Innovative wheelchairs allow individuals to change position easily for comfort and social situations. While these wheelchairs are beneficial in multiple ways, the effects of position changes on blood pressure might exacerbate hypotension and cerebral hypoperfusion, particularly in those with spinal cord injury (SCI) who can have injury to autonomic nerves that regulate cardiovascular control. Conversely, cardiovascular benefits may be obtained with lowered seating. Here we investigate the effect of moderate changes in wheelchair position on orthostatic cardiovascular and cerebrovascular reflex control.™ wheelchair. Participants with SCI were stratified into two groups by the severity of injury to cardiovascular autonomic pathways. Beat-to-beat blood pressure, heart rate and middle cerebral artery blood flow velocity (MCAv) were recorded non-invasively.Nineteen individuals with SCI and ten neurologically-intact controls were tested in supine and seated positions  in the ElevationSupine blood pressure and MCAv were reduced in individuals with lesions to autonomic pathways, and declined further with standard seating compared to those with preserved autonomic control. Movement to the elevated position triggered pronounced blood pressure and MCAv falls in those with autonomic lesions, with minimum values significantly reduced compared to the seated and lowered positions. The cumulative duration spent below supine blood pressure was greatest in this group. Lowered seating bolstered blood pressure in those with lesions to autonomic pathways.Integrity of the autonomic nervous system is an important variable that affects cardiovascular responses to orthostatic stress and should be considered when individuals with SCI or autonomic dysfunction are selecting wheelchairs.This work was supported in part by the Heart and Stroke Foundation of British Columbia and the Yukon (V.E.C). Innovative variable positioning wheelchairs facilitate mobility and improve quality of life for wheelchair users. Some of these new devices permit dynamic modification of seating position, height, and tilt, to better navigate physical and social barriers. Seating positions can easily be adjusted in real time to suit particular activities, maximizing function, efficiency and independence , 2. TherMore upright seating positions challenge blood pressure regulation due to increases in orthostatic stress, which cause large fluid shifts to the lower body and abdomen, thus reducing venous return to the heart. This would normally be mitigated by autonomically-mediated baroreflex responses that increase heart rate and contractility, and increase sympathetic vasoconstriction. However, if these reflexes are impaired then this compensation can be insufficient to maintain blood pressure . Indeed,Here we tested the effect of wheelchair seating position on cardiovascular and cerebrovascular function using a variable positioning manual wheelchair. We aimed to determine the effects of elevated, standard and lowered wheelchair seating positions on blood pressure, heart rate and cerebral blood flow . ResponsWe certify that all applicable institutional and governmental regulations concerning the ethical use of human volunteers were followed during the course of this research. This study conformed to the principles outlined in the Declaration of Helsinki , and rec™ wheelchair, PDG Mobility Technologies, Vancouver, BC) [All participants were ≥18 years old, apparently healthy and free of hypertension, diabetes mellitus and other overt cardiovascular disease. Nineteen individuals with SCI (8 women) who were regular wheelchair-users for at least one year participated. All participants with SCI and ten healthy able-bodied controls (4 women) were studied in elevated, lowered, and standard seating positions (Elevationand b) low supine plasma noradrenaline spillover (<0.5 nmol/L); and c) low systolic blood pressure variability in the low frequency range , as is standard in our laboratory [Neurological classification of level and severity of SCI was determined from the American Spinal Injury Association Impairment Scale (AIS) . Particiboratory , 33, 34.ETCO2) were recorded on a breath-by-breath basis . All recordings were sampled at 1 KHz , acquired using LabChart (AD Instruments), and stored for offline analysis.Beat-to-beat blood pressure and lead II electrocardiogram (ECG) were recorded continuously . Middle cerebral artery (MCA) blood flow velocity was measured bilaterally using transcranial Doppler ultrasound with 2 MHz probes through the temporal windows  attached to a headband to maintain constant angles of insonation. Partial pressures of expired oxygen and carbon dioxide (P™ wheelchair (back height 30 cm) in the neutral seated position  for 15 minutes. In a crossover design, individuals were randomly assigned to move to the maximally elevated , or lowered position , and then returned to the neutral seated position, followed by the opposite position, with each block lasting 15 minutes , diastolic (MCAdia), and mean (MCAmean) cerebral blood flow velocities, and breath-by-breath PETCO2 were determined using cyclic peak detection measurement algorithms in LabChart. For each individual, the most reliable and consistent signal from either the left or right MCA was used for analysis (the side with the greatest number of beats with faithful envelope detection). Stroke volume (SV) and cardiac output (CO) were derived using the Modelflow™ technique [We applied a low-pass filter (<50 Hz) to remove electrical noise from the ECG signal and a median filter  to remove artifacts from the MCA signal. Beat-to-beat heart rate (HR), systolic (SAP), diastolic (DAP), mean (MAP) arterial pressure, as well as MCA systolic . Values from the two neutral seated conditions were averaged as they were not significantly different from each other.duration of hypotension following postural change and ability to recover blood pressure during orthostasis have been identified as key measures of severity of OH [In addition to the five minute averages, we computed three additional variables: minimum blood pressure (nadir), the timing of the nadir, and the overall orthostatic burden. The timing and size of the blood pressure nadir in response to orthostatic stress varies between individuals and together this information can provide insight into the severity of sympathetic dysfunction . Nadir vty of OH , 37. We Data processing was conducted using R Version 3.0.1 and data were analysed using JMP Version 10.0 and SigmaPlot Version 12. Descriptive statistics were calculated by group for the supine variables. Non-parametric data were log transformed prior to statistical analyses. SCI-specific measures such as duration of injury were compared using t-tests. Distribution of level and severity of injury between groups was compared using Fisher’s exact test. One-way ANOVAs were used for comparison of demographic information and supine variables, with Tukey’s post-hoc test to examine between group differences. Cardiovascular responses to different wheelchair positions were compared using a two-way ANOVA (participant subgroup and seat position) with repeated measures on one factor (position). The dependent variable was the absolute cardiovascular parameter. Where main effects were present, post-hoc comparisons were conducted using the Holm-Sidak method. Statistically significant differences were assumed where α<0.05.Participant characteristics are shown in dia and MCAmean compared to the autonomically-incomplete group . The autonomically-incomplete SCI group had higher DAP (p = 0.015) and MAP (p = 0.035) compared to the control group. The remaining supine cardiovascular and cerebrovascular parameters were not significantly different between groups.Supine cardiovascular and cerebrovascular recordings showed that the autonomically-complete SCI group had significantly lower SAP, DAP, MCAMovement from a supine to seated position had different effects on SAP depending on autonomic completeness of injury . In the autonomically-complete SCI group only, the HR in the elevated position was higher than in the seated and lowered positions.SV decreased in all groups from supine to all seated positions . In the sys was reduced compared to supine in those with autonomically-complete SCI (p = 0.02), but not in those with autonomically-incomplete SCI or controls .Group average cerebrovascular parameters in different wheelchair positions are also reported in controls . In all dia) was particularly affected by orthostatic challenge in the autonomically-complete SCI group, similar to our previous report [dia was significantly lower in the autonomically-complete SCI group compared to both groups in the seated, elevated, and lowered positions . Movement from the seated to the elevated position did not further decrease MCAdia in the autonomically-complete SCI group. Similar group results and changes with position were seen in MCAmean. Significant changes in PETCO2 were not detected and do not explain these results.Diastolic cerebral blood flow velocity dia) was dia was lower in the autonomically-complete SCI group compared to both groups in all wheelchair positions .In the seated and elevated positions, nadir SAP was significantly lower in the autonomically-complete SCI group compared to both autonomically-incomplete p<0.05,  and contThe cumulative orthostatic burden in each position is shown in Wheelchair technologies continue to improve to meet the needs of individuals living with disability. Our results show that caution is warranted before encouraging all individuals to adopt and use new wheelchairs without prior education and planning. Individuals with high-level SCI and damage to autonomic pathways tend to have low resting blood pressure, particularly when seated. In this population, moderate changes in body position can result in periods of low blood pressure and cerebral blood flow that can potentially trigger symptoms of presyncope or even syncope , 34; lowWe showed that cardiovascular homeostasis in individuals with autonomically-complete SCI is perturbed by positional changes. Similar to our previous work , 34, avesys. This failure to improve cerebral perfusion despite improvements in blood pressure could be an indicator of impaired autoregulation, as we have previously reported in this population [We found that lowered seating improved SAP, HR and SV compared to elevated seating in those with autonomically-complete SCI  and coulpulation .The benefit of the lowered seating position may be more apparent during dynamic exercise. However, we focused on static positioning and did not test cardiovascular function while wheeling. Body movement and dynamics during wheeling may accentuate the differences in cardiovascular parameters between positions. For example, the lowered position provides improved ergonomics for wheeling compared to the seated or elevated position, and individuals often lean forward to move the center of gravity forward . This woautonomic completeness of injury [While not the main focus of this study, our results reiterate the dissociation between AIS Score, which classifies motor and sensory injury impairment, and the f injury , 33, 34.Given the disruption of sympathetic nerve pathways in those with autonomically-complete injuries, we might have expected greater impairments in cardiovascular control during orthostatic stress in this group; however, compensatory physiological adaptations, such as changes in the renin-aldosterone-angiotensin system  and antiHere we considered only the acute impact of dynamic seating and associated orthostatic stress on cardiovascular control. However, there may be a training effect of repeated exposure to orthostatic stress . This coETCO2 [We employed well-used techniques to assess cardiovascular function. However, the assessment of cerebral blood flow from indirect measurements of velocity using Doppler ultrasound relies on the assumption that the insonated vessel diameter remains constant . AlthougETCO2 , 55, whiunderestimate the severity of cardiovascular compromise. It is possible that this reflects self-selection of these individuals, because of known orthostatic intolerance or difficulty completing the transfers inherent in this study. In practice, it is likely that many individuals with high-level SCI would not elect to use wheelchairs with dynamic seating due to trunk instability; for those who do, cardiovascular complications should be taken into consideration.One limitation of this study is the smaller number of participants with cervical SCI—who comprise about half of all individuals living with SCI . Given tpowered mobility alternatives have recently been developed for individuals with high-level SCI that pose similar challenges to cardiovascular control. These power wheelchairs permit a wide range of position flexibility, spanning from supine to standing [Several new standing , 58, enastanding  and willstanding . Devicesstanding . StudiesThe integrity of the autonomic nervous system is an important variable that affects cardiovascular responses to orthostatic stress and should be considered when individuals are selecting and configuring wheelchairs with dynamic seating options. These results have implications for individuals with SCI and also non-SCI wheelchair users with cardiovascular autonomic impairment such as individuals with multiple sclerosis, diabetic neuropathy, and autonomic failure syndromes. We hope this research will encourage clients, physicians and seating specialists to consider cardiovascular stressors when they are selecting possible wheelchairs. Discussion and education around identification of early symptoms of OH and presyncope should be included when individuals are making wheelchair decisions. The ability to make rapid position changes to recover blood pressure if individuals begin to feel symptoms of presyncope is an important consideration for wheelchair users—especially for those with severe autonomic impairment. With modest education and key contingency procedures in place, all wheelchair users should be able to access the myriad benefits of dynamic position changes to their health, independence, and quality of life.


