Neurohumoral Profile Research Articles

Safety and efficacy of initiation SGLT in heart failure with a reduced left ventricular ejection fraction and chronic kidney disease on top of standard therapy with ARNI or ACE-i

Abstract Quadruple therapy remains underused in cases of heart failure with a reduced ejection fraction (HFrEF). Among eligible patients most of them take ACE-i/ARB and B-blockers, less MRAs and ARNI. There are many questions of adding new foundational drugs, especially in the case of coexisting of HFrEF and chronic kidney disease (CKD). The aim was to compare the safety and effectiveness of initiation SGLT in patients (P) with HFrEF and CKD on standard therapy with ARNI or ACE-I. Methods we identified 54 symptomatic P with HFrEF (EF≤40%) and CKD 3 (eGFR between 30 and 60 ml/min) on standard therapy (ACE-I or ARNI, B-blockers, MRAs). All P were divided into 2 groups: group 1- 26 P on ARNI, B-blockers, MRAs; group 2- 28 P on ACE-I, B-blockers, MRAs. All P started on dapagliflozin (D) with a dose of 10 mg daily. The potassium (K), creatinine levels, eGFR, clinic BP were estimated at baseline and at weeks 1, 2, 4, 6, 8, 12. At baseline and at weeks 4, 12 NT-proBNP, urine albumin-to-creatinine ratio (UCAR) were estimated and P underwent 24-hour BP measurements. Results At week 1 after initiation of D a mean eGFR deсreased not significant in both group. At week 2 in group 1 mean eGFR decreased by 1,9±1.1 ml/min/1.73m2, P<.05 and group 2-2,5±1.9 ml/min/1.73m2, P<.05. At week 4 in both groups mean eGFR deсreased significantly, but in group 2 the decline of eGFR was more pronounced (-2,4±2.6 ml/min/1.73m2 vs.-3,3±2.5 ml/min/1.73m2, P=.04), with not significant decreasing to 6, 8, 12 weeks. At week 1mean K changed not significantly after start of therapy in both groups. At week 4 in group 1mean K deсreased significantly from 4.97±0.6 to 4.63±0.57 mEq/l (P<.05), in group 2 K deсreased not significant. At week 4 in group 1 was a greater reduction NT-proBNP than in group 2 (-234±42 vs. -143±32 ng/L, P<.05). At week 12 in both groups a significant decrease NT-proBNP were observed, but in group 1 more pronounced (-865±89 ng/L and -573±78 ng/L, (P<.01; P<.05 respectively). UCAR was also reduced significantly in both groups, but in group 1 more pronounced (P<.01; P<.05 respectively). In group 1, there were more cases of symptomatic hypotension (10 vs. 8, P<.05) and greater decrease mean BP than in group 2 (P<.05), but it didn’t result in a withdrew. In return, maen doses diuretics were carefully decreased in both groups. At baseline in patients with HFrEF was an inverse correlation between GFR and NT-proBNP level (r=−0.328, P<.05). By linear regression analysis the eGFR was associated with NT-proBNP change (P<.05). Conclusion In patients with HFrEF and CKD, adding SGLT to standard therapy with ARNI, B-blockers, MRAs were paralleled by marked improvements in the neurohumoral profile by significantly reduced NT-proBNP compared with ACE-I, B-blockers, MRAs. SGLT initiation caused an early drop in eGFR, but in group ARNI the decline of eGFR was less pronounced with greater reduction in the albuminuria and was accompanied by decreased potassium level.

Features of neuroimmune and genetic profile in men with clinical manifestations of vegetative vascular dystonia of hypertensive type

