The aim of this study was to determine changes in exercise variables in PAH patients and to relate these changes to survival.Exercise variables determined in patients with pulmonary arterial hypertension (PAH) at the time of diagnosis, predict survival. It is unknown whether upon treatment, subsequent Baseline cardiopulmonary exercise test (CPET) variables and six-minute-walk-distance (6MWD) were available from 65 idiopathic PAH patients . The same variables were determined after treatment (13months) in a sub group of 43 patients. To estimate the association between changes in exercise variables and changes in cardiac function, right-ventricle ejection fraction (RVEF) was measured by cardiac MRI at baseline and after treatment in 34 patients. Mean follow-up time after the second CPET was 53 (range: 4-111) months. Kaplan-Meier analysis was used to relate survival to baseline and treatment-associated changes in exercise variables.p<0.0001), maximal heart rate (p<0.0001) and the slope relating ventilation with carbon dioxide production (p≤0.05) were significant predictors of survival, whereas baseline oxygen uptake and oxygen pulse held no predictive value. Treatment associated changes in 6MWD (p<0.01), maximal heart rate (p<0.05), oxygen uptake (p<0.001) and oxygen pulse predicted survival (p<0.05), whereas changes in the slope relating ventilation with carbon dioxide production did not.Survivors showed a significantly greater change in maximal oxygen uptake than non-survivors and this change in aerobic capacity was significantly related to changes in RVEF. From baseline until the end of the study period, two patients underwent a lung transplantation and 19 patients died. Survival analysis showed that baseline 6MWD (Exercise variables with prognostic significance when determined at baseline, retain their prognostic relevance after treatment. However, when changes in exercise variables upon treatment are considered, a different set of variables provides prognostic information. For thaate (HR) –6.It was recently reported that in PAH, important prognostic information is provided by treatment induced changes in several established predictors of outcome . That chThe study protocol was approved by the VU University Medical Centre Institutional Review Board and informed consent was waived due to the retrospective nature of this study.All idiopathic and heritable PAH patients referred to the VU University Medical Centre in Amsterdam between December 2000 till December 2012 who underwent CPET and six minute walk test were included in this retrospective analysis.At the time of diagnosis, hemodynamic variables were measured in all patients by a diagnostic right heart catheterization including right arterial pressure, mean pulmonary arterial pressure, pulmonary vascular resistance, wedge pressure and cardiac output.Pulmonary hypertension was diagnosed by a mean pulmonary arterial pressure > 25 mmHg and a mean pulmonary capillary wedge pressure <15 mmHg measured at rest. Idiopathic PAH was diagnosed when all other causes of pulmonary hypertension were excluded. Heritable PAH was diagnosed in patients with a known family history of PAH.Patients were treated by a standardized treatment strategy, as reported before , and vis-1) to maximum tolerance. The mean exercise test duration was 10 minutes  in all patients.CPET was performed on an electromagnetically braked cycle ergometer  according to international guidelines . Brieflymax. 229, CareFusion, Yorba Linda, USA) and analyzed as 20 seconds averages. O2pulse was calculated as VO2/HR. VE/VCO2 was derived from the first linear part of the curve, from unloaded work till the anaerobic threshold [2) was determined by pulse-oximetry . No patients were using supplemental oxygen during CPET. Heart rate (HR) was measured by electro-cardiography . Exercise induced shunt was scored using the criteria as described by Sun et al. [All ventilatory variables, calculated from breath by breath measured flow and inspiratory and expiratory gas fractions at the mouth were calculated by a commercial available metabolic computer  or on a Siemens 1.5T Avanto scanner  equipped with a 6-element phased-array receiver coil. Briefly, stroke volume (SV) was calculated as end-diastolic volume (EDV) minus end-systolic volume and RVEF was calculated as (SV/EDV) * 100% .2, HR, O2pulse, SaO2 and VE/VCO2. Absolute exercise variables at baseline and their subsequent changes after the start of treatment were related to survival, which was 63±5 months in the whole group and 53±5 months in the subgroup with available follow-up data. Statistical analysis was performed with the SPSS-15package . All data were expressed as mean values ± standard error of the mean. The unpaired student’s t test was used to check for differences between survivors and non-survivors.Exercise variables included in baseline and change to treatment analyses were 6MWD, maximal VO2 and VEVCO2slope), pulmonary vascular resistance  and RVEF (determined by MRI). Multivariate Cox regression  analysis was used to identify the independent predictors of survival.Pearson correlations were calculated to check for linear associations between relevant exercise variables  were considered significant.Receiver operating characteristics (ROC) were determined to identify optimal cut-off points for predicting survival based on the highest sum of sensitivity and specificity values. Areas under the ROC curve are presented with a 95% confidence interval (CI). Based on these optimal cut-off points, univariate Kaplan-Meier survival curves were calculated. In all analyses, Of the initial group of 65 patients, 19 died and two underwent a lung transplantation (<111 months). Both patients receiving the lung transplant and ten of the deceased patients were included in the subgroup analysis with exercise data after treatment (n=43) . For sur2max and VEVCO2slope correlated significantly with PVR and RVEF. Baseline 6MWD was not associated with PVR or RVEF. Non-survivors were randomly represented in the correlation figures .The cumulative proportion of survival was 94 ± 3% at 1 yr, 86± 5% at 2 yr, 75 ± 6% at 3 yr, 71 ± 7% at 5 yr, 58 ± 8% at 7 yr and 51 ± 10% at 9 yr. ROC analysis of initial exercise variables identified no significant areas under the curve . Baselinanalysis .. MaximaThe cumulative proportion of survival of the subgroup of patients with two complete sets of exercise tests was 90 ± 5% at 1 yr, 84± 6% at 2 yr, 77 ± 7% at 3 yr, 73 ± 8% at 4 yr and 69 ± 8% at 5 yr.2 and the change in maximal O2pulse showed significant areas under the curve by ROC analysis . Only the change in 6MWD, maximal VOanalysis .. Changeanalysis .. The chNone of the patients with an exercise induced shunt died during the follow-up period.2pulse showed no significant prognostic relevance for survival after treatment , patients likely improved their stroke volume. An improved stroke volume has been shown to predict survival after PAH specific therapy [Because changes in maximal HR were similar in survivors and non-survivors, the increased VO therapy ,27.2 on treatment were not significantly different between subsequent survivors and non-survivors, so that after treatment differences in ventilatory efficiency remain prognostic relevant (2) and do not affect dead space ventilation and/or peripheral chemoreceptor activation. A persistent inefficient ventilation was also shown in patients with left heart failure after heart transplantation [Despite differences in ventilatory efficiency at the time of diagnosis, changes in VE/VCOrelevant . This isantation . In addiantation .A limitation of this study is the relatively small number of patients with available complete sets of exercise - and MRI data at baseline and after treatment. However, it can be judged from the data  and S2 tIn conclusion, after PAH specific therapy, a change in aerobic capacity reflects an altered cardiac function and has important prognostic relevance. All exercise variables which have prognostic significance when determined at baseline, retain their prognostic relevance after treatment. However, when changes in exercise variables upon treatment are considered, a different set of variables provides prognostic information.Table S1Baseline demographic, hemodynamic and exercise characteristics of cohort with exercise data after treatment.PAP: pulmonary arterial pressure, CO: cardiac output, PVR: pulmonary vascular resistance, RAP: right arterial pressure, SVO2: venous oxygen saturation, 6 MWD: six minute walk distance, VO2:maximal oxygen uptake, HR; maximal heart rate, SaO2: oxygen saturation measured by pulse oximetry, ve/VCO2; linear regression slope of ventilation to carbon dioxide production.(PDF)Click here for additional data file.Table S2Baseline demographic, hemodynamic and exercise characteristics of MRI cohort. PAP: pulmonary arterial pressure, CO: cardiac output, PVR: pulmonary vascular resistance, RAP: right arterial pressure, SVO2: venous oxygen saturation, 6 MWD: six minute walk distance, VO2: maximal oxygen uptake, HR; maximal heart rate, SaO2: oxygen saturation measured by pulse oximetry, VE/VCO2; linear regression slope of ventilation to carbon dioxide production.(PDF)Click here for additional data file.