This study aimed to evaluate the association between cardiovascular autonomic neuropathy (CAN) and left ventricular diastolic dysfunction (LVDD) in type 2 diabetes patients. 315 type 2 diabetes patients from inpatients of Drum Tower Hospital were included and classified into no CAN (NCAN), possible CAN (PCAN), and definite CAN (DCAN) based on cardiovascular autonomic reflex tests. The left ventricular diastolic function was assessed by tissue Doppler imaging echocardiography.P = 0.001). Patients with DCAN had higher filling pressure (E/e′ ratio)  and impaired diastolic performance (e′)  compared with NCAN. CAN was found to be an independent risk factor for LVDD from the multivariate regression analysis . The distribution of NCAN, PCAN, and DCAN was 11.4%, 51.1%, and 37.5%, respectively. The proportion of LVDD increased among the groups of NCAN, PCAN, and DCAN (39.4%, 45.3%, and 68.0%,  Our results indicated that CAN was an independent risk marker for the presence of LVDD in patients with diabetes. Early diagnosis and treatment of CAN are advocated for preventing LVDD in type 2 diabetes. Cardiovascular autonomic neuropathy (CAN) is one of the most common complications in patients with diabetes. It is defined as an impairment of cardiac autonomic nerve fibers in the cardiovascular system after excluding other causes . DecreasIt was demonstrated that CAN is associated with increased risk of morbidity and mortality in patients with diabetes , 7. AftePatients with diabetes show a high frequency of heart failure accompanied by an increased risk of mortality . DiastolIn the present study, we aimed to clarify the relationship between CAN and LVDD in Chinese patients with type 2 diabetes.This study included 315 patients with type 2 diabetes admitted to Drum Tower Hospital, Nanjing, China, from September 2015 to December 2016. Inclusion criteria were confirmed type 2 diabetes according to American Diabetes Association criteria and age between 18 and 75 years. Patients with stroke, hypothyroidism, alcohol addiction, and other causes of neuropathy except diabetes were excluded. This study was approved by the ethics committee of Drum Tower Hospital.CAN was assessed according to four cardiovascular autonomic reflex tests (CARTs): heart rate variation during deep breathing (HRV_DP), HRV during Valsalva maneuver , HRV during the lying-to-standing test (HRV 30 : 15), and blood pressure variability (BPV) in response to standing up.In HRV_DP, the patients were instructed to rest in the supine position at least 5 min before the test and breathe deeply at a rate of six breaths per minute while being monitored on a 12-lead electrocardiography (25 mm/s). The maximum and minimum heart rates during each breathing cycle were measured, and the mean difference of the six cycles was calculated .In HRV_Valsalva, the patients were instructed to perform forced exhalation with a pressure of 40 mmHg for 15 s. The ratio of the maximum R-R interval after the maneuver to the minimum R-R interval during the maneuver was calculated. The test was performed three times, and the mean ratio was used .In HRV 30 : 15, the patients were instructed to rest in the supine position at least 5 min before the test. The 30 : 15 ratio was determined as the longest R-R interval (measured around the 30th beat after standing up) divided by the shortest R-R interval (measured around the 15th beat after standing up) .For BPV in response to standing up, the patients were instructed to rest in the supine position at least 5 min before the test. Systolic pressure was measured when changing from the supine to the upright position, and measurements were taken every minute for at least 3 min .Each test had normative values according to previous report . Two or E) and atrial (A) transmitral flow velocities, and TDI parameter of peak early diastolic (e′) velocities were evaluated. The TDI parameter was obtained by placing a tissue Doppler volume at the septal annulus in the apical four-chamber view. E/e′ ratio and e′ were calculated as measures of left ventricular filling pressure and diastolic performance, respectively [E/e′ ratio, E/A ratio, and e′ velocity were used to diagnose LVDD according to the European Association of Echocardiography consensus paper [Patients underwent echocardiography examination using the Philips 5500 ultrasound machine instrument, with data analyzed with the corollary software . Both two-dimensional and tissue Doppler imaging (TDI) were performed. Left ventricular ejection fraction (using the modified Simpson's biplane method), traditional Doppler parameters of peak velocities of early  cholesterol, hemoglobin A1c (HbA1c), pulse pressure, corrected QT interval (QTc), and CAN as independent variables to explore whether CAN is an independent risk factor for LVDD.Data were presented as mean ± standard deviation (SD) for continuous variables and percentages for dichotomous variables. SPSS22.0  was used for all statistical analyses. Student's P = 0.002), had longer diabetic duration  with a higher low density lipoprotein (LDL) cholesterol level , and had higher proportion of family history of diabetes  compared with the PCAN and NCAN groups. Pulse pressure and corrected QT intervals (QTc) were significantly different among the three groups. 48.1% of the patients with DCAN had diabetic retinopathy and 52.3% had diabetic sensorimotor polyneuropathy, indicating much higher rates compared with the other two groups  and lower E/A ratios  in patients with DCAN compared with those with PCAN and NCAN. Left ventricular (LV) mass and LVMI showed significant differences among the subjects with NCAN, PCAN, and DCAN . TDI measures indicated higher filling pressure (E/e′ ratio)  and impaired diastolic performance (e′)  in DCAN patients compared with the PCAN and NCAN groups (P = 0.001)  .e′ value was correlated with HRV 30 : 15 , HRV_DP , and HRV_Valsalva . Other indicators of diastolic dysfunction, including E/e′ ratio, E/A ratio, LV mass, and LVMI, showed significant associations with CAN parameters  and HRV 30 : 15 , and QTc was correlated with HRV 30 : 15  and BPV . Pulse pressure was also correlated with QTc . CAN stage was shown to be an independent risk factor for LVDD  after adjustment for known determinants of LVDD, including age, gender, diabetic duration, smoking, LDL, HbA1c, pulse pressure, and QTc (LVDD, pulse pressure, and QTc are risk factors for mortality. The rameters . Pulse p and QTc .This study demonstrated a close correlation between CAN and LVDD in type 2 diabetes. The severity of left ventricular filling pressure and diastolic performance dysfunction increased among the NCAN, PCAN and DCAN groups. CAN was found to be an independent risk factor for LVDD occurrence after multivariate adjustment. Among the four CAN parameters, HRV 30 : 15, HRV_DP, and HRV_Valsalva, which reflect the parasympathetic function, were associated with LVDD.CAN represents an impairment of autonomic nerve fibers that could result in abnormalities in heart rate variation and vascular dynamics . It is ue′ and increased E/e′ ratio as assessed by TDI, after adjustment for age, sex, coronary artery disease, hypertension, and HbA1c [e′, and diastolic impairment central to autonomic cardiopathy was linked to cardiac sympathetic denervation, which was carefully assessed by myocardial uptake of 123I-MIBG [LVDD is characterized by an impairment of left ventricular passive filling and relaxation, and considered the earliest manifestation of diabetic cardiomyopathy , which ind HbA1c . Sacre e23I-MIBG . The preQT interval prolongation was shown to be correlated with CAN in type 1 diabetes , 27. In Pulse pressure is positively correlated with cardiovascular mortality in diabetes . In addiConsequently, CAN was associated with left ventricular diastolic dysfunction, increased pulse pressure, and prolonged QTc. Further multivariable logistic analysis revealed CAN to be an independent risk factor for LVDD. It may be more meaningful to focus on cardiovascular disease outcomes in diabetic patients with CAN in future studies.In conclusion, CAN was found to be an independent risk factor for LVDD in type 2 diabetes. The increase among the groups of NCAN, PCAN, and DCAN was correlated with deteriorated LVDD. Early diagnosis and treatment of CAN are advocated for preventing LVDD and related cardiovascular comorbidities in type 2 diabetes.