Background. Identification of immune, neurohumoral and genetic markers of vegetative vascular dystonia of the hypertensive type is relevant in the aspect of prevention and early diagnosis of cardiovascular pathology in middle-aged men.
 Aim. To study the features of the immune and neurohumoral profile in middle-aged men with clinical manifestations of vegetative vascular dystonia of the hypertensive type, associated with polymorphic variants of candidate genes for blood vessel tone regulation.
 Material and methods. 113 middle-aged men (mean age 46.13.9 years) were examined. The observation group included 65 men (average age 45.34.6 years) with clinical manifestations of vegetative vascular dystonia of the hypertensive type. The comparison group included 48 men without signs of autonomic regulation dysfunction (average age 48.33.2 years). The groups were comparable in age (p=0.593), ethnic and social composition. The content of CD3+CD95+ lymphocytes was determined by flow cytometry; interleukin-6, total immunoglobulin E, adrenaline, serotonin by enzyme immunoassay. Polymorphic variants of the genes ADRB2 (rs1042713), ADD1 (rs4961), GNB3 (rs5443), HTR2A (rs7997012) were identified by real-time polymerase chain reaction. Statistical processing: comparison of arithmetic means using Student's t-test or MannWhitney U-test, calculation of odds ratio (OR) and 95% confidence interval (CI).
 Results. The immune profile of men with disorders of autonomic regulation was characterized by a deficiency of CD3+CD95+ lymphocytes against the background of overproduction of total immunoglobulin E and interleukin-6. The neurohumoral profile was characterized by excessive synthesis of adrenaline and serotonin. The development of symptoms of vegetative vascular dystonia of the hypertensive type was associated with the G allele of the ADRB2 gene (rs1042713) (OR=1.80; 95% CI=1.053.08; p 0.05), the G allele of the ADD1 gene (rs4961) (OR=3.51; 95% CI=1.279.67; p 0.05), C allele of the GNB3 gene (rs5443) (OR=2.30; 95% CI=1.214.37; p 0.05), A allele of the HTR2A gene (rs7997012) (OR=2.38; 95% CI=1.374.15; p 0.05).
 Conclusion. Changes in the immune profile were identified (deficiency of CD3+CD95+ lymphocytes, excess of total immunoglobulin E, interleukin-6), associated with hyperproduction of adrenaline and serotonin against the background of polymorphism of candidate genes for vascular tone regulation [ADRB2 (rs1042713), ADD1 (rs4961), HTR2A (rs7997012 ), GNB3 (rs5443)].

Immune and neurohumoral profile of the children population living in the conditions of exposure to benzo(a)pyrene

Introduction. Benzo(a)pyrene induces disorders of immune and neurohumoral regulation that are aggravated by the influence of unfavourable climatic and geographical factors in the Far North. In this regard, studies of the features of the immune and neurohumoral profile are of particular relevance for the identification of markers of early health disorders of the population of industrially developed circumpolar territories (using the example of benzo(a)pyrene). Materials and methods. Five hundred 3-6 year children living in the circumpolar territory of Eastern Siberia were examined. Observation group consisted of 352 children living in conditions of exposure to benzo(a)pyrene. Comparison group included 148 children residing at a relatively clean territory. Determination of the content of benzo(a)pyrene in the blood was carried out by HPLC. Phenotyping of CD3+-, CD19+-, CD3+CD95+-, Annexin V-FITC+7AAD- and Annexin V-FITC+7AAD+-lymphocytes was performed by flow cytofluorometry. The level of IgA, IgM, IgG was determined by Mancini radial immunodiffusion, the IgG content to benzo(a)pyrene was determined by allergosorbent testing. The content of acetylcholine, serotonin, and neurotropin-3 was determined by ELISA. Results. Children living in the industrially developed circumpolar territory of Eastern Siberia have an increased level of blood contamination with benzo(a)pyrene (p<0.05). The immune profile is characterized by inhibition of cellular (CD3+ deficiency) and humoral immunity (decreased IgA, IgM, IgG with an excess of CD19+). Violations of apoptosis (decrease in Annexin V-FITC+7AAD-, Annexin V-FITC+7AAD+-lymphocytes; increase in Bcl-2 and CD95+) were revealed (p<0.05). An increased IgG to benz(a)pyrene content were found (p<0.05). The neurohumoral profile of the examined children is characterized by hyperexpression of serotonin with acetylcholine and neurotropin-3 deficiency (p<0.05). Limitations. The results of the study are intended for specialists in the field of hygiene, immunology and allergology. Conclusion. Revealed features of the immune status (deficiency of CD3+, Annexin V-FITC+7AAD-, and Annexin V-FITC+7AAD+-lymphocytes IgA, IgM, IgG, excess CD19+, CD95+, Bcl-2, IgG to benzo(a)pyrene), associated with changes in sympathetic-parasympathetic balance (excess serotonin, deficiency of acetylcholine, neurotropin-3) characterize the features of the immune and neurohumoral profile in the children population of the circumpolar territories of Eastern Siberia under the conditions of exposure to benzo(a)pyrene.

