypertension. Besides, other cardiovascular risk factor markers such as glycosylated hemoglobin and physical fitness parameters that can be improved with combined training and could respond differently if performed using more sessions per week will be evaluated in this trial. The results will have implications for the exercise prescription targeted to aging individuals who have essential hypertension.S1 Checklist(DOCX)Click here for additional data file.S1 File(DOCX)Click here for additional data file.S2 File(DOCX)Click here for additional data file.


Are left ventricular structure and function in preterm-born adults more susceptible to remodeling in association with blood pressure elevation?In this cross-sectional cohort study of 468 adults with cardiac magnetic resonance imaging, left ventricular mass index and mass to end-diastolic volume ratio were greater for each 1–mm Hg elevation in systolic blood pressure in preterm-born adults than in term-born adults, with the greatest rise in those born very and extremely preterm (<32 weeks’ gestation).The findings of this study show that adults born preterm demonstrate greater remodeling in response to systolic blood pressure elevation and may require earlier interventions to prevent cardiovascular disease progression. Preterm-born individuals have higher blood pressure with an increased risk of hypertension by young adulthood, as well as potentially adverse cardiac remodeling even when normotensive. To what extent blood pressure elevation affects left ventricular (LV) structure and function in adults born preterm is currently unknown.To investigate whether changes observed in LV structure and function in preterm-born adults make them more susceptible to cardiac remodeling in association with blood pressure elevation.This cross-sectional cohort study, conducted at the Oxford Cardiovascular Clinical Research Facility and Oxford Centre for Clinical Magnetic Resonance Research, included 468 adults aged 18 to 40 years. Of these, 200 were born preterm (<37 weeks’ gestation) and 268 were born at term (≥37 weeks’ gestation). Cardiac magnetic resonance imaging was used to characterize LV structure and function, with clinical blood pressure readings measured to assess hypertension status. Demographic and anthropometric data, as well as birth history and family medical history information, were collected. Data were analyzed between January 2012 and February 2021.Cardiac magnetic resonance measures of LV structure and function in response to systolic blood pressure elevation.2 vs 0.157 g/m2 per 1 mm Hg; P < .001) and a 1.6-fold greater LV mass index per 1–mm Hg elevation in systolic blood pressure in moderately preterm-born adults (32 to 36 weeks’ gestation) . The LV mass to end-diastolic volume ratio per 1–mm Hg elevation in systolic blood pressure in the very and extremely preterm-born adults was 3.4-fold greater compared with those born moderately preterm  and 3.3-fold greater compared with those born at term .The cohort was primarily White (>95%) with a balanced sex distribution (51.5% women and 48.5% men). Preterm-born adults with and without hypertension had higher LV mass index, reduced LV function, and smaller LV volumes compared with term-born individuals both with and without hypertension. In regression analyses of systolic blood pressure with LV mass index and LV mass to end-diastolic volume ratio, there was a leftward shift in the slopes in preterm-born compared with term-born adults. Compared with term-born adults, there was a 2.5-fold greater LV mass index per 1–mm Hg elevation in systolic blood pressure in very and extremely preterm-born adults (<32 weeks’ gestation) (0.394 g/mPreterm-born adults have a unique LV structure and function that worsens with systolic blood pressure elevation. Additional primary prevention strategies specifically targeting cardiovascular risk reduction in this population may be warranted. This study investigates whether changes observed in left ventricular structure and function in preterm-born adults make them more susceptible to cardiac remodeling in association with blood pressure elevation. Part of this risk may be associated with altered cardiac physiology because preterm-born individuals have potentially adverse structural and functional changes across developmental stages from birth to young adulthood.3 This includes impaired left ventricular (LV) diastolic function, smaller internal LV dimensions, and a greater rate of LV hypertrophy from childhood to young adulthood.3Individuals born preterm are at greater relative risk of early heart failure5 In humans, the preterm heart is less able to cope under acute physiological stress, with impairments in ejection fraction, stroke volume, and cardiac output during moderate- to high-intensity exercise.7 It is thus conceivable that the observed patterns of cardiac remodeling seen in individuals born preterm make their hearts more vulnerable to chronic insults, such as the hemodynamic stress of sustained blood pressure elevation. Of related concern is that, compared with their term-born peers, individuals born preterm have higher systolic and diastolic blood pressures,8 with preterm birth now recognized as a risk factor for hypertension in adulthood.9In a rat model of preterm birth conditions, early cardiac remodeling, similar to that observed in humans, makes rodents more susceptible to heart failure following hemodynamic pressure overload.11 they have been limited by small numbers of individuals with blood pressures in the clinically elevated and hypertensive range. We have therefore performed a cardiac magnetic resonance (CMR) imaging study in 468 individuals, of whom more than 25% were clinically hypertensive, to determine how systolic blood pressure elevation may be associated with LV structure and function in adults born preterm. Furthermore, we have investigated whether the strength of the association between LV changes and systolic blood pressure is dependent on the degree of prematurity. We hypothesized that preterm-born individuals have an altered cardiac phenotype that is more susceptible to further cardiac remodeling in association with blood pressure elevation.While earlier studies have shown associations between cardiac structural and functional alterations with increasing blood pressure,12 Data were coded with participant- and study-specific identifications to ensure anonymity and blinded analysis. Ethical approval was granted by the South Central Oxford A research ethics committee, the South Central Berkshire research ethics committee, and the South Central Oxford B research ethics committee. All participants provided signed informed consent.Participants were recruited as part of a program of ongoing research in Oxford, England, into the association between preterm birth and cardiovascular outcomes. All participants had been identified through open recruitment including prospective recruitment from birth, targeted online recruitment, as well as invitation from general practice records, the local hypertension clinic, and hospital birth registers. Inclusion and exclusion criteria for this analysis included being between ages 18 and 40 years, having a body mass index  less than 40, and no history of hypertension treatment, cardiac, or cerebrovascular disease. All research study visits were conducted at the Oxford Cardiovascular Clinical Research Facility (CCRF) and Oxford Centre for Clinical Magnetic Resonance Research (OCMR). Birth and family history data were attained via a combination of prospective collection, access to medical notes, and by questionnaire. Individuals were classified based on gestational age as either being born preterm (<37 weeks’ gestation) or at term (≥37 weeks’ gestation). Classification of normotensive and hypertensive was based on cutoff levels derived from the American College of Cardiology/American Heart Association blood pressure classification guidelines (systolic blood pressure ≥130 mm Hg and/or diastolic blood pressure ≥80 mm Hg).13 trained clinical research investigators completed all height and weight measurements as well as blood sample collection. Participants were seated for 5 minutes before 3 resting brachial blood pressure readings  were taken on the left arm with a 1-minute interval in between. These measurements were done on the same day as the CMR scan. The final 2 readings were averaged for analysis. Twenty-four–hour ambulatory blood pressure monitoring and central blood pressure measurements were done in a subgroup as part of the same study visit  to quantify LV structure and function. A previous comparison performed by our center showed the feasibility and consistency of cardiac volume and mass measurements across field strengths.15 Average LV wall thickness was measured on the midventricular short-axis slice at end diastole. Relative wall thickness (RWT) was calculated on the midventricular short-axis slice at end diastole as the LV inferolateral plus anteroseptal wall thickness, all divided by LV cavity diameter. Length of the LV was measured as the length from the LV apex to the middle of the mitral valve annulus at end diastole. Sphericity index was calculated as the ratio of LV end-diastolic volume, divided by the volume of a sphere, with LV length as the diameter. Myocardial deformation analysis was performed using feature tracking. Endocardial and epicardial borders of the LV for the horizontal long-axis cine and basal, mid, and apical short-axis cines were manually contoured on the end-diastolic frame. The deformation of the myocardium was then automatically tracked through the phases of the cardiac cycle.All LV analysis was done using analytic software . To evaluate LV volumes, mass, and dimensions, both the epicardial and endocardial borders were manually contoured on short-axis cine images for each slice at end diastole and endocardial borders at end systole. The end-diastolic and end-systolic cardiac phases and basal and apical LV slices were visually determined as previously described.t test for normally distributed data and the Mann-Whitney test for skewed data. All group comparisons of birth history and gestational age categories were adjusted for age and sex. After bivariate regression analyses, multivariable regression analyses were conducted to identify the association between key LV parameters (dependent variables) and systolic blood pressure, adjusting for potential confounders . For each analysis, unstandardized coefficients (B) with 95% confidence intervals and P values were computed. One-way analysis of covariance (ANCOVA) was conducted to determine whether there were significant differences in the regression lines between the groups. Sum squares, F statistics, and P values were calculated for each parameter within each model. P values of .05 or less were considered statistically significant unless multiple subgroup comparisons were made, in which case, 2-tailed P values of .01 or less were considered statistically significant.Statistical analysis was performed using SPSS, version 25 (IBM) and R, version 3.6.1 . All statistical analyses were done based on a comparison of birth history (preterm and term groups) and gestational age categories . Data were presented as mean (SD) or number (percentage) for all comparisons. Shapiro-Wilk testing was used to verify data normality. To compare continuous variables between groups, we used the P < .001; diastolic: +16.4%, P < .001) and term-born individuals .A total of 493 participants recruited to the Oxford program on preterm birth and cardiovascular outcomes had undergone CMR scans. For this study, 25 participants were then excluded: 3 owing to missing clinic blood pressure readings; 16 who were receiving antihypertensive medications; 4 who had a BMI of at least 40; and 2 who had preexisting cardiac conditions. Of the remaining 468 participants, 200 were born preterm and 268 were born at term. There were no significant differences in age and sex between the preterm-born and term-born groups   greater LV mass index per 1–mm Hg elevation in systolic blood pressure compared with 0.250 g/m2  in those born moderately preterm (32-36 weeks’ gestation) (ANCOVA P = .03) and 0.157 g/m2  in those born at term (≥37 weeks’ gestation) (ANCOVA P < .001)  but not in term-born adults, with a significant difference between regression lines (ANCOVA P < .001). This association was greatest in adults born very and extremely preterm , with the regression line differing significantly for this group compared with moderately preterm (ANCOVA P < .001) and term-born adults (ANCOVA P < .001) (The association between systolic blood pressure and LV mass index was significant in both the preterm-born and term-born groups but was greater in those born preterm in the multivariable regression models per 1–mm Hg elevation in systolic blood pressure (0.318 g/m < .001) . When di < .001) . The adj < .001) . Althoug < .001) . The reg < .001) . Subgrou < .001) .In a large cohort of young adults, we have investigated the association between systolic blood pressure elevation and LV structure and function in preterm-born individuals using CMR. In regression analyses of systolic blood pressure and LV mass index and LV mass to end-diastolic volume ratio, there was a leftward shift in the slopes in the young adults born preterm compared with those born at term. In addition, there was a 2.5-fold greater LV mass index per 1–mm Hg systolic blood pressure elevation in very and extremely preterm-born young adults and a 1.6-fold greater LV mass index per 1–mm Hg systolic blood pressure elevation in moderately preterm-born young adults compared with term-born young adults. Furthermore, LV mass to end-diastolic volume ratio per 1–mm Hg systolic blood pressure elevation in the very and extremely preterm-born young adults was 3.4-fold greater compared with those born moderately preterm and 3.3-fold greater compared with those born at term, with no difference between the latter 2 groups.16 In sheep born preterm, this early transition leads to a disruption in normal postnatal myocardial maturation that may increase later cardiac susceptibility to failure.17 Hearts from piglets delivered preterm were unable to maintain LV cardiac output when challenged ex vivo with an increased afterload.18 Similarly, in a rat model of preterm birth conditions, there was accelerated myocardial hypertrophy, diffuse fibrosis, and impaired systolic function in the LV prior to systemic blood pressure elevation.5 As a result of their reduced LV functional reserve, they were more likely to go into heart failure when hemodynamically challenged with angiotensin II infusion, although angiotensin receptor blocker treatment prevented the development of cardiac alterations.4 Human studies from birth through to young adulthood have now demonstrated that LV function and structure are altered in individuals born preterm,3 including an inability to meet the demands of physiologic stress in adolescence and young adulthood.20 The lower myocardial functional reserve seen in preterm-born young adults in response to acute stress may in part explain why the risk of early heart failure is so much greater in this population.21As the immature heart transitions to the ex utero environment, it must undergo cellular, structural, and functional adaptations to deal with the dramatic shift in pressure and oxygen.24 Our study adds to the limited cardiac imaging data available in young adults with