During a mean of 2.2 years, the mean eGFR change was −3.6 ml/min/1.73 m2/year, and 31.6% of patients were classified as having rapid decline. Older age, causes of CKD, increased heart rate, systolic blood pressures, and proteinuria were associated with the highest baPWV quintile. In multivariate logistic regression analyses, the odds of a rapid decline in eGFR was 1.9 times higher in the fifth quintile than in the first quintile (P = 0.013). In a subset with baPWV and hfPWV (n = 1182), high baPWV was associated with rapid eGFR decline only when accompanied by a high hfPWV. These findings suggest that central and peripheral PWVs may simultaneously affect rapid eGFR decline.The impact of brachial-ankle pulse wave velocity (baPWV) and heart-femoral pulse wave velocity (hfPWV) on rapid decline of estimated glomerular filtration rate (eGFR) has been inconclusive. The database of a multicenter prospective study of 2238 patients in Korea enrolled from 2011 to 2016 was reviewed. After excluding patients with missing baPWV (n = 257) and eGFR change (n = 180), the study included 1801 non-dialysis chronic kidney disease (CKD) patients. The eGFR change <−5ml/min/1.73 m As CKD progresses, decreased kidney function can increase arterial stiffness3. Conversely, increased arterial stiffness can lead to deterioration of kidney function4. Whether there is a bidirectional association between increased arterial stiffness and decreased kidney function is unclear, but a recent study suggested that increased arterial stiffness affected the decline of kidney function uni-directionally5. This can be explained by the fact that increased arterial stiffness limits the dampening of ventricular ejection which transmits more pressure to the end organs6, and the increased pressure that is transmitted to the low-resistance renal afferent arterioles can damage the glomerular capillaries, resulting in reduced kidney function7.Chronic kidney disease (CKD) is a common form of chronic disease8, and the most validated PWV is carotid-femoral PWV (cfPWV), but its measurement requires expert techniques9. For more convenient and reproducible results, a device has been developed that uses an oscillometric method to record the pulse waves of the brachial and posterior tibial arteries, and it can calculate the brachial-ankle PWV (baPWV)10. The baPWV correlates well with cfPWV11, and evidence has shown that the baPWV is also a good marker of arterial stiffness13.The standard method to evaluate arterial stiffness is measuring the pulse wave velocity (PWV)16. However, different results have also been reported20. In addition, despite one Taiwanese group’s extensive efforts24, studies using the baPWV to predict the decline of kidney function have been insufficient, and their results were also inconclusive due to small patient numbers from single centers29. Therefore, we performed the current multicenter study to identify the clinical importance of the baPWV on the decline in kidney function using data on a large number of adults who were enrolled in the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD).Until now, many studies have suggested that increased arterial stiffness is associated with an increased risk of kidney function decline2 and 0.5 g/g creatinine, respectively. The mean ΔeGFR was −3.6 ml/min/1.73 m2/year, and 31.6% of the participants were classified as having a rapid decline in the eGFR. Of 1801 patients, data on dialysis initiation and CV events were available for 1784 (99.1%). During a mean of 2.4 years, 225 (12.5%) initiated dialysis and 74 (4.1%) developed CV events.There were 1801 patients in this study, of which 60.6% were men. The mean age of all patients was 54.0 years. The causes of CKD were diabetic nephropathy in 24.7% of patients, glomerulonephritis in 32.6%, hypertensive nephropathy in 19.9%, and other causes in 22.9%. At enrollment, the mean baseline estimated glomerular filtration rate (eGFR) and median urine protein-to-creatinine ratio (UPCR) were 51.7 ml/min/1.73 mWe compared the baseline characteristics of the patients according to the quintile of baPWV Table . Older a2/year  after adjusting for age, sex, systolic BP, pulse pressure, baseline eGFR, bilirubin, albumin, cholesterol, hemoglobin, and UPCR. We also analyzed the association between baPWV and the rapid decline of eGFR , suggesting that there was a non-linear association between the baPWV and a rapid decline in the eGFR. This non-linear association was confirmed in the penalized smoothing spline analysis, which was still unidirectional . Increased baPWV was inversely associated with the ΔeGFR Fig. . In the P = 0.035), we created four combined groups according to the status of baPWV and hfPWV: the low-ba/low-hf group , high-ba/low-hf group , low-ba/high-hf group  and high-ba/high-hf group . Participants in the high-ba/high-hf group had 2.1 times higher odds for having a rapid decline in the eGFR than those in the low-ba/low-hf group (P = 0.003) after adjusting for age, sex, diabetes, causes of CKD, pulse pressure, eGFR, logarithm of UPCR, albumin, cholesterol, hemoglobin, serum calcium levels, and beta blocker use. However, the odds for a rapid decline in the eGFR of participants in the high-ba/low-hf and low-ba/high-hf groups were not different from that of participants in the low-ba/low-hf group. In the subgroup analysis  with a rapid decline in the eGFR in a subset of 1182 participants with both baPWV and hfPWV Table . In the 16, their results do not always agree20. These previous studies used cfPWV as a marker of arterial stiffness. However, because cfPWV mostly reflects central or aortic stiffness8, using a broader marker of arterial stiffness may have a different clinical importance on the progression of CKD. In this regard, baPWV, which is a more convenient and reproducible marker of arterial stiffness than cfPWV30 may be an important alternative, because baPWV correlates well with both central and peripheral arterial stiffness31. Su and Chen et al. reported that increased baPWV was associated with an increased risk of the decline in kidney function24. However, studies that evaluated the association between baPWV and the decline in kidney function have been insufficient; the results were positive in some27, but negative in others29. Therefore, we performed the current study to identify the effect of baPWV on the decline in the eGFR, particularly focusing on its rapid change.Although many previous studies have suggested that increased arterial stiffness predicts a decline of eGFR levels33. Wang et al. reported that the eGFR was associated with decreased odds of a high baPWV  in 344 Chinese adults34. In their study, people with high baPWV showed higher urine albumin-to-creatinine ratio (7.52 mg/g) than those with normal baPWV , but the significance was not maintained in multivariate logistic regression analysis. These results were opposite from those of our study, in which the baseline eGFR was significantly associated with an increased baPWV in the univariate analysis, but not in the multivariate analysis. UPCR was associated with an increased baPWV in both the univariate and multivariate analyses. The participants in the study by Wang et al. were younger (median 37 years) than those in our study and had normal kidney function without overt proteinuria. Because different clinical settings might affect study results, subsequent studies are needed to confirm our results.We explored the factors that were associated with an increased baPWV. Among others, older age, causes of CKD, and increased systolic BP and heart rate were independently associated with an increased baPWV, which was similar to the results of previous studies27. However, previous researchers did not further evaluate the association between baPWV and a rapid decline in the eGFR. In our study, the odds of a patient being in the 5Q of baPWV with a rapid decline in the eGFR were 1.9 times higher than that of the 1Q of baPWV. The central arteries act as a buffer to dampen the pressure from the left ventricle, whereas the peripheral arteries absorb energy during systolic blood flow6. Since the relative contribution of central and peripheral arterial stiffness to the rapid decline of the eGFR has not been fully determined, we further compared the association between the hfPWV and baPWV and a rapid decline in the eGFR. In the analysis, only the baPWV was independently associated with a rapid decline in the eGFR, which suggested that central arterial stiffness alone was not sufficient to predict a rapid decline in the eGFR levels. However, this did not mean that central arterial stiffness was not an important determinant for the rapid decline in the eGFR, because a high baPWV was not associated with a rapid decline in the eGFR if it was not accompanied by a high hfPWV.In this study, baPWV was inversely associated with the ΔeGFR, which was concordant with the results of previous studiesIn the subgroup analysis, the odds of both high central and peripheral PWV for a rapid eGFR decline was evident in patients with diabetes, diabetic nephropathy, glomerulonephritis, and decreased kidney function, which are risky, but not yet established CV diseases. However, both high central and peripheral PWV was not associated with a rapid eGFR decline in patients with established CV disease which pulse pressure was already increased, and systemic inflammation was elevated. This signifies that high both peripheral and central PWV may reflect subclinical organ damage. Therefore, our results suggest that patients with both high peripheral and central PWV need to be treated more meticulously with special attention to the development of a rapid eGFR decline.This study has several strengths. First, this was the largest study that examined the clinical significance of the effect of the baPWV on the rapid decline in the eGFR levels. Second, because the study design was elaborate, we did not miss major variables. Third, simultaneous measurement of the hfPWV and baPWV enabled us to analyze these factors’ contributions to the rapid decline of eGFR levels. The study also has several limitations. First, the follow-up period was relatively short. The ΔeGFR may be exaggerated. Therefore, a longer follow-up period may stabilize the ΔeGFR value. However, the concordance of our results with those of previous studies may partly compensate for this limitation. Second, we did not evaluate other PWV data such as the cfPWV, heart-carotid PWV and femoral-ankle PWV. Therefore, a more detailed analysis of the contribution of central and peripheral arterial stiffness to the rapid decline in the eGFR was not possible. Third, the association between baPWV and hfPWV and eGFR change was modest, which may be affected by the imprecision of the measurement method. Finally, the single ethnicity of the patients in this study limits our ability to generalize our findings.In conclusion, an increased baPWV independently predicted a rapid decline in the eGFR levels. Although increased central PWV alone did not sufficiently lead to a rapid decline in the eGFR levels, an increased central PWV positively affected the association between the baPWV and the rapid decline in eGFR levels. This suggested that both central and peripheral arterial stiffness are important determinants of the rapid decline of eGFR. Future studies are needed to confirm the results of our study.http://www.clinicaltrials.gov)35. The protocol of the KNOW-CKD adhered to the principles of the Declaration of Helsinki and was approved by the institutional review board at each participating hospital, including Seoul National University Hospital, Yonsei University Severance Hospital, Kangbuk Samsung Medical Center, Seoul St. Mary’s Hospital, Gil Hospital, Eulji Medical Center, Chonnam National University Hospital, and Busan Paik Hospital. Written informed consent was obtained from all subjects. CKD and its stages were defined using the Kidney Disease Improving Global Outcomes 2012 guidelines36.The KNOW-CKD is a multicenter, prospective cohort study in Korea of 2238 patients with non-dialysis CKD stages 1–5 who were enrolled between February 2011 and January 2016. The detailed design and methods of the KNOW-CKD were previously published  were measured, and baPWV were automatically calculated by the VP-1000 analyzer using the following formula: baPWV = [La-Lb]/[pulse transit time] (cm/s), where Lb is 0.2195* patient’s height (cm) − 2.0734 and La is 0.8129* patient’s height (cm)+12.32810. The mean value of the right and left baPWV was used as the main study factor. In this study, we transformed the unit from cm/s to m/s.The baPWV was automatically generated using a VP-1000 analyzer 31. Electrocardiogram electrodes were placed on both wrists. The heart sounds S1 and S2 were detected by a microphone on the left edge of the sternum at the fourth rib