Indicators of Immune and Neurohumoral Profile in Women of Fertile Age with Functional Disorders of the Autonomic Nervous System Associated with Polymorphic Variants of the HTR2A (rs7997012) and TP53 (rs1042522) Genes.

In women of fertile age with functional disorders of the autonomic nervous system (ANS), a complex of indicators of the immune and neurohumoral profile associated with polymorphic variants of the HTR2A (rs7997012) and TP53 (rs1042522) genes was revealed. In patients with the diagnosis "G90.8. Other disorders of the autonomic nervous system", the neurohumoral profile is characterized by excessive content of cortisol and serotonin (p<0.05), which indicates the development of the hypersympathicotonic variant of autonomic regulation disorders. The cellular immune profile in the examined individuals was characterized by a significant decrease in the content of CD3+CD4+ and CD3+CD8+ lymphocytes (p<0.05). At the same time hyperactivation of the humoral immune response was observed. In particular, we revealed enhanced production of IgG and IgM antibodies accompanied by increased count of CD19+ lymphocytes (p<0.05), which characterized clinical and laboratory manifestations of the asthenic syndrome. The women with ANS disorders had increased frequency of the G allele (OR=3.00; 95%CI 1.20-7.47) and GG genotype (OR=3.91; 95%CI 1.00-15.24) of the HTR2A (rs7997012) serotonin receptor gene, as well as the G allele (OR=1.93; 95%CI 1.04-3.57), CG genotype (OR=2.38; 95%CI 1.02-5.53) and the GG genotype (OR=1.48; 95%CI 0.42-5.24) of the TP53 (rs1042522) oncosuppressor protein gene (p<0.05). The polymorphic G allele and GG genotype variants of candidate genes (HTR2A (rs7997012) and TP53 (rs1042522) genes) in women with ANS pathology are associated with an imbalance of the neurohumoral (excess of cortisol and serotonin) and immune regulation (deficiency of the CD3+CD4+ and CD3+CD8+, excess of CD19+, IgG and IgM). These parameters form a complex of the immune, neurohumoral, and genetic profile indicators in women of fertile age that characterize functional disorders of ANS manifestations by hypersympathicotonic type with an asthenic component.

Features Neurohumoral and Immune Profile in Children with Functional Disorders of the Autonomic Nervous System Associated with Sirtuin Gene SIRT1 (rs7069102) Polymorphism.

We revealed some features of the neurohumoral and immune profile in preschool children with functional disorders of the autonomic nervous system (ANS) associated with the polymorphism of the SIRT1 gene (rs7069102) responsible for stability of the cell cycle, energy and plastic metabolism of organic substances, and Ca2+ exchange. The neurohumoral profile of the surveyed children is characterized by excessive content of glutamic acid and serotonin, which leads to excessive synaptic activation and disorders of ANS inhibition (p<0.05). The cell immune profile is characterized by a reduced immunoregulatory index CD4+/CD8+ with a simultaneous deficiency of CD3+CD4+ and excess of CD3+CD8+ lymphocytes (p<0.05). These etiopathogenetic disorders of the neurohumoral and immune profile are associated with variant G-allele of the SIRT1 gene (rs7069102) and the corresponding homozygous GG-genotype (p<0.05), which leads to disturbances in the control of the cell cycle stability, including apoptosis, cytochrome deacetylation, inhibition of the glutamate dehydrogenase enzyme activity with excessive glutamate accumulation, energy metabolism in mitochondria, and Ca2+ exchange. The revealed features of neurotransmitters content (excess of serotonin and glutamic acid) and indicators of cell immunity (reduced proportion of CD4+/CD8+ cells) associated with the variant G allele and GG genotype of the SIRT1 gene (rs7069102) form a complex of neurohumoral, immune, and genetic markers in children with functional disorders of ANS (G90.8). This allows recommending them as indicators for early diagnosis and prevention of autonomic disorders in children.

Neurohumoral Profiles and Childhood Adversity of Patients with Multisomatoform Disorder and Pain as the Leading Bodily Symptom.