The role of hypertension in the loss of cognitive function is controversial. Relationships between hypertension and increases in cerebral vascular resistance, diffused lesions and multiple lacunar infarcts of the white matter are well known. Thus, the objectives of this study were: to evaluate the relationship between hypertension and cognitive dysfunction (CD), identify risk factors and determine the association between early markers of vascular disease and CD in hypertensive individuals.Two hundred individuals aged between 40 and 80 years old were evaluated in this cross-sectional prospective study. Fifty participants were controls (CT). The remaining 150 hypertensive patients were subdivided into two groups, those with CD (HCD) and those without CD (HNCD). All participants underwent clinical evaluations and biochemical blood tests were performed. CD was investigated using the Mini Mental State Examination (MMSE) following the guidelines for its use in Brazil. The impact of hypertension on the arterial bed was assessed by identifying and measuring changes in the intima-media thickness (IMT) by vascular ultrasonography of the carotid arteries and analyses of the central blood pressure and Augmentation Index by applanation tonometry of the radial artery.There were no significant differences in the total cholesterol, high-density lipoprotein cholesterol and triglycerides plasma concentrations between the three groups. The serum creatinine and estimated glomerular filtration rate were within normal ranges for all three groups. A significantly lower MMSE score was recorded for the HCD Group compared to the HNCD and CT Groups .The IMT was significantly different between the HNCD and HCD Groups . A significant difference in the IMT was also observed between hypertensive patients and the CT Group . Age, low-density cholesterol, high-density cholesterol, triglycerides and IMT increased the Odds Ratio for cognitive dysfunction.The central systolic pressure was significantly higher in the HCD and HNCD Groups compared to CT Group .Hypertensive patients with CD have changes in the vascular morphology characterized by an increased carotid IMT, enhanced atherosclerotic lipid profile and impaired hemodynamic functional manifested by elevated central systolic blood pressure. Hypertension is a major risk factor for cardiovascular disease including strokes , coronary heart disease  -3, left Cognitive deficiency (CD) is considered a form of dementia and defined as a “persistent or permanent decline in varying dimensions of intellectual function in a way that it interferes with the individual’s normal social or economic activities. Currently, the Diagnostic and Statistical Manual of Mental Disorders defines dementia as an ‘organic brain syndrome’ ; this is mainly to differentiate it from other cognitive function disorders such as mental retardation and reversible episodes of amnesia or other changes in focal elements of cognitive components such as language disorders,18.The role of hypertension in determining the loss of cognitive function is not well defined ,20. It iThe effect of antihypertensive treatment on the cognitive function in older adults is also controversial. Some studies suggest that treatment improves cognitive function while others found no effect or even the opposite effect -34. In gThus, the objectives of this study were to evaluate the relationship between hypertension and CD, to identify risk factors associated to the development of CD , dyslipidemia, diabetes and chronic kidney disease) and to determine associations between different early markers of vascular disease  and CD in hypertensive individuals on regular antihypertensive treatment.The sample population of this prospective study consisted of two hundred consecutive male and female individuals aged between 40 and 80 years old selected in the specialized hypertension center of the Medicine School in São José do Rio Preto (FAMERP). All participants were submitted to ultrasound assessment and the Mini Mental State Examination between February 2009 and October 2011. Of these, one hundred and fifty were stage II hypertensive patients according to JNC VII ; Forty-tThe Control Group (CT), made up of non-hypertensive, non-cognitive dysfunction individuals, was selected from subjects referred to investigate stage I primary hypertension but whose blood pressures proved to be normal after standard measurements in the physical examination and whose biochemical blood tests were normal.This study was approved by the Research Ethics Committee of the Post Graduation Program in Health Sciences of the Medicine School in São José do Rio Preto (FAMERP). Informed written consent was obtained from all participants before their enrollment in the study. The sample size was estimated based on an 80% statistical power to demonstrate the objectives of the study with a type I alpha error rate of 5%.The inclusion criteria of the hypertensive patients were: age between 40 and 80 years under treatment for stage II hypertension - VII JNC, optimal response to pharmacological treatment (BP < 140/90 mmHg) with no acute medical illness in the previous month and the ability to understand, verbalize and answer questions related to the study. The exclusion criteria were the presence of atherosclerotic plaque defined as a focal structure that encroaches into the arterial lumen by at least 0.5 mm or 50% of the surrounding IMT or demonstrates a thickness > 1.5 mm as measured from the media-adventitia interface to the intima-lumen interface.Participants were submitted to clinical evaluations, physical examinations and investigations of their family history for cardiovascular disease. Blood pressure of the right arm was measured during the morning by a trained healthcare professional with the patient in the seated position and using an appropriately sized cuff.The age, gender, weight, height, and the results of an electrocardiogram and biochemical blood tests were recorded. Patients with secondary hypertension, those taking anticholinesterase drugs, those that had suffered strokes, had diagnosis of dementia or had recently had an acute infection were excluded in order to rule out the possibility of acute confusional state. Additionally, patients with family history of Alzheimer’s disease (parents and siblings), or history of psychiatric illness or substance abuse were excluded.The Mini-Mental State Examination (MMSE) is a test that uses two specific types of responses, verbal and nonverbal, to identify cases of CD. Diagnosis of dementia or any specific dementing illness is not an objective of this test. Responses to questions are studied through verbal sub-tests that measure time-space orientation, immediate memory, attention and calculation, and recall and language and nonverbal subtests that assess perceptual-motor coordination and comprehension of instructions. The test quantifies responses through simple, easy to use criteria that are compatible with the application. Administration of the test takes about 5 to 10 minutes by duly trained professionals. The test is dependent on the level of education of the interviewee. The MMSE results in a maximum score of 30 points where the lower the score, the greater the CD with 24 points originally being considered as the cutoff point -46.The starting point to evaluate hypertension is the accuracy of the BP measurement. The average of three measurements of the systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded. Measurements were made by the indirect technique using OMRON equipment and employing cuffs with appropriate dimensions for the perimeter of the arm (a width-length ratio of 1:2). The readings were taken after the patient had remained resting in the seated position with the arm on a support at the same height as the apex in a quiet environment for 5 to 15 minutes, at least 60 minutes after the ingestion of coffee and 30 minutes after smoking. BP analyses were performed at least three times with an interval of five minutes between readings and the mean of measurements was calculated.The carotid intima-media thickness (IMT), the mean thickness of the anterior and posterior walls of the left and right carotid arteries, was evaluated using high resolution ultrasound. Patients were always examined between 7:00 a.m. and 11:00 a.m. in the supine position with the head at a 45° angle on a support.th Report of the Bethesda Conference Task Force #3 Noninvasive Atherosclerosis Measurement” [This method is established and standardized according to the “34urement”  using a urement” .The ultrasound analysis was performed by a physician experienced in vascular studies and certified by the Cardiovascular Imaging Department of the Brazilian Society of Cardiology and blinded to the patient's clinical data. The examination was carried out according to a previously established protocol  standardThe IMT data were analyzed offline by two independent observers by computer program analysis  which allows measurement of the IMT from images obtained during four cardiac cycles identified by the R wave of the ECG. The analysis, based on the tone of the gray scale and a specific algorithm to recognize tissue, is automatic. The average measurements of the near and far walls of the left and the right common carotid arteries were used to compare the results between the three study groups. The variability between IMT measurements should be less than 2%, as in this study.Central (aortic and carotid) blood pressures are more strongly related to the pathogenesis of cardiovascular disease than peripheral pressures . It is tBecause of pulse pressure amplification between central and peripheral arteries, it is inaccurate to use the brachial pulse pressure as a surrogate for carotid or aortic pulse pressure, particularly in young subjects. The carotid femoral Pulse Wave Velocity (PWV) is considered the “gold standard” measurement of arterial stiffness. Pulse-wave analysis should be obtained at the central level, i.e. at the site of the carotid artery or the ascending aorta, and either directly recorded or computed from the radial artery waveform using a transfer function. The pulse waveform should be analyzed by three major parameters: central pulse pressure, central systolic blood pressure and augmentation index .Arterial stiffness is one of the determinants of increased pulse pressure (PP) and central BP, which are considered predictors of cardiovascular risk.Tonometry of the radial artery provides an accurate, reproducible, noninvasive assessment of the central PP waveform. Radial artery applanation tonometry (AT) is performed by placing a hand-held tonometer (strain gauge pressure sensor) over the radial artery and applying mild pressure to partially flatten the artery. The radial artery pressure is then transmitted from the vessel to the sensor (strain gauge) and is recorded digitally. A mathematical formula using a fast Fourier transformation algorithm, approved by the Food and Drug Administration of the USA, permits derivation and calculation of central systolic blood pressure indices from a peripheral brachial blood pressure with concomitant recording of a PP wave with radial AT. This provides information on the functional condition of arteries by the Augmentation Index, which calculates the ratio of the reflected wave and the ejection wave . The preThe examination to evaluate the AT was made with the patient in a quiet environment, after resting for at least 5 minutes, sitting with the legs uncrossed and the bladder empty, away from acute stressors, without having drunk alcoholic beverages and without having smoked for at least 30 minutes. The OMROM AT equipment with a radial ultrasound transducer was employed with cuffs of suitable dimensions and correct proportion for the arm circumference.Descriptive statistics were performed to describe the sample in relation to demographic and clinical characteristics. Means, standard deviation and 95% confidence interval were calculated for all variables. Antihypertensive drugs by class  were entered as binary values.t-test and Mann–Whitney test were used to compare aspects of hypertensive patients with or without changes in cognitive function and control individuals. The chi-square test and proportions were adopted for qualitative variables.For the analysis of quantitative parameters, the Analysis of variance (ANOVA) was used to compare the mean of the carotid intima thickness, central SBP and Augmentation Index between the three groups.Logistic regression, with the STATA 12.1 statistics program , was used to determine if independent variables can predict the outcome, in this case CD (the dependent variable). The independent variables were the clinical and demographic variables including, age, gender, BMI, blood sugar levels, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, creatinine, estimated glomerular filtration rate, microalbuminuria, 24-hour urinary sodium excretion, systolic blood pressure, diastolic blood pressure, pulse pressure, mean blood pressure, augmentation index (Ai75), central systolic blood pressure (CSBP) and carotid IMT. Statistical significance was set for a p-value < 0.05.There were statistically significant differences between the groups in respect to age  and BMI . No significant differences were found between the two hypertensive subgroups in relation to the duration of hypertension  and in relation to the use of different anti-hypertensive drug classes . There was no statistically significant difference for DBP and heart rate (HR) comparing the three groups Table .The biochemical values of the three groups are described in Table The results of the MMSE for the three groups  expressed as means ± standard deviation are summarized in Table The logistic regression analysis of risk factors for predictive effect on CD in hypertensive patients  showed that only age HDL cholesterol, LDL cholesterol, triglycerides and increased IMT were associated with increased odds ratios (OR) in hypertensive patients with declines in MMSE scores  are shown in Figure Table There were no statistically significant differences in respect to the Augmentation Index (corrected for HR) between the three groups .The main results of this study show: 1) morphological changes characterized by an increased carotid IMT and functional changes qualified as an increase in central SBP in hypertensive patients with CD; 2) Among the risk factors for the development of CD, the age, HDL cholesterol, LDL cholesterol, triglycerides and increased IMT were significantly associated with a drop in MMSE scores in hypertensive patients.Several factors have been associated with loss of cognitive function in older adults. According to many studies the educational level is considered to be one of the most important determinants ,59,60 wiIn this study, the atherosclerotic profile, confirmed by increases in LDL cholesterol, triglycerides and subclinical atherosclerosis characterized by increased carotid IMT were associated with higher ORs for cognitive dysfunction in hypertensive patients independently of the pharmacological antihypertensive treatment and the other risk factors for cardiovascular disease.Elevation of LDL cholesterol levels increase the risk of cognitive dysfunction by 17% in hypertensive patients in agreement with a few previous reports that showed negative effects of the atherosclerotic lipid profile on the cognitive function in adults ,75.On the other hand, epidemiological studies in Rotterdam, Netherlands, demonstrated a significant association between various cardiovascular risk factors including hypertension , cerebraScuteri et al. demonstrated the role of vascular health in determining cognitive function in older individuals using multiple regression models and showed that arterial stiffness was a strong predictor of loss of cognitive function independent of age, gender, education and traditional cardiovascular risk factors .Similarly, vascular remodeling detected by estimating the carotid IMT has been linked to increased risk of cardiovascular, coronary and brain events; this represents an important step in carotid plaque formation and progression and is a characteristic marker of atherosclerosis. -85. Of tWith clinical observation, there is a non-consensual understanding that the different forms of hypertension and the results of complications in target organs, related to stiffening of the vascular wall and atherosclerotic plaque formation among other things, are associated to micro- and macro-infarcts of the white substance and is an important causal agent of CD ,76,88,89There are also few publications in the literature regarding functional hemodynamic changes in hypertensive patients with CD. Our study shows that hypertensive patients, both with and without CD, have significantly higher CSBP compared to the CT group. However, there was no statistically significant difference in the CSBPs of hypertensive patients with and without CD.There were no statistically significant differences for the Augmentation Index corrected for HR between the three groups .Several hypotheses may explain the absence of significant differences between hypertensive patients with and without CD. Antihypertensive therapy using renin-angiotensin-aldosterone blockers and calcium channel blockers interferes in the hemodynamics of arterial, central and peripheral BP thus favoring a reduction in the height of the central pressure wave, thereby reducing the Augmentation Index and the central SBP. However, this does not invalidate the important structural finding represented by the main alteration found in the hypertensive group with CD; vascular remodeling characterized by increased carotid IMT.Potentially confounding effects of antihypertensive therapy on vascular structural and hemodynamic changes may influence cognitive function. In this study the antihypertensive medication did not influence the results .This study has some limitations: the results are based on a cross-sectional study and so a longitudinal approach is needed to confirm the influence of age on results. Additionally we cannot exclude the influence of genetic factors on the pathophysiology of CD in hypertensive patients. However, new opportunities for structural and functional hemodynamic evaluations are presented for prospective studies on hypertensive patients who have risk factors for CD which may reinforce the importance of achieving the goal in the treatment of hypercholesterolemia in high-risk patients to prevent CD.Hypertensive patients with CD have vascular morphological changes characterized by increased carotid IMT, enhanced atherosclerotic lipid profile and impaired hemodynamic functional manifested by elevated central systolic blood pressure.The authors declare that they have no competing interests.EMD: participated in the study design, clinical assessment of participants, ultrasound examinations, participated in the discussion of the results and helped to write the manuscript. LTG Jr: participated of the clinical assessment of participants, measurement of the central blood pressure and in the discussion of the results.DDM: participated in the collection of clinical data, the blinded measurement of the ultrasound examinations and helped to draft the manuscript. CM: participated in data collection, assessments of peripheral blood pressure and the central blood pressure examination and elaborated the figures. HM Jr: participated of the study design, assessment of the methodology, blinded evaluation of ultrasound examinations and helped with the final discussion. JFVM: participated in the clinical assessment of patients and participated in the discussion of the results. JCYT: participated of the study design, methodological assessment, statistical review, discussion of the results and helped to write the manuscript, corrected the final version in English and submitted the article. All authors read and approved the final manuscript.


