The aim of this study was to examine in elderly men a relationship between depressive symptoms, peripheral vascular disease and cerebral blood flow (CBF).99mTc-HMPAO-SPECT to estimate CBF, Zung-Self-Rating-Depression Scale (ZSDS), and Ankle-Brachial Index (ABI). Analysis was performed on men free from stroke and dementia which defined the final study population to 120 subjects.Population-based cohort study started with an examination of 809 men at age 55, followed by the first (age 68ys) and second follow up (age 82ys). 128 survivors were examined at age 82 with mild depression (ZSDS 0.55-0.71) and 22 subjects at 88th percentile and above of the normal range (ZSDS index 0.48-0.54). Cases were more often current smokers at age 68  and had lower systolic blood presure (SBP), lower social and physical activity, and suffered from fatigue, nausea, freezing and leg edema at age 82. Within the case group, ZSDS-index correlated negatively with CBF in subcortical area (r = -.42*), left and right thalamus , and right basal nuclei (r = -.35*). ZSDS-index correlated also with ABI at age 82 , and with Δ between ABI at age 82 and 68 . Despite decreasing SBP from age 68 to 82, adjusted multiple regression analysis showed in the case group that higher SBP determined CBF changes in the frontal and parietal areas, independently of ZSDS index, Δ ABI, and smoking.ZSDS in the whole cohort ranged from 0.26 to 0.71 (reference 0.25-1.0). As the frequency of depressive symptoms was low, the case group (n = 31) was defined by ZSDS index above 75th percentile (≥0.48), comprising 9 subjects with In this population-based cohort of octogenarian men free from stroke or dementia, a proportion of subjects with depressive symptoms was low. Still, men with borderline or mild depression scores had lower social and physical activity, persistent smoking habit, worse peripheral circulation in legs, and cerebral perfusion changes in basal nuclei, thalamus and subcortical white matter. Regional CBF decline could be partly mediated by higher SBP. The pattern of depression in the elderly differs from that observed in a younger population. Several somatic symptoms, eg.: constipation, weight loss, restlessness, feeling of dependence, and poor self-perception of health, coexist with emotional symptoms and are included in Geriatric Depression Scale or Zung Self-Rating Depression Scale. The conThe aim of this study was to examine, in a general population sample of 82-years-old men, a frequency of self-rated depressive symptoms and their association with peripheral vascular disease in legs, as well as with regional changes in cerebral blood flow.A prospective population study ”Men born in 1914” has been in progress since 1968 and included all men born in even months in 1914 in the city of Malmö, Sweden. Totally, 809 men were invited to and 703 men took part in the first health examination at age 55 . Medical history was also retrieved from spouses and/or relatives. Hypertension was defined according to WHO guidelines from 1986, i.e. systolic and diastolic brachial blood pressure ≥ 160 mmHg or ≥ 90 mmHg respectively, or medication for hypertension, as these guidelines were used for initiation of therapy at the time for both follow-ups. 15 questions considering social and physical activites were included into the questionnaire. Dementia diagnosis was classified by a geriatrician according to DSM IV. Mini Mental State Examination was performed in 125 men by a neuropsychologist and all but one subject had score ≥ 24 . Information on incidents of stroke during whole follow up was registered during health examination, or retrieved from medical records and local stroke-registry. Stroke was defined according to ICD-9 classification codes 430.00-438.99. Two groups were defined concerning the smoking habit at age of 68: non-smokers together with former smokers, and current smokers.ZSDS scale was used to survey the depressive symptoms and was performed by a research psychologist. The scale consists of 20 items using four-point-grading system, ranging from “none or a little of the time” to “most of or all the time”, and is Cerebral blood flow has been estimated using single photon emission tomography (SPECT). An intravenous injection of 800 MBq 99mTc-HMPAO  was given. The acquisition was performed during resting conditions on a triple headed gamma camera system . Technical specifications and image processing have been described previously[Ankle blood pressure was estimated with the same manner at the ages of 68 and 82 years, by a technician at the department of Clinical Physiology, using standardized method, by placing a cuff around the ankle, and using a Doppler signal on the tibial posterior artery or dorsal foot artery to detect peripheral blood flow. The reference pressure in the arm was calculated using the strain gauge system. The ankle-brachial pressure index (ABI) was calculated for each leg by dividing the ankle systolic blood pressure by the highest individual upper arm systolic blood pressure value. ABI values greater than 1.3 was considered abnormal and subjects would be excluded. As a marker of progression of peripheral arterial disease, an arithmetic difference between ABI at age 82 and at age 68 has been calculated on each side and used in analyses  and ZSDS index, Systolic Blood Pressure, Δ Ankle Brachial Index left side - age 82-68ys., and non/previous smokers against active smokers at age 68, as independent variables in a fully adjusted model. A two tailed P value of less than 0.05 was considered statistically significant. All data analyses and statistical calculations have been performed using SPSS  data package. Local ethical committee had approved the study, and informed consent was obtained from all participants.Summary values were expressed as mean ± standard deviation or as percentage if dichotomous. Comparing background data between cases and controls, Chi-square test/Fisher’s test was used for frequencies. The analyses of difference in CBF and ABI were made with either T-test for Independent Samples or Mann–Whitney The study was approved by the local ethics committee at Lund University (LU 111–82). All subjects gave their informed consent.mild depression (ZSDS index 0.55-0.71) and 22 subjects at 88th percentile and above of the normal range (ZSDS index 0.48-0.54).Of the 128 subjects in the study population, eight suffered from a stroke during the preceding years and were excluded from the analysis. In the remaining 120 subjects, the 75th percentile of ZSDS index was estimated to 0.48. Thus, 31 subjects with ZSDZ index ≥0.48 were defined as case group, compared to 89 subjects with ZSDS index < 0.48 points. According to the qualitative description of symptom grades, our case group comprised 9 subjects with p = .042) (Table p = .02). Systolic blood pressure was over 10 mmHg lower  in the case group compared to the controls, as previously reported[Case group was characterized by a double frequency of current smokers at age 68, i.e. 14 years before the depression survey, compared to the controls , which wEven if the subcortical localisation and a grade of CBF decline were associated with ZSDS index in a non-adjusted model, the adjustment for vascular risk factors influencing depression independently supported a vascular rather than a degenerative background of a perfusion decline. Previously introduced concept of vascular depression compriseIn the regression analysis, the associations between ZSDS index and CBF after adjustment for vascular risks were reduced to right thalamus, which maybe explained that not only vascular but also degenerative processes could answer for subcortically mediated elderly depression. Another result worth attention is an association between systolic blood pressure and CBF in both frontal and especially in both parietal areas, independently of ZSDS score and other vascular risk factors. It could mean that CBF changes in a large part of the brain in early depression could be at least in some subjects caused by a high blood pressure. This result is surprising, since we previously have shown that a grade of depression in this cohort is related to the blood pressure decline from age 68 to age 82, especially in those who were hypertensive at age 68, thereafter reached an inflection point in blood pressure trajectories, followed by a pressure decline until age 82. We explThe strengths of this study are: a well-examined cohort sample, lack of age and gender bias and a good quality of longitudinal follow-up. The medical examination was performed by an experienced geriatrician and the psychological interview by a clinical neuropsychologist. Among the limitations of this study, we should include a possible underrepresentation of institutionalized and non-native-Swedish elderly. Elderly with cognitive decline could also be more likely to decline participation in the last follow-up, and elderly men with depressive symptoms might be less inclined to answer openly on the questions included in the ZSDS. There are also epidemiological aspects in assessing older adults with questionnaires and interviews, e.g. difficulty remembering symptoms. We did not use criteria of depression for assessing cohort subjects, except ZSDS scoring, which could result in a restricted validity and specificity.In this population-based cohort of octogenarian men free from stroke or dementia, a proportion of subjects with depressive symptoms evaluated by Zung Self-Rating Depression Scale was low. Even so, men with borderline or mild depression scores had lower social and physical activity, persistent smoking habit, worse peripheral circulation in legs and cerebral perfusion changes in basal nuclei, thalamus and subcortical white matter. In these men, cerebral perfusion decline in parietal and frontal lobes was associated with higher systolic blood pressure, even if blood pressure decrement was more frequent over time than in non-depressed subjects.Authors declare that they have no financial or non-financial competing interests.ASL was involved in data analysis and manuscript preparation. LAP carried out the neuropsychological analysis and supervised ZSDS estimation. PW carried out the cerebral blood flow estimation. SE was involved with study design, data collection and manuscript preparation. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-244X/13/347/prepub