cage. The time intervals between S2 and the notch of the carotid pulse wave (Thc), and between the carotid and femoral artery pulse waves (Tcf) were measured at the left carotid and femoral arteries by the VP-2000 analyzer. The sum of Thc and Tcf gives the time required for pulse waves to travel from the heart (aortic orifice) to the femoral artery (Thf). The hfPWV was calculated using the following formula: hfPWV = Lhf/(Thc + Tcf), where Lhf is the distance from the heart to the femoral artery37.In a subset of the participants (n = 1182), we also measured hfPWV, which is a marker of central stiffness, using a VP-2000 analyzer The PWVs of the first (1Q), second (2Q), third (3Q), fourth (4Q), and fifth quintiles (5Q) were <12.6 m/s, 12.6–13.9 m/s, 13.9–15.4 m/s, 15.4–17.7 m/s, and ≥17.7 m/s, respectively, for baPWV and <8.1 m/s, 8.1–9.1 m/s, 9.1–10.2 m/s, 10.2–11.9 m/s, and ≥11.9 m/s, respectively, for hfPWV. We defined high baPWV and hfPWV as a PWV value that was in the highest quintile of each PWV group (baPWV ≥17.7 m/s and hfPWV ≥11.9 m/s).38. At least two eGFR measurements that were taken 6 months apart were required to estimate the ΔeGFR. For each individual, the ΔeGFR was determined with a regression coefficient using a least-square linear regression analysis, with eGFR as a function of time in years, applied to all eGFR values that were obtained during the follow-up period in units of ml/min/1.73 m2/year. The main study outcome was the rapid decline of the eGFR, which was defined as a ΔeGFR <−5 ml/min/1.73 m2/year39. Mean follow-up time of ΔeGFR was 2.2 years.The serum creatinine concentrations were measured at a central laboratory  using an Isotope Dilution Mass Spectrometry-calibrated Jaffe method. eGFR was calculated using the Modification of Diet in Renal Disease study formula2. High pulse pressure and hsCRP were defined as above median values (50 mmHg in pulse pressure and 20 nmol/l in hsCRP). CV disease was defined as a physician diagnosis of cerebrovascular accidents, myocardial infarction, congestive heart failure, or peripheral arterial diseases. Body mass index was calculated as weight (kg) per square meter of height (m2). CV events were defined as hospitalization due to myocardial infarction , coronary revascularization, and stroke and new onset or aggravation of congestive heart failure.Clinical data, including detailed demographic information and baseline laboratory results, were extracted from the electronic data management system (PhactaX). When measuring baPWV, the VP-1000 device automatically measured systolic and diastolic blood pressure (BP) and heart rate. The difference between systolic and diastolic BP was pulse pressure. Hypertension was defined as systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mmHg or treatment with anti-hypertensive drugs. Diabetes was defined as fasting glucose ≥126 mg/dl, or treatment with insulin or oral anti-diabetic drugs. Low eGFR was defined as eGFR <60 ml/min/1.73 mP-trend was analyzed for normally distributed continuous variables using a linear-term of one-way analysis of variance (ANOVA), for non-normally distributed continuous variables using Jonckheere-Terpstra tests, and for categorical variables using a linear-by-linear association. Differences were analyzed using Bonferroni post-hoc analysis of a one-way ANOVA for normally distributed continuous variables, Mann-Whitney U tests for non-normally distributed continuous variables, and chi-square tests for categorical variables. The logarithms of hsCRP and UPCR were utilized in regression analyses. To assess linearity, we analyzed the regression coefficient (β) and 95% confidence interval (CI) with a linear regression analysis. The odds ratio (OR) and its 95% CI were calculated with a logistic regression analysis. A P-value of <0.05 was considered statistically significant. In the multivariate analysis, age, sex, and variables with statistical significance for the outcome variables that were determined in the univariate analysis were chosen as covariates. The interaction was analyzed by adding interaction-term in the regression modeling. The relationship between baPWV and the rapid decline of the eGFR was plotted using the penalized smoothing spline method, using the “pspline” package in R Statistics (version 3.03). All analyses, unless otherwise specified, were performed using SPSS Version 22 .The distributions of continuous variables were evaluated using histograms and Q-Q plots. Two variables, hsCRP and the UPCR, were not normally distributed. Normally distributed continuous variables are expressed as the mean ± standard deviation, non-normally distributed continuous variables are expressed as the median (interquartile range), and categorical variables are shown as percentages. The Available as supplementary material when accepted.Supplementary Information


Stress echocardiography is well validated for diagnosis and riskstratification of coronary artery disease. Exercise stress echocardiography(ESE) has been shown to be the most physiological among the modalities ofstress, but its safety is not well established.To study the complications related to ESE and clinical and echocardiographicvariables most commonly associated with their occurrence.Cross-sectional study consisting of 10250 patients submitted to ESE forconvenience, from January 2000 to June 2014. Cardiac Arrhythmias (CA) werethe most frequent complications observed during the examination. Thevolunteers were divided into two groups according to the occurrence of CAduring ESE: G1 group, composed of patients who have CA, and G2 formed byindividuals who did not show such complication. Results: Group G1,consisting of 2843 patients (27.7%), and Group G2 consisting of 7407patients (72.3%). There was no death, acute myocardial infarction,ventricular fibrillation or asystole. Predominant CAs were: supraventricularextrasystoles (13.7%), and ventricular extrasystoles (11.5%). G1 group had ahigher mean age, higher frequency of hypertension and smoking, larger aorticroots and left atrium (LA) and lower ejection fraction than G2. G1 groupalso had more ischemic changes (p < 0.001). The predictor variables wereage  and LA .ESE proved to be a safe modality of stress, with non-fatal complicationsonly. Advanced age and enlargement of the left atrium are predictive ofcardiac arrhythmias. However, literature on the method's safety and its complicationsis scarce.33 Therefore, the objective of this study is toanalyse the complications related to ESE and the clinical and echocardiographicalvariables that are predictors of these events.Although both methods of testing yield similarly accurate results in patients withwell-preserved physical capacity, Exercise stress echocardiography (ESE) is thebetter choice over pharmacological stress testing, with the latter being reserved tophysically impaired individuals or those with low motivation to exercise.This is an analytical and descriptive cross-sectional study conducted between January2000 and June 2014Clínica eHospital São Lucas (ECOLAB) in Aracaju, state of SãoPaulo. All patients over 25 years old, referred to the service by assistingdoctors, were included, with the exception of those who refused to participatein the study. The recommendations for the exam were: pre-operative, typical oratypical chest pain, risk stratification, positive or negative ET, inefficientET, check-up.The convenience sample was made up of 10250 patients with suspected orestablished CAD who were submitted to stress echocardiography through physicaleffort at the Echocardiography Laboratory of the Patients were divided into two groups according to the occurrence of the mostfrequent complications observed in ESE: G1 group - patients who presented suchcomplications in the exam, and G2 group - individuals with no complications.Clinical data were collected and recorded through interviews conducted prior tothe procedure. A structure questionnaire investigating weight, height, symptonssuch as dyspnea and chest pain, medications, CAD risk factors and history ofpersonal or family heart disease was used, together with relevant data such asprevious CADs such as acute myocardial infarction, percutaneous and surgicalrevascularization. In addition, previous results from lab work and examinationsof the cardiovascular system were registered.2.Hypercholesterolemia was defined as total serum cholesterol levels of over 200mg/dL (after fasting for 12 hours), and hypertriglyceridemia as serumtriglycerides levels greater than 150 mg/dL (after fasting for 12 hours) or useof antilipêmico agent (statins and / or fibrates).Obesity was characterized when body mass surpassed 30 kg/mSystemic arterial hypertension was considered when blood pressure levels measuredin the arm, in resting condition, were systolic blood pressure ≥ 140 mmHgand/or diastolic ≥ 90 mmHg, or when there was use of antihypertensivemedication.Diabetes mellitus was defined by the presence of fasting glucose over 126 mg/dLor by the use of insulin or oral hypoglycemic agents.Old myocardial infarction was defined through clinical history and/or previoussupplementary exams, such as ECG, echocardiogram and/or coronaryangiography.Firstly, the protocol consisted of the 12-lead ECG and resting echocardiogramafter clinical investigation. After that, physical effort on treadmill wasperformed, and soon after echocardiographic images were acquired again.2max)was obtained indirectly through the following formula: VO2max = 14.76- 1.379t + 0.451t2 - 0.012t3, in which t is the durationof the test34 in minutes. Theload was expressed as metabolic equivalents, in which 1 MET corresponds to 3.5mL/kg·min of inspired VO2, in resting.35 Throughout the test, the individuals werecontinuously monitored by 3-lead ECG.All patients were submitted to the standard Bruce or Ellestad protocols protocolsduring ergometric tests. There was continuous monitoring of heart rate, and thepatients were encouraged to reach their maximum physical effort. For metaboliccalculations, the volume of inspired oxygen at peak exercise  wall was evaluated byexperienced echocardiographer, with level III, as required by the AmericanEchocardiography Society. Segmental wall thickening of the LV was quantitativelyevaluated in resting and after physical effort through the 16 segment model withthe following gradual rank: 1, normal; 2, hypokinetic; 3, akinetic; 4,dyskinetic. The left ventricular motion score index (LVMSI) was calculated inresting and during physical exercise as the sum of the scores given to each ofthe 16 segments divided by the number of segments evaluated at that moment.LVMSI of 1 corresponds to normality; from 1.1 to 1.6 corresponds to milddysfunction; from 1.61 to 2, moderate dysfunction. Values of over 2 representsevere dysfunction.36 Thedifference between resting and physical exercise LVMSIs is called ΔLVMSI.The development of a new change in the parietal motility or worsening ofexisting dyssynergy (ΔLVMSI ≠ 0) were considered indicative of myocardialischemia.Exams were carried out with Hewlett Packard/Phillips SONOS 5500 up to 2012 andthen with Phillips IE-33, with due observance of technical aspects described bySchiller et al.29Patients were monitored for possible complications by 12-lead ECG before, duringand after physical exercise stress. The researched complications and theirrespective definitions were based on those described by Geleijnse etal.Major complications considered were: death, acute myocardial infarction, cardiacrupture, ventricular fibrillation and cardiac asystole.Minor complications were defined as: atrioventricular block (AVB), coronaryspasm, stroke, hypotension and hypertension at peak exercise, sustainedventricular tachycardia (> 30 beats / min), non-sustained ventriculartachycardia, sustained supraventricular tachycardia, non-sustainedsupraventricular tachycardia, ventricular premature beats and supraventricularextrasystoles.2) or Fisher's exact test. Continuous variableswere represented by mean +/- standard deviation and compared with the aid ofStudent's unpaired t test or Mann-Whitney U test, as appropriate.Categorical variables were presented as percentages and analyzed using thechi-square test  21.0 .To assess the risk factors predictive of complications to ESE we used univariateand multivariate Cox regression analysis. The variables included in themultivariate model were all of those with p < 0.1 in the univariate analysis.Multicollinearity problems were resolved prior to insertion of the variables inthe model. Forward selection of variables was used. Variables that remained inthe model were tested for possible interactions. Proportional hazards assumptionwas tested by Schoenfeld residual testing for each of the variables thatremained in the final model. Values of p < 0.05 were considered significant.Statistical analysis were processed by the software