mild to moderate hypertension using CMR, which is widely considered the criterion standard modality for assessing LV structure and function.25 While most LV parameters did not differ significantly between term-born young adults with and without hypertension, LV ejection fraction was higher in the hypertensive group, with a significant, positive association between LV ejection fraction and systolic blood pressure that was not seen in those born preterm. Higher midventricular peak systolic circumferential strain accompanied the higher LV ejection fraction in the term group, which could indicate systolic hypercontractility to compensate for increased afterload. This was not observed in the preterm-born young adults, which may suggest an inability to adapt to early stages of blood pressure elevation. Interestingly, in the preterm-born young adults, we did not see the extent of LV structural or functional changes we might have expected when comparing individuals with and without hypertension. Nevertheless, when quantifying the continuous association between LV parameters and increasing systolic blood pressure, there was a steeper slope in the adjusted regression line between both LV mass index and LV mass to end-diastolic volume ratio with systolic blood pressure in the preterm group that increased with the degree of prematurity. Furthermore, the leftward shift in the preterm regression lines meant that both LV mass index and LV mass to end-diastolic volume ratio were greater for any given systolic blood pressure. This suggests that blood pressure alone is not the driving factor for the observed LV differences between preterm-born and term-born young adults and that there are unique drivers of increased cardiovascular risk in the preterm population.26Given the underlying morphologic impairments in the preterm heart, it is conceivable that blood pressure elevation would have a greater effect on cardiac remodeling in this population. Hypertension is known to cause LV structural and functional adaptations, including wall thickening and impaired systolic and diastolic function, especially with more advanced disease in older populations.27 Although we were able to identify that the greatest increase in LV mass index and LV mass to end-diastolic volume ratio in association with increasing systolic blood pressure was in those born at less than 32 weeks’ gestation, our sample size of individuals born at less than 28 weeks’ gestation (extremely preterm) was too small to investigate in isolation. In a study by Goss et al,28 it was shown that extremely preterm-born adolescents and young adults had smaller LV volumes and mass, as well as a more hypercontractile LV compared with their term-born peers. However, all participants in that study were normotensive. Given that this more premature group is at an exponentially greater risk of early heart failure,1 further work is needed to understand cardiac remodeling in response to hypertension in the most premature individuals. Owing to retrospective perinatal data collection in a significant proportion of our cohort, we did not have complete information on all perinatal complications, such as infection rates, days of ventilation, and hypertensive pregnancies. Further studies will be needed to explore whether these factors affect the findings. Nevertheless, our complete gestational age and birth weight data allowed us to determine that the degree of prematurity may be important to how the preterm heart responds to blood pressure elevation and could add value to young adult risk stratification. While our study sample size of individuals with stage II hypertension was limited, because most young adults in this blood pressure range would be taking medication, the leftward shift in the association between LV changes and systolic blood pressure suggests that, even in the early stages of blood pressure elevation, appropriate clinical screening and monitoring may be warranted. Further research is needed to investigate this and to exclude the possibility of coassociation between LV changes and higher systolic blood pressure.A limitation of the study was that the main analyses were based on single-arm clinic blood pressure measurements. Despite this, we were able to perform subgroup analyses in approximately 75% of the cohort using 24-hour and surrogate central blood pressure measures, which showed consistent results. Future studies to more accurately quantify the effect of pulse pressure amplification are needed, using methods such as CMR aortic distension waveforms to assess central systolic blood pressure.In summary, young adults born preterm have an altered cardiac structure and function compared with their term-born peers, with greater remodeling in response to systolic blood pressure elevation. Further research should include serial study visits with cardiac imaging in the same individuals over time to better understand how the heart remodels in response to blood pressure elevation and which factors may increase or decrease risk to guide potential interventions. Given that preterm birth affects more than 10% of live births and that survival of even the most premature individuals continues to rise, lifelong clinical follow-up may be needed to prevent the emergence of early cardiovascular disease in this population.


Essential hypertension in adults may begin in childhood. The damages to the heart and blood vessels in children with essential hypertension are hidden and difficult to detect. We noninvasively examined changes in cardiovascular structure and function in children with hypertension at early stage using ultrasonography.All patients with essential hypertension admitted from March 2020 to May 2021 were classified into simple hypertension  and hypertension co-existing with obesity  isolation. Meanwhile 32 healthy children were detected as control heathly group (group 3). We used pulse-wave Doppler to measure carotid–femoral pulse wave velocity (cfPWV), intimal–medial thickness (cIMT) and distensibility of carotid artery (CD). Cardiac structure and function  were measured by echocardiography.The cfPWV of children in group 1 and group 2 were significantly higher than healthy children in group 3. Significant differences were observed in LVM, LVMI, RWT, LVIDd, IVSd, LVPWd, LAD, A peak, E' peak, A' peak, and E/E’ among three groups.Children and adolescents with essential hypertension demonstrate target organ damages in the heart and blood vessels. Essential hypertension (HTN) in adults may begin in childhood  is the most commonly measured non-imaging parameter to assess arterial stiffness. Carotid intimal–medial thickness (cIMT) is the primary index for measuring vascular structure.This study aimed to noninvasively evaluate changes in cardiovascular structure and function in children with hypertension by ultrasonography to verified the target organ damages.。