Many markers have been proposed for CVD risk assessment in dialysis population. Apelin is a peptide that has roles in cardiovascular functions and volume regulation namely vasodilation, decreased blood pressure (BP), positive inotropic effect and inhibition of antidiuretic hormone release. The aim of this study was to examine relationship of apelin levels with echocardiographic findings and laboratory parameters related with cardiovascular function and bone mineral metabolism among peritoneal dialysis (PD) patients.This is a cross-sectional study in which chronic PD patients aged between 18 and 80 without active cardiac, infectious or malignant diseases and hypervolemia have been included. Apelin-36 levels and echocardiographic findings were recorded as well as clinical and laboratory data.Of the 53 patients, the mean age and female/male ratio was 52.8 ± 15.3 years and 30/23, respectively. Mean apelin level was 1.45 ± 0.37 ng/ml. Gender, drugs , presence of left ventricular hypertrophy, diabetes mellitus, hypertension, hyperlipidemia and significant residual renal function did not affect apelin-36 levels. Apelin-36 was correlated negatively with age and left atrium diameter; and positively with diastolic BP, ejection fraction (EF), total cholesterol, LDL-cholesterol, HDL-cholesterol, parathyroid hormone and alkaline phosphatase (ALP) levels. Diastolic BP, LDL-cholesterol, ALP and EF were found to be the independent determinants of apelin-36 levels with linear regression analysis.Apelinergic system has important roles in volume regulation, cardiovascular functions, lipid metabolism and bone mineral disorders in PD patients. Prospective studies with large population are required. The mortality rate of patients with end stage renal disease (ESRD) is markedly elevated compared with the general population; and the major reason of this finding is cardiovascular disease (CVD) which is responsible for 40-60% of these deaths . Left vePeritoneal dialysis patients are different than HD patients in terms of CVD risk. About one third of PD patients are hypervolemic that is found to be related with increased mortality rate . MoreoveMany markers have been proposed for CVD risk assessment in dialysis population. Apelin is a peptide of which the pathophysiological effects have been elucidated recently. It has been described in 1998 as the selective endogenous ligand of APJ receptor which is a G protein coupled membrane receptor ,8. APJ rApelin is thought to play roles in cardiovascular functions and volume regulation like vasodilation and decreased blood pressure ; vasoconThe knowledge about the role of apelin in pathophysiology of cardiovascular disease is not sufficient enough in uremic patients, especially in PD patients. The aim of this study was to examine relationship of apelin-36 levels with echocardiographic findings and laboratory parameters which may be related with cardiovascular function and bone mineral metabolism among PD patients.Among 69 chronic PD patients followed in our PD unit; those aged between 18 and 80, with dialysis duration more than three months and without active cardiac , infectious or malignant disease and hypervolemia  and those who gave informed consent have been included in the present study. Ethical approval was not gained due to the design of the study that does not necessitate invasive procedures or drug use.Age, gender, body mass index (BMI), systolic, diastolic and mean blood pressures, primary kidney disease, dialysis duration, dialysis modality , Kt/V values, mean daily urine volume, residual glomerular filtration rates, residual and total creatinine clearances and all medications were recorded. The comorbidities of the patients including hypertension, hyperlipidemia, ischemic heart disease and diabetes mellitus were recorded. Pateints who were dignosed to have hypertension before, and those with blood pressure more than 140/90 mmHg in at least two measurements were regarded to have hypertension. Patients on antidiabetic treatment with previous diagnosis of diabetes mellitus; or those with fasting blood glucose above 126 mg/dl; or blood glucose level above 200 mg/dl at any time or blood glucose level above 200 mg/dl on second hour measurement of oral glucose tolerance test were recorded as diabetic. The diadnosis of hyperlipidemia was put according to the criteria of National Cholesterol Education Program-Adult Treatment Panel (NCEP-ATP) III regarding the age and other risk factors of the patients. Ischemic heart disease was diagnosed in patients with previous medical history , those with typical symptoms of coronary artery disease , patients with typical findings on electrocardiography, echocardiography, stress tests or coronary angiography.Blood samples for hematological and biochemical measurements were obtained after 12-hour fasting with their abdomen left empty the night before. Serum glucose, urea, creatinine, uric acid, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglyceride, sodium, calcium, phosphorus, alkaline phosphatase (ALP), total protein, albumin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), parathyroid hormone (PTH), high sensitive C reactive protein (hsCRP), ferritin, hemoglobin and hematocrite levels were measured by appropriate methods.Blood samples of 4 ml were drawn to tubes coated with ethylen diamin tetra acetic acid (EDTA). The samples were centrifuged at 1600 g for 15 minutes, and the plasma samples obtained were kept at -80°C for one month. The samples and the reactives were turned to room temperature prior to study. Plasma apelin-36 levels were studied by competitive enzyme immunoassay method using Phoenix Pharmaceuticals, Inc, Human Apelin-36 Enzyme Immunoassay kit (Range: 0-100 ng/ml). The concentration of the samples were calculated through calibration curves obtained from study of samples and standards with known levels.2 and 134 gr/m2 for females and males, respectively [General Electric VIVID-7 machine was used for echocardiographic examination by the same physician. Diameters of cardiac chambers were measured by M-mode ultrasonography. Ejection fraction (EF) was calculated by modified Simpson method. Left ventricular mass (LVM) was calculated by Devereux formula and left ventricular mass index (LVMI) was found by dividing LVM by BSA. Left ventricular hypertrophy was defined as LVMI above 110 gr/mectively .Statistical analysis was conducted by SPSS  15 for Windows standard version. Numerical values were expressed as mean ± standard deviation (SD). Intergroup comparisons were made by paired Student t-test and Mann Whitney U test when necessary. For nonnumerical parameters, for 2×2 contingency tables chi-square test and Fisher’s exact test when appropriate. Correlation analysis was conducted with Pearson test for parametric variables and Spearman’s rho correlation test for nonparametric variables. Linear regression analysis was performed by enter method with variables found to be related with apelin-36 levels in univariate analysis.Fifty three patients were included in the study. Mean age and female/male ratio was 52.8 ± 15.3 years and 30/23, respectively. Dialysis modality was CAPD in 33 (62.3%), APD in 17 (32.1%) and CCPD in 3 (5.7%) patients. Demographic and clinical data are presented in Table The biochemical and hematological data are presented in Table Echocardiographic findings are presented in Table 2, respectively. Patients with significant residual renal function meaning GFR ≥ 2 ml/min/1.73 m2 (n = 32) had similar apelin-36 levels with those without significant residual renal function . All patients met the criteria for dialysis adequacy with mean total, dialysate and renal Kt/V values of 2.51 ± 0.66, 1.80 ± 0.47 and 0.71 ± 0.71 respectively. The mean total creatinine clearance was 79.1 ± 29.2 ml/min/1.73 m2.Mean urine volume and residual GFR of patients were 820 ± 790 ml and 3.4 ± 3.3 ml/min/1.73 mAmong the demographic parameters, only age was negatively correlated with apelin-36 levels . Apelin-36 was positively correlated with diastolic blood pressure , total cholesterol , LDL-cholesterol , HDL-cholesterol , PTH  and ALP  levels. There was no correlation of apelin-36 with hematological variables, hsCRP, Kt/V, creatinine clearance and residual renal function. Among the echocardiographic parameters; apelin-36 was positively correlated with EF , and negatively with left atrium diameter .Linear regression model was applied with parameters found to be correlated with apelin-36 in univariate analysis besides gender, PD modality and primary kidney disease. Diastolic blood pressure, LDL-cholesterol, ALP and EF were found to be the independent determinants of apelin-36 levels Table . When thIt is very difficult to mention a standard normal level of apelin due to the presence of various forms of apelin  in the circulation. Besides this factor; different kits for measurement and the cross reaction between the types of apelin lead to various levels mentioned in the literature. Foldes et al. reported normal apelin levels as 89.8 ± 5.3 pg/ml . MalyszkThe literature data about apelin levels in patients with ESRD is limited, so there is no cut-off value for it. But studies reported lower values in dialysis patients compared with the general population . Apelin et al.[The increased rate of CVD in uremic population is well known. One of the factors increasing cardiovascular risk in PD population is hypervolemia. In our study we found relationships between apelin-36 levels and diastolic blood pressure, left atrium diameter and EF all of which are related with volume status of the patients. Although patients with evident hypervolemia were excluded from the study; these relations which are present especially in the hypertensive group mark the relationship of apelin-36 with volume status. Positive correlation with EF may be an evidence for its positive inotropic action reported in previous studies ,29,30. Met al. reportedWe did not investigate directly the relationship between apelin-36 and body fluid status. But, when results of our study are considered together with literature data; it may be speculated that hypervolemia that is prevalent in dialysis population causes elevations in apelin levels to maintain compensatory diuresis, increased cardiac contractility and vasodilation. But there is not enough data to accept this theory as a fact.The physiological effects of apelin mentioned before  seem to antagonize deleterious effects of renin-angiotensin-aldosteron system (RAAS) . It is cet al.[Malyszko et al. found apet al.[et al.[The strong correlation of apelin-36 with LDL and HDL-cholesterol is an interesting finding. Although apelin is secreted also from adipose tissue, this is not sufficient to explain the relationship. Malyszko et al. found nel.[et al.,26 foundet al.[Another effect of apelin is diuresis resulting from inhibition of ADH release. Hus-Citharel et al. reportedIt has been shown by studies that there may be a relationship between apelin levels and inflammation . MalyszkApelin has been found as an independent predictor of bone mineral density in post- menopausal women . Other sApelinergic system has important roles in volume regulation, cardiovascular functions, lipid metabolism and bone mineral disorders in PD patients. Prospective studies with large population are required.The authors declared that they have no competing interests.SK: Mainly planned and conducted the study; and wrote the paper. SO: Participated in the design of the study and performed statistical analysis. MG: Participated in the design of the study and preparation of the manuscript. AG: Organized the planning and analysis of the cardiological part of the study; and helped writing the manuscript. FB: Performed the biochemical analysis and helped statistical analysis. SY: Performed the biochemical analysis and helped statistical analysis. ZA: Participated in the design of the study and preparation of the manuscript. SU: Participated in the design of the study and preparation of the manuscript AS: Participated in the design of the study and preparation of the manuscript. HO: Organized the planning and analysis of the cardiological part of the study; and helped writing the manuscript. RK: Conceived of the study, and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2369/15/18/prepub