The ethical principles for human experimentation were followed thoroughly, andall patients signed an informed consent. The study was approved by the EthicsCommittee of the Federal University of Sergipe (CAAE 1818.0.000.107-06).A total of 10250 patients participated in the study; 4936 males (48.2%), with a meanage of 57.19 ± 11.24 years, limited to 25 and 93 years of age. There was norecord of major complications such as death, acute myocardial infarction, cardiacrupture, ventricular fibrillation and cardiac asystole.Cardiac arrhythmias were the most frequent observed complication during the exam, andthus the distribution of the groups was as follows: 2843 patients in the G1 group(27.7%), and 7407 patients in the G2 group (72.3%).One case of each of the following complications was recorded: AVB; coronary spasm;stroke; and arterial hypotension, which represented 0.009% of the sample. Arterialhypertension at the peak of physical effort was observed in 1011 individuals (9.9%of the population), of which 82% presented with systemic arterial hypertension (SAH)before the exam.The most frequently observed complications in this study were cardiac arrhythmias.The observed rates were non-sustained ventricular and supraventricular tachycardiaand ventricular and supraventricular extrasystoles be it isolated, in saves,bigeminal, monomorphic or polymorphic. Their frequency is described in The 10250 patients were divided into two groups: G1 group - made up of 2843 patients(27.7%) that presented with cardiac arrhythmias during the exam, and G2 group - madeup of 7404 patients (72.3%) with no arrhythmias.G1 group presented higher mean age, higher SAH frequency and smoking. Withregoards to gender and other associated comorbidities, both groups presentedsimilar frequencies In the transthoracic Doppler echocardiography there was significant difference inthe diameters of the aorta and the left atrium and in the left ventricular massand thickness. Ejection fraction of the LV was preserved in both groups, whichwas lower in G1 patients .In the ESE, there was a difference in the left ventricular motion score index inresting and during physical effort. There was also frequent presence ofmyocardial ischemia in G1 patients.The test to determine the presence of possible confounders in the model showedthat only two variables were independently associated to the occurrence ofcomplications. There was no interaction between the analysed variables .29 This may be dueto the mechanism through which stressor drugs act in the heart: dobutaminestimulates adrenergic receptors, increasing chronotropism and inotropism, and withgreat arrhythmogenic and hypertensive potential; dipyridamole stresses the heartmuscle by stimulating adenosine receptors and reducing subendocardial flow - it alsohas a negative chronotropic and dromotropic effect as well as bronchoconstrictoractivity. However, physical exercise represents a more physiological modality ofstress free of the side effects described above.18 There is also a selection bias: candidates eligible for thetest physical effort present with preserved ejection fraction, while pharmacologicalstress testing patients may have more advanced heart diseases.ESE proved to be safe in this study, with low frequency of complications, none ofwhich led to death. Death is more frequently observed in SE than in pharmacologicalstress testing.32In a large multicenter study with 85,997 patients undergoing SE - 26,295 of whichwere tested by physical stress and the others by pharmacological stress - there wasno death outcome in the group tested by ESE. In the pharmacological stress group,however, five deaths were observed. With regards to the frequency of lifethreatening events, the proportion of the in the ESE group was 1 in 6574, whereas inthe group receiving dipyridamole and dobutamine, we saw 1 in every 1294, and 1 inevery 557, respectively.33According to Sicari et al.18pharmacological stress from dobutamine triggers severe complications in 3 of 1,000patients, and pharmacological stress from dipyridamole triggers severe complicationsin 1 of 1,000 patients.In a Moroccan study with 311 patients, 206 of whom were submitted to ESE, no major orlethal events were registered.32The most frequente minor complications were arrhythmias, especially those with lesshemodynamic repercussions and easily reversible upon cessation of effort, such assupraventricular and ventricular extrasystoles. This is according to one study andis not mentioned in other bigger studies.32Arterial hypertension due to effort was observed in a significant portion of thesample (9.9% of cases) mostly in chronic hypertensive individuals. One of thereasons for this marked decompensation in the pressure response to stress may be theprotocol for exam preparation of our institution, which includes a suspention ofbeta-blockers for three days prior to the exam. There was a significant differenceconsidering the available literature, which may be because most studies usepharmacological stress, which may have severe hypotension and cardiogenic shock as aresponse in up to 7.6% of cases.33 In this study, agewas similar to that of this paper (59.2 years of age). However, diabetes mellitusand smoking were more prevalent and SAH was lower, differently from ourfindings.The clinical and demographic profile of the sample is only mentioned by Fennich etal.39 Thus, senescencewould provide changes that would culminate with left atrium dilatation anddysfunction, thus increasing predisposition to atrial arrhythmias,39 which may influence theiroccurrence when the patient is submitted to stress, as in ESE. Still with regards toage, this finding as an independent predictor of complications during ESE is veryimportant, considering this is a commonly observed fact in clinical practice.However, it is not yet described in relation to physical effort in literature.The predictor independent variables, left atrium, and age presented a closerelationship with each other. Some studies have reported that the size of the leftatrium would naturally increase with age.40 but still without supporting evidence for ESE.Another gap in the literature concerns the relation between the echocardiographicvariables and the occurrence of complications during ESE, considering that our studyfound several significant differences, and there are no studies about them. Anotherrelevant observation is that of a very significant difference in the presence ofmyocardial ischemia in patients who had adverse events during ESE, maybe due tocoronary arterial disease, which alters the cardiac electrical conduction system andinduces arrhythmias; a frequently studied event during pharmacological stress,included in the work of Abreu et al.41recommend the use of this methodology in moderate-risk patients, in clinicalpractice we often see it used in high-risk individuals. However, even in thosecases, no identifiable complications were found.Although current guidelinesThis study shows us interesting data that is still scarcely study in the field of ESE- a method that has been growing due to its versatility, reproducibility, andcost-effectiveness. We expect that this growth prompt new studies around thistheme.About the limitations of this study, we would highlight those applicable to anyobservational study, in which unmeasured variables may corroborate the statisticaldifference between the groups. In this sample, we also find a pre-selection bias,since patients submitted to ESE presented with based heart diseases or fisk factorsto their development.ESE is a safe stress modality, with no risk-of-death complications observed. Adverseevents recorded were minor and easily reversed by cessation of physical effort. Thesafety and feasibility of this stress mode associated with its important diagnosticand prognostic validity, justify its use in clinical practice.


Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders with an inflammatory basis. It is associated with hyperandrogenism in women and can be also associated with increased activity of the renin-angiotensin system (RAS). Approximately 5% to 10% of women of reproductive age are affected by this disease. This syndrome is the main cause of infertility. Blood pressure may be one of the complications of the syndrome.In this study, we sought to assess the role of the IL-17 inflammatory cytokine in increasing blood pressure in patients with PCOS.In this cross-sectional study, after obtaining informed consent, we evaluated 85 patients with PCOS. IL-17 serum level was measured after separating the serum via ELISA method. The results obtained for the two groups of patients with high blood pressure and normal blood pressure were compared with each other.P = 0.001). High blood pressure during the night also showed a direct relation with theIL-17 serum level (P = 0.001). In addition, increasing of ambulatory 24-hourblood pressure was significantly related with IL-17 serum level, in such a way that the IL-17 serum level of people with high blood pressure rose by almost 22 ρg/ml during 24 hours (P = 0.001).The daytime blood pressure was abnormal in eight patients, while it was normal in 72 patients. The blood pressure during the day had a direct correlation with the IL-17serum level; as a result, the mean IL-17 serum level in patients with high blood pressure was 77.10 ± 17.94 ρ g/ml while in those with normal blood pressure it was 55.20 ± 13.71 ρ g/ml (Our results showed an association between PCO syndrome and inflammatory factors. The IL-17 serum level was directly associated with the increase in blood pressure. This study has implication for the researcher as well as practitioners, gynecologist and internist.Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders which is associated with increased activity of the renin-angiotensin system (RAS) and hyperandrogenism in women. Approximately 5% to 10% of women of reproductive age (12-45 years old) are affected by this disease. This syndrome is considered to be one of the main causes of infertility . AccordiThere are strong evidence on the role of androgens in the development of hypertension in patients with PCOS . The mecThe clinical condition of hypertensive-associated vascular disease is an inflammatory process, in which chronic inflammation plays a key role in the pathophysiology of hypertension . This inNowadays, there are many evidences suggesting the role of IL-17 in inflammation of tissues. IL-17 acts via the induced release of pro-inflammatory cytokines and other cytokines which stimulate neutrophils . IL-17 cSince at least three different main pathways  are involved in the inflammatory responses, the identification of the major immunological pathway responsible for the development of any kind of inflammatory disease can play a potential important role in the treatment of the disease. Hence, any medical and therapeutic measure aimed to inhibit IL-17 cytokine can greatly help to treat various inflammatory responses . So far,According to the mentioned above findings, it is logical to assume that the activation of Th17/IL-17 pathway is at least one of the factors causing the inflammatory process in Hypertensive-associated vascular disease in patients with PCOS. It probably acts through stimulating the RAS. As a result, given the need to control hypertension in patients with PCOS , the conTo confirm the above mentioned hypothesis, in this study we tried to investigate the possible association between increased IL-17 serum level and 24-hour blood pressure in patients. Compared with the conventional measurement methods, the 24-hourambulatory measurement provides more reliable and accurate data about blood pressure, especially in individuals with hypertension . This stIn this cross-sectional study, after obtaining an informed consent, 85 patients with PCOS were enrolled to the study. Based on the inclusion criteria, patients with PCOS must meet at least two out of the three following criteria;A) Polycystic ovary confirmed by ultrasoundB) Oligomenorrhea C) Clinical hyperandrogenism .’ unwillingness to continue participation in the study.Exclusion criteria were the followings; hypothyroidism, hyperprolactinemia, androgen secreting tumor, non-classic adrenal 21-hydroxylase deficiency, chronic kidney injury, congestive heart disease, confirmed diabetes mellitus, chronic hypertension, acute illness, all autoimmune and non-autoimmune inflammatory diseases, different types of cancer, and patients (FBS), thyroid stimulating hormone (TSH), prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEAS), triglyceride (TG), cholesterol, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), CRP, insulin, free testosterone, and 17-hydroxyprogesterone were measured. The 24-hour ambulatory blood pressure monitoring was performed by every patient at regular time intervals via using a mobile device. Blood pressure was measured during the day and at night separately. A blood pressure over 125/75 mm Hg during the night and over 140/90 mm Hg during the day and an overall blood pressure over 135/85 mm Hg were considered abnormal. When a patients’ blood pressure was 15% above the normal values, the condition was considered as abnormal. In addition, when a patient’s blood pressure over the night did not lower by 15% relative to the day time blood pressure, the condition was also considered as abnormal.For all the studied subjects; BMI and levels of fasting blood sugarIL-17 serum level was measured after separating the serum via ELISA method and using USCN kit made in the United Kingdom with a catalog number of E90384Hu and Lot number of L120605095.After collecting the data, the results obtained for the two groups of patients with high and normal blood pressure were compared with each other. First, the statistical indicators of IL-17 serum level, blood pressure, and demographic factors  were calculated.1) The research followed the tenets of the Declaration of Helsinki; 2) informed consent was obtained, and they were free to leave the study at any time and 3) the research was approved by the ethical committee of Kashan University of Medical Sciences.Pearson’s correlation coefficient or Spearman’s test were used to assess the correlation between systolic and diastolic blood pressure and the mentioned factors. In addition, multiple regression analysis was conducted to examine the association between IL-17serum level and blood pressure; it was also used to adjust for potential confounding variables such as age and BMI.A total of 85 patients were enrolled in the study. The mean age of the patients was 26.31 ± 4.1 years, ranging from of 17 to 39 years. The mean IL-17 serum level was 57.3 ± 15.6 ρg/ml. The data of patients illustrated in tables 1 to 3.2 which was higher than the normal range. However, this index did not show a significant relationship with IL-17 serum level (P=0.05). On the other hand, the FBS levels in the studied patients was 88.48 ± 19.14 mg/dl, which did not show a significant relationship with IL-17 serum level (P=0.25). Around 16 patients had high insulin levels; however, this hormone did not show a significant relationship with IL-17 serum level (P=0.21) (The mean BMI in the studied subjects was 27.65 ± 5.05 kg/m(P=0.21) .P=0.001) (P=0.001). In addition, the increase in ambulatory 24-hour blood pressure was significantly related with IL-17 serum levels. Our study showed that, IL-17 serum level of people with high blood pressure rose by almost 22 ρg/ml during 24 hours (P=0.001).The daytime blood pressure was high in eight patients while it was normal in 72 patients. The daytime blood pressure value was associated with IL-17 serum levels. There was an increase in daytime blood pressure which was correlated with increasing the IL-17 serum levels. The results showed that, the mean IL-17 serum level in patients with high blood pressure was 77.10 ± 17.94 ρg/ml while in those with normal blood pressure it was 55.20 ± 13.71 ρg/ml, which showed a statistically significant increase (P=0.001) . Moreove2 in people with high ambulatory blood pressure while it was 27.10 ± 4.69 kg/m2 in those with normal ambulatory blood pressure. With an increase in blood pressure level, BMI was increased too (P=0.009)  .The mean IL-17 serum level in the studied patients was 57.33 ± 15.6 ρg/ml. The BMI of the patients was also high which was in an agreement with the results of a study by Elting et al in 2001 . On the Another important finding in our study was no significant association of FBS and insulin levels in patients with PCOS with levels of IL-17. Although insulin level had increased to some extent, but this increase was not associated with IL-17. Considering other inflammatory cytokines, our results was contradictory with the results of some other studies. For example, some studies have shown that IL-18 cytokine is closely associated with insulin resistance and metabolic syndrome, including high blood pressure, hyperlipidemia, diabetes mellitus, obesity, and hypertension ,31. MoreIn our study, serum TSH level was normal in all the studied patients and we did not observe any increase or decrease in thyroid function. In addition, prolactine and FSH levels were normal in all the patients and they did not have any significant relationship with IL-17 serum level. In our study, LH levels increased only in three patients and its relationship with serum IL-17 was not significant. Considering other inflammatory cytokines, our results are inconsistent the results of a study by González et al in 2010. They showed that the macrophage migration inhibitory factor (MIF) chemokine macrophage in patients was significantly higher than that in the control group and its level was directly associated with the trunk obesity, CRP, LH, testosterone, and androstenedione . In addiIn this study, the levels TG and cholesterol were high in five patients. There was no significant relationship between IL-17 serum level and TG-C, cholesterol, LDL-C, and HDL-C levels. This finding is inconsistent with the results of a study by González et al. They showed that the IL-6, sICAM-1, CRP, PAI-1, systolic and diastolic blood pressure, TGs, fasting insulin, and insulin resistance (HOMA-IR) levels were higher in patients with PCOS than in the controls. MCP-1 chemokine was associated with NFκB activation, hyperglycemia, and increased androstenedione. In addition, the levels of sICAM-1, IL-6, and CRP were higher in patients with PCOS who were obese . In addiIn this study, we found that the ambulatory 24-hour blood pressure during the day and night had a significant relationship with IL-17, hence, the IL-17 level was higher in patients with high blood pressure. This finding is in line with the results of a study by Kaya et al in 2010. In this study, we aimed to determine the relationship between IL-6, CRP, fibrinogen, and nitric oxide levels and ambulatory blood pressure in women with PCOS. The results showed that the increased levels of IL-6 were probably associated with 24-hour systolic and diastolic blood pressure of the patients. The study showed that the level of IL-6 in patients with high blood pressure was higher while the level of NO was lower . It is pOur study showed that the ambulatory blood pressure had a direct relationship with BMI, while an increase in BMI, blood pressure increased too. The results of this study are consistent with the results of a study by Elting et al which was conducted on women with PCOS. The mentioned study showed that blood pressure of the patients was significantly higher than the control group. On the other hand, the studied patients had significantly higher levels of BMI and weight gain .In our study, insulin level in patients with high blood pressure was lower than that in patients with lower blood pressure. However, the difference was not significant. This result is inconsistent with the results of a study by Bentley-Lewis et al  that exaConsidering the significant association between blood pressure level and IL-17 pro-inflammatory cytokine secreted from Th17 cells, it can be concluded that metabolic syndrome, which is a major cause of mortality and morbidity in patients with PCO, is under the influence of inflammatory factors. Therefore, the increased level of such factors can enhance the related complications in the patients. Therefore, control of inflammation and prevention of autoimmune processes by treatmental modalities and also the interruption of inflammatory cascade can affect both the disease and its complications.Small proportion of the patients was a limitation of our study. It is recommended to conduct further studies to determine the factors which interfere with or are associated with the immune system and other inflammatory pathways such as Th22 pathway. It is also recommended to study the protective factors and methods used to prevent the onset or exacerbation of inflammatory processes.This study is adapted from the M.D. thesis of Elham Arbab. The authors gratefully acknowledge from Dr. Alireza Moraveji, Dr. Hassan Nicoeinejad and Mr. Mehrdad Zahmatkesh who have otherwise contributed to the preparation of the manuscript.All authors contributed equally and signed the manuscript.The authors declared no competing interests.This study was a funded thesis at Kashan University of Medical Sciences (Grant# 91087).


Hemodialysis is usually required for the patients with end-stage renal failure. In the hemodialysis patients, abnormal blood pressure is commonly seen. In addition, the abnormalities of blood biochemical components are also common in hemodialysis patients. Recently much attention has been directed toward the blood pressure level and serum uric acid concentration in hemodialysis patients. However, the result of studies are contradictory and the linkage between observed serum uric acid and blood pressure requires further investigation.Hemodialysis is usually required for the patients with end-stage renal failure. In the hemodialysis patients, abnormal blood pressure is commonly seen. In addition, the abnormalities of blood biochemical components are also common in hemodialysis patients. Recently much attention has been directed toward the blood pressure level and serum uric acid concentration in hemodialysis patients . In a stVW is the single author of the manuscript.The author declared no competing interests.Ethical issues  have been completely observed by the author.None.


Metabolic syndrome is a cluster of the most dangerous heart attack risk factors such as diabetes and prediabetes, abdominal obesity, high cholesterol and high blood pressure. Hyperuricemia is a condition in which the serum uric acid concentration is greater than 5.5 mg per deciliter for child and greater than 7.2 and 6.0 mg per deciliters for male and female adults respectively.A cross-sectional study was conducted to determine the magnitude of hyperuricemia and associated factors among type 2 diabetes mellitus patients at Hawassa Comprehensive Specialized Hospital (HCSH) from February 28 to May 30 /2017. A random sampling technique was used to include 319 study subjects and a signed consent had been provided by each study subject before running any data collection. An interviewer administered structured questionnaire was used to collect socio-demographic and some clinically useful data. In addition to this, we reviewed the records of the study subjects to obtain other useful clinical data. Five milliliter blood specimen was collected from each study subjects after overnight fasting. A25TM Bio-System Random Access chemistry analyzer was used for blood sample analysis. All data were checked visually, coded and entered into epi-data version 3.4 and statistical analysis was performed using SPSS version 20.0 software. Bi-variate and multivariate logistic regressions were used to determine the association between explanatory and the outcome variables.n = 106) and 70.1% (n = 220) respectively. Having age greater or equal to 45 years  and having metabolic syndrome  were the determinant variables for hyperuricemia among type 2 diabetic patients.The prevalence of hyperuricemia and metabolic syndrome among type 2 diabetic patients in the study area were 33.8%(There was high prevalence of hyperuricemia among type 2 diabetic patients with high prevalence of metabolic syndrome. Therefore, regular health information about life style modification, early diagnosis and treatment for hyperuricemia and metabolic syndrome are essential to reduce hyperuricemia and metabolic syndrome in type 2 diabetic patients. Diabetes is a chronic, progressive disease characterized by elevated levels of blood glucose. Type 2 diabetes mellitus (T2DM) results from the body’s ineffective use of insulin and it accounts for the vast majority of people with diabetes around the world. If diabetes is not well managed complications that may threaten and endanger life may develop –3. MetabHyperuricemia is a condition in which individuals have higher levels uric acid concentration in the serum or when serum levels of uric acid concentration is greater than the upper normal reference limits particularly greater than 5.5 mg per deciliter(mg/dl) for children and greater than 7.2 and 6.0 mg/dl respectively for both male and female adults. Uric acid is a final enzymatic product in the degradation of purine nucleotides and it has the ability to scavenge oxygen radicals and protect the erythrocyte membrane from lipid oxidation , 14. It The main aim of the current study was to determine the prevalence of hyperuricemia and MetS in T2DM patients and associated risk factors. Furthermore, the study was also aimed to identify the correlation between biochemical measurements such as high density lipoprotein cholesterol, triglycerides, glucose and