[We continously retrospectively studied 45 children  with newly diagnosed essential hypertension admitted in the cardiology department in the Children’s Hospital of Soochow University from March 2020 to May 2021, and 32 healthy children matched with age and sex were recruited from the community-based population as the control healthy group 3. Clinical parameters . We took the K1 tone as the standard for systolic blood pressure and the K5 tone as the standard for diastolic blood pressure. We performed measurements twice continuously and averaged the two measurements. The interval between each measurement was 3 min. If the difference between the first two readings was > 5 mmHg, we used the average value after obtaining a third reading. The first diagnosis of hypertension was verified by a third examination.Echocardiography was performed using a Philips EPIQ7C color Doppler ultrasound machine , equipped with S8-3, S5-1 and L12-5 probes ranging from low to high frequency . According to American Society of Echocardiography guidelines for pediatric echocardiogram from 2006 [The Doppler spectrum of the mitral valve pulse was recorded in an apical four-chamber view. The peak velocity of the filling peak in the early diastolic period (E) and the peak velocity of the filling peak in the late diastolic period (A) were measured, and the E/A ratio was calculated. Three cardiac cycles were measured, and the average value was used. We used the Tissue Doppler Imaging technique to measure the velocity of the mitral annulus (E') and calculated the E/E' value by combining this with the velocity of early diastolic blood flow (E) through the mitral valve orifice. This study defined left ventricular diastolic dysfunction as an E/E' > 15 or an E/A < 1.0.The calculations of left ventricular mass (LVM), LVM index (LVMI), and relative wall thickness (RWT) were based on Devereux formulas:2.7 in children. An RWT > 0.41 was considered abnormal [Three cardiac cycles were measured, and the average value was taken. The criterion for left ventricular hypertrophy (LVH) was a LVMI > 38.6 g/m Carotid–femoral PWV (cfPWV) was calculated as the ratio of the travel distance (D) to carotid–femoral pulse transit time (T). The path length of the direct carotid-femoral distance segment (D) was estimated based on the surface distance (Ds) from the carotid arteral measurement point to the femoral measuremental point using the formula: D = Ds × 0.8  . The so-Patients assumed a supine position to expose the neck. Ultrasonography of the carotid artery lumen was performed, and cIMT of the anterior and posterior walls was measured. At 1–2 cm below the bifurcation plane, the thickness of the internal–medial carotid membrane were automatically measured by the built-in software package.Carotid distensibility (CD) can be measured by acquiring carotid artery diameter in end diastole and the systo-diastolic change also called distension or the diameter changes of carotid artery (∆D). The systolic and diastolic diameter of carotid artery were manually measured, then calculated ∆D. After that CD is calculated according to the reneman formula:where Dd is the end diastolic diameter of the vessel, Ds is the systolic diameter of the carotid artery. PP is the central pulse pressure .P value of < 0.05 was considered statistically significant.We used SPSS 25.0 software  to perform statistical processing of the data. Measurement data are expressed as mean ± standard deviation. As we were primarily interested in comparing both disease groups (hypertension and hypertension + obesity) with the healthy control group, we performed one-way analysis of variance (ANOVA), where the disease groups were considered mutually exclusive. All results are presented from the one-way ANOVA. A P > 0.05). There were significant differences in body weight, BMI, systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP) in group 1 and group 2 compared with group 3 (P < 0.05).The clinical characteristics and biochemical parameters of hypertension and control groups are shown in Table There were significant differences in LVM, LVMI, RWT, LVIDd, IVSd, LVPWd, LAD, A peak, E' peak, A' peak and E/E' among the three groups (P < 0.05). LVM, RWT, LVIDd, LVPWd, LAD and E/E’ in group 1 and group 2 were significantly higher than the healthy control group. The two hypertension groups were not significantly different from each other. IVSd and LVMI were significantly different among the three groups by S–N-K test. A peak and A' peak were significantly higher in group 1 compared with group 2 and group 3 in a post-hoc analysis. Moreover, E’ peak was significantly lower in group 2 compared with group 1 and group 3. However, there was no difference in AO, E peak and E/A ratio among the three groups , 2 children were eccentric hypertrophy  and 1 child were concentric remodeling , respectively. Of the 34 HTN patients, 2, 6 and 5 children had concentric hypertrophy, eccentric hypertrophy and concentric remodeling, respectively.There were significant differences in cfPWV among the three groups. cfPWV was significantly higher in both hypertension groups in comparison with the healthy control group Fig. . There wIn 2017, with the blood pressure standards for Chinese children by sex and age, and height developed, hypertension in children and adolescents aroused great concern in pediatrics. It is the most widely used diagnostic criteria. Our definition of hypertension is based on this criterion, and our study found the structural changes in heart, cardiac diastolic dysfunction and vascular stiffiness.There were significant differences in LVM, LVMI, RWT, LVIDd, IVSd, LVPWd, LAD in hypertensive children. An increase in afterload caused by high blood pressure leads to an increase in ventricular wall stress and eventually changes in myocardial structure, which is called left ventricular hypertrophy or remodeling. In patients with continuous hypertension in the systemic circulation, cardiac afterload increases, resulting in an increase in left ventricular end-systolic residual blood volume and diastolic volume. This in turn results in left ventricular compensatory hypertrophy, a decrease in myocardial elasticity, and an increase in left ventricular volume. Then an increasing in left atrial residual blood volume at the end of diastole and gradual left atrial enlargement maintain an atrioventricular pressure difference and excessive cardiac output . Left veHigh blood pressure leads to an increase in myocardial mass, which is reflected by an increase in LVIDd, IVSd, LVPWd of cardic morphology and structure. An increase in LVM is a manifestation of left ventricular hypertrophy (LVH) and an independent risk factor for LVH . Using tRWT is also an important indicator of cardiovascular remodeling in hypertension. Although the RWT of hypertensive groups were higher than that of the control group, their values were all within the normal range in our study. A 0.31 cut-off value had 85.7% sensitivity and 77.4% specificity for hypertension patients while a 0.41 cut-off value only had 21.4% sensitivity and 100% specificity. We should establish a new cut-off value for RWT in children with hypertension.Among children with 45 hypertension, 12  ones had LVH and 6 children(13.3%) had left ventricular remodeling. The incidence of LVH was consistent with the 27% reported by Sorof , so LVMIStudies had shown a positive correlation between high blood pressure and obesity in children and adolescents , 11. The. [In addition to changes in left ventricular structure, changes in left atrial structure and function have been confirmed as early pathological changes in patients with hypertension . In our .  