The excess burden of hypertension among blacks has been a prominent feature of the heath disparities literature, and many scientists presume it to be a stable and inevitable phenomenon. The underlying causes of this disparity can only be disentangled in a setting in which the population does not experience racial stratification of socioeconomic opportunities. While such conditions of racial equality remain uncommon, they may be approximated in Cuba, a country with a persistent policy of social inclusion over the last 5 decades.We report on a 2010–2011 stratified probability sample of those aged 15–74 years from the urban population of Cienfuegos in central Cuba. A total of 1496 adults (880 women and 616 men) were recruited and assessed for blood pressure and anthropometrics according to standardized protocols, as well as medication use, educational attainment and observed skin tone (dichotomized into “black” and “white”). Weighted tabular and regression analyses were conducted to estimate adjusted prevalences of hypertension (> 140/90 mmHg) and adjusted prevalence odds ratios for contrasts between the two skin color groups.Mean pressures were higher for men than for women, but overall did not differ importantly between racial groups. About half of all diagnosed hypertensive men were on medication, a proportion that did not vary by racial group. For women, however, adjusted prevalence was somewhat higher among blacks, and treatment and control rates were also somewhat advantaged for white women.Overall, skin color was unrelated to mean blood pressure or hypertensive status in this population, although among women specifically some racial advantage appears evident in adjusted prevalence and control, and should be investigated further. The overall null result suggests that Cuba may exemplify the social conditions in which racial excess in hypertension, characteristic of much of the western world, is not a necessary reality. Despiteo whites. Environo whites,5. Likewo whites.One line of argument regarding racial/ethnic differentials in hypertension holds that the cumulative effects of social disadvantage  would explain the observed excess risk if it could be measured. EpidemiThe “social-structural” theory, which invokes the net effect of discrimination, can only be tested under counterfactual conditions of social equality between blacks and whites. Unfortunately these conditions cannot be found in North America, the UK, or Brazil, where the vast majority of persons in the African Diaspora live. We previously examined racial hypertension differentials in Cuba, a country with a persistently implemented policy of social inclusion stemming from the 1959 revolution, and we found consistent evidence of a diminished prevalence gap between blacks and whites compared to the US,11. We rth largest in the country[The city of Cienfuegos is located in the south and center of the main island of Cuba; with an adult population of 161,828 inhabitants it is the 10 country. Cienfue country. The CieWith assistance from the Provincial Department of Statistics and Census, a multi-stage, probability sample was selected from urban Cienfuegos to provide 180–200 persons in gender by 10-year age groups. The sampling design aimed to recruit roughly 2200 adults selected with equal probability within each of the defined age-gender groups. For population estimations, the proper weights were computed taking into account the Cienfuegos city resident adult population as most recently estimated in July 2008. The 201Data were collected by self-report on a variety of health-related conditions, and anthropometrics were measured directly. Body mass index was calculated as weight in kilograms divided by height in meters squared. Blood pressure was measured three times at the same sitting using a mercury manometer by trained personnel, and analyses were based on the mean of the last two readings. No terminal digit was assigned more than 25 percent of the values, suggesting an adequate measurement technique. Blood pressure medication use was verified by the physician, who examined the pill bottles. Assignment to the categories of white (n = 1077), black (n = 131), and “mulatto” (i.e. mixed race) (n = 288) was made by trained professional interviewers who had participated in the most recent national census. The black and mixed-race categories were combined in the primary analyses, reflecting the standard North American convention of racial dichotomy. Education was dichotomized at “pre-universitario” and above, roughly equivalent to more than high school in the US.Hypertension was defined as a systolic blood pressure (SBP) of ≥140 mmHg, a diastolic blood pressure (DBP) of ≥90 mmHg, or current treatment with antihypertensive agents. “Control in the population” was defined as the percentage of all hypertensives with a SBP of <140 mmHg and a DBP of <90 mmHg, irrespective of whether they had been previously diagnosed or whether treatment had been recommended. “Control in treated patients” was defined as the number of treated patients achieving the same goal (<140/90 mmHg) divided by the number of patients on treatment.http://www.paho.org/english/sha/epidat.htm). Unconditional logistic regression analyses were used to estimate the ratio of prevalence odds (POR) adjusted for multiple covariates. Weighted prevalences were obtained for estimations of the awareness, treatment and control rates at population level.Descriptive analysis was conducted of means and frequencies by gender and skin-color group taking into account the complex sampling design and using EPIDAT, a freely distributed software package developed by the Service of Epidemiology of the Dirección Xeral de Saúde Pública from the “Consellería de Sanidade”  and the Health Situation Analysis Program (SHA) of the Pan American Health Organization  of the University of the Medical Sciences of Cienfuegos (UCMC). Participants signed informed consent statements when they enrolled, and again prior to each clinic visit.A total of 2193 individuals completed the questionnaire, 1496 of which also participated in the clinical examination (68%). There was no evidence of differential response by measured characteristics of the participants. A total of 880 women were measured, along with 616 men. The combined non-white group (referred to henceforth as “blacks”) comprised 27.9% of the weighted sample, which matches the most recently available census data. Mean pressures were higher for men than for women , the age-adjusted adjusted hypertension prevalence differential was more pronounced (31.0 percent vs. 26.6 percent), and increased with further adjustment. This is a consistent pattern observed in previous surveys as well, and aloThe implications of this finding for Cuba itself are relevant to its overall policy emphasis on primary prevention and public health, as well as health and social equity along numerous dimensions. The pattern observed here contrasts with other Western Hemisphere nations where evidence suggests a more pronounced racial disparity-23. It iThe broader implications for understanding hypertension etiology and the comparison with entrenched racial disparities in the US are less clear. As in all of Latin America, admixture between persons of African and European descent in Cuba has been common since the early days of colonization. AdmixtuFurthermore, it is crucial to recognize that relative to other world populations, US whites are in fact the exception, not US blacks. Thus, compared to many European countries, particularly Eastern Europe, Russia and Finland, blood pressure levels in US blacks are the same or substantially lower. A standThe data presented here of course have important limitations. The sample size in this study is relatively small, and restricted to a single urban center. Racial group was assigned based on observations by interviewers and, particularly in the Spanish Caribbean, is a categorization scheme with ambiguous borders. Nonetheless, in the context of a growing appreciation for the unique social environment created in Cuba for the study of racial disparities, this stmmHg: Millimeters of mercury; US: United States; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; POR: Prevalence odds ratioThe authors declare no financial conflict of interests. Although the conduct of the survey was supported by the Ministry of Public Health of Cuba, authors received no additional financial payments for the analyses reported here, and the Ministry had no role in the analysis or interpretation of the data. JSK reports support from the Canadian Research Chairs Program, which also defrayed the publication charges for the article but which had no influence on the conduct of the study or on the content of the paper.PO, JSK, DAS and RSC drafted the manuscript. PO, MB, AM and LCS designed the study and oversaw the collection of the data. JSK and LCS provided statistical analysis and support. All authors provided critical comments on the manuscript, participated in revisions of the text, and approved the final version of the manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/13/169/prepubAge-adjusted heart disease mortality rate per 100,000 inhabitants in Cuba and its provinces, 2011.Click here for filePopulation pyramid from Cienfuegos and Cuba, 2002.Click here for file


The present study aimed to analyze the adverse effects of the therapy using the passive bicycle in the intensive care unit (ICU).This was a longitudinal, experimental, non-randomized controlled trial study. Performed with patients hospitalized in the ICU from Vita Curitiba and Batel Hospitals, and the Institute of Neurology from Curitiba, between 10 March and 30 June 2010. The total sample was 41 patients, with a total of 215 events, of both genders, being 23 men and 18 women, with an average age of 64 years, Glasgow average 11 ± 3 and APACHE II average score was 19 ± 6. Of the total sample, only two patients were evaluated according to the Ramsay scale, with an average of 4 ± 0.7. The passive bicycle activity was performed while the patient was in a bed or chair. The hemodynamic variables  were collected at the beginning (before start of activity), 3 minutes after the start, and at the very end of the activity, and there was no pre-established activity time. The adverse effects accidental extubation; monitoring loss, like electrode, pulse oximetry and non-invasive blood pressure measures; change of balance, as lack of trunk control; fall; probe removal ; peripheral venous/arterial access were observed during the whole therapy time. The passive bicycle activity was performed 113 times in a chair (53%), and 102 times in bed (47%), having an average of 7.8 ± 2.29 minutes.t test (P < 0.05), mean arterial pressure, heart rate and respiratory rate, did not have significant change, without any hemodynamic instability during the activity  and one for skin lesion (0.467%), and there was no statistic significant from the proportion test. The adverse effects fall, probe removal, change of balance and extubation did not occur during the activity application. For the hemodynamic variables, using the Student The results show that using the passive bicycle in the ICU as a physiotherapy feature is secure and has a low risk of adverse effects related to ICU conduct.