The study investigated the optimal threshold value of renal arterial resistive index as assessed by Doppler ultrasonography determining chronic kidney disease stage 4 or higher in patients with renal allograft.In a cross-sectional study the renal arterial resistive index were obtained in interlobar arteries by Doppler ultrasonography in 78 patients with renal allograft. The stage of chronic kidney disease was determined by the estimated glomerular filtration rate equation.The median renal arterial resistive index was 0.61 . We observed a significant association between renal arterial resistive index above the upper quartile and chronic kidney disease stage 4 or higher . Multivariate logistic regression analysis showed that renal arterial resistive indices (p = 0.02) and time since transplantation (p = 0.04), but not age, gender, or blood pressure were significantly associated with chronic kidney disease stage 4 or higher.A renal arterial resistive index higher than 0.66 may determine the threshold value of chronic kidney disease stage 4 or higher in patients with renal allograft. Impaired renal function is frequently observed in patients with renal allograft. Deterioration of renal transplant function is mostly due to chronic allograft nephropathy, which is characterized by chronic interstitial fibrosis, tubular atrophy, vascular occlusive changes, and glomerulosclerosis All research involving human participants was approved by the local ethics committee . Informed consent was obtained and all clinical investigation has been conducted according to the principles expressed in the Declaration of Helsinki. Written informed consent was obtained from all patients before entry into the study.In a cross-sectional study Doppler ultrasonography of the kidney graft was performed in 78 consecutive patients  with renal allograft at least three months after transplantation who were seen in our outpatient clinic. Inclusion criteria were the following: 1. Patient with renal allograft at least three months after transplantation. 2. No signs of apparent intercurrent illness. 3. Presence of informed consent. Exclusion criteria were the following: 1. Absence of informed consent. 48 patients (62%) received kidneys from living related donors, 30 patients (38%) from deceased donors, and median time interval since transplantation was 35 months .At the time of the present investigation all patients were ambulatory and free of intercurrent illness. None of the patients showed signs for acute rejection of kidney allograft. Patient’s history was raised by trained personal using medical records and a standardized questionnaire and comprised personal history and previous history of renal disease and cardiovascular disease. None of the patients had severe tachycardia or bradycardia, which may affect Doppler measurements. Blood pressure was obtained by conventional sphygmomanometric methods on three occasions in a sitting position after a rest of 10 minutes. Phases I and V of the Korotkoff sounds were considered as systolic blood pressure and diastolic blood pressure, respectively.2 indicated chronic kidney disease stage 4 or higher. Glomerular filtration rate was calculated according to the chronic kidney disease epidemiology collaboration (CKD-EPI) equation A glomerular filtration rate less than 30 mL/min/1.73 mA Philips HD-11 XE digital ultrasound machine  with a broadband curved array multifrequency transducer L12-3 with a 2-to-5-MHz extended operating frequency range, field view of 75°, was used for pulsed Doppler measurements. Waveforms were optimized for measurement using the lowest pulse repetition frequency without aliasing, the highest gain without obscuring background noise, and the lowest wall filter Continuous data are presented as median and interquartile range. Non-parametric Mann-Whitney test was used to detect differences in continuous variables between the groups. Frequency counts were calculated for categorical data such as gender, specific medications, and diagnostic classifications. Differences in these categorical variables between the groups were analyzed by Fisher's exact test. The product limit method of Kaplan and Meier was used to show the fraction of patients presenting with chronic kidney disease stage 4 or higher according to renal arterial resistive index. Curves were compared using the logrank test. Logistic regression analysis was used to determine those variables independently associated with chronic kidney disease stage 4 or higher. The variables tested were renal arterial resistive index, age of renal allograft recipient, time since transplantation, systolic blood pressure, diastolic blood pressure, and pulse pressure. For multivariate analysis, the effect of multiple variables on the presence of chronic kidney disease stage 4 or higher was evaluated in 78 patients with stepwise forward regression analysis . Data were analyzed using GraphPad prism software  and SPSS for windows . All statistical tests were two-sided. Two-sided p-values less than 0.05 were considered to indicate statistical significance.Doppler ultrasonography of kidney graft was performed in 78 patients with renal allograft. 53 (68%) transplant recipients were male, and 25 (32%) were female. Median age of recipients was 54 years . The cause of chronic kidney disease was hypertensive nephropathy in 7 patients (9%), diabetes mellitus in 9 patients (11%), glomerulonephritis in 24 patients (31%), polycystic kidney disease in 13 patients (17%), reflux nephropathy in 4 patients (5%), and others/unknown in 21 patients (27%). Median time on dialysis  was 20 months .2), stage 2 (glomerular filtration rate between 60 to 89 mL/min per 1.73 m2), stage 3 (glomerular filtration rate between 30 and 59 mL/min per 1.73 m2), stage 4 (glomerular filtration rate between 15 and 29 mL/min per 1.73 m2), and stage 5 (glomerular filtration rate <15 mL/min per 1.73 m2) were 5 (6%), 22 (28%), 38 (49%), 12 (16%), 1 (1%), respectively.48 patients (62%) received kidneys from living related donors, and 30 patients (38%) from deceased donors. Median donor age was 49 years . Median time interval since transplantation was 35 months . The number of patients with renal allograft presenting with chronic kidney disease stage 1 . The median renal arterial resistive index was not significantly different in male patients , compared to female patients . Patients were stratified according to renal arterial resistive index below or above the upper quartile. Using receiver-operating-characteristic curve this threshold showed a specificity of 85% and sensitivity of 62%. The clinical and biochemical characteristics of patients and their allograft are shown in We observed a significant association between renal arterial resistive index above the upper quartile and chronic kidney disease stage 4 or higher . Univariate logistic regression analysis showed that renal arterial resistive index (p = 0.008), time since transplantation (p = 0.018), and pulse pressure (p = 0.021) were significantly associated with chronic kidney disease stage 4 or higher, whereas age, gender, systolic and diastolic blood pressure where not associated with chronic kidney disease stage 4 or higher (each p>0.05). Using multivariate logistic regression analysis we observed that renal arterial resistive index (p = 0.02) and time since transplantation (p = 0.04), but not age, gender, systolic blood pressure, diastolic blood pressure, nor pulse pressure were significantly associated with chronic kidney disease stage 4 or higher.In the present study we show that a renal arterial resistive index higher than 0.66 in the kidney allograft allows optimal distinction of patients with chronic kidney disease stage 4 or higher from the other patients with renal allograft. Normal values for renal arterial resistive index in healthy subjects have been reported previously. In 135 healthy subjects without preexisting disease  the mean renal arterial resistive index was 0.59 The renal arterial resistive index was advanced as a useful parameter for quantifying the alterations in the kidney that may occur with renal disease. However, the origin of resistive index and the causes of increased resistive index in kidney diseases are not completely evaluated. Experiments on isolated perfused rabbit kidneys revealed that the renal arterial resistive index increased with decreases in the cross-sectional area of the distal arterial bed Conflicting data have been reported concerning the use of renal arterial resistive index to predict future events, i.e. loss of renal allografts and deaths. A cohort study by Radermacher et al. showed that a renal arterial resistive index of 0.80 or higher measured at least three months after transplantation was predictive of a combined endpoint including a decrease of 50% or more in creatinine clearance, allograft failure, or death In our cohort the percentage of living kidney donors (62%) was much higher compared to previous reports. The cohort reported by Radermacher et al. contained only 7% living kidney donors, and in the study by Gerhart et al. no living kidney donors were reported In summary, a renal arterial resistive index higher than 0.66 may determine chronic kidney disease stage 4 or higher in patients with renal allograft.


Neurogenic orthostatic hypotension is a distinctive and treatable sign of cardiovascular autonomic dysfunction. It is caused by failure of noradrenergic neurotransmission that is associated with a range of primary or secondary autonomic disorders, including pure autonomic failure, Parkinson’s disease with autonomic failure, multiple system atrophy as well as diabetic and nondiabetic autonomic neuropathies. Neurogenic orthostatic hypotension is commonly accompanied by autonomic dysregulation involving other organ systems such as the bowel and the bladder. In the present review, we provide an overview of the clinical presentation, pathophysiology, epidemiology, evaluation and management of neurogenic orthostatic hypotension focusing on neurodegenerative disorders. According to consensus guidelines, orthostatic hypotension (OH) is defined as a sustained fall of systolic blood pressure by at least 20 mmHg or diastolic blood pressure by 10 mmHg within 3 min of standing or head-up tilt . Since tHallmark symptoms upon postural challenge include dizziness, visual disturbances, presyncope and syncope , 52. HowConsciousness is critically dependent on continuous cerebral blood flow, and is lost within 6 s of shutdown of cerebral blood flow in human subjects . Thus anIt is noteworthy that two distinct kinds of pathological processes can dramatically alter autonomic blood pressure regulation in human subjects: baroreflex failure (BF) and neurogenic orthostatic hypotension (NOH). In BF, there is loss of afferent baroreflex engagement of central mechanisms of blood pressure control. However, central stimuli  can still engage an otherwise functional peripheral sympathetic system. These BF patients have extreme surges of blood pressure largely dependent on emotional state. Some of these surges (elevations above 250 mmHg have been observed) are among the highest blood pressures encountered in contemporary clinical medicine , 33, 59.In contrast to the afferent or central lesion of BF, there is failure of noradrenaline release from sympathetic vasomotor neurons in NOH . Loss ofOrthostatic hypotension is influenced by a range of factors; cross-sectional analysis not only suggests an influence of age, but also drug effects and orthostatic stress in neurological disorders, particularly PD, DLB and MSA as well as autonomic neuropathies , 66, 80.Another factor massively influencing OH prevalence is the effect of medication. Elderly subjects commonly require medications altering blood pressure, such as diuretics or antihypertensives, which are well known to either cause or exacerbate OH. In addition, alpha-adrenoceptor antagonists in the treatment of benign prostatic hyperplasia, tricyclic antidepressants, vasodilatators, sympatholytics, and antiparkinsonian agents can increase risk of OH by impairing sympathetic tone or reducing peripheral vascular resistance . FurtherNeurogenic orthostatic hypotension can arise from primary neurodegenerative disorders or can be secondary to systemic conditions that influence peripheral nerve function . PD, DLBPatients with NOH may split into two groups according to the site of the lesion with (1) disturbed central autonomic pathways and intact peripheral noradrenergic innervation or (2) loss of