Objective Patients suffering from chronic pain often present with multifactorial underlying conditions, sometimes without concrete pathological physical findings. Functional somatic syndromes (FSS) and somatoform disorders show a high prevalence of 8-20% and are often associated with adverse childhood experiences (ACE) and chronic stress. As many different FSS have overlapping symptoms, the concept of multisomatoform disorder (MSD) has been introduced as an encompassing concept. We hypothesize that a common neurohumoral profile is present in patients with MSD that is distinct from gender- and age-matched controls and thus provides insight into possible common underlying mechanisms. Design In 151 patients with MSD (138 females) and 149 matched controls (131 females), we determined ACE by the Childhood Trauma Questionnaire (CTQ) and chronic stress by the Trier Inventory for Chronic Stress (TICS). Furthermore, the serum levels of leptin, FSH, LH, cortisol, DHEA-S, and IGF-1 have been assessed. Results There were significant differences in the levels of leptin, FSH, IGF-1, and cortisol between patients and controls, mainly driven by female participants. Levels of leptin were significantly correlated with BMI in patients, in controls, and in the female subgroup. This correlation was exaggerated in female patients when compared to female controls. Both CTQ and TICS predicted MSD directly and indirectly through the levels of leptin. Conclusion There is evidence of a distinct neurohumoral profile in female patients with MSD when compared to matched healthy controls, similar to what has been demonstrated in other chronic pain states. The observed profile can be taken as possible evidence for a dysregulated response to chronic stress and metabolic balance as well as a state of hypocortisolism and HPA-axis dysfunction. ACE and chronic stress play a major role in the development of MSD and altered neurohumoral profile.

The risks and benefits of spironolactone use in heart failure with a reduced left ventricular ejection fraction and chronic kidney disease

Abstract Purpose Mineralocorticoid receptor antagonists (MRAs) remain underused in cases of heart failure with a reduced left ventricular ejection fraction (HFrEF) and chronic kidney disease (CKD), largely due to the fear of inducing worsening of renal function (RF) and hyperkalemia (HK), particularly in combination with renin angiotensin inhibitors. The aim was to investigate the safety use of spironolactone (SP) in patients with HFrEF (ejection fraction &amp;lt;40%) and CKD and determine predictors of worsening of RF and developing HK. Methods 208 patients with HFrEF (on top of standard therapy including ACE-I or an ARB) and CKD (baseline eGFR between 30 and 60 ml/min) were included in the study. The potassium (K) and creatinine (C) levels, plasma aldosterone (AS) and NT-proBNP were estimated at baseline and at week 12. After biochemical evaluation, 101 patients started on SP treatment with a median dose of 23 mg daily (titrated). K and RF were checked at weeks 1, 2, 4, 6, 8, 12. Results K and C levels increased significantly after start of SP: mean K levels increased from 4.47±0.59 to 5.23±0.57 mEq/l, (P&amp;lt;0.01) and was dose dependent. After 12 weeks of treatment the incidence of severe HK (K+ ≥6.0 mmol/L) was &amp;lt;5%, K 5.5–5.9 mmol/L occurred in 13 patients (13%) and it was predicted by baseline eGFR≤35 ml/min/1.73 m2. and K ≥5.0 mmol/L/. Subsequently, these patients required a prescription of K binders. Mean eGFR on SP decreased from 48.34±2.23 to 42.19±2.65 ml/min/1.73 m2 (P&amp;lt;0.01) and a significant decrease in GFR was observed only during the first month (P &amp;lt;0.01) with not significant increasing to 6 and 12 weeks after the start of SP. Five patients (5%) on SP experienced significant decline of RF result in withdrew SP. Age, NT-proBNP concentration &amp;gt;1550 ng/L and eGFR ≤35 ml/min/1.73 m2 at baseline had modest discriminative powers for predicting decline of RF (0.456, P&amp;lt;0.01; 0.542, P&amp;lt;0.001; 0.712, P&amp;lt;0.001; respectively). At baseline in patients with HFrEF was an inverse correlation between GFR and NT-proBNP level (r=−0.298, p&amp;lt;0.001). The SP treatment resulted in significantly reduced NT-proBNP and AS (P&amp;lt;0.01; P&amp;lt;0.05 respectively). By linear regression analysis in SP group the eGFR was associated with NT-proBNP change (0.362, P&amp;lt;0.05). Conclusion In patient with HFrEF and CKD the risk-benefit ratio of spironolactone with respect to renal failure appears favourable due to improvement of the neurohumoral profile. Although the renal disfunction and hyperkalemia on spironolactone are common: approximately 18% patients required the prescription of K binders and 5% required the withdrew SP duo to decline RF, the occurrence of hyperkalemia was predicted by baseline potassium level and eGFR. Age, higher level of NT-proBNP and eGFR were identified as potential predictors of worsening of RF. So, caution should be advised when using spironolactone in HFrEF with CKD and potassium of ≥5.0 mmol/L and eGFR ≤35 ml/min/1.73 m2 and NT-proBNP concentration &amp;gt;1550 ng/L for safety reasons. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): National Medical University