To examine a potential association between longitudinal changes in intraocular pressure (IOP), arterial blood pressure and body mass index (BMI) in a population-based setting.The longitudinal population-based Beijing Eye Study included 2355 subjects with an age of 45+ years who were examined in 2006 and in 2011. The participants underwent a detailed ophthalmic examination including tonometry and measurement of arterial blood pressure and BMI.2. In multivariate analysis, the 5-year change in IOP was significantly associated with a higher change in mean blood pressure :0.01,0.03) after adjusting for younger age , shorter body stature , thicker central corneal thickness , deeper anterior chamber depth , and lower intraocular pressure at baseline . If the analysis included only longitudinal parameters, the change in IOP was significantly associated with a higher change in mean arterial blood pressure  and a higher change in body mass index .Data on IOP, arterial blood pressure and BMI measured in 2006 and in 2011 were available for 2257 (95.8%) subjects with a mean age of 59.5±9.7 years. The mean change in IOP was −1.25±2.26 mm Hg, mean change in mean blood pressure −7.4±12.1 mmHg, and mean change in BMI was 0.01±2.04 kg/mIn the 5-year follow-up of our population-based sample, a change in IOP was associated with a corresponding change in arterial blood pressure and with a corresponding change in body mass index. These longitudinal data support the notion of a physiological relationship between arterial blood pressure, intraocular pressure and body mass index. These findings may be of interest for the discussion of the pathogenesis of glaucomatous optic neuropathy. Previous cross-sectional studies have suggested that intraocular pressure (IOP), arterial blood pressure and cerebrospinal fluid pressure are associated with each other The Medical Ethics Committee of the Beijing Tongren Hospital approved the study protocol and all participants gave informed written consent, according to the Declaration of Helsinki.The Beijing Eye Study is a population-based study in Northern China, which was carried out in the urban district of Haidian in the North of Central Beijing and in the village area of Yufa of the Daxing District south of Beijing In the surveys, the study participants underwent an interview with standardized questions on their family status, level of education, income, quality of life, psychic depression, physical activity, known major systemic diseases such as arterial hypertension and diabetes mellitus and quality of vision. The ophthalmic examination included measurement of presenting visual acuity and uncorrected visual acuity. Refractive error was assessed by automatic refractometry , if uncorreccted visual acuity was lower than 1.0. Best corrected visual acuity was assessed by subjective refractometry. IOP was measured using a non-contact pneumotonometer  by an experienced technician. Three measurements were taken, and the mean of the three measurements was used for further statistical analysis. In the surveys of 2006 and 2011, blood pressure was measured with the participant sitting for at least 5 min. The study participants had refrained from smoking and drinking of coffee, tea, or alcohol for at least 3 h. In addition, any exercise was not performed for the last 30 min prior to the blood pressure measurements. A standardized mercury sphygmomanometer was used, and the cuff size was chosen according to the measured circumference of the upper arm. Body height and weight were recorded. Using optical low-coherence reflectometry , biometry of the right eyes was performed for measurement of the anterior corneal curvature, central corneal thickness, anterior chamber depth, lens thickness and axial length. A slit lamp examination carried out by an ophthalmologist examined the anterior segment of the eyes. The pupil was dilated using tropicamide once or twice, until the pupil diameter was at least 6 mm. Digital photographs of the cornea and lens and retro-illuminated photographs of the lens were taken using the Neitz CT-R camera . Monoscopic photographs of the macula and optic disc were taken using a fundus camera . In all three surveys, the scheme and flow of the different examination steps were similar, so that they were carried out at approximately the same daytime.P-value was ≤0.10 in the univariate analysis. We removed from the multivariate analysis, step-by-step, those parameters that were no longer associated significantly with IOP as dependent parameter, starting with those parameters that showed the least probable association . 95% confidence intervals (CI) were presented. Only one randomly selected eye per subject was taken for statistical analysis.Only those subjects from the surveys from 2006 and 2001 with available data on IOP, arterial blood pressure and body mass index were included into the present study. Statistical analysis was performed using a commercially available statistical software package . In a first step, we determined the mean values  and medians of the main outcome parameters. In a second step, we performed univariate analyses of the associations between the change in IOP and systemic and ocular other parameters. In a third step, we carried out a multivariate regression analysis with change in IOP as dependent parameter and all those variables as independent parameters for which the P<0.001) and more myopic . Both groups did not differ significantly in gender (P = 0.21).Data on IOP, arterial blood pressure and body mass index in 2006 and in 2011 were available for 2257 (95.8% of the 2355 subjects with examinations in 2006 and 2011) with a mean age of 59.5±9.7 years and a mean refractive error of –0.17±2.08 diopters . The sub2 . In absolute terms, the mean change in IOP was 1.96±1.67 mmHg, in systolic blood pressure 13.9±10.7 mmHg, diastolic blood pressure 11.9±8.1 mmHg, mean blood pressure 11.6±8.2 mmHg, and in body mass index 1.47±1.44 kg/m2.The mean change in IOP was −1.25±2.26 mm Hg , mean change in systolic blood pressure was −3.3±17.2 mmHg, diastolic blood pressure −9.4±11.0 mmHg and mean blood pressure −7.4±12.1 mmHg, and the mean change in body mass index was 0.01±2.04 kg/mP<0.001; r = −0.18), female gender (P = 0.004), lower body height , lower systolic  and lower mean  blood pressure, thinner central corneal thickness , deeper anterior chamber depth , lower IOP , higher change in systolic blood pressure , higher change in diastolic blood pressure , higher change in mean blood pressure , and higher change in body mass index . The change in IOP was marginally significantly associated with body weight (P = 0.06). The change in IOP was not significantly associated with the systemic parameters of body mass index (P = 0.59), level of education (P = 0.70), diastolic blood pressure (P = 0.75), and axial length (P = 0.18).In univariate analysis, the change in IOP was significantly associated with the systemic parameters of younger age (P = 0.79), body weight (P = 0.79), mean arterial blood pressure (P = 0.74), gender (P = 0.66), change in systolic blood pressure (P = 0.46), change in diastolic blood pressure (P = 0.46), and systolic blood pressure (P = 0.07), the 5-year change in IOP was eventually significantly associated with younger age (P<0.001), shorter body stature (P = 0.002), thicker central corneal thickness (P<0.001), deeper anterior chamber depth (P = 0.01), lower IOP (P<0.001), and higher change in mean blood pressure (P<0.001)  .P<0.001; standardized regression coefficient Beta: Beta: 0.10; regression coefficient B: 0.02  and a higher change in body mass index .If the analysis included only the parameters on the 5-year change, the change in IOP was significantly associated with a higher change in mean arterial blood pressure (P<0.001) associated with a higher change in mean blood pressure after adjustment for age, body height, central corneal thickness, anterior chamber depth, and IOP. If the analysis included only parameters of the 5-year change, the change in IOP was significantly associated with a higher change in mean arterial blood pressure and a higher change in body mass index. If the body mass index is taken as surrogate for cerebrospinal fluid pressure, these longitudinal data support the notion of a physiological relationship between arterial blood pressure, IOP and cerebrospinal fluid pressure.In our population-based longitudinal study, the 5-year change in IOP was significantly , a lower intraocular pressure (P = 0.004), lower mean blood pressure (P = 0.02), and higher ocular perfusion pressure, after adjustment for optic disc size, presence of open-angle glaucoma, refractive error, age and gender. The findings of the present longitudinal investigation fit with the results of the previous cross-sectional study on the associations between intraocular pressure, body mass index, and arterial blood pressure.The present investigation is a follow-up of previous studies from the Beijing Eye Study in which among others, the topic of a cross-sectional analysis of the association between body mass index and neuroretinal rim area was examined Other previous studies have discussed issues related to body mass index and to glaucoma or glaucoma-related indices P-value of <0.05, the low coefficients showed that only a fraction of the variability in the change in IOP could be explained by that relationship. Strengths of the study were the relatively large study population size and its design as a population-based investigation.Potential limitations of our study should be mentioned. First, a major concern in any population-based study is nonparticipation. The non-participation of eligible subjects may however have a more marked effect in cross-sectional prevalence studies than in longitudinal investigations such as our study. Second, the measurements of IOP and arterial blood pressure in 2006 and 2011 depended on single measurements. IOP and blood pressure were however measured in a standardized manner at the same time of the day since the study design of the Beijing Eye Study 2006 and 2001 did not differ markedly. It may suggest that variations in diurnal factors physiologically influencing IOP and blood pressure and variations in factors such as agitation and previous caffeine intake may not have markedly influenced the measurements. The alternative for single IOP measurements would have been diurnal pressure curve measurements, however that option may not be feasible for a population-based study. Third, the coefficients for the relationships between the change in IOP and the changes in blood pressure and the in body mass index were relatively low. Although these relationships were statistically significant with a In summary, we demonstrated that in the 5-year follow-up of our population-based sample, a change in IOP was strongly associated with a corresponding change in arterial blood pressure and with a corresponding change in body mass index. These longitudinal data support the notion of a physiological relationship between arterial blood pressure, IOP and body mass index. Since body mass index is correlated with cerebrospinal fluid pressure, future studies may address whether changes in cerebrospinal fluid pressure are associated with changes in IOP and arterial blood pressure, supporting the notion that all three pressure-related parameters are correlated with each other. The findings may be of interest for the discussion of the pathogenesis of glaucomatous optic neuropathy.