peripheral noradrenergic fibers . DisruptThe first step in the work-up of patients presenting with symptoms suggestive of NOH is the exclusion of potentially harmful causes such as acute bleeding and dehydration. Next, non-neurogenic causes (reviewed in ) includiA 77-year-old female was admitted to the hospital after a transient loss of consciousness. At the hospital, she indicated that she did not perceive the present “attack” and quickly felt comfortable again. Moreover, she was not aware of any dizziness, visual disturbances or light-headedness prior to her fainting spell. A history of recurring syncope that began in childhood was noted previously. Of note, the patient reported several cardiac risk factors including hyperlipidaemia, arterial hypertension and type 2 diabetes. Third-party descriptions did not suggest epileptic-like convulsions. During inpatient stay, another fainting fit was observed and measurements indicated low blood pressure. Subsequently, Holter monitoring and 24-h blood pressure profiles remained within normal range. Arterial hypertension was classified as non-dipper with nocturnal blood pressure drop of 3.8 % systolic and 4.9 % diastolic.Tilt-table testing elicited a marked NOH with a supine blood pressure of 112/61 mmHg dropping to 68/46 mmHg after 3 min of head-up tilt, despite a constant heart rate of 62 bpm. A tilt-induced syncope occurred after 3.5 min. Video monitoring observed orofacial automatisms and dystonic-myoclonic movements of the upper limbs as manifestations of cerebral hypoperfusion.In the present case, medical history and clinical examinations suggest severe NOH in the context of cardiovascular autonomic diabetic neuropathy.A 67-year-old male reported a 2-year history of progressive gait unsteadiness which initially started with slight balance difficulties. More recently, slurred speech, recurring falls without serious injuries and impaired fine motor skills appeared. In addition, the patient described symptoms suggestive of presyncope. In the clinical examination a cerebellar syndrome accompanied by mild akinetic-rigid parkinsonism was observed. Cerebral magnetic resonance imaging detected pontine and cerebellar atrophy. Presyncopal symptoms were further investigated by a simple standing test which confirmed the suspected diagnosis of OH. Within 3 min of head-up tilt in tilt-table testing, a blood pressure drop of 76 mmHg systolic and 51 mmHg diastolic associated with an inadequate increase of 8 bpm in heart rate appeared and further underscored the diagnosis of NOH. Overall, the patient met the Gilman criteria of probable MSA and received 9-α-fluorohydrocortison which alleviated OH symptoms substantially as well as levodopa–benserazide which mediated a modest benefit towards parkinsonian symptoms only.A structured approach is important in the management of patients with NOH. Wherever possible, underlying causes should be identified by thorough work-up and the treatment strategy adapted accordingly. In addition, the magnitude of symptoms and the presence of asymptomatic OH should be considered. Available treatment options range from non-pharmacological options to aggressive drug therapy. While therapy of non-neurogenic OH is mostly straight-forward, NOH is often difficult to treat and a combination of non-pharmacological measures and drugs is required. Pharmacological agents can lead to different responses in patients with central neurodegeneration compared to those with peripheral neurodegeneration, and the latter has to be considered in the treatment as well.Nevertheless, NOH massively affect patients’ quality of life because of the disabling symptoms of autonomic failure. However, most of these symptoms could be alleviated by non-pharmacological and pharmacological measures. Therapeutic interventions should be implemented stepwise depending on the severity of symptoms. If non-pharmacological measures do not attenuate NOH symptoms sufficiently, pharmacological interventions may become necessary. Nevertheless, supine hypertension has to be taken into consideration in pharmacological treatment .Non-pharmacological measures should be considered first in NOH. Such measures include a stepwise raising from supine to standing position, physical exercise in order to avoid deconditioning, taking care of proper defection and compression stockings . An abdoTwo different mechanistic targets are approached in the pharmacological treatment of NOH, namely volume expansion and vasoconstriction. In patients failing to respond appropriately to high salt diet and increased fluid intake, the prescription of 9-α-fluorohydrocortison, a synthetic mineralocorticoid, is indicated in order to increase plasma volume by renal sodium retention. Intriguingly, both of the latter effects return to normal over time, suggesting that increased peripheral vascular resistance (PVR) contributes to the observed pressor effect . At the On rare occasions, the vasopressin-analogue desmopressin could be applied to reduce nocturnal diuresis and expand plasma volume , 63; how1-adrenoreceptor agonist midodrine. In two multi-centre double-blind placebo-controlled studies midodrine mediated beneficial effects that ameliorated orthostatic symptoms and increased standing blood pressure [l-dihydroxyphenylserine  was shown to be effective in NOH-associated neurodegenerative conditions [2-adrenoceptors [Bearing in mind that impaired norepinephrine release from sympathetic neurons is the central mechanism in NOH pathophysiology, sympathomimetic drugs yielding to vasoconstriction may be helpful in the treatment of NOH, particularly in patients where plasma volume increase was insufficient to abolish orthostatic symptoms. However, so far, the only drug which has been approved by regulatory authorities  for the treatment of NOH is the peripheral and directly acting αpressure , 81. Mornditions , 53, andnditions . Other snditions  or were nditions . Howevernditions , 26, 56.nditions . Anotheroceptors . Intriguoceptors , 69.Neurogenic orthostatic hypotension can seriously impair patients’ quality of life and is associated with increased morbidity, especially in the elderly. In several neurological diseases associated with autonomic failure, NOH is a major contributor to disease burden and reduced quality of life. A structured approach is important in the management of patients with NOH. Non-pharmacological interventions should be the first line of therapy. If the symptoms persist and the patients are severely affected, pharmacological interventions are required.


Atherosclerotic cardiovascular disease (CVD) is the most common cause of morbidity and mortality among hemodialysis (HD) patients. It has been attributed, among other causes, to hypertension and dyslipidemia. The aim of the present study was to investigate the effect of a year-long consumption of Pomegranate juice (PJ), on two traditional cardiovascular (CV) risk factors: hypertension and lipid profile, as well as on cardiovascular events.101 HD patients were randomized to receive 100 cc of PJ (0.7 mM polyphenols) or matching placebo juice, three times a week for one year. The primary endpoints were traditional CV risk factors; blood pressure and lipid profile. Systolic, diastolic and pulse pressure, plasma levels of triglycerides (TG), high density lipoprotein (HDL), low density lipoprotein (LDL) and total cholesterol were monitored quarterly during the study year. Secondary endpoint was incidence of cardiovascular events.PJ consumption yielded a significant time response improvement in systolic blood pressure, pulse pressure, triglycerides and HDL level; an improvement that was not observed in the placebo intake group. These beneficial outcomes were more pronounced among patients with hypertension, high level of triglycerides and low levels of HDL.Regular PJ consumption by HD patients reduced systolic blood pressure and improved lipid profile. These favorable changes may reduce the accelerated atherosclerosis and high incidence of CVD among HD patients.NCT00727519ClinicalTrials.gov registry, Identifier number:  Patients on renal replacement therapy (RRT) are at increased risk of cardiovascular (CV) mortality and morbidity compared to the general population . Every yIt has been known for many years that high intake of fruits and vegetables is associated with reduced risk of coronary heart disease . The benPJ antioxidant activity was studied mainly with regard to cardiovascular function among non HD patients. Different studies demonstrated the anti-atherogenicity properties of PJ by its ability to lower serum angiotensin converting enzyme (ACE) activity which resulted in systolic blood pressure reduction , decreasThe present study aims to characterize for the first time, the long term effects of PJ consumption by HD patients on hypertension, lipid profile and incidence of CVD.One dialysis center at the Western Galilee Hospital, Nahariya, Israel participated in the study. Eligible participants were chronic HD patients aged >18 years who underwent 3 h HD sessions weekly using low-flux high performance cellulose-triacetate  or polysulfone membranes . Exclusion criteria included: HD treatment for less than 3 months, simultaneous participation in other clinical trials, patient's refusal or inability to give informed consent due to mental or physical state, or pregnancy  during study period. One hundred and forty-nine HD patients were identified as eligible. Of these, 101 HD patients were recruited  received 0.7 mmol of polyphenols in the form of 100 cc of PJ (Naturafood) and the other (n = 35) received a matching 100 cc placebo juice three times a week during the first dialysis treatment hour, for one year. Patients, medical and laboratory staff were all blinded to patient’s group allocation. The smaller randomization ratio of 2;1, with only a modest loss in statistical power  was chosDuring the study period patients were instructed not to drink any other fresh fruit juice at home. Verification of juice intake was carried out by the study investigator and was documented. Patients who did not drink the juice at least 3 times were excluded from the study. Blood for lipid profile measurements was drawn at 0, 3, 6 and 12 months of study intervention, always before dialysis, from the arterial sampling port closest to the patient. Three sequential blood pressure (BP) measurements performed before dialysis initiation were used to calculate the mean systolic and diastolic blood pressure  at 0, 3, 6 and 12 months of study intervention. Pulse pressure (PP) was calculated by SBP minus DBP.In order to choose the commercial PJ with the highest polyphenols levels, several hand squeezed and different commercial juices available in Israel were analyzed by the colorimetric assay in Migal Galilee Technology Center, as previously described ,21. PJ fThe placebo was chosen to resemble the pomegranate juice in color and taste and was prepared especially for this study by food engineers. The placebo contained: pomegranate artificial extract of Frutarom Ltd; Citric acid; Caramel as color material; Aspartame and Acesulfame as sugar substitutes. Analyzing the placebo juice using colorimetric assay verified that the juice has no polyphenols. During placebo juice preparation, comparisons tests of flavor between placebo juice and Pomegranate Juice were performed by two independent testers to verify that placebo and Pomegranate Juice had a similar taste.The