Adenosine plasma levels and adenosine receptor levels determine the outcome of adenosine test and head-up tilt test in syncopal patients with a normal heart

Abstract Background/Introduction The neurohumoral profile underlying the manifestation of reflex syncope remains incompletely understood. Adenosine plasma (ADP) and adenosine receptor (ADR) levels may differentiate the outcomes of head-up tilt table test (HUTT) and adenosine test (ADT) but their role in the diagnostic evaluation of patients with syncope has yet to be determined. Purpose We sought to assess the ADP and ADR levels in patients without structural heart disease who underwent HUTT and ADT tests as part of the diagnostic workup of syncope. We specifically investigated differences in the outcomes of the HUTT and ADT tests as well as to the ADP levels during HUTT. Methods HUTT and ADT were performed as per the standard protocols. ADT was considered positive in the event of asystole &amp;gt;6 seconds or heart block for &amp;gt;10 seconds after intravenous Adenosine 0.15 mg/kg administration in the supine position. ADP levels were assessed at three timepoints during the HUTT: at baseline (supine), immediately after bed tilt and, in cases of a positive HUTT, at the time of syncope. Patients were categorized in quintiles of very low, low, intermediate, high and very high baseline ADP levels. We also assessed the A2A ADR levels of monocytes. Results We prospectively analyzed 124 patients (71 women, age 46.78±21.01 years). ADT was positive in 12.9% of patients and HUTT in 44.4% of patients. Patients with very low baseline ADP levels (lowest quintile) more frequently presented with a positive ADT (odds ratio [OR] 4.08, 95% Confidence Interval [CI] 1.40 to 13.13, p&amp;lt;0.05). Baseline ADP did not differ between patients with positive and negative HUTT. However, patients with vasodepressor response to HUTT exhibited increase in ADP from baseline to bed tilt (0.33±1.03 vs. 0.42±1.14 ppm/Um/L, p&amp;lt;0.05) and in syncope (0.70±1.89, P&amp;lt;0.05), while no difference was noted in patients with cardioinhibitory or mixed response. Patients with positive ADT and negative HUTT had higher ADR levels (221.5±88.56 MFI) as compared to patients with negative ADT and positive HUTT (59.78±83.65 MFI, p&amp;lt;0.05) and to patients with positive ADT and HUTT (33.29±35.77 MFI, p&amp;lt;0.05). Within patients with positive HUTT, those with onset of syncope in the Isoprenaline provocation phase (&amp;gt;20 min) had lower ADR levels (80.88±238.98 vs 89.43±96.08 MFI, p&amp;lt;0.05). Conclusion(s) Baseline ADP levels are related to the outcome of ADT while an ADP increase immediately after bed tilt and in syncope is evident in vasodepressor response to HUTT. Higher ADR levels are related to positive ADT and negative HUTT. Lower ADR levels are associated with more delayed onset of syncope during HUTT. ADP and ADR levels warrant further investigation as they may characterize a subset of patients with specific responses to ADT and HUTT and may be implicated in the pathophysiology of reflex syncope. Funding Acknowledgement Type of funding sources: None.