Cerebral vessels in the premature newborn brain are well supplied with adrenergic nerves, stemming from the superior cervical ganglia (SCG), but their role in regulation of blood flow remains uncertain. To test this function twelve premature or two-week-old lambs were instrumented with laser Doppler flow probes in the parietal cortices to measure changes in blood flow during changes in systemic blood pressure and electrical stimulation of the SCG. In lambs delivered prematurely at ∼129 days gestation cerebral perfusion and driving pressure demonstrated a direct linear relationship throughout the physiologic range, indicating lack of autoregulation. In contrast, in lambs two-weeks of age, surgical removal of one SCG resulted in ipsilateral loss of autoregulation during pronounced hypertension. Electrical stimulation of one SCG elicited unilateral increases in cerebral resistance to blood flow in both pre-term and two-week-old lambs, indicating functioning neural pathways in the instrumented, anesthetized lambs. We conclude cerebral autoregulation is non-functional in preterm lambs following cesarean delivery. Adrenergic control of cerebral vascular resistance becomes effective in newborn lambs within two-weeks after birth but SCG-dependent autoregulation is essential only during pronounced hypertension, well above the normal range of blood pressure. This phenomenon is called cerebral autoregulation and has been demonstrated in adults, newborns, and even in fetal sheep The extra-parenchymal arteries supplied by the Circle of Willis, including the pial arterioles, are richly innervated by sympathetic nerve fibers Preterm infants are particularly susceptible to dysregulation of CBF and suffer from intracerebral hemorrhage n = 6) that were delivered by C-section on gestational day 127 to 132 (term 147) or on two-week-old lambs (n = 6) following natural delivery. Anesthesia was induced in the ewes (for the preterm lamb group) and two-week-old lambs with an intra-jugular injection of thiopental sodium (10 mg/kg), followed by intubation and mechanical ventilation with 2% isoflurane throughout the surgical instrumentation. The umbilical cord of the preterm lamb was kept intact during the surgery with only the head and thorax exteriorized through a midline incision in the maternal abdomen.Animal protocols were pre-approved by the Institutional Animal Care and Use Committee of Loma Linda University. All sheep were mixed Western breed. Experiments were conducted on either preterm lambs  and pancuronium (0.1 mg kg−1 hr−1).Both preterm and two-week-old lambs were instrumented with bilateral laser Doppler flow probes , inserted through 1.5 mm burr holes drilled 5 mm lateral to the sagittal suture and 15 mm posterior to the coronal suture 2O, positive end-expiratory pressure of 5 cm H2O, inspiratory:expiratory ratio time of 1:3, and respiratory rate of 60 bpm, with subsequent adjustments made to target an arterial PO2 of ∼200 Torr and PCO2 of 35 to 45 Torr. The target arterial PO2 was set higher than the physiologic range to overcome ventilation-perfusion mismatch in the lambs and thereby to ensure cerebral autoregulation was not influenced by hypoxia. Trometamol; tris-hydroxymethyl aminomethane  was administered to treat metabolic acidosis as needed. Rectal temperature was maintained at 39±1 °C by use of a radiant warmer .Both preterm and two-week-old lambs were mechanically ventilated  with initial settings at a peak inspiratory pressure of 25 cm HLambs were placed in the supine position and both SCG were exposed via an incision from the angle of the mandible to the transverse process of the second cervical vertebrae. One SCG was randomly chosen for insertion of two platinum wire stimulating electrodes connected to a Grass S-48 model stimulator .Baseline measurements were made after a four-hour recovery period following placement of the LDF probes. The lambs where then given an intravenous bolus of norepinephrine (5 μg/kg) and angiotensin II (10 μg/kg) to cause hypertension. Systemic hypertension was obtained by pharmacological means because it enabled the study of higher arterial blood pressures than could be obtained by occlusion of the descending aorta, and with the rationale that a favorable comparison with mechanical means would strengthen interpretation of the results. Each bolus was followed by a 5- to 15- minute recovery period until blood pressure returned to baseline. Following pharmacologically induced hypertension lambs were subjected to 100% occlusion of the brachiocephalic trunk for 30 seconds to reduce cerebral perfusion pressure. This was followed by 3 to 5 minutes of recovery to return to a stable baseline. Next, a graded 30-second occlusion was administered to generate a fall in arterial pressure equivalent to 50% of the decrease caused by the 100% occlusion, followed by another recovery period. Finally, a third occlusion was administered to achieve a 25% decrease in arterial pressure compared to the 100% occlusion. The lambs were then subjected to a similar series of 100%, 50%, and 25% occlusions of the descending aorta to generate an increase in pressure perfusing the cerebral circulation. Next, to assess the effects of electrical stimulation of the SCG, electrical impulses were administered directly to the SCG, at an interval of 1 millisecond with a frequency of 8 Hz and intensity of 6 to 8 volts. A total of four stimulations (two at 6 volts and two at 8 volts) were performed on each lamb. Each stimulation lasted for 30 seconds and was followed by a 3- to 5-min recovery period. To confirm that CBF responses were through the SCG itself in three lambs the surrounding tissue was stimulated and found to be without effect.Lastly, the SCG that had been instrumented with electrodes was surgically removed and occlusions of the brachiocephalic trunk and descending aorta were repeated, as were the infusions of angiotensin II and norepinephrine. After completion of the experiment, the lambs were euthanized with Euthasol® .Arterial blood pressure, heart rate, and CBF were recorded digitally at 400 Hz using an A/D converter  and software . Because LDF provides only relative changes in flow, CBF and cerebral vascular resistance were expressed as a percent of baseline values. Cerebral vascular resistance was calculated as mean arterial blood pressure divided by CBF and also normalized to baseline values. The effect of electrical stimulation was measured by averaging CBF signals into 5-second blocks, beginning 30 seconds prior to the beginning of the electrical stimulation and continuing until 30 seconds after the end of the stimulation.Cerebral blood flow and arterial blood pressure during the last 15 seconds of each graded occlusion of the brachiocephalic trunk and aorta, and at the peak response to norepinephrine and angiotensin II injection, were normalized to the 30 seconds of data recorded just prior to each intervention. Autoregulation of CBF was then evaluated by comparison of CBF with mean arterial blood pressure in 2.5 mmHg intervals as previously described n  =  6 for an α of 0.05 and a β of 0.20. All data are presented as mean ± SE.A one-way ANOVA was used to assess the significance of the effects of electrical stimulation of the SCG on mean arterial blood pressure. The effects of stimulation on ipsilateral vs. contralateral (with respect to the side of SCG stimulation) CBF and cerebral vascular resistance time series data . However, within each group baseline mean arterial blood pressures prior to each intervention were comparable before and after removal of the SCG (58±9 mmHg vs. 56±9 for preterm lambs and 74±8 vs. 75±10 for two-week-old lambs). The effect of the blood pressure interventions on upper body arterial blood pressure and CBF are given in The relationship between mean arterial blood pressure and CBF across all ranges of arterial blood pressure studied before and after removal of the SCG is shown in The present experiments demonstrate that the sympathetic innervation of the cerebral vasculature serving the cortex is functionally intact and, if stimulated, modulates CBF in both preterm lambs following cesarean delivery and two-week-old lambs born naturally at term. The work also demonstrates a lack of cerebral autoregulation in anesthetized and mechanically ventilated preterm lambs following cesarean delivery, in contrast to similarly instrumented and anesthetized two-week-old lambs in which effective autoregulation was observed. Finally, the experiments indicate that the SCG does contribute to autoregulation in the two-week-old lambs, but that it is only essential during episodes of supraphysiological hypertension.The development of functional adrenergic innervation of vasculature occurs in stages, with postsynaptic components of the system maturing before presynaptic components are in place in vivo results in decreased CBF in newborn lambs in vivo comparisons of presynaptic function in newborns and adults of the same species have not been performed. Although we did not observe a significant decrease in CBF in the two-week-old lambs, our findings are consistent with these previous newborn reports in that we also observed a significant increase in ipsilateral cerebrovascular resistance to flow in response to unilateral SCG stimulation . In this study the probe was positioned in the parietal cerebral cortex, approximately 0.5 cm below the surface of the brain, a location in the forebrain where blood flow has been shown to be under the influence of sympathetic input Laser Doppler flowmetry is limited in that it can only detect changes in flow in a relatively small volume of tissue (∼2 mm2 to the lambs in both groups may have attenuated cerebral autoregulation. However, this possibility appears unlikely as studies of the administration of high inspired O2 in humans find no change 2. Other limitations include failure to monitor and maintain glucose and renin levels, and an uneven ratio of right-to-left SCG chosen for stimulation and removal, which may have biased the results if the effects of the two ganglia are asymmetrical. Also, the experimental preparation required instrumentation that may have injured cerebral blood vessels, altering blood flow responses. And finally the sheep is a species whose young are quite mature at birth and vascular control is likely to develop more slowly in infants. Furthermore, the anatomy of the vasculature supplying the sheep brain differs from that of the human as blood passes through a carotid rete before reaching the Circle of Willis in the sheep. The effect of these species differences on autoregulation and the role of the SCG are not known.Both the SCG stimulations and interventions in arterial blood pressure in our study were of relatively short duration in order to ensure that the lambs remained in stable condition throughout the experiment. However, this limited time prevented assessment of long-term decreases in CBF, which may be limited by a time-dependent ‘escape’ mechanism in some animal models in utero at an early stage of development, it may be lost with premature delivery and following treatments common to the clinical care of premature infants, such as intubation and mechanical ventilation. The present findings indicate that sympathetic control of cerebral vascular resistance during marked hypertension may be limited immediately following preterm birth. Furthermore, excessive sympathetic activation may potently decrease CBF after birth, contributing to inadequate flow observed in some pathologies.Dysregulation of CBF, resulting in intraventricular hemorrhage and periventricular leukomalacia, is a common problem in the care of premature infants. The present study demonstrates that, although cerebral autoregulation is intact in the fetal sheep