primary endpoints were traditional CV risk factors including: number of antihypertensive drugs taken at the end of follow up compared to study initiation, mean SBP, DBP and PP, as well as lipid profile .Secondary outcome was incidence of CVD. CVD events as a composite variable, consisted of hospitalizations due to acute myocardial infarction (MI) ; ischemic stroke; new events of peripheral vascular disease (excluding the arterio-venous fistula) and unstable angina. Non fatal MI was defined as the presence of at least two of the following criteria: chest pain of typical duration and intensity, and/or increased cardiac enzymes and diagnostic electrocardiogram changes. Fatal MI was defined as a death occurring within 24 h from hospital admission. Death occurring outside hospital for which no other cause was assigned was regarded as sudden death and was included in the definition of CVD event.Data analysis was done with SPSS statistical analysis software. Continuous data are reported as mean ± SD. The t-test for independent samples, or Mann Whitney test when appropriate, were used to detect differences in continuous variables between treatment groups. Frequency counts were calculated for categorical data. Differences in these variables were assessed by Chi Square Tests. In cases when expected values were lower than necessary, Fisher Exact Test was used. In order to study the time effect of PJ/Placebo on hypertention and lipid profile, repeated measures and Bonferroni post hoc analyses were done separately in each of the groups. In order to retain the intention to treat analysis we used the last observation carried forward method for missing data.Survival curve comparing the effect of treatment on CVD events was calculated by the Kaplan-Meier method using the intention-to-treat (ITT) principle.All statistical tests were two-sided, and statistical significance was defined as P < 0.05.Characteristics of the 101 patients are described in our previous paper . BrieflyThe distribution of the number of anti-hypertensive medications used at study entry was similar between the two studied groups . After one year of intervention a significant (P = 0.01) change in this distribution, as an ordinal variable  was noticed between the two group. The number of antihypertensive drugs decreased in 22.7% of the PJ patients, compared to 8.6% in the placebo group, while an increase was documented in 10.6% of the PJ patients compared to 31.4% in the placebo group  the significant effect of PJ consumption on blood pressure reduction occurred earlier (after 6 m of intervention) and was more pronounced: SBP was reduced by 5.3% after 6 m, and by 8.7% after 12 m of intervention  or may be due to a direct effect on serum ACE activity . FurtherImportant questions related to interpretation of our above results are whether the associations found are real and causal. Taking into consideration the uncompromising methodology described, there is no reason to believe that biases have been introduced. As for causality, all Hill’s criteria were met: the clinical trial methodology assured temporal relationship issues; the protective associations between PJ exposure and cardiovascular events were found strong; our findings regarding the association between polyphenols- rich juice and its anti-hypertensive and hypolipemic properties were consistently described across other studies of divergent designs and populations ,16,25; aThe significant beneficial effect of PJ intake on SBP, PP and lipid profile among HD patients, in addition to its beneficial effect on oxidative stress and inflammation, suggests that constant PJ consumption can offer wide protection against cardiovascular events - the main cause of morbidity and mortality among HD patients.Furthermore, as controlled consumption of PJ has been shown to lower morbidities in HD patients it is expected to reduce costs associated with those patients' care. Further multi centered clinical studies are needed to substantiate our findings that while directly improving patients' quality of life, PJ can also significantly reduce health expenditure. Such studies might well influence future policy makers to include PJ as part of state-funded standard care for HD patients.CVD: Cardiovascular disease; HD: Hemodialysis; PJ: Pomegranate juice; CV: Cardiovascular; TG: Triglycerides; HDL: High density lipoprotein; LDL: Low density lipoprotein; RRT: Renal replacement therapy; CKD: Chronic kidney disease; ACE: Angiotensin converting enzyme; RAAS: Renin angiotensin aldosterone system; IMT: Intima-media thickness; BP: Blood pressure; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; PP: Pulse pressure; MI: Myocardial infarction; ITT: Intention-to-treat.The authors declare that they have no competing interests.All authors have contributed to the conception and design of the work. We had full access to all of the data in this study, and we take complete responsibility for the integrity of the data and the accuracy of the data analysis. We declare that we have seen and approved the final version.


To investigate the effects of a 10-week water aerobic exercise on the resting blood pressure in patients with stage 1 or 2 hypertension referring to Tehran University Clinics.Forty men with stage 1 or 2 essential hypertension were assigned to two groups of intervention  and control . Subjects in the intervention group participated in a supervised 10-week water aerobic training program of 55 min sessions, 3 days per week on alternate days, while those in the control group were not involved in any regular training program during this period. Blood pressure of the participants was recorded and compared at the beginning and at the end of the study (48 hours after the last training session).Exercise lowered systolic blood pressure and mean arterial pressure by 11.71  and 5.90  mm Hg respectively. The lowering effect of exercise on diastolic blood pressure was neither statistically significant nor clinically important . There was no significant effect of age, baseline body mass index and stage of hypertension on the exercise-induced changes in blood pressure.A 10-week course of water aerobic exercise markedly reduced the systolic and mean arterial blood pressure of patients with essential hypertension and is especially recommended for the obese and the elderly who have orthopedic problems or bronchospasm. The primary goal of the treatment of hypertension is to prevent cardiovascular disease and mortality. All guideline statements emphasize life style modification as the first step in the treatment of hypertension. In this regard, physical activity is recommended for the hypertensive patients as a part of life style modification, 5.Hypertension, defined as resting systolic blood pressure of >= 140 and/or diastolic blood pressure of >= 90 mmHg, remains the most common risk factor for cardiovascular morbidity and mortality. Currently, more than a quarter of the world adult population suffer from hypertension and it is expected that this number will increase to 1.56 billion (29%) by 2025–8. The majority of these studies have used walking, jogging, cycling, running or a combination of these activities as training modalities. In addition to these sports, swimming has been widely recommended by authoritative guidelines as an appropriate means of the prevention and treatment of hypertension–12. Nevertheless, evidence arising from scientific investigation on the effect of swimming on blood pressure is scant. Swimming is an inexpensive, available and attractive sport with a dynamic nature. The minimal weight-bearing stress, humid environment, and a reduced heat load makes swimming especially convenient for overweight individuals and those with exercise induced bronchospasm and/or orthopedic problems, 14.Several clinical trials have studied the effects of dynamic aerobic exercises on resting blood pressure. The meta-analyses of these studies support the role of aerobic exercises in prevention and treatment of hypertension–18. According to these studies, blood pressure and heart rate increase during immersion and swimming, particularly in the elderly. Also for the same heart rate, mean arterial blood pressure is higher during swimming compared to running. Moreover, systolic and diastolic blood pressure in trained swimmers is higher than in other endurance-trained athletes, 18.Some cross-sectional studies suggest that swimming training might not be effective in modifying the resting blood pressure, 19. In any case, longitudinal trials investigating the long-term (and not acute) effect of swimming on blood pressure are few and somewhat controversial, 19. Considering the paucity of evidence in this area, this study aimed to investigate the effects of water aerobic training on blood pressure in hypertensive patients with stage 1 or 2 hypertension referring to Tehran University Clinics.Distinguishing features of swimming such as supine body position, facial immersion, hydrostatic pressure exerted on the athlete, possible effects of water temperature and increased thermal conductivity of water can merely explain the immediate increase in blood pressure following swimmingAmong patients referred to Tehran University Clinics in Tehran in 2006, forty individuals who had received the diagnosis of mild or moderate hypertension (140≤ systolic blood pressure <180 or 90≤ diastolic blood pressure <110) by a cardiologist and met the inclusion criteria entered the study. Inclusion criteria consisted of between 20 and 70 years of age, diagnosis of essential hypertension after clinical and laboratory exclusion of secondary hypertension by a cardiologist, absence of severe or refractory hypertension, absence of evidence of target organ damage , no evidence of coronary artery disease  and absence of any chronic illness that may limit the patient's capacity to participate in exercise. The patients were excluded from the study if they were absent for more than two sessions from the training or if they started drug therapy or developed complications like unstable angina, myocardial infarction, or cerebrovascular accidents.The participants were assigned to two groups of intervention and control. Both groups were recommended to reduce weight, to limit salt consumption, and to stop smoking and drinking alcohol. Subjects in the intervention group participated in a supervised 10-week water aerobic training program of 55 min sessions, 3 days per week on alternate days in addition to the general recommendations. Blood pressures were measured using mercury sphygmomanometers  in the sitting position according to the standard guidelines for measurement of blood pressure by sphygmomanometry. Briefly after the subjects rested for five minutes in the seated position, a minimum of 2 readings were taken at intervals of at least 1 minute and the average of those readings was used to represent the patient's blood pressure. If there was >5 mmHg difference between the first and second readings, additional (1 or 2) readings were obtained, and then the average of these multiple readings was used. Blood pressure was measured at baseline and 48 hours after the last exercise session to avoid the acute effects of a single bout of exercise. Each training session consisted of warm-up (10 min), water aerobic training (25 min), swimming skills training (10 min), and cool-down (10 min).Participants’ heart rates were recorded after the warm up and each training phase. The