also fouPrevious study defined left ventricular diastolic dysfunction as an E/E' of > 15 or an E/A of < 1.0. We compared E/E' ratio between the three groups and found that although E/E' in children with hypertension was < 15, children in these groups had a significantly increased E/E' compared with the healthy group. This indicated that left ventricular diastolic function decreases in the groups with hypertension. We found that the E' peak of the ventricular septum in group 2 was significantly decreased, and A' peak of the ventricular septum and A peak of mitral valve were higher in group 1 than the other two groups. These results proved that increased left atrial pressure and impaired left atrial function were common in children with hypertension. There was no significant difference in E/A ratio between the three groups but the E/E' in children with hypertension whatever obese or not was significantly increased. E/A probably is less sensitive than E/E’ as previously reported literatures ..In addition to the above cardiac damage, hypertension can also cause changes in vascular structure and function. Arterial stiffness or arterial compliance can be measured as PWV which was the speed of pulse wave transmitted across the length of the arterial tree. A higher PWV indicates a stiffer blood vessel, contributing to increased afterload and subsequent cardiac remodeling . In adulThe predictors of PWV were age, SBP, heart rate, BMI, antihypertensive treatment and drug classes, not related to race, gender, smoking, dyslipidaemia, diabetes, kidney disease, or genetic factors. Two factors were identified as being responsible for accelerated progression of PWV after correction for HR: age and BP values . HoweverDoppler methods to assess cfPWV is feasible. It is not the preferred one compared to the automatic one using tonometey or pressure sensor, but it’s a good replacement to assess cfPWV when you don’t have the automatic machine. Although Doppler-PWV measurements determined more evaluation error than ones of applanation tonometry, piezoelectric mechano-transducer or cuff-based oscillometry, Doppler-PWV exactly showed close correlation with invasive assessment as well. Styczynski G. et al.  found thIn our study, absolute cfPWV values in the three groups were much lower than the threshold for severe cardiovascular events in adults (10 m/s), but both HTN groups had significantly higher values than the healthy children. We found that 4.55 m/s cut-off value of cfPWV had 88.9% sensitivity and 53.6% specificity for hypertension patients. Although 10 m/s cut-off value had gained independent predictive value for fatal and nonfatal cardiovascular events in hypertensive adult patients, this threshold did not distinguish HTN let alone stratify them in child and adolescents. We need more studies of vascular PWV in children to further determine the cut-off value and reclassify intermediate risk patients into higher or lower target organ damage risk.There were no significant difference in carotid IMT and CD between the three groups of children, probably because our sample size was too small to stratified analysis based on age, weight and height. Carotid ultrasound measurement of IMT is the most commonly used assessment of vascular structure, since it is considered to reflect overall atherosclerotic burden. Currently, many machines had built-in software that can automatically measure IMT to reduce manual measurement error. Kollias et al.  studied Carotid distensibility is probably the most standardized and used carotid arterial stiffness index. Measuring CD means quantify changes in arterial diameter in response to BP changes from diastole to systole. Like cIMT distensibility has also been related to all cause mortality, cardiovascular morbidity and mortality and the presence and severity of cardiovascular diseases in adults . It reprThere are some limitations of this study that should be noted. First, this was a retrospective study, thus selection bias was inevitable. Second, the sample size was small, and the regional distribution was uneven, and because of the small sample size of children with obesity, we did not evaluate the effects of obesity on cardiovascular structure and function alone. Finally, a coefficient of variation of the mean value of the intra-session within- and between-operator variability respectively was missing and there was no agreement data between the Doppler technique and tonometry or piezoelectric mechano-transducer technique, as well as intra- / inter- reproducibility for our center when assessing cfPWV. In view of these limitations, follow-up studies should expand the sample size and increase the analysis of cardiovascular effects in individuals with obesity. Our future research directions include longitudinal studies to assess changes in cfPWV over time in healthy children and children with hypertension and obesity. We can do further consistency study between ultrasonographic and automatic tonometey methods.In conclusion, although essential hypertension has no obvious clinical symptoms, Doppler ultrasonography showed that the heart and blood vessels of children with hypertension undergo structural and functional changes. Our data provide fundamental support for the argument that hypertension is having an effect on target organ damage of cardiovascular system in adolescents and young adults.Doppler ultrasonography shows that the heart and blood vessels of children with hypertension undergo structural and functional target organ damages.


After kidney transplantation neurologic manifestations may develop, including Parkinson’s disease (PD). An enlarged substantia nigra (SN) by transcranial sonography has been recognized as a marker of PD.n = 20), measurement of mesencephalon, SN, third ventricle, spleen and carotid intima-media thickness (cIMT) and middle cerebral artery (MCA), kidney and spleen arteries Doppler resistive index (RI) were performed.In renal transplant recipients (RTRs = 95) and controls (RTRs had larger SN, third ventricle and cIMT and higher renal RI than controls. The SN was larger in the CNIs group than in controls and rapamycin group, while the third ventricle was similar between patients but larger than in controls. In RTRs, SN showed a direct linear correlation with spleen and the third ventricle with age, cIMT and RI of the MCA, kidney and spleen. In CNIs group the SN correlated positively with age and cIMT, while the third ventricle reproduced RTRs correlations. Rapamycin group showed a direct linear relationship between the third ventricle and age and RI of the MCA, kidney and spleen; SN showed no correlations.RTRs on CNIs present a larger SN area than on rapamycin, probably due to the antiproliferative effect of rapamycin. This finding might be relevant when interpreting TCS in RTRs.The online version contains supplementary material available at 10.1186/s12882-022-02741-7. The 2 . The use2 , 11. How2 . In rece2 . The fin2 .The pathophysiology of increased SN echogenicity is still not fully understood, but iron deposition seems to account for it . It is wInflammation is another relevant issue in renal transplant recipients (RTRs), mainly as a risk factor for cardiovascular events . BesidesWith these premises in mind, the aim of the current study was to evaluate long-term RTRs to determine brain structure values by TCS and their relationship with derived Doppler RI of the middle cerebral artery, kidney graft and spleen, as well as cIMT.This was a single-center prospective observational survey in which long-term RTRs irrespective of renal function and healthy controls who agreed to participate in the study were selected. Between May 2018 and November 2020, consecutive RTRs referred for renal sonography were eligible for the study group, provided the following criteria were fulfilled: a) on triple-drug immunosuppression; b) without known neurological or psychiatric disease (not treated on an inpatient or outpatient basis); c) without known hepatobiliary disease and portal hypertension; d) aged at least 18 years; and e) with a transplant duration of at least 360 days. Control group participants were deemed to be eligible if they did not have proteinuria (urinary spot > 30 mg/dL) or increased serum creatinine (> 1.4 mg/dL) and denied having systemic arterial hypertension on treatment or diabetes mellitus. No neurological examination was carried out in any participant.Data collection included demographic data , underlying cause of renal failure, donor type, transplant duration, dialysis vintage, serum creatinine level, immunosuppressive regimen; transcranial sonographic measurement of mesencephalon and