P3568The relationship between plasma renin and aldosterone levels and the reduction of blood pressure with spironolactone in patients with resistant hypertension

Abstract The group of patients with resistant hypertension (RH) is not homogeneous on concentration of renin and aldosterone (AS). A lot of studies have shown that spironolactone (SP) was by far the most effective blood pressure-lowering treatment for patients with RH. However, it has been unknown whether SP would be the most effective in patients with different plasma renin profile. The aim was to determine whether plasma renin and AS predict the most effective treatment of SP. Methods 79 patients with RH were included in the study (a mean of 3.4±1.4 drugs per patient including diuretic, ACE-I or an ARB). The plasma AS and active renin concentration (ARC), the plasma aldosterone-to-renin ratio (ARR) were estimated at baseline. After chemical evaluation patients started on SP treatment with a mid-dose 25 mg daily (range 12.5–50 mg). At baseline and after 12 weeks of therapy patients underwent clinic and 24-hour BP measurement, also hematocrit, potassium (K), serum creatinine (C), eGFR were checked. Results In patients with RH the ARC varied widely and they were divided into low 46%, normal 29% and high renin 25% subgroups. All groups of patients had similar AS levels. Patients with high renin hypertension (HRH) had significantly worse renal function than patients with low renin (LRH) or normal renin hypertension (NRH), also hematocrit were significantly higher in HRH patients than in patients with LRH and NRH. At baseline in patients with RH was an excellent correlation between ARC and eGFR (P&lt;0.001). After SP in whole group, the change from baseline in the clinic BP was −13.4/−6.8 mm Hg (P&lt;0.0001 for both) and in 24-hour BP was −10.6/−6.1 mm Hg (P&lt;0.001 for both), but patients with HRH showed less efficacy than patients with LRH and NRH (−5.4/−3.1 mm Hg; P&lt;0.05 for both) and in 24-hour BP was −4.8/−2.9 mm Hg (P&lt;0.05 for both). Moreover, in HRH patients the hematocrit and C levels increased significantly after the start of SP (P&lt;0.001; P&lt;0.0001 respectively). By regression analysis in whole group patients RH ARC and AS levels were not associated with the changes in BP, only eGFR was significantly associated with BP change for DBP (0.391, P&lt;0.05); in patients with LRH and NRH was a mild relation between the change for SBP and ARR (P&lt;0.05 for both), but not for HRH patients. Conclusion SP showed additional antihypertensive effect in the whole group of patients with RH, but in patients with HRH was less effective than in patients with LRH and NRH and lead to the worsening of renal function. In the whole group of patients with RH plasma renin and aldosterone levels were not associated with BP response to SP, but the change in DBP was correlated with baseline eGFR. Only in patients with LRH and NRH was a mild association between BP response to SP and ARR. So, we can't treat all RH patients with the help of one universal algorytm and treatment should be tailored to each patient according to neurohumoral profile and renal function.

Distinct neurohumoral biomarker profiles in children with hemodynamically defined orthostatic intolerance may predict treatment options.

Studies of adults with orthostatic intolerance (OI) have revealed altered neurohumoral responses to orthostasis, which provide mechanistic insights into the dysregulation of blood pressure control. Similar studies in children with OI providing a thorough neurohumoral profile are lacking. The objective of the present study was to determine the cardiovascular and neurohumoral profile in adolescent subjects presenting with OI. Subjects at 10-18 yr of age were prospectively recruited if they exhibited two or more traditional OI symptoms and were referred for head-up tilt (HUT) testing. Circulating catecholamines, vasopressin, aldosterone, renin, and angiotensins were measured in the supine position and after 15 min of 70° tilt. Heart rate and blood pressure were continuously measured. Of the 48 patients, 30 patients had an abnormal tilt. Subjects with an abnormal tilt had lower systolic, diastolic, and mean arterial blood pressures during tilt, significantly higher levels of vasopressin during HUT, and relatively higher catecholamines and ANG II during HUT than subjects with a normal tilt. Distinct neurohumoral profiles were observed when OI subjects were placed into the following groups defined by the hemodynamic response: postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension (OH), syncope, and POTS/syncope. Key characteristics included higher HUT-induced norepinephrine in POTS subjects, higher vasopressin in OH and syncope subjects, and higher supine and HUT aldosterone in OH subjects. In conclusion, children with OI and an abnormal response to tilt exhibit distinct neurohumoral profiles associated with the type of the hemodynamic response during orthostatic challenge. Elevated arginine vasopressin levels in syncope and OH groups are likely an exaggerated response to decreased blood flow not compensated by higher norepinephrine levels, as observed in POTS subjects. These different compensatory mechanisms support the role of measuring neurohumoral profiles toward the goal of selecting more focused and mechanistic-based treatment options for pediatric patients with OI.