exercise intensity was set at 60-65% of the maximal heart rate and increased gradually up to 70-75% during the program. Maximal heart rate was adjusted on the basis of the observation that the maximal heart rate during swimming is 10–13 beats lower compared with land-based activities. The heart rate of individuals participating in aerobic exercise is expected to rise from 60-65% to 70-75% of maximum capacity. It is notable that knowing how to swim was not necessary to enter the study but the participants acquired the skills during the ten weeks of training. The study was approved by the ethics committee of Tehran University of Medical Sciences and written informed consent was obtained from each patient., 22. The assumptions of ANCOVA including lack of interaction between variables, i.e. baseline values of blood pressure and treatment group, normal distribution of studentized residuals  and constancy of residual variance  were assessed. For inferential purpose 95% Confidence intervals were presented for the contrast between groups . We also used Bayesian statistics to combine existing evidence of the effects of water aerobic exercise on blood pressure with the present data, 24.Continuous variables  were summarized for each group by the mean and standard deviation [presented as mean (SD)]. Baseline values of systolic and diastolic blood pressure are potentially confounding factors in analyzing the effects of exercise. In order to improve the precision of the estimated effects and to achieve an unbiased estimate and confidence interval for the magnitude of effect, we used Analysis of Covariance (ANCOVA), assuming baseline systolic and diastolic blood pressure values as the covariates.The sample size was estimated based on change score analysis. According to the study by Tanaka et al, and considering a type I error probability of 5%, the power of this study in detecting a 5 mmHg reduction in systolic blood pressure is 80%The baseline characteristics of the patients in the intervention and control groups are depicted in In ANCOVA, the coefficient of group variable  is the effect of interest: the estimated difference between the two treatment groups . As a tywhere X, Y, and Z represent group, baseline systolic blood pressure, and final systolic blood pressure values respectively. Based on this equation, a patient who has a systolic blood pressure of 140 mmHg at the time of entering the 10-week course of training will have a final systolic blood pressure of 129 mmHg. In It is notable that the results shown in According to data analysis, the minimum Bayes factors were 0.005, 0.97, and 0.055 for systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure respectively .–12. Early recommendations (before 1997) have been extrapolated from the effects of other aerobic exercise forms  and are not based on scientific evidence, 25–27. Current recommendations (after 1997) are based primarily on the results of a trial involving 18 men and women with hypertension, of whom 12 were assigned to a 10-week swimming training program done by Tanaka et al–11. Most people enjoy swimming and water aerobic exercises due to its rhythmic and dynamic nature and also because of its humid and minimal weight-bearing stress environment. These activities are particularly useful for people who have orthopedic problems or bronchospasms, or those who are obese, 14. The present study is among the first to examine the effects of water aerobic exercise on the resting blood pressure in individuals with essential hypertension.Swimming has been specifically and widely recommended for the prevention and treatment of hypertension by the relevant national and international health organizations. Considering the confidence interval, the effect of exercise on mean arterial pressure reduction is also significant. Exercise as a lifestyle modification can be recommended for all patients with hypertension, since even small reductions in blood pressure are associated, in long-term, with a reduced risk of cardiovascular diseases.Our data suggest that a 10-week course of water aerobic exercises (including swimming training) reduces the systolic and mean arterial blood pressure of the participants by 11.71 and 5.9 mmHg respectively. Based on this study, a 10-week water aerobic exercise has an impressive effect on the resting systolic blood pressure in individuals with hypertension. 5 mmHg reduction of systolic blood pressure, the lower bound of confidence interval in the population would result in a 14 percent overall reduction in mortality due to stroke, a 9 percent reduction in mortality due to coronary heart disease, and a 7 percent decrease in all-cause mortality.Although we could not reject the null hypothesis that "water aerobic exercise has no effect on resting diastolic blood pressure", it must be considered that: 1) Our sample size was calculated based on an estimated systolic blood pressure reduction. We do not have adequate power to detect real and clinically worthwhile diastolic blood pressure reduction. Confidence interval suggests that the result is inconclusive. 2) Diastolic blood pressure is a more potent cardiovascular risk factor than systolic blood pressure until the age of 50 and systolic blood pressure is more important thereafter. The greatest burden of hypertension-related cardiovascular disease at present occurs in the middle-aged and elderly, in whom systolic hypertension predominates, 8. However sparsity of comparison cells makes it difficult to draw conclusions based on the subgroup analysis.For example, only five patients in the control group had stage II hypertension and overall, only eight patients had BMI less than 25.Subgroup analysis reveals that there is no significant effect of age, baseline BMI and stage of hypertension on the exercise-induced changes in blood pressure, which is in accordance with the results of meta-analyses by Whelton and colleagues (2002) and Fagard and colleagues (1999) . HThe minimum Bayes factor for systolic blood pressure (i.e. 0.005) is so powerful that can reduce the 0.92 probability of the null hypothesis, lack of effect of water aerobic exercises on systolic blood pressure, down to 0.05 . Conside. The intensity and duration of the training were similar to those of our study, but the main part of the exercise session was dedicated to swimming workout. On the other hand, in contrast to our study, most subjects were able to swim continuously for at least 10 minutes at recruitment. Moreover, while in the study by Tanaka et al participants were both men and women and the water temperature was kept constant between 27-28oC, our study included only men and was performed at a temperature of 31-32oC. The less the temperature of water, the more will the superficial skin vessels constrict and hence the more will the total peripheral resistance increase; this might be a reason for less reduction of blood pressure in Tanaka et al's study.Our findings are in accordance with the results of the first randomized clinical trial examined the effects of swimming on blood pressure in hypertensive patients . In their trial, training lowered seated systolic blood pressure by 6 mmHg, on average, and resting heart rate by 10 beats/min, while diastolic blood pressure did not change significantly. However, their study differed in several ways from our intervention: Firstly, their study shows the relative effects of swimming on blood pressure compared with walking but they could not determine the absolute effects of swimming on blood pressure that we are looking for. Secondly, the participants in Cox et al's study were all women with different levels of blood pressure, from normal to high. Additionally, some but not all of hypertensive subjects were receiving anti-hypertensive therapy. In the present study, the participants were men with stage 1 or 2 essential hypertension who did not receive anti-hypertensive therapy. It is very likely that aerobic exercise in water has differentially affected these dissimilar target groups. Finally, In Cox et al's report the mean water temperature was 26.5oC, whereas the water temperature in our study was 31-32 oC.Cox and colleagues (2006) have performed a randomized controlled trial in which 116 healthy sedentary women, aged 50–70 years, entered randomly into a 6-month program of either swimming or walking exercise of similar intended intensity. Their results indicated that compared to walking, regular swimming significantly elevates blood pressure in previously sedentary, normotensive, older women–36. Based on these studies decreased total peripheral resistance appears to be the primary mechanism by which resting blood pressure is reduced after exercise training. Reductions in vascular resistance after training are mediated by changes in sympathetic nervous activity, altered vascular responsiveness and changes in vascular structure , 37–39. As an aerobic exercise, swimming could lower the blood pressure through the above mentioned mechanisms, and psychological and stress-reducing effects of aquatic environment may have an additional role. On the other hand, several mechanisms such as supine position assumed during swimming, facial immersion , and a predominance of arm-work have been proposed for elevated blood pressure in swimmers, 20. These mechanisms, however, discuss short term and in-event effects; whereas, in general, any aerobic exercise is acutely associated with an increase in cardiac output, a reduction in vascular resistance due to vasodilatation in the exercising muscles, a rise in systolic blood pressure and no change or even a slight reduction in diastolic pressure. Most experimental studies, if not all, suggest that swimming lowers both systolic and diastolic blood pressure in hypertensive rats. Increased muscular blood flow followed by a reduction in peripheral vascular resistance, increased insulin sensitivity of muscles, suppression of sympathetic system, and reduction of vasoconstrictor prostaglandins are among the suggested mechanisms–45.Numerous studies have investigated the mechanism of blood pressure reduction after dynamic and aerobic exercise. As mentioned earlier, the current study enjoys enough power to detect any important reduction (if present) in systolic blood prssure. In general, further randomized trials with adequate sample size are required to more closely investigate the effects of water aerobic exercises on systolic and diastolic blood pressure in hypertensive patients.The most important limitations of our study are non-random assignment of participants to groups, absence of female participants, and relative paucity of the sample size. These limitations can clearly affect the external and internal validity of the study in an undesirable manner. Values of measurable variables, like baseline values of blood pressure, have been adjusted during analysis but the same could not be done for immeasurable variables (e.g. participant motivation). No evidence exists in recent meta-analyses in favor of a preferential effect of exercise in menOur data suggest that a 10-week water aerobic exercise (supervised by a trainer) has an impressive effect on the resting systolic blood pressure and mean arterial blood pressure in individuals with mild to moderate hypertension. This mode of exercise can be particularly beneficial for elderly individuals with orthopedic problems, overweight individuals and those who have not learned how to swim.