SN area, third ventricle width and middle cerebral artery (MCA) Doppler RI; abdominal sonographic measurement of spleen size, Doppler RI of native or graft kidney and spleen; sonographic measurement of cIMT.All examinations of the brain, kidney, spleen and carotid were performed at the same run. Ultrasound Doppler examinations were performed using an Aplio 400  equipment. A convex transducer (3.5 MHz) was used for native and graft kidney and spleen, a phased-array (2.0 MHz) for TCS and a linear probe (10.0-MHz) for cIMT. All TCS and carotid examinations were performed by two senior operators (RCLF and NCA) and all kidney graft and spleen Doppler ultrasound examinations were performed in the morning by the same operator (NCA) with the same routine.A more extended description of the protocol has been provided in a previous publication . Images On the workstation of the equipment, the ipsilateral mesencephalon and the mesencephalic SN hyperechogenicity seen in both sides of brain were manually encircled. For each patient, only the largest SN and mesencephalic area was chosen for analysis, or, in the case of a unilateral permissive bone window, the only one available was chosen irrespective of the side. The width of the third ventricle was measured as the distance corresponding to the anechoic space between inner hyperechogenic lines formed due to significant acoustic impedance between ependymal walls and the cerebrospinal fluid.The goal was to compare the TCS parameters values between both groups studied and their relationship with demographic data, Doppler RI, spleen size and cIMT. Additionally, a subset of RTRs were compared according to immunosuppressive regimen.A more detailed description of sampling has been already provided elsewhere for the kidney graft and spleen . BrieflyThe RI was manually measured with built-in software and the average of the measurements in kidney and spleen was taken. Machine settings were adjusted for optimal performance. The Doppler angle was always zero.The ultrasound exam to determine the cIMT of the left and right common carotid arteries was performed according to standardized protocols previously reported , 26. Brip-value less than 0.05 was used as a cut-off for statistical significance.Data were analyzed using SPSS software, version 17. Differences in demographics, TCS parameters and laboratory variables between renal transplant recipients and controls, were calculated using the Mann–Whitney U Test for continuous variables and chi-squared tests for categorical variables. Data analysis among different immunosuppressant regimens and controls was performed using the Kruskal–Wallis test, and Bonferroni post hoc tests were used to determine the differences between particular pairs of groups. Statistical relationships between variables were assessed using Pearson’s correlation coefficient. A The study was approved by the local ethics committee . All participants gave written informed consent.n = 156) and controls (n = 28). Out of 156 RTRs, 61 were excluded because of bilateral poor transtemporal insonation window (n = 15), short transplant duration time of less than 360 days (n = 34) or on only two-drug immunosuppression (n = 12). Among participants with normal renal function (28 controls) initially recruited for the study, one was excluded because of a poor window, three were ruled out because of hypertension, three because of proteinuria and one because of diabetes mellitus. After exclusions, 115 participants remained eligible for the study; 95 were RTRs . Immunosuppressant regimens included rapamycin (n = 22) or a calcineurin inhibitor (CNIs)  in addition to an antimetabolite (mycophenolate or azathioprine); in all instances, treatment regimens were administered in combination with steroids.TCS was performed in 184 participants, including RTRs , glomerulopathy , diabetes mellitus , polycystic kidney disease , unknown causes  and miscellaneous causes . Patients with lupus erythematosus were assigned to the glomerulopathy group. None of the participants were on treatment for any neurologic disorder or had complaints of tremor.The main underlying etiologies (95 cases) of end-stage kidney disease were hypertension (p = 0.517). Table Controls and RTRs had similar patterns of sex distribution  of brain tissue TCS may provide new and complementary pathophysiological insights into disease states.Different lines of evidence from experimental studies shed light on this topic. It is known that lipopolysaccharide injected into the rat SN evokes a typical inflammatory response that is followed by dopaminergic neurodegeneration , and an In hemodialysis patients, iron deposition in gray matter, including the SN, have been already reported . In lineThe increased cerebral third ventricle width found in our patients deserves to be highlighted, since it has been reported as a parameter for cerebral atrophy , 49. MorArterial Doppler RI increases with age . In the Further subgroup analysis according to immunosuppressive regimen showed that although the rapamycin and control groups displayed a similar mean SN echogenic area, patients receiving CNIs had significantly larger SN echogenic area than those receiving rapamycin and controls, an unexpected result. This finding could not be assigned to age mismatch. Controls and rapamycin groups had the larger age mismatch and nonetheless there was no difference in SN area. On the other hand, despite CNI and rapamycin groups were matched for age, rapamycin group showed a smaller SN area. Moreover, the direct correlation between spleen size and SN echogenic area in RTRs, seen in this study, suggests that this finding may have similar underlying mechanisms. There is evidence supporting the role of inflammation in spleen enlargement commonly found in CKD . This fiConsidering that inflammation might be involved in the pathophysiology of the enlargement of SN in RTRs, one can speculate that the larger echogenic area of SN in patients receiving CNIs in comparison to rapamycin could be explained by differences in the mechanisms of action of each medication on cell proliferation. Indeed, in experimental models of PD, tacrolimus was unable to inhibit glial proliferation , while rAlthough RI of the kidney and spleen and cIMT has been suggested to reflect the burden of cardiovascular factors and systemic atherosclerosis , 63, 64,As patients were free of neurologic complaints, a correlation could not be established between our imaging findings and neurological symptoms. Nonetheless, our results provide the first evidence that SN echogenic area is increased in renal allograft recipients taking CNIs, even though none of them actually have a history of PD.It is tempting to also speculate that increased SN echogenic area might be related to the well-known neurotoxicity of CNIs, leading to some movement disorders , in a siAlthough the present study results show an enlarged echogenic SN area in patients without complaints of tremor, any implication of this finding for the diagnostic approach of preclinical PD is beyond the scope of the current study.One weakness of this study is that, even in the absence of neurological-related complaints, the participants should have been submitted to a thorough neurological evaluation in order to detect eventual mild symptoms not reported. The second weakness is that serum markers of inflammation were not included in the the study. However, cIMT can be used as surrogate marker of inflammation. Indeed, the association between cIMT and inflammatory markers like interleukin-6 , 69 and RTRs taking CNIs present a larger SN area than patients with a rapamycin-based immunosuppressive regimen.Additional file 1. Supplemental FigureS1 and Supplemental Figure S2.