hyperuricemia.The aim of the current study was to determine the magnitude of hyperuricemia and metabolic syndrome and associated risk factors in T2DM patients. The Study was conducted at Hawasa University comprehensive specialized Hospital (HUCSH) from February 28 to May 30 /2017. HUCSH was established in November, 2006 and it is providing service for more than 15 million people of the Region. Currently, the hospital has over 400 beds and offers services at general and specialty level. There are 1323 registered T2DM patients at HUCSH, of which 1015 were T2DM and the remaining were type 1 diabetes mellitus. An institution based cross-sectional study design was implemented. All T2DM patients attending HUCSH diabetic clinic were source population. Those T2DM patients visiting HUCSH diabetic clinic during study period and selected based on inclusion criteria were considered as study subjects.A single population proportion formula was used to calculate the minimum sample size required and a random sampling technique was used to select 319 T2DM subjects by lottery method from 982 T2DM patients attending HUCSH. And those T2DM patients who had been taking blood lipid lowering therapy, pregnant, contraceptive users and history of hospitalization for thyroid disorders were excluded from the study.2 in kg/m2). Waist circumference (WC) was measured at the midpoint between the lower margin of the least palpable rib and the top of the iliac crest, using a stretch-resistant tape. WC was measured after instructing each study subject to stand with feet close together, arms at the side and body weight evenly distributed, wearing light clothes. The measurement was taken twice and the average was taken when the difference between the two measurements was within 1 cm and repeated measurements were taken when the difference between the two measurements was greater than 1 cm. Based on the WHO guideline manual of 2008 WC greater than 80 cm and 94 cm was considered abnormal for female and male respectively .Training was given for data collectors before any data collection. Interviewer administered structured questionnaire was developed for this study and used to collect all socio-demographic, and some clinical data. The medical record was reviewed to collect some secondary data. The data were collected by trained professional nurses working at diabetic clinic. Anthropometric data (weight and height) were collected according to WHO guideline manual . Body maSystolic blood pressure (SBP) and diastolic blood pressure (DBP) was measured using mercury based sphygmomanometer after the subjects had rested for more than 10 min. For those study subjects with a SBP ≥ 140 mm of mercury (mmHg) and a DBP ≥ 90 mmHg, blood pressure was measured again and finally the average value was taken.First five milliliter of venous blood was collected from each study subject after over night fasting. Secondly, the blood specimen was allowed to stay for 20–30 min for clot formation. Then, the specimen was centrifuged at 3000 revolution per minute (rpm) and the serum was separated from the whole blood. Finally, the serum was analyzed for HDL-C triglycerides (TGs), fasting blood sugar and uric acid by using A25™ Biosystem random access chemistry analyzer .Triglyceride (TG) was measured enzymatically in serum using a series of coupled reaction in which TG is hydrolyzed to produce glycerol. Glycerol is then oxidized to produce 4-(benzoquinone- monoimino)-phenazone that absorbs light and the amount of absorbed light that is directly proportional to the concentration of TG in the sample was measured spectrophotometrically at 500 nanometer (nm). HDL-C is measured directly in serum in which apo-B containing lipoproteins such as chylomicrons(CM), very low density lipoprotein(VLDL) and low density lipoprotein (LDL) in the specimen are reacted with a blocking reagent that makes them non-reactive with the enzymatic cholesterol reagent under conditions of the assay. As the result, the apo-B containing lipoproteins are effectively excluded from the assay and only HDL-C is detected under the assay condition.Uric acid was also measured enzymatically in which uric acid is oxidized by uricase enzyme to produce allatoin and hydrogen peroxide. The hydrogen peroxide reacts with 4-aminoantipyrine and 3.5-dichloro-2-hydroxybenzene sulfonate in a reaction catalyzed by peroxidase enzyme to produce a colored product. The amount of light absorbed by the colored product which is directly proportional to the concentration of uric acid in the sample was measured spectrophotometrically at 520 nm.Fasting blood sugar was measured enzymatically based on the glucose oxidase test principle in which glucose oxidase oxidizes beta D-glucose into D-gluconic acid and hydrogen peroxide. The hydrogen peroxide enters in to the second reaction involving p-hydroxybenzoic acid and 4-aminoantipyrine in the presence of peroxidase with the formation of a quinoneimine dye complex. This complex whose concentration is directly proportional to the concentration of glucose in the sample was measured spectrophotometrically at 510 nm.All collected data were checked for consistency and completeness daily by principal investigator. The pre-analytical, analytical and post analytical factors that can interfere to the results of biochemical measurements were controlled and maintained by medical laboratory technologist doing the specimen analysis. The proper functioning of instruments, laboratory reagents and technical performance were checked daily by using quality control samples before running patient samples and along with the patient samples and the run was repeated for the result fallen outside established values.P value less than 0.25 in bivariate logistic regression model were moved to multivariate logistic regression to control possible confounder variables as well as to identify independent predictor variables that have statistically significant association with high concentration of uric acid (hyperuricemia). P value less than 0.05 in multivariate logistic regression was considered as statistically significant association.All data were checked for consistency and completeness visually, and coded and entered into epidata version 3.4. SPSS version 20.0 software was used statistically for data analysis. Descriptive statistics like frequency and percentages were also used to describe data. Categorical variables were expressed as percentages. In addition, evaluation of differences in means of study groups was evaluated using student’s t-test and categorical variables was analyzed using chi-square tests and or fisher exact test. Pearson correlation coefficient was used to see the correlation between the dependent variable and MetS components. Bivariate and multivariate logistic regression models were used to assess statistically significant association between independent and dependent variables and those independent variables whose The study design was a cross-sectional which is referenced only about a single point in time. We did not also measure serum insulin concentration.MetS: is defined according to National Cholesterol Education Program, Adult Treatment Panel (USNCEP-ATP) III guideline. Patients who have at least three of the following risk features to categorize in MetS: abdominal obesity ; elevated TGs (≥ 150 mg/dl); low HDL-C ; elevated blood pressure and fasting blood sugar (FBS) > 110 mg/dl .Raised Blood pressure or hypertensive: When systolic blood pressure is ≥ 130 or diastolic blood pressure is ≥ 85 mmHg according to national Cholesterol Education program (NCEP) definition criteria .Hyperuricemia: Patients having serum uric acid levels more than 7.2 mg/dl in males and more than 6.0 mg/dl in females .http://www.WHO.int/dietphysicalactivity/pa/en/.].Regular physical activity: moderate physical activity such as walking, cycling or doing sport that has significant benefits for health [n = 211) of the study subjects were males and the remaining were females. The mean age of the study subjects was 49.8 ± 9.8 with the range of 30 to 80 years. Fifty one percent (n = 159), 88.5%(n = 278), 68.2%(n = 214) study subjects were urban dwellers, married, unemployed respectively. Majority, 82.5%(n = 259) study subjects travelled either by public transport or on foot. The educational status of about 40.4% (n = 127) study subjects was identified as greater or equal to secondary education. The prevalence of hyperuricemia and MetS were 33.8% (n = 106) and 70.1%(n = 220) respectively. The serum uric acid concentration was higher among male study subjects when compared to female (22.3% versus 11.5% respectively) and the prevalence was also higher among greater or equal to 45 years age group than age groups less than 45 years old (24.2% versus 9.6% respectively). The prevalence of hyperuricemia was also higher among study subjects with non-family history of diabetes as compared to study subjects with family history of diabetes (25.2% versus 8.6% respectively). Higher prevalence of serum uric acid concentration was determined among study subjects with less or equal to 10 year duration of diabetes as compared to the study subjects with greater duration of diabetes (26.4% versus 7.3% respectively). Moreover, higher serum uric acid concentration was determined among T2DM patients with MetS and among those with no history of regular exercise (27.7% and 24.8% respectively) as compared to those study subjects without MetS and with history of regular exercise (6.0% and 8.9% respectively).A total of 319 study subjects were enrolled in this study and a 98.4% response rate was obtained. Majority, 67.0% . However, the highest prevalence of hyperuricemia, 16.6% (n = 52), was determined among overweight study subjects (BMI: 25–29.9 kg/m2) when compared to those study subjects with under (< 18.4 kg/m2) or normal (18.5–24.9 kg/m2) body weight and central obesity (≥ 30 kg/m2). There was no significant difference in serum uric acid concentration between non-hypertensive and hypertensive T2DM patients (19.7% versus 14.0% respectively) (Table The serum uric acid concentration had no significant difference among study subjects with body mass index (BMI) of 25–29.9 kg/mn = 106) hyperuremic T2DM patients, about 27.7%(n = 87) of them had MetS. This indicates that the prevalence of MetS is significantly high among type 2 diabetic patients with abnormal serum uric acid concentration. There was positive correlation between high prevalence of MetS, 70.1%(n = 220) and abnormal serum uric acid concentration, 27.7%(n = 87) in T2DM patients . Abnormal serum uric acid concentration was determined among 12.7%(n = 40) study subjects with both central obesity and higher diastolic blood pressure  and among 15.6%(n = 49) study subjects with higher systolic blood pressure . Hpertriglyceridemia, reduced HDL-C and hyperglycemia were determined among 70.4%(n = 221), 39.2%(n = 123) and 80.0% (n = 252) study subjects respectively. The abnormal serum uric acid concentration was determined among 31.2%(n = 98) of study subjects with hypertriglyceridemia  and among 12.1%(n = 38) study subjects with reduced HDL-C9 P value = 0.4) and in 29.3%(n = 92) subjects with hyperglycemic   more likely to develop hyperuricemia when compared to those with less than 45 years old. T2DM patients with MetS were about 2.6 times  more likely to develop hyperuricemia when compared to those without MetS. Those study subjects with history of alcohol consumption during the study period were about 1.6 times  more likely to develop hyperuricemia than those without history of alcohol consumption. Similarly study subjects with history of cigarette smoking were about 1.1 times  more likely to develop hyperuricemia than those who did not smoke and also those who did not perform regular exercise were about 1.5 times  more chance to develop hyperuricemia than those who had been performing regular exercise  was used to determine the prevalence of MetS in the current study. According to NCEP-ATPIII, the prevalence of MetS in current study was higher than the finding reported from Cameroon by similar criteria  and muchAge greater or equal to 45 years and MetS were the only two parameters identified as independent predicator variables for high prevalence of hyperuricemia in T2DM patients. Clinical parameters like high BMI, hypertension, WC, fasting blood sugar and biochemical parameters like TG and low HDL-C were not identified as risk factors for hyperuricemia unlike the study reported from China .High prevalence of hyperuricemia and MetS was determined in T2DM patients. Both MetS and age greater or equal to 45 years were identified as independent predictor variables for the high prevalence of hyperuricemia in T2DM patients. Hypertriglyceridemia, hyperglycemia and low HDL-C had positive correlation with the high prevalence of hyperuricemia in T2DM patients.