Enhanced external counterpulsation (EECP) enhances coronary perfusion and reduces left ventricular afterload. However, the role of EECP on renal function in cardiac patients is unknown. Our aim was to assess renal function determined by serum cystatin C in cardiac patients before and after EECP treatment.A prospective observational longitudinal study was conducted in order to evaluate renal function using serum cystatin C (Cys C) and estimated glomerular filtration rate (GFR) after 35 sessions of EECP treatment in 30 patients with chronic stable angina and/or heart failure. The median (IQR) time for follow-up period after starting EECP treatment was 16 (10–24) months.2 (p = 0.006) after EECP treatment. Subgroup analysis showed that patients with baseline GFR <60 mL/min/1.73 m2 or NT-proBNP >125 pg/mL had a significant decrease in Cys C when compared to other groups (p < 0.01).Cys C significantly declined from 1.00 (0.78-1.31) to 0.94 (0.77-1.27) mg/L (p < 0.001) and estimated GFR increased from 70.47 (43.88-89.41) to 76.27 (49.02-91.46) mL/min/1.73 mThe study demonstrated that EECP could improve long-term renal function in cardiac patients especially in cases with declined renal function or with high NT-proBNP.ISRCTN11560035.The study was registered in the clinical trial as International Standard Randomized Controlled Trial Number  A close relationship between the function of the heart and the kidneys has long been recognized. The bidirectional nature of this interaction forms an important concept in the classification of the cardiorenal syndrome. A decrease in cardiac function could adversely impact renal function . ImpaireEECP is a nonpharmacologic therapy for outpatients with angina pectoris and CHF ,5. EECP EECP is a low risk procedure, approved by US Food and Drug Administration for refractory angina and CHF ,8,9. Nev2. This study was approved by the Institutional Review Board of Piyavate hospital and written informed consent was obtained from each patient. The study was registered in the clinical trial as International Standard Randomized Controlled Trial Number ISRCTN11560035.This study was a prospective observational longitudinal study. Outpatients at cardiology clinic of Piyavate hospital were included during January 2007 and November 2009. Inclusion criteria were (1) age 18 years or more (2) having chronic stable angina and/or CHF. Exclusion criteria were (1) having unstable angina or acute myocardial infarction or decompensated CHF in the preceding one month (2) undergoing coronary angiography or coronary artery bypass grafting in the preceding one month (3) blood pressure >180/110 mmHg (4) severe symptomatic peripheral vascular disease and (5) GFR <15 mL/min/1.73 mth session as well as every 2–3 month interval.After recruitment, all patients underwent a standard round of 35 sessions of 1-hr daily EECP treatment using EECP machine  over a period of 7–8 weeks. Demographics, baseline characteristics, clinical presentations and laboratory findings were collected in the case record forms. Prior to EECP treatment, fasting blood samples were collected and then also immediately collected at the end of 35The samples were centrifuged at 5000 rpm for 5 minutes at 4°C and the supernatant was separated and stored at −30°C until analysis. Renal function was evaluated by changes in Cys C and estimated GFR using an equation that combined both serum creatinine and cystatin C with age, sex and race . This eqCr was measured based on isotope-dilution mass spectrometry standardized enzymatic method using the SRM 967 as control. The mean concentrations with the acceptable ranges of 2 SRM levels were 65.4 (66.5 ± 1.9) and 343.9 (346.2 ± 7.3) μmol/L, respectively. Cys C was measured by a particle-enhanced immunonephelometric assay using a BN Prospec nephelometer . The assay range is 0.23 mg/L to 8.00 mg/L. Within-run precision was assessed at the low (0.92 mg/L) and high (1.97 mg/L) concentrations which yielded coefficients of variation (CoV) of 1.92% and 1.08% and day-to-day CoV of 2.03% and 1.28%, respectively. NT-proBNP was also evaluated before and after 35 sessions of EECP treatment. NT-proBNP was determined by a sandwich immunoassay using Elecsys proBNP 2010 . The analytical range extends from 5–35,000 pg/mL.et al., diastolic blood pressure [ mmHg] and heart rate [ beats/min] were within normal limits.A total of 30 patients with chronic angina  and/or CHF  were recruited to the prospective observational longitudinal study during January 2007 and November 2009. The median (IQR) follow up time was 16 (10–24) months after starting EECP treatment. Baseline characteristics, clinical parameters and laboratory findings are shown in Table Of the study patients, 29 (96.7%) patients had coronary artery disease before EECP treatment followed by hypertension in 27 (90%), diabetes in 23 (76.7%), stroke in 8 (26.7%), CHF in 7 (23.3%) and peripheral artery disease in 4 (13.3%), respectively. Ten (33.3%) patients had smoking history in which 7 (70%) patients were past smokers and 3 (30%) patients were current smokers. The majority  of patients had undergone coronary angiography before EECP treatment. Twelve patients (40%) underwent percutaneous coronary intervention and six patients (20%) underwent coronary artery bypass grafting. Of 7 patients with prior history of CHF, 6 had EF < 40% consistent with systolic heart failure due to ischemia and 1 had diastolic dysfunction. According to recent medications before EECP treatment, 93.3% (28/30) of patients received statin therapy, 90% (27/30) aspirin or clopidogrel, 76.7% (23/30) angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), 63.3% (19/30) beta-blockers, 56.7% (17/30) nitrate and 33.3% (10/30) calcium channel blockers including diltiazem and verapamil. The doses of ACEI, ARB and beta-blockers were unchanged during EECP treatment and no new medications were added during follow- up.1C [7.5 (1.3) %] were higher than normal limits. The mean (SD) left ventricular ejection fraction (LVEF) was 55.0 (17.9) % before EECP treatment. The median (IQR) Cr, GFR, Cys C and NT-proBNP before EECP treatment were 1.02 (0.84-1.36) mg/dL, 70.47 (43.88-89.41) mL/min per 1.73 m2, 1.0 (0.78-1.31) mg/L and 244 (120–1067) pg/mL, respectively.Baseline laboratory findings showed that the mean (SD) of hemoglobin [12.9 (1.8) g/dL], albumin [4.2 (0.4) g/dL] and lipid profiles including cholesterol [146.0 (27.0) mg/dL], triglyceride [103.3 (48.7) mg/dL], HDL cholesterol [49.5 (12.2) mg/dL], LDL cholesterol [77.8 (19.6) mg/dL] were within normal limits except fasting blood sugar [118.3 (27.6) mg/dL] and hemoglobin ADuring EECP treatment period, there was no withdrawal of EECP treatment or any serious adverse effect occurred. Only two patients reported the development of skin blebs which resolved after supportive treatment and none of the patients had clinical heart failure. After EECP treatment, systolic blood pressure, diastolic blood pressure and heart rate were not significantly changed. Overall, there was an improvement in cardiac symptoms [NYHA Classification Class I/II/III/IV (n): Baseline 0/15/13/2 versus Follow-up 13/16/1/0 (p < 0.001)]. New York Heart Association Classification Class was improved by at least 1 class in 26 patients (86.7%).th sessions of EECP treatment, Cys C was not significantly different from the baseline , but Cys C declined significantly at the end of the follow-up period . Similarly, GFR was not significantly different at the end of 35th session of EECP treatment  but GFR significantly increased at the end of the follow-up period   at baseline. According to the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) workgroup, stage 3 CKD was defined as the presence of GFR <60 mL/min/1.73 m3 months . Among p3 months ,14. Thus2 had significant decrease in Cys C  and corresponding increase in GFR at follow-up after EECP therapy .Subgroup analysis showed that patients with baseline GFR <60 mL/min/1.73 m2 versus 62.26 (46.97-83.18) mL/min/1.73 m2, p = 0.001]  was lower than normal population. In such patients, several mechanisms of chronic heart impairment including systolic dysfunction, increased venous congestion and activation of neurohormonal axis might lead to decrease renal function [In the present study, the majority of patients had diabetes and hypertension co-existing with advanced heart disease. The baseline GFR  or high NT-proBNP (>125 pg/mL) at baseline. Among these patients, Cys C decreased approximately 0.12 mg/L which corresponded to increased Cys C–based GFR of 6 mL/min/1.73 m2[2). Regarding two-way interactions of the heart and the kidney, the small improvement in GFR after EECP in this study could benefit for the cardiac function and vice-versa.We found that EECP treatment did not have immediate effect on renal function but improved long term renal function during 16-month follow-up period. The beneficial effect of EECP was greater for those with diminished renal function . Serum Cr can be affected by many factors such as muscle mass and protein intake. It is possible that improvement in cardiac function after EECP might have led to improved nutritional status and masked the small improvement in renal function when serum Cr is used as a marker. Previous studies have suggested that Cys C is a more accurate and sensitive marker of GFR compared to Cr in diabetic and non-diabetic patients [The effects on renal function were not apparent using serum Cr or Cr-based GFR equation . Routine measurement of LVEF after treatment was not available. We used endogenous markers of renal function rather than formal clearance studies. This would tend to underestimate any changes in renal function especially if the GFR was relatively well preserved. The effects on renal function by EECP as a group were modest, and the clinical significance of such minor improvement in GFR on cardiovascular or renal outcome is uncertain. Given the within-person individual variability of renal function measurements ,42 and tThe results from this study provide support for larger comparative studies between EECP and placebo measuring Cys C level and GFR in well-matched groups to be done in the future in order to determine the benefits of EECP treatment. In particular, the observation that the beneficial effect of EECP was greater for patients with diminished renal function and for those with elevated NT-proBNP very much supports the need for such studies in patients with moderate to severe reduction in GFR or in those with congestive heart failure.EECP is a safe, effective and feasible treatment for cardiac patients. This is the first study to demonstrate that EECP did not show the immediate effect on renal function but could augment the renal function as measured by Cys C and estimated GFR in cardiac patients after long term follow up, especially in the groups with decreased GFR or high NT-proBNP.ACEI: Angiotensin-converting enzyme inhibitors; ARB: Angiotensin receptor blockers; CHF: Congestive heart failure; Cr: Plasma creatinine; Cys C: Serum cystatin C; EECP: Enhanced external counterpulsation; GFR: Glomerular filtration rate; LVEF: Left ventricular ejection fraction.The authors declare that they have no competing interests.PR designed the study and wrote the manuscript; NM and OR recruited the patients; PR supervised the EECP treatment; CK helped in the design of the study and in writing manuscript; AC and DP performed the statistical analyses; SA participated in the collection of data and data analysis; SV and AC measured plasma creatinine, serum cystatin C and NT-proBNP; TS critically revised the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2369/14/193/prepub


Hypertension was thought to be rare in Africa, but it is now recognized as one of the most important cerebrovascular diseases contributing to about 40% of these diseases in the continent.Hypertension is the 3The aims of this study were to describe the pattern of blood pressure distribution among adults, and determine prevalence of prehypertension and hypertension among adults in Northern Ethiopia.The study was done on a community-based sample of 1183 adults of 697 (58.8%) urban and 486 (41.1%) rural residents using statistical multistage sampling procedures. The study was based on the recent WHO and JNC-7 classification of blood pressure. Multi-item structured questionnaires were also developed to elicit additional information on the subjects.The overall prevalence of hypertension and prehypertension in the study population was 18.1% and 37.2%, respectively. The prevalence of hypertension positively correlated with body mass index and age in both urban and rural residents (P = 0.001). Sex and age adjusted mean systolic blood pressure (SBP) was statistically higher in urban than in rural population (P = 0.001).Hypertension was found to have high prevalence in the study region. However, people’s awareness and control of hypertension was found to be very poor. Lack of a clear hypertension prevention guidelines and strategies nationwide can aggravate the impact of cardiovascular diseases. Accororldwide . The oveAccording to the recent guideline of Joint National Commitee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VII), blood pressure in adults aged at least 18 years is categorized as normal; < 120/80, prehypertension; 120-139/80-89, and hypertension; ≥ 140/90 . CurrentHypertension is one of the major factors for high mortality of adults in sub-Saharan Africa . AccordiCross–sectional descriptive study was conducted on non-institutionalized civilian adult population of 18 years or older living in Humera (902 Km North of Addis Ababa) representing the rural population and Mekelle (783 Km North of Addis Ababa) representing the urban population of Tigray Region which is one of the four biggest regions of Ethiopia. Tigray Region is located in the Northern part of the country, shares