Surgery in the prolonged extreme Trendelenburg position may lead to elevated intracranial pressure and compromise cerebral hemodynamic regulation. We hypothesized that robot-assisted radical prostatectomy with head-down tilt causes impairment of cerebral autoregulation compared with open retropubic radical prostatectomy in the supine position.Patients scheduled for elective radical prostatectomy were included at a tertiary care prostate cancer clinic. Continuous monitoring of the cerebral autoregulation was performed using the correlation method. Based on measurements of cerebral oxygenation with near-infrared spectroscopy and invasive mean arterial blood pressure (MAP), a moving correlation coefficient was calculated to obtain the cerebral oxygenation index as an indicator of cerebral autoregulation. Cerebral autoregulation was measured continuously from induction until recovery from anesthesia.There was no significant difference in cerebral autoregulation between robot-assisted and open retropubic radical prostatectomy during induction (p = 0.089), intraoperatively (p = 0.162), and during recovery from anesthesia (p = 0.620). Age  and a higher difference between baseline MAP and intraoperative MAP  were associated with impaired cerebral autoregulation, whereas surgical technique was not .Compared with open radical prostatectomy in the supine position, robot-assisted surgery in the extreme Trendelenburg position with capnoperitoneum did not lead to an impairment of cerebral autoregulation during the perioperative period in our study population.Trial registration number: DRKS00010014, date of registration: 21.03.2016, retrospectively registered.The online version of this article (10.1007/s10877-020-00549-0) contains supplementary material, which is available to authorized users. Radical prostatectomy is one curative treatment option for localized prostate cancer in patients with a life expectancy greater than 10 years . CompareTo allow for visual inspection of the surgical field, RARP requires peritoneal insufflation of carbon dioxide and the extreme Trendelenburg position with a 45-degree head-down tilt . In contCerebral blood flow is tightly regulated to ensure constant cerebral perfusion by autoregulation of the cerebral circulation . VasoactThis study was approved by the local Ethics Committee at Hamburg Medical Chamber (PV4782). All patients gave written informed consent before study participation. The study was performed in accordance with the 1964 Declaration of Helsinki and its later amendments. This prospective observational study was performed at a tertiary care prostate cancer clinic between June 2015 and March 2016. The choice for open versus robot-assisted surgery was based on surgical  and oncological considerations, including Gleason score and T stage, patient-related risk factors, such as stenotic valvular disease or obesity, and patient preference.Patients were chosen by convenience and were included if they were scheduled for elective radical prostatectomy for prostate cancer and were fluent in German in order to understand the informed consent form. We did not include patients with a history of cerebrovascular or neurodegenerative disease or any other intracranial pathology. The Mini-Mental Status Examination was used to identify patients with mild cognitive impairment . PatientBefore anesthesia induction, three blood pressure values were obtained by repeated oscillometric measurement in three-minute intervals with the patient in the supine position. The baseline blood pressure was calculated as the mean of these three initial measurements.Invasive blood pressure monitoring was performed in all patients from the beginning of anesthesia induction and was continued for one hour after arrival in the post-anesthesia care unit (PACU) or until the patient was considered hemodynamically and respiratory stable for transfer to the normal ward. Under aseptic conditions, a 20G arterial cannula  was inserted in the left radial artery after local anesthesia with plain lidocaine 1%. If placement of the cannula was not feasible in the left radial artery, the right radial artery was chosen for invasive blood pressure measurement. The arterial cannula was connected to tubing filled with saline that transmits a pressure wave to a transducer and a flushing system consisting of 500 ml saline pressurized to 300 mmHg. The transducer was placed at the level of the right atrium.Cerebral autoregulation was measured continuously using the time correlation method, which has been described in detail previously . This apGeneral anesthesia was induced using sufentanil 0.3–0.7 µg/kg, propofol 2–3 mg/kg and rocuronium 0.5–0.6 mg/kg. Anesthesia was maintained using sevoflurane at MAC 0.8–1.2 in combination with sufentanil 0.1–0.2 µg/kg. Anesthesia depth was monitored with the bispectral index.2) was continuously monitored and maintained between 32 and 42 mmHg.Muscle relaxation was performed intermittently with rocuronium 0.15 mg/kg when the anesthesiologist deemed it necessary. Intraoperative hypotension (MAP < 65 mmHg or a decrease in MAP > 20% of baseline for more than 5 min) was managed with a bolus application of norepinephrine 5–10 µg followed by an incremental administration of continuous norepinephrine infusion. End-tidal carbon dioxide  from bolus administration of sufentanil for anesthesia induction until the patient was transferred from the anesthesia induction room to the operating theater (induction), (2) from incision to closure (intraoperative), (3) from incision until the start of capnoperitoneum , (4) 20 min from the start of capnoperitoneum , (5) during the Trendelenburg position (RARP patients only), (6) 10 min following bolus application of norepinephrine, (7) during the first 60 min of PACU stay and (8) throughout the entire monitoring period . Variability of MAP and COx were calculated as the variance of all MAP/COx values throughout the measurement period. Impaired cerebral autoregulation was defined as a COx > 0.3. The percentage of the entire monitoring period with the COx > 0.3 was calculated for each patient and defined as primary endpoint.Data are presented as median (interquartile range) or n (%) unless stated otherwise. Continuous variables were compared between groups with the Mann–Whitney U test. For categorical variables, the Chi-square test or the Fisher’s exact test was used as appropriate. Mean COx levels during different perioperative episodes  were compared with the Wilcoxon signed-rank test and Bonferroni corrected for multiple comparisons.To determine the influence of surgical technique on cerebral autoregulation, an analysis of covariance was performed with the time with COx > 0.3 in % as the dependent variable. Augmented stepwise backward elimination was used to identify factors associated with impaired autoregulation. Surgical technique and clinically relevant parameters that did not fulfill the criteria for collinearity were included as fixed factors  or covariates . Subsequently, variables that were significant on a 0.2 level were eliminated to create a preliminary model. Using a stepwise approach eliminated variables were included in the preliminary model and checked for a change in parameter estimate  of > 10%.All data were analyzed with SPSS 22 . Figures were designed with GraphPad Prism 8.2 .A total of 189 patients were enrolled. Data on cerebral autoregulation were available from 183 patients. Of these, 102 (55.7%) patients underwent RARP in the steep Trendelenburg position, and 81 (44.3%) patients had ORP in the supine position. The flow of study participants is presented in Fig. Estimated blood loss, requirement of fluid resuscitation, and vasopressor support were significantly higher during ORP Table . PatientThe