Hypervolemia is a common complication in patients on hemodialysis (HD). To determine the effect of volume change on blood pressure in HD population, this cohort was conducted.n=26) and normotensive group B (n=34). Data were collected by a questionnaire. Pre and post-dialysis blood levels of urea, sodium, total protein, and hemoglobin were measured and intradialytic change of plasma volume were calculated. Data analyses were performed by the SPSS v.16.The study population was composed of 60 non-diabetic patients on maintenance HD, with mean age of 59.95±15.28 years. They were divided into hypertensive group A . No correlation was found between intradialytic change in plasma volume or body weight and alterations of SBP or DBP during HD in the study groups . Intradialytic changes of body weight did not correlate to intradialytic changes of plasma volume (P=0.15).Out of 60 patients, 58.3% were male and 41.7% female. Post-dialysis systolic blood pressure (SBP) and diastolic blood pressure (DBP) were significantly lower than pre-dialysis values in both groups (HD effectively reduces blood pressure and volume expansion, however, intradialytic changes of plasma volume and body weight do not influence on SBP and DBP. Chronic renal failure (CRF) is a clinical syndrome due to various renal damages, which result in progressive and irreversible nephron loss. The most common causes of CRF include: diabetes mellitus, hypertension, glomerulonephritis, cystic disease, and interstitial nephritis.2 Hemodia57n=26), who were hypertensive  and received antihypertensive drugs and group B (n=34), who were normotensive without antihypertensive therapy. Data including demographic characteristics, underlying diseases, drugs, body weight and blood pressure records , and biochemistry analyses were collected by a questionnaire. Pre- and post-dialysis  blood samples were drawn to obtain respective serum urea, sodium, total protein, and hemoglobin concentrations. Intradialytic change of plasma volume (∆ PV) was calculated by the Leypoldt equation[This cohort study was performed on 60 non-diabetic patients, at the Mustafa Khomeini Hospital; Tehran; Iran, who were undergoing conventional (3 h for three times/weekly) maintenance HD. Indeed, patients with diabetes mellitus, symptomatic cardiac disease, severe illness, and history of hospitalization during prior 2 months were excluded. All participants were informed of study purposes and designed the consent forms. According to pre-dialysis blood pressure records during 2 months before the study, patients were assigned into group A  equation according to the Daugirdas formula:[In addition, urea clearance was calculated by logarithmic single pool  formula:R is the post–pre serum urea nitrogen (SUN) ratio, t is session length (in hours), UF is the volume of fluid removed during dialysis (in liters), and W is post dialysis body weight (in kilograms). In order to calculate spKt/V, the post-dialysis blood sample was drawn from arterial bloodline 20 s after dialysis session termination while the pump speed was reduced to 80 ml/min.Where P-value <0.05 was considered statistically significant. The student’s t-test and Spearman’s test were used to detect significant differences between groups and correlations between variables.Data analyses were carried out, using the statistical software package SPSS, version 16. P=0.001, each). P>0.05, each). In addition, no correlation was found between intradialytic change of body weight with intradialytic change in plasma volume (P=0.15). The Spearman test revealed only a positive correlation between the age and blood pressure (SBP and DBP) decrement (P=0.01 and P=0.026).The study population consisted of 35 males (58.3%) and 25 females (41.7%), with mean age of 59.95 ± 15.28 years, who were undergoing maintenance HD . Post-dialysis systolic blood pressure (SBP) and diastolic blood pressure (DBP) were significantly lower than pre-dialysis values in both groups , the total body contents of sodium (Na) and water are increased modestly which contributes to hypertension. When the glomerular filtration rate (GFR) falls to 5–10 ml/min, extracellular fluid volume (ECFV) expansion under these circumstances usually means that dialysis is indicated. PatientsThis study revealed that despite lower values of post-dialysis blood pressure, plasma volume, and body weight, compared to pre-dialysis values, there was no significant correlation between intradialytic volume status or body weight change and pre- or post-dialysis SBP and DBP. Such a result regarding the discrepancy between blood pressure and volume status has been reported previously.–20et al., and Ventura et al., have also got similar findings in this issue separately.[et al.[However, some researchers have shown the correlation between these variables. For instance, Lins and co-workers reported a positive correlation between SBP alteration and plasma volume change. Leypoldtparately.22 Furtheparately. This finy.[et al.P=0.03) and blood pressure (P<0.001) between two study groups, the intradialytic plasma volume change was relatively similar in both groups In our study, although eight patients in group B (normotensive) whose post-dialysis body weights were below 60 kg showed SBP reduction about 10 mmHg, however, we could not find significant correlation between intradialytic change in body weight and SBP. As mentioned previously, comparing to HEMO study, which had included patients with diabetes and cardiac disease, we excluded the categories that might have influences on refilling rate and hemoRocco and colleagues reportedAs a whole, our findings are in agreement with previous researches and indicate that body weight change and plasma volume monitoring are not proper methods for evaluation of hydration status in HD patients. With regard to relation of SBP with intradialytic change of plasma volume in normotensive HD patients (which reflects absence of excessive extracellular fluid volume and high refilling rate) in some studies, it seems better to monitor combination changes of plasma volume and extracellular fluid volume, in HD population, to detect the influence of volume status on blood pressure.Despite, effective reduction of SBP, DBP, and plasma volume during hemodialysis, intradialytic changes of plasma volume and body weight do not influence on SBP and DBP. Many studies are proposed with consideration of other factors including residual renal function and extracellular fluid volume monitoring for evaluation of hydration status in hemodialysis patients.


Posttraumatic intravasation of fat and debris can lead to a cascade of events. Hydroxyethyl starches (HES) markedly suppress neutrophil influx by decreasing pulmonary capillary permeability and facilitating tissue oxygenation by improving microcirculation. It was hypothesized that in hypoxemic femur injury patients undergoing operative stabilization, HES administration will prevent the deterioration of respiratory variables and facilitates recovery. This prospective, double-blind, randomized preliminary study, enrolled twenty posttraumatic hypoxemic patients  > 5) scheduled for femur fracture stabilization under general anesthesia. Patients were allocated to receive either; 6% HES 130/0.42, 15 mL/kg or 0.9% normal saline (NS) to maintain their central venous pressure (CVP) 12 + 2 mm Hg. Blood was transfused according to the maximum allowable blood loss and by serial hematocrit estimations. Perioperative Glasgow Coma Scale (GCS), physiological variables, arterial oxygen saturation (SpO2), arterial blood gas (ABG), SS and P/F ratios were recorded until recovery. The partial pressure of oxygen in arterial blood / fraction of inspired oxygen ratio (PaO2/FiO2) improved from a preoperative value of 273.33 ± 13.05 to 435.70 in the 6% Hydroxyethyl starch group (HES) and from 275.24 ± 15.34 to 302.25 ± 70.35 in the NS group over a period of six days . Time taken to achieve a P/F ratio > 300 and for persistent reduction of Murray’s lung injury score (LIS) were comparable . The number of ventilator, intensive care unit (ICU) and hospital stay days, did not differ . There were no adverse sequelae or mortalities. A trend showing relatively fast improvement in the P/F ratio and an early reduction in LIS values was observed in hypoxemic, femur injury patients receiving intraoperative colloid supplementation. Posttraumatic intravasation of fat and debris can lead to a cascade of events including neutrophil activation which results in acute lung injury. Various surgical and pharmacological techniques have been developed in an attempt to reduce the intravasation of fat, or to prevent alveolar damage during trauma surgery . Colloid2) < 70 mm Hg, on room air and Schonfeld fat embolism index (SS) score > 5) , Chandigarh and written informed consent, this prospective, randomized-trial enrolled twenty consecutive ASA I or II adults of either gender, aged 18 - 45 years, with acute femur injury and post traumatic hypoxemia  .2), invasive blood pressure (IBP), fraction of inspired oxygen (FiO2), airway pressures (Paw), end tidal carbon dioxide (EtCO2), central venous pressure (CVP) and urine output (UO). All patients were allocated to receive one of the two intravenous fluid regimens intra operatively using a computer generated permuted block randomization method , while CVP was maintained, 10 - 14 mmHg. The hydroxyethyl starch group (n = 10) patients were administered 6% HES 130/0.4 (2-4 mL/kg/h). If CVP was < 10 mmHg, 6% HES (130/0.4) was infused at the rate of 8 - 10mL/kg, but the maximum amount of colloid administered during surgery was limited to 15 mL/kg. Patients in the 0.9% normal saline (NS) group (n = 10) were infused crystalloids intraoperatively. In all patients, whole blood was transfused when blood loss exceeded the calculated maximum allowable blood loss (MABL), or intraoperative hemoglobin estimations revealed values below 8 mg/dL. Perioperative Glasgow Coma Scale (GCS), heart rate, blood pressure, SpO2, arterial blood gases, SS, P/F ratio and LIS were continually recorded until the patient was taken off oxygen therapy. Lung injury scores indicate the severity of lung injury . Discrete variables such as gender were analyzed by a Chi-square test. Continuous data such as heart rate, blood pressure, and CVP, were analyzed by repeated measure ANOVA, followed by one way ANOVA to assess the trend of change in the serial values and to find out the interaction of trends in the two groups. For time to event data, survival analysis using Kaplan Meier and log rank tests were carried out. Quantitative data has been reported as Mean ± SD with graphical presentation as 95% confidence interval error bars. Categorical data is shown as frequencies. The frequency distribution of the study characteristics is shown separately for HES and NS group patients. Statistical significance was defined as P value (two tailed) ≤ 0.05. Chest roentgenogram, 12 - lead electrocardiography, arterial blood gas analysis and Murray’s lung injury score (LIS) calculations  were recP > 0.05). The two groups effectively maintained intraoperative physiological variables (P = 0.00). Estimated blood loss was 820 ± 154.91 mL in the HES group and 950 ± 158.11 mL in the NS group (P = 0.094). There were no relevant differences in the amount of whole blood transfused amongst the groups (P = 0.789). None of the patients required any other blood products. Urine output was adequate in both the groups and diuretics were not required. The P/F ratio increased from 280.84 ± 13.05 to 435.70 in the HES group and from 272.69 ± 15.34 to 302.25 ± 70.35 in the Normal Saline group over a period of six days . The trend of improvement in the P/F ratio was faster in the HES group compared to the NS group. Time taken to achieve P/F ratio > 300, was 1.60 ± 0.31 days in the HES group and 1.80 ± 0.44 days in the NS group (P = 0.75) (P = 0.348)   . LIS val= 0.348) . The intNS group . The serNS group  - 4. Fou, 0.301) .There were no anaphylactic reactions, HES-induced pruritus or central venous cannulation related complications . Wound infections requiring debridement/reoperation did not occur. None of the patients was readmitted to the hospital within 30 days after discharge. There were no mortalities.Surgery is known to elicit a stress response of combined endocrine and inflammatory origin. It can affect major organ functions including alveolar gas exchange and overall clinical outcomes (secondary insult) . Various