common borders with Eritrea in the north, the State of Afar in the east, the State of Amhara in the south, and the Republic of the Sudan in the west. Data were collected during Aug 2010 – Jan 2011. Blood pressure measurement was made by standard cuff and relevant interviewing procedures were used to elicit medical history, socio-demographic and life style characteristics. Prior to the survey, piloting was conducted in order to standardize measurement procedures and reduce inter-observer bias.Blood pressure was measured from left arm of each subject with a standard cuff as described by WHO . The mea2), normal BMI (18.5 kg/m2 ≥ BMI < 25 kg/m2), over weight or obese (BMI ≥ 25 kg/m2) [Body weight was measured, to the nearest 0.5 kg, with the subject standing motionless on the weighing scale, feet about 15 cm apart, and weight equally distributed on each leg. Subjects were instructed to wear minimum outerwear and no footwear while their weight is being measured . Height 5 kg/m2) .In order to ensure the accuracy, completeness, and comparability of blood pressure and anthropometric variables, and interview responses across the study sites, different quality control measures were incorporated in the study design. All data collectors had a common training program on how to get reproducible measurements of blood pressure, weight, and height.Ethical approval was obtained from the Mekelle University Ethics Review Board. Written informed consent was obtained from participants after a comprehensive explanation of the purpose and procedure of the study in local language. For participants who do not read and write, verbal agreement was obtained. Subjects incidentally found with hypertensive conditions during the survey were advised to seek medical attention in the nearby health facility and make lifestyle modifications.Descriptive statistics were used to calculate proportions. Means were calculated with corresponding 95% confidence intervals (C.I). T-test for continuous variables and chi-square statistics for categorical variables were used in the bivariate analysis. The effects of age, sex, and body mass index on blood pressure were investigated by multiple linear regression using SPSS 15 software package . A p-value < 0.05 was taken as statistically significant.Data were collected from 443 (37.4%) males and 740 (62.4%) females aged at least 18 years of which 697 (58.9%) were urban and 486 (41.1%) were rural residents. About 652 (55%) of the study population were in the age group of 18–29 years. Those in the age group of 30–49 were 25.6% (302) and only 225 (19.1%) of the population had a minimum age of 50 years. About 784 (66.4%) of the study population had normal body mass index with 89.2% (1055) of the population had a monthly income of less than 600 Eth birr. Almost 50% of the study group had an educational background of at most elementary level with majority had no formal education. The prevalence of overweight was 28 (12.6%) in urban males and 79 (16.6%) in urban females (p < 0.05). On the other hand the prevalence of overweight was 20 (9.0%) in rural males and 43 (16.2%) in rural females (p < 0.05). However, there was no significant difference in overweight between urban and rural residents (p > 0.05)  are shown in Table The overall prevalence of hypertension and prehypertension in the study population were 18.1% and 37.2%, respectively. In urban residents 22.5% of males and 19.0% of females were found to be hypertensive. However, 19.5% males and 11.5% of females in rural residents were hypertensive. The prevalence rate increased with age in both males and females and in both urban and rural residents (Table P < 0.01 for each). Similarly, in the urban residents the mean systolic pressure and diastolic pressure of males were higher than females by 1.7 mm Hg and 1.04 mm Hg, respectively, having controlled for BMI and age (P < 0.01 for each). When rural and urban populations combined, age was the leading predictor of the mean systolic pressure (P < 0.01). However, sex and age were almost equally dominant predictors of the mean diastolic pressure (p < 0.01) as shown in the Table Sex was the leading predictor of mean systolic pressure and diastolic pressure in both rural and urban residents. In the rural residents the mean systolic pressure and diastolic pressure of males were higher than females by 4.5 mm Hg and 2.8 mm Hg, respectively, having controlled for BMI and age . Multiple linear regression indicated that sex was the leading predictor of increased mean SBP and DBP in both rural and urban residents. But in the overall population the dominant predictor of increased mean SBP and mean DBP were age  and sex , respectively. It has been clear that aging leads to a multitude of changes in the cardiovascular system including increased vascular stiffness. The age-related increases in blood pressure are mainly attributable to an increase in systolic blood pressure while maintaining or having a slight decrease in a diastolic blood pressure .About 70% of the hypertensive population  were in stage I and the remaining 30%  were in stage II. According to JNC 7, stages of hypertension are two with stage I of 140/90-159/99 mm Hg and stage II of ≥ 160/100 mm Hg -13,18-21The present result of hypertension prevalence in Northern Ethiopian population (18.1%) is higher than the 13.2% of Southwest Ethiopia . It is aDifferent studies have shown that prehypertension is also increasing the risk of cardiovascular diseases ,7. BeginThe overall mean SBP was higher in urban residents 119.4+/−18.0) than in rural residents 113.9+/−14.3) with P < 0.01. This might be partly because rural residents have low rate of alcohol consumption, less western diet, low salt consumption, lean body build, low level of blood lipid, and engaged in physical activities. However, the mean DBP of urban and rural residents were comparable (P > 0.05). The mean SBP of males was higher than the female counterparts in both rural and urban residents (P < 0.001). The mean SBP correlated positively with both age and BMI in both urban and rural residents (P = 0.01). This is consistent with previous studies done in Ethiopia ,13,20,21.9+/−14.3.0 than iThis study has some limitations. Since inclusion of participants was made based on voluntary participation, this might influence the results. In addition, the age of the study participants generated by questioner may not be accurate as most of the study participants were illiterate and there was no recorded biodata system. Hence this might also influence the results of the study. Furthermore, the study did not employ hematological lipid profiles.Hypertension has high prevalence in both urban and rural residents of the region and hence is a public health concern. However, the people’s awareness and control of hypertension was found to be very poor. Therefore, the dogmatic notion that ‘our health problems are solely communicable diseases and non-communicable diseases are merely problems of the West’ must be changed. Lack of a clear hypertension prevention guidelines and strategies nationwide can aggravate the impact of cardiovascular diseases. Hence this is high time to design appropriate control strategies and prevention guidelines involving all stakeholders from government to community levels. The prevalence of prehypertension is also very high in the study area. It is also important to firmly recommend practicing of life style modifications for prehypertensive population in order to reduce the risk of developing hypertension in the near future. In the study population, the rise in the blood pressure correlated with BMI. This requires life style modification to maintain desirable weight. Consumption of diet rich in fruits and vegetables, rich in low-fat dairy products, and reduced in saturated fat and cholesterol are recommended. Finally, further study to uncover the hidden burden of hypertension nationwide is recommended.The authors declare that they have no competing interests.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2261/14/33/prepub


The aim of this retrospective study is to identify intraoperative patient’s characteristics predicting the need for blood transfusion during CABG in our local cardiac surgical service.This study included 1835 consecutive patients, 1311 males and 524 females with mean age 58.8±9.9 years, undergoing coronary artery bypass grafting. Risk factors detected by univariate study were entered in a multivariate logistic regression model of the relationship between preoperative variables and blood transfusion. P<0.001), CPB use  and female gender  as independent risk factors for blood transfusion.Blood transfusion was used in 435 patients (29.9%). Univariate analysis identified hemoglobin, smoking, hypertension, sex, diabetes, BMI and use of cardiopulmonary bypass (CPB) as significant predictors. Multivariate analysis revealed hemoglobin (OR: 0.8; CI: 0.74-0.86;The predictors of RBC transfusion after isolated CABG were performing CPB, preoperative hemoglobin and female gender. These factors can be used as a clinical tool to preserve blood bank resources without increasing patient’s risk. Coronary artery bypass grafting (CABG) surgery is a surgical procedure associated with one of the highest rates of transfusion. Nearly The transfusion of red blood cells (RBCs) in cardiac surgery is associated with increased morbidity and mortality ,4. It haThe identification of pre‑operative variables associated with the need for transfusion will reveal the transfusion risk and thus allows for the use of cost-effective blood conservation methods. The aim of this study was determine the clinical and demographic variables associated with blood product transfusion in patients undergoing elective CABG.We reviewed the records of patients undergoing CABG surgery at the Division of Cardiovascular Surgery Shariati Hospital from May 2007 to October 2012. Standard demographic and clinical characteristics were obtained from institutional cardiac surgery database. These included history of diabetes mellitus (DM), hypertension (HTN), preoperative hemoglobin, operative transfusion data, cardiopulmonary bypass, ejection fraction (EF), chronic obstructive pulmonary disease (COPD), and preoperative creatinine . Preoperative hemoglobin data were measured closest to the time of surgery. Apheresis products were not used. Indications for allogeneic transfusion were based on routine laboratory measurements of International Normalized Ratio (INR) platelet counts and hemoglobin values, in addition to measurements of hemodynamic data, the rate of blood loss, and existing concomitant diseases. Transfusions of allogeneic packed red cells were given at the discretion of the attending surgeon. Student’s test was used to compare differences in pre-operative hemoglobin, ejection fraction and BMI between patients with and without transfusion. The relationship between transfusion requirements and categorical variables was examined using the chi-squared test. The relationship between transfusion requirements and all variables adjusted to one another was examined using backward stepwise multiple logistic regression.Between May 2007 to October 2012, 1992 patients underwent CABG surgery. We excluded 157 patients who underwent concomitant cardiac surgical procedures, leaving 1835 patients who underwent isolated primary CABG surgery for the study. The study population had a mean age of 58.8 ± 9.9 SD years. Baseline patients’ characteristics stratified by transfusion of RBCs are shown in P<0.001). Of those who received blood, 380 (87.2%) received 1 unit; 47 (10.8%), 2 units, 8 (1.8%), 3 units, and 1 (0.2%), 4 units.Blood transfusions (mean quantity 1.1 units) were given to 435 of 1835 patients (24%); 187 of 524 women (35.6%) required transfusion, compared with 250 of 1311 men (19.0%) (P-values are summarized in The results of the univariable analysis are given in This study was undertaken to determine variables indicating allogeneic RBC transfusion in patients undergoing CABG, which is associated with a high risk of blood transfusion. Despite Society of Thoracic Surgeons guidelines and other reports, blood transfusion rate varies significantly between institutions -7. AllogAlthough several variables showed association with the need for Allogeneic RBC transfusion during CABG in the univariate analysis in our study, three of these including preoperative hemoglobin, on‑pump surgery and female gender proved to be independent predictors of intraoperative blood transfusion.Several studies have reported anemia as a major predictor for need of transfusion. However it is still unclear what hemoglobin level vindicates the need for transfusion. Latest Published guideline for blood transfusion and conservation in cardiac surgery by The Society of Thoracic Surgeons, recommends transfusion for a hemoglobin level of <7 g/dl. However, the level of evidence is ‘C’ with a recommendation of ‘Class 2a’, which means that supporting evidence is still insufficient . VariousIn agreement with other studies, the present authors found that female sex is a predictive factor for the transfusion of RBCs -15. The Several studies have shown differences in blood loss and allogeneic transfusion requirements between on‑pump and off‑pump CABG. Nuttall et al. showed tThere are a number of potential limitations to this study. First, this study was performed at a large tertiary‑care teaching hospital that followed current bloodconservation and transfusion guidelines; thus, the practice pattern should be comparable to similar institutions. Second, the effects of unknown or unmeasured confounders on the observed association cannot be ruled out. Taking into account the limitations of the present study, we conclude that the best predictor for transfusion risk is the preoperative hemoglobin level, female gender and on‑pump surgery.