mean MAP during anesthesia induction did not differ significantly between groups. Mean MAP values from incision to closure, during the PACU stay, and throughout the monitoring period were significantly lower in ORP patients compared with RARP patients. Changes from baseline MAP to intraoperative MAP and from baseline MAP to PACU MAP differed significantly between surgical groups. For details on blood pressure levels, see Table baseline—intraoperative were associated with reduced cerebral autoregulatory function  and time with impaired autoregulation in the multivariable model Table . Age andon Table .Table 3M2 and during the head-down position  and ΔMAPbaseline – intraoperative  differed significantly between patients with and without arterial hypertension.About one-half of the study population  had a history of arterial hypertension. We compared COx levels during anesthesia induction, from incision to closure, during the PACU stay, and after bolus administration of norepinephrine between patients with and without arterial hypertension. In the RARP group, COx levels before capnoperitoneum, 20 min after the beginning of capnoperitoneum and in the head-down position were compared between patients with and without arterial hypertension. There was no significant difference in COx levels during any of these episodes (Online Resource 3a). Eighty-eight patients (54.0%) for whom baseline MAP values were available suffered from arterial hypertension. In these patients, baseline MAP was significantly higher (109 mmHg [IQR 101–116]) than in patients without arterial hypertension . Accordingly, ΔMAPWhen analyzing COx in hypertensive patients only, we did not find a significant difference between RARP and ORP during any perioperative episode (Online Resource 3b).The aim of this prospective observational study was to compare continuous analyses of cerebrovascular autoregulation between RARP in the Trendelenburg position and ORP in the supine position. (1) We found that cerebral autoregulation did not differ between robot-assisted and open surgery during the perioperative period. (2) Increasing age and a high difference between pre-induction and intraoperative MAP were associated with impaired cerebral autoregulation. (3) Compared with anesthesia induction and recovery from anesthesia, intraoperative cerebral autoregulatory function was reduced in both surgical groups independently from positioning.Concern about the steep Trendelenburg position with capnoperitoneum is in part attributable to case reports of postoperative visual loss because of ischemic optic neuropathy , 21, 32.Elevated intracranial pressure during Trendelenburg position may compromise cerebral perfusion and the regulation of cerebral blood flow . InteresUnder physiological conditions, adequate cerebral blood flow is preserved independently from systemic blood pressure, if cerebral perfusion pressure is between 50 and 150 mmHg, referred to as the lower and upper limits of cerebral autoregulation . If systIn the present study, arterial hypertension was not associated with prolonged perioperative impairment of the cerebral autoregulation. However, patients with a history of arterial hypertension had more elevated pre-induction blood pressure levels, and the difference between pre-induction MAP and intraoperative MAP was significantly associated with the duration of impaired autoregulation.2, Oudegeest-Sander and colleagues showed that cerebral autoregulation and reactivity to CO2 were preserved in healthy elderly individuals [We found increasing age to be associated with impaired cerebral autoregulation during the perioperative period in patients undergoing radical prostatectomy. This effect was present regardless of surgical technique. There are conflicting results regarding age-dependent alterations in cerebrovascular autoregulation. Inducing changes of MAP and arterial COividuals . Interesividuals . Conversividuals . Intraocividuals . CompareIn addition to patient-related factors such as age and hypertension, extrinsic factors may affect cerebral autoregulation. Anesthetics may have an impact on the cerebrovascular tone, alter autoregulatory limits and narrow the autoregulatory plateau . Lower lWe found decreased cerebral autoregulation during the intraoperative period, compared with anesthesia induction. The transient decrease of cerebral autoregulation intraoperatively was observed in both RARP and ORP patients, suggesting that factors other than positioning may have contributed to the impairment of cerebral autoregulation. General anesthesia was maintained with sevoflurane in both surgical groups. Sevoflurane has a dose-dependent cerebral vasodilatory effect . CerebraThis study has several strengths and limitations that should be addressed. Different blood pressure measurement techniques were used throughout the perioperative period. Baseline blood pressure before anesthesia induction was measured non-invasively with the oscillometric method, whereas invasive blood pressure monitoring was used from induction to recovery from anesthesia. However, both methods for blood pressure measurement were consistently applied in both groups.We defined baseline blood pressure based on pre-induction measurements, which may be influenced by anxiety and may not be representative of ambulatory blood pressure in the resting sedentary position.2 is a potent regulator of the cerebral vascular tone [2 values as a surrogate for arterial partial pressure of CO2. Provided that ventilation and perfusion are stable, arterial partial pressure of CO2 and end-tidal CO2 are highly correlated in mechanically ventilated patients [2 has been shown during RARP in the Trendelenburg position [2 values between 32 and 42 mmHg a potential effect of mild to moderate hypercapnia on the cerebral vasculature has to be taken into account.Arterial COlar tone . We did patients . Moreoveposition . By acceIn order to rule out impaired cerebral autoregulation because of cerebrovascular disease, we did not include patients with a history of stroke, transient ischemic attack, or carotid and/or vertebral artery disease. These strict exclusion criteria limit the generalizability of our results, since patterns of cerebral autoregulation in patients with preexisting cerebrovascular disease may react differently to head-down positioning, capnoperitoneum, and anesthesia.One strength of this trial is the continuous monitoring of cerebrovascular autoregulation during different episodes throughout the perioperative period, including anesthesia induction, posture changes, and recovery from anesthesia. Rather than assessing patients only in the steep Trendelenburg position, we performed additional monitoring during open surgery in the supine position and compared a homogenous patient population exposed to two surgical techniques for radical prostatectomy.Based on these observational data an estimate of the cerebral autoregulation is unaffected by the position in patients undergoing radical prostatectomy. Our findings suggest that particularly older patients with comorbid conditions such as arterial hypertension may be at risk of undercutting autoregulation limits during general anesthesia. Patients at risk might require blood pressure targets substantially higher than 65 mmHg to maintain cerebral perfusion pressure above their individual lower autoregulatory limit and to ensure adequate regulation of cerebral blood flow. The time correlation method for the continuous measurement of cerebral autoregulation may support perioperative care of high-risk patients in the future.Supplementary file1 (DOCX 20 kb)Supplementary file2 (DOCX 15 kb)Supplementary file3 (DOCX 16 kb)Supplementary file4 (DOCX 15 kb)Below is the link to the electronic supplementary material.