Background. Lung recruitment maneuver (LRM) during thoracic surgery can reduce systemic venous return and resulting drop in systemic blood pressure depends on the patient's fluid status. We hypothesized that changes in systemic blood pressure during the transition in LRM from one-lung ventilation (OLV) to two-lung ventilation (TLV) may provide an index to predict fluid responsiveness. Methods. Hemodynamic parameters were measured before LRM (T0); after LRM at the time of the lowest mean arterial blood pressure (MAP) (T1) and at 3 minutes (T2); before fluid administration (T3); and 5 minutes after ending it (T4). If the stroke volume index increased by >25% following 10 mL/kg colloid administration for 30 minutes, then the patients were assigned to responder group. Results. Changes in MAP, central venous pressure (CVP), and stroke volume variation (SVV) between T0 and T1 were significantly larger in responders. Areas under the curve for change in MAP, CVP, and SVV were 0.852, 0.759, and 0.820, respectively; the optimal threshold values for distinguishment of responders were 9.5 mmHg, 0.5 mmHg, and 3.5%, respectively. Conclusions. The change in the MAP associated with LRM at the OLV to TLV conversion appears to be a useful indicator of fluid responsiveness after thoracic surgery. Trial Registration. This trial is registered at Clinical Research Information Service with KCT0000774. According to the Frank–Starling relationship, patients on the ascending portion of the cardiac function curve should show an increase in stroke volume and cardiac output (CO) by volume expansion, whereas patients on the flat portion of the relationship are not expected to show a significant change in the stroke volume and CO with similar volume expansion . TherefoDynamic parameters such as stroke volume variation (SVV) and pulse pressure variation (PPV) have been introduced to determine the exact condition of the patients, namely, fluid responsiveness; these parameters are useful for ensuring optimal fluid therapy –5. CycliThoracic surgery, using thoracotomy or video-assisted thoracic surgery (VATS), is typically performed in the lateral decubitus position, which is associated with decreased pulmonary blood flow, altered lung compliance, and increased intrathoracic pressure, thereby affecting SVV and PPV accuracy , 10. MorThe lung recruitment maneuver (LRM) is routinely used toward the end of thoracic surgery during the transition from one- to two-lung ventilation (OLV to TLV) to improve oxygenation and confirm the absence of air leakage –14. HoweThe aim of the present study was to identify useful parameters for fluid management in thoracic surgery patients. Herein, we hypothesized that changes in systemic blood pressure during transition in LRM from OLV to TLV may provide an index to predict fluid responsiveness.http://cris.nih.go.kr (KCT0000774). Written informed consent was obtained from patients undergoing thoracic surgery under thoracotomy or VATS with OLV at a university teaching hospital between May 2013 and December 2013; patients were studied prospectively. The exclusion criteria were (1) urgent or emergency case; (2) age <18 years or >80 years; (3) an arterial partial oxygen pressure (PaO2)/fraction of inspired oxygen (FiO2) ratio < 300 mmHg before anesthesia induction; (4) impaired left and right ventricular function (ejection fraction < 40%); (5) preoperative dysrhythmia; (6) cardiac valvular or shunt disease; and (7) peripheral vascular disease. Using a parallel study design, patients were divided into responder (group R) and nonresponder (group N) groups. To determine responder or nonresponder status, colloid solution , at 10 mL/kg of ideal body weight, was administered toward the end of the surgical procedure with patients in a supine position  × 7 mL; respiratory rate was controlled using end-tidal carbon dioxide pressure  administration according to hemodynamic parameters  and the discretion of the attending anesthesiologist. Crystalloid solution with plasma solution A Inj.®  2 mL/kg/h was administered according to fluid maintenance requirements, redistribution, and evaporative surgical fluid losses. The attending anesthesiologist performed additional separate laboratory tests in cases of acute surgical bleeding. If hematocrit (Hct) was >30%, then colloid solution with Volulyte  was administered to replace blood loss and maintain stable hemodynamic status. If Hct was <30%, then transfusion was started.During anesthesia, systemic mean blood pressure (MAP) was maintained at >60 mmHg, and the cardiac index (CI) at >2.0 L/min/m2O for 10 s, repeated three times) was applied to improve oxygenation and confirm an absence of air leakage. After thorax closure, the patient was moved from the lateral to supine position, and colloid solution at 10 mL/kg of ideal body weight was administered for 30 min to confirm and determine assignment to group R or N. MAP (mmHg), HR (beats per minute), and central venous pressure  derived by an invasive arterial and central pressure monitoring device and cardiac output , CI (L/min/m2), SVI, and SVV (%) derived by a pulse contour analysis device were measured before (T0) and after LRM at the point of lowest MAP (T1) and at 3 min (T2) before administration of colloid solution at 10 mL/kg of ideal body weight (T3) and 5 min after its cessation . For changes between T0 and T1, a minimum detected difference of 40% (MAP of 10 mmHg) among groups was considered clinically significant. A sample size of 38 in each group was calculated as appropriate to achieve a power of 0.9 and α value of 0.05.The primary outcome variable was change in MAP from t-test with the normality test or the Mann–Whitney rank-sum test. Within-group analysis of continuous variables was performed using one-way repeated measures analysis of variance of Friedman or repeated measures analysis of variance on ranks test. Categorical variables were analysed using the chi-squared test. To obtain cut-off values for changes in hemodynamic parameters (to distinguish responders and nonresponders), area under the curve (AUC), using receiver operation characteristic (ROC) curve analysis, was performed and the Youden index was used. Data are expressed as mean ± SD, median values (25%–75%), or numbers of patients. A value of p < 0.05 was taken to indicate statistical significance.Statistical analyses were conducted using the SPSS for Windows software package . Between-group analysis of continuous variables was performed using Student's n = 38 in each group) and 31 excluded; of these, 14 declined to participate, 8 exhibited preoperative dysrhythmia, and 5 were characterized by a PaO2/FiO2 ratio < 300 mmHg before anesthesia induction; in four cases there was an instrumental error . SVI in group R at T1 was significantly lower compared with group N (p = 0.003 at T1). SVV in group R at T1 was significantly higher compared with group N  and increased to the before LRM level (T0). CVP and SVV were increased significantly at T1. All hemodynamic parameters at T1 were definitely different compared with those at T0. In comparisons of hemodynamic profiles within group N, MAP, CO, CI, and SVI were decreased significantly at T1 and T3. HR, CVP, and SVV were unchanged by LRM  and after (T1) LRM, compared among groups, were calculated by subtracting values for T0 from T1. Changes in MAP, CVP, and SVV, between T0 and T1 in group R, were significantly greater compared with group N ; however, no other value differed, especially CI and SVI , 0.759 , 0.820 , 0.596 , and 0.653 , respectively. The optimal threshold values for changes in MAP, CVP, SVV, CI, and SVI between T0 and T1, used to distinguish responders from nonresponders according to the ROC curve analysis, were 9.5 mmHg , 0.5 mmHg , 3.5% , 0.65 L/min/m2 , and 4.5 mL/m2/beat , respectively  during thoracic surgery with OLV. However, the difference in, and cut-off value for, CVP for fluid responsiveness was insufficiently large to infer clinical applicability. Additionally, the AUC derived from ROC curve analysis for change in SVV was smaller than that observed for MAP. Therefore, changes in MAP, of approximately 10 mmHg derived during LRM, could represent a useful indicator of fluid responsiveness in patients undergoing thoracic surgery with OLV.Fluid therapy during thoracic surgery is important for oxygenation and hemodynamic stability. First, thoracic surgery with OLV is itself a risk factor for pulmonary dysfunction due to lung manipulation and attendant risk of ischemic or reperfusion-reexpansion injury. Second, excessive intravascular volume can induce pulmonary edema and exacerbate ventilation-perfusion mismatch and insufficient oxygenation. In contrast, restrictive intraoperative fluid administration, used to prevent pulmonary dysfunction, can induce unstable hemodynamic status . GeneralT0, SVV was <10.5% for both groups, which is notable because both were considered nonresponders during OLV. This latter observation indicates that volume status following transition from OLV to TLV, during thoracic surgery with OLV, might be inadequate, although adequate volume status was maintained with SVV during OLV. For both groups at T2, in the lateral position with TLV, and at T3 in the supine position with TLV, the increase in SVV was limited compared with T0 in the lateral position with OLV. Therefore, additional fluid management is not necessary according to the values of SVV because the increase in SVV was limited and within the normal range.Dynamic parameters, such as SVV and the PPV-derived heart-lung interaction, have been established previously as good indicators of fluid responsiveness during thoracic surgery with OLV , 20. AccT0 observed herein might be associated with the low tidal volume of 7 mL/kg.There are some reasons to use a low SVV cut-off value to discriminate between responders and nonresponders during OLV versus TLV , 21, 22.T0). The anesthesia during surgery was maintained by the same attending anesthesiologist with constant guideline  so that the intraoperative fluid management might be similar in both groups. Finally, LRM was applied to patients toward the end of the operation, when OLV was converted to TLV, such that the technique did not facilitate fluid management during the major part of the operation. However, LRM was a good predictor of fluid responsiveness; therefore, if employed during operations, this technique could aid fluid management. The standardization of LRM was crucial. Because it was performed on the patients with good lung compliance, not poor lung compliance, by a single anesthesiologist, the effect on the heart was not different.Several other caveats are discussed presently, the first of which pertains to patients' position. Generally, large blood vessels  involved in venous return to the heart are located on the right side of the thorax; the influence of lung inflation by LRM on LVSV might differ according to whether the operation site is on the right or left. However, in our patients the operation sites were distributed similarly in both groups, which might have limited any effect of operation site. Second, there was no data about fluid balance during surgery before LRM. However, the hemodynamic profiles in both groups were in normal range and stable before LRM (We evaluated the cardiac performance and SVV using arterial pulse contour analysis. Although the gold-standard method of measuring cardiac performance is the thermodilution technique, numerous evidences have supported that it can be substituted by arterial pulse contour analysis , 27. It As mentioned previously, it had been established that excessive perioperative fluid administration was risk factor of postoperative respiratory dysfunction and mortality in thoracic surgery so that the restrictive fluid management has been considered as standard therapy –31. HoweIn conclusion, changes in MAP before and after LRM, during transition from OLV to TLV, might be a useful predictor of fluid responsiveness in thoracic surgery with OLV; the optimal threshold value to discriminate between responders and nonresponders was 9.5 mmHg.