The haemodynamic response to critical care intubation is influenced by the use of sedation and relaxant drugs and the activation of the vagal reflex. It has been hypothesized that different disease states may have a contrasting effect on the cardiovascular response to vagal stimulation. Our objective was to determine whether the blood pressure response to vagal stimulation was modified by endotoxaemia or hypovolaemia.New Zealand White rabbits were anaesthetised with urethane before tracheotomy. The exposed left Vagus nerve of randomised groups of control (n = 11), endotoxin , hypovolaemia 40% (n = 8) and hypovolaemia 20% (n = 8) rabbits were subjected to 10 Hz pulsed electrical stimulations of 25 s duration every 15 min. Haemodynamic parameters were recorded from a catheter in the right carotid artery connected to an iWorx monitor. Serum catecholamines were measured every 30 min using reverse-phase ion-pairing liquid chromatography. The change in blood pressure after vagal stimulation was compared to controls for one hour after the first death in the experimental groups.29% of the rabbits died in the hypovolaemia 40% group and 27% in the endotoxin group. One rabbit died in the hypovolaemia 40% group before vagal stimulation and was excluded. Following electrical stimulation of the Vagus nerve there was a fall in blood pressure in control rabbits. Blood pressure was conserved in the hypovolaemic rabbits compared to controls (p<0.01). For the endotoxaemic rabbits, there was a non-significant trend for the mean blood pressure to decrease more than the controls. Serum catecholamines were significantly raised in both the hypovolaemic and endotoxaemic rabbits.Pathology may contribute to modifications in blood pressure when vagal activation occurs. Patients who are either already vasoconstricted, or not vasoplegic, may be less at risk from intubation-related vagally mediated reductions in blood pressure than those with vasodilatory pathologies. The intubation of children during critical care illness can provoke alterations in both heart rate Changes in blood pressure during intubation in critical care illness are more complex. In adults there is a tendency for the mean blood pressure to fall by 30 mmHg Our objective was to determine whether the blood pressure response to vagal stimulation was modified by endotoxaemia or hypovolaemia. Haemodynamic, biochemical and hormonal parameters were used to evaluate the effects of endotoxaemia and hypovolaemia on the rabbits.ad libitum.The study was approved by the ComEth Anses/ENVA/UPEC . All research animals were maintained under anaesthesia from the start of experimentation to the end when they were euthanised with a lethal dose of anaesthetic (5 g/kg urethane). Male New Zealand White (NZW) rabbits were obtained from Hypharm, La Corbière, 49450, Roussay, France. In line with recommendations, a maximum of 15 rabbits at a time were maintained in an aired pen 3 m by 4 m and 3 m high with a dense layer of straw and hay The rabbits were anaesthetised by the injection urethane in a marginal vein of an ear. 1.8 g/kg was used for rabbits weighing ≤1.8 kg and 2.0 g/kg for rabbits weighing >1.8 kg. The level of anaesthesia was monitored using paw and corneal reflexes. Urethane was chosen as an anaesthetic because of its single dose regimen and because it has previously been established to have minimal effect on haemodynamic parameters in anaesthetised rats Sterile surgical conditions were used to make a midline incision in the anterior aspect of the neck. The trachea was opened before being intubated with a 7 cm plastic tube of with an internal diameter of 4.0 mm and 5.6 mm external diameter . The right carotid artery was cannulated with a 22gauge canula, and the left Vagus nerve was exposed. Continuous mean blood pressure readings were made using an iWorx® 214 monitor connected to the carotid artery catheter . Arterial blood gas measurements were made using an i-STAT® system . The rabbits were entered into the experiment when baseline blood pressure had been stable for at least 15 minutes and arterial pH was between ≥7.35 and ≤7.45 , endotoxaemia 1 mg/kg (11 rabbits), hypovolaemia 20% reduction in blood volume  and hypovolaemia 40%reduction in blood volume .Rabbits in the hypovolaemia groups were bled  and serum lactate . A three-minute interval was left after taking blood before a vagal stimulation. Stimulations were made at baseline, then at 15 minute intervals for all rabbits until 180 minutes and then half-hourly for the control and endotoxaemic rabbits until 300 minutes, see et al. in 2002 All catecholamine analyses were performed at the Hôpital Robert Debré, Paris, France in accordance with the reverse-phase ion-pairing liquid chromatography methodology described by Candito 2O3) and 100 µl of the internal control were added to the 600 µl of plasma. The alumina was washed three times before separation of the catecholamines from the alumina. Fifty microlitres of the supernatant were removed for injection through a 717 Waters auto-sampler onto a C18 Purospher (Merck) column  equipped with a guard column. The aqueous isocratic mobile phase adjusted to pH 3.9 consisted of citric acid 20 mM, sodium acetate 50 mM, sodium heptane sulfonate 0.4 mM in methanol 10%. Mobile phase was pumped at a flow rate of 1 ml/min by a Waters Model 550 pump. Quantification of the catecholamines was carried out using an amperometric 2465 Waters detector set at 0.5 V. Millennium Waters Empower Chromatography software was used for all calculations.Briefly, the plasma was removed from storage and thawed at room temperature. Six hundred microlitres was drawn from the plasma samples and 20 mg of alumina  according to their Gaussian distribution. An unpaired t-test, or a Mann-Whitney test, were used for continuous data according to their distribution. All statistical tests were 2-sided and the probability of a type 1 error (α) was determined at <0.05. All statistical tests were carried out using SPSS (version 19).versus the control group  and three in the endotoxin group . No rabbits died in the HV20% group. The first death after vagal stimulation in the HV40% group occurred between +15 and +30 minutes from bleeding and between +240 and +270 minutes in the endotoxin group. According to protocol, the rabbits' parameters were analysed from +15 minutes in the hypovolaemia groups and +240 minutes for the endotoxin group for a period of one hour.The hypovolaemia groups showed decreases in pH, CO2, HCO3, haematocrit and pulse pressure, mean blood pressure and heart rate with a increases in adrenaline and lactates compared to the control group  and 2. TIn the endotoxin group there were significant decreases in CO2 and bicarbonate with no change in pH, lactates and haematocrit and a significant increase in noradrenaline . There wDuring electrical stimulation of the Vagus nerve there was significant, and dose dependent, maintenance of mean blood pressure in the hypovolaemic rabbits compared to controls . For theWe disproved our hypothesis. Following vagal stimulation the blood pressure of the hypovolaemic rabbits was significantly conserved when compared to controls. When compared to controls, endotoxaemic rabbits displayed a non-significant tendency towards a greater fall in blood pressure.Classically the effect of hypovolaemic shock on haemodynamic integrity is biphasic and asymmetric. Mean blood pressure is maintained during the early compensatory Phase I by combination of increasing heart rate and vasoconstriction despite a fall in cardiac output In a similarity with Phase I hypovolaemia, sepsis is associated with a reduction in pre-load and left ventricular stroke volume In the hypovolaemia model, mean blood pressure fell markedly after bleeding (75 mmHg to 20 mmHg in the HV40% model) before increasing marginally (vasoconstrictive Phase I) to reach a plateau and then falling (vasodilatory Phase II) . Generalet al.The effect of the endotoxin in our model is more difficult to interpret. Our rabbits did not demonstrate the decrease in blood pressure as early as 1–2 hr after injection that has been observed in other studies in rabbits (1 mg/kg) Raised levels of noradrenaline and adrenaline have previously been demonstrated in animal models of hypovolaemia et al.All four experimental groups displayed raised levels of baseline circulating catecholamines after surgical preparation and before vagal stimulations. These were possibly due to the stress of anaesthetic induction and/or preparation. Another possibility is that the rabbits were improperly anaesthetised despite each being tested for paw and corneal reflexes Vagal stimulations at baseline and in control rabbits reduced blood pressure in the order of 20 to 30 mmHg . After vThe endotoxaemic rabbits they had similar baseline blood pressure compared to control rabbits  but diedThe most appropriate animal model of human sepsis is subject to conjecture Clearly the haemodynamic response to intubation is a multi-factorial process with operator experience, method of intubation, sedation and relaxant drugs all potentially contributing to change in blood pressure. Inevitably, the more that the associated influences around intubation are controlled for in an experimental environment the less that the model resembles the clinical situation. However, our vagal stimulation model retains some relevance where vagal activation is frequent, such as during the intubation of children who have predominant parasympathetic balance in the early part of life Pathology may contribute to modifications in blood pressure when vagal activation occurs. Patients who are either already vasoconstricted, or not vasoplegic, may be less at risk from intubation-related vagally mediated reductions in blood pressure than those with vasodilatory pathologies. Our results require confirmation in a model with a larger cohort where vascular resistance, ejection volume and cardiac output are measured.