In addition, blood was extracted from the radial artery at T0, T1, T2, T3, T4 and T5 in order to detect the presence of tumor necrosis factor-α (TNF-α), IL-6 and IL-10 in the blood serum. Between T1 and T4, the tidal volume, airway plateau pressure and end-expiratory positive airway pressure were recorded, in order to calculate the lung dynamic compliance (Cdyn). Heart rate, mean arterial pressure, central venous pressure, cardiac output and the duration of OLV (OLV-T) were recorded at T0–5. Compared with T0, the levels of TNF-α, IL-6 and IL-10 significantly increased during T2 to T4 in both groups (P<0.05). PA-aDO2 and RI increased during T1 to T4, and Qs/Qt increased at T2 (P<0.05). Compared with T1, Cdyn decreased during T2 to T4 in the S group, whereas Cdyn was reduced at T2 in the P group (P<0.05). Compared with the P group, TNF-α level increased and IL-10 decreased at T3 and T4 in the S group. PA-aDO2 and RI increased, but Cdyn decreased at T2 and T3 in the S group. Qs/Qt increased at T2 in the S group. The results of the present study demonstrated that, in comparison with propofol, sevoflurane exhibited an enhanced capacity to aggravate injury to pulmonary function during the perioperative stages. This occurred via the release of inflammatory factors, the aggravation of lung edema and the inhibition of hypoxic pulmonary vasoconstriction.This study compared the effects of sevoflurane and propofol on the inflammatory response and pulmonary function of patients with lung cancer during the perioperative period. Forty patients who underwent a selective resection of the inferior lobe of the left lung were randomly divided into two groups, with one group anesthetized with sevoflurane and the other with propofol . Radial arterial and mixed venous blood were extracted for blood gas analysis, in order to calculate the alveolar-arterial oxygen partial pressure difference (PA-aDO This technology has enhanced the field of thoracic surgery by reducing the contamination of the contralateral lung, which has helped to ensure the efficacy of the surgery and the safety of the patient. However, OLV may cause major physiological disorders, such as a non-ventilated lung with hypoxic pulmonary vasoconstriction (HPV), increased pulmonary shunt, decreased arterial oxygen tension, variation in the alveolar-arterial oxygen gradient, inflammation caused by the release of cytokines and changes in pulmonary vascular resistance –3. Proloet al revealedet al. In addiet al. Therefo2. The exclusion criteria included a history of hypertension, asthma, chronic obstructive pulmonary disease, difficult airway, perioperative risk factors of aspiration, chronic cough and a history of recent respiratory tract infection. The patients were randomly assigned by computer to either the sevoflurane (S) or propofol (P) group, with ≥20 cases per group. The study was conducted in accordance with the Declaration of Helsinki, and with approval from the Ethics Committee of the Second Hospital of Shandong University , and the Institutional Review Board (IRB) of the Second Hospital of Shandong University. Written informed consent was obtained from all participants.Forty patients with lung cancer, who underwent elective thoracotomy lobectomy between January and June, 2010, were included in the study. The patients were ASA level I–II, and included 29 males and 11 females, aged 45–74 years, with a body mass index of 22–29 kg/mAll patients were injected with 0.1 mg/kg midazolam and 0.01 mg/kg penehyclidine hydrochloride 30 min prior to surgery. Following entry into theatre, radial artery catheterization was performed under local anesthesia, the right internal jugular vein was punctured and a Swan-Ganz floating catheter was inserted .Anesthesia was induced as follows: in the S group, the patients were treated with 6–8% sevoflurane , 0.6 mg/kg rocuronium and 4–6 μg/kg fentanyl; whereas in the P group, patients were treated with 1.5–2 mg/kg propofol , 0.6 mg/kg rocuronium and 4–6 μg/kg sufentanil. A left double-lumen catheter was used for endobronchial intubation, under optical fiber bronchoscopy. Following this, the patients were placed either in the left or right lateral position, depending on the side of the lung requiring surgery.2), was performed. Blood pressure was measured three times prior to anesthesia, and the average was taken as the standard for blood pressure. Blood pressure and heart rate fluctuations were maintained at <20% of the base value by adjusting the depth of anesthesia during surgery. The mechanical ventilation parameters were as follows: tidal volume (VT) lung ventilation, 8–10 ml/kg; respiratory rate, 10–12 times/min; inspiratory to expiratory ratio, 1:2; and PETCO2, 35–45 mmHg. The low VT lung protective ventilation strategy was used for the OLV, where the VT, respiratory frequency and respiratory ratio were adjusted to maintain the airway pressure at <30 cm H2O, PETCO2 at 35–45 mmHg, pulse oxygen saturation at >90% and inspired oxygen concentration at 100%. Intraoperative transfusion was performed by Ringer’s solution and Wan Wen infusion  in a 3:1 ratio.In the S group, anesthesia was maintained through the inhalation of 1–3% sevoflurane. By contrast, 6–10 mg/kg propofol by continuous intravenous infusion was used to maintain the anesthesia in the P group. Fentanyl and rocuronium were added, depending on the condition of the patient, in order to maintain the bispectral index (BIS) level at 40–50 . Routine intraoperative monitoring, including a five-lead ECG, and measurements of invasive blood pressure, pulse oxygen saturation and end-tidal carbon dioxide partial pressure (PETCO0), immediately prior to the commencement of OLV (T1), 1 h subsequent to the commencement of OLV (T2), 1 h following restoration of two-lung ventilation (T3), 2 h following restoration of two-lung ventilation (T4) and 24 h post-surgery (T5). Blood gas analysis was performed using the i-STAT® portable clinical blood gas analyzer . The alveolar-arterial oxygen partial pressure difference (PA-aDO2), respiratory index (RI) and pulmonary shunt ratio (Qs/Qt) were calculated using the following formulae: 2, fraction of inspired oxygen; PaCO2, partial pressure of CO2 in arterial blood; PaO2, partial pressure of O2 in arterial blood); RI=PA-aDO2/PaO2; and Qs/Qt=(CcO2-CaO2)/(CcO2-CvO2) . Radial arterial blood samples (3 ml) were extracted at T0, T1, T2, T3, T4 and T5 in EDTA-tubes, and centrifuged at 1000 × g for 10 min at 4–10°C. The supernate was maintained at −80°C. The concentrations of plasma TNF-α, interleukin (IL)-6 and IL-10 were determined by enzyme-linked immunosorbent assay (ELISA), in accordance with the kit’s instructions . VT, airway plateau pressure (Ppiat) and the end-expiratory positive airway pressure (PEEP) were measured at T1, T2, T3, and T4, and the lung dynamic compliance (Cdyn) was calculated using the following formula: Radial arterial and mixed venous blood samples (1 ml) were extracted prior to the induction of anesthesia  statistical software, version 13.0 , and are presented as the mean ± standard deviation. Repeated measures analysis of variance was used to compare data within a group, and the Students t-test was used to compare date between the groups. Fisher’s exact test was used to compare count data. P<0.05 was considered to indicate a statistically significant difference.No significant differences were observed between the two patient groups with regard to gender, age, body mass index, ejection fraction, forced expiratory volume in one second, forced vital capacity ratio and OLV-T P>0.05; .2 and T4 in the two groups were significantly increaseed compared with the concentrations at T0 .The Qs/Qt includes the functional (QvA) and anatomical (Qs) shunts. The former is caused by a ventilation/perfusion (V/Q) imbalance, whereas the latter is caused by anatomical defects in the pulmonary blood flow, as a direct result of the mixed pulmonary venous system. OLV V/Q may increase Qs/Qt and reduce PaO2(HPV, in which OLV is important, is a critical mechanism that confers protection to the pulmonary circulation under hypoxia. The prevention of hypoxia may reduce pulmonary shunt ,5. Studi2,20,21.In the present study, the Qs/Qt in the two patient groups increased significantly during OLV, with higher values in the the S group than the P group. This suggested that the inhibitory effect of sevoflurane on HPV was stronger than that of propofol, and that the increase was potentially dangerous in hypoxia. In a previous study, it has been demonstrated that the impact of 1 MAC sevoflurane inhalation on HPV and oxygenation was similar to that of clinical doses of propofol . Therefo0. The TNF-α and IL-6 concentrations in the S group were significantly higher than those in the P group, whereas the IL-10 concentration in the S group was significantly lower than that in the P group. These results suggested that compared with propofol, sevoflurane anesthesia induced a strong inflammatory response in the lung tissue in OLV. This may be due to the fact that, following a certain period of time, inhalation anesthesia increases the release of inflammatory mediators, and induces an upregulation of proinflammatory cytokine gene expression, thereby increasing lung damage (TNF-α and IL-6 are proinflammatory cytokines that are important in the body’s inflammatory response. IL-6 is generated by the activation of different cells in the lung tissue, including alveolar macrophages and endothelial cells, due to various stimuli, such as stretching, which are closely associated with lung injury and lung inflammation ,24. By cg damage ,25,26.2, RI, and Qs/Qt returned to normal levels in the two groups 24 h post-surgery, suggesting that the effects of sevoflurane and propofol anesthesia on the OVL perioperative inflammatory response and pulmonary function were temporary. Neither sevoflurane or propofol exerted any significant effects on the recovery of lung function.In the present study, the concentrations of TNF-α, IL-6 and IL-10, and the PA-aDOIn conclusion, the perioperative inflammatory response and the risk of hypoxemia induced by intravenous propofol anesthesia were lower than those of sevoflurane anesthesia, and the pulmonary damage observed with propofol anesthesia was less than that observed with sevoflurane anesthesia. Therefore, the use of propofol for total intravenous anesthesia in OLV may be safer for patients than the use of sevoflurane.