Neurohumoral and Hemodynamic Profile in Children with Chronic Nausea and Orthostatic Intolerance

Neurohumoral and Hemodynamic Profile in Children with Chronic Nausea and Orthostatic Intolerance

Beneficial neurohumoral profile in left ventricular systolic dysfunction following acute myocardial infarction

Abstract

PREDICTING PRECLINICAL THROMBOGENIC ABNORMALITIES IN PATIENTS WITH ESSENTIAL ARTERIAL HYPERTENSION

Aim. To identify early (preclinical) markers of thrombogenic abnormalities in patients with essential arterial hypertension (EAH). Material and methods. The study included 137 EAH patients, aged 30–60 years. The parameters of both coagulation and platelet haemostasis were assessed. Results. In patients with EAH and obesity (O), the following parameters were elevated: activated partial thromboplastin time (aPTT); fibrinogen; and soluble fibrin monomer complex (SFMC). In EAH patients without O, the levels of spontaneous platelet aggregation were elevated. Among overweight patients, the levels of adreno-reactivity were associated with leptin levels (rs=0,8; р=0,007). In obese patients, there was a significant correlation between insulin and leptin levels (rs=0,7; р=0,0049). The correlation analysis of the neurohumoral and haemostatic parameters demonstrated an association between leptin and SFMC levels (rs=0,8; р=0,0007). In EAH patients, the changes in neurohumoral profile are linked to increased body mass, elevated levels of insulin (Н=9,6; р=0,0082), leptin (Н=12,1; р=0,0024), and adreno-reactivity (Н=8,8; р=0,0122). Conclusion. In patients with EAH and O, the observed haemostatic abnormalities could be characterised as hypercoagulation syndrome. The findings obtained suggest that fibrinogen and SFMC could be regarded as early markers of thrombosis development in patients with EAH and O. Therefore, these parameters can be used in the screening programme, in order to identify the individuals with abnormalities of coagulation haemostasis and fibrinolysis.

Thyroid Function and Clinical Outcomes in Kidney Failure

Thyroid hormone synthesis is finely tuned to respond to the variable energy needs of the human body ([1][1]). This process is controlled by two fundamental mechanisms. The first, based on the thyroid-stimulating hormone (TSH)–thyroxine (T4) and triiodothyronine (T3) feed-back loop, constitutes a

Hemodynamic and neurohumoral profile in patients with different types of hypertension in pregnancy

Hypertension in pregnancy is a frequent disorder that includes a spectrum of conditions. We aimed at comparatively evaluating the hemodynamic, echocardiographic and biohumoral profile of a sample of pregnant Caucasian women with different form of pregnancy-related hypertension. We enrolled 39 non-hypertensive pregnant women (NP), 26 with Chronic HBP in pregnancy (CH), 24 with gestational hypertension (G-PIH), and 33 with pre-eclampsia. We recorded and compared blood pressure (BP), echocardiographic parameters, resting plasma renin activity (PRA) and plasma aldosterone (PA), Plasma levels of atrial (ANP) and brain natriuretic peptide (BNP). PE patients had a significantly higher BP than either G-PIH or NP patients. PE patients had also significantly lower cardiac output than NP, G-PIH and CH. In comparison to NP patients, the total peripheral vascular resistance was 61% higher in PE women and 38% higher in CH patients. All echographic parameters were significantly more altered in PE patients when compared with NP, in respect to any other form of hypertension. Either ANP (+35%) and BNP (+40%) were significantly higher in PE patients than in controls. The PRA was reduced in PE and CH patients when compared either with NP (-38 and -35%, respectively) or G-PIH (-47 and -43%, respectively). On the basis of our data, we can conclude that PE is the gestation associated hypertension with the largest anatomical, functional and biohumoral involvement, and so it has to be involved in a more intensive monitoring and evaluation.

Thyroid Hormone Treatment to Mend a Broken Heart

Thyroid Hormone Treatment to Mend a Broken Heart

Unique Neurohumoral and Renal Hemodynamic Profile in Patients Who Develop the Cardiorenal Syndrome during Treatment of Decompensated Heart Failure

Unique Neurohumoral and Renal Hemodynamic Profile in Patients Who Develop the Cardiorenal Syndrome during Treatment of Decompensated Heart Failure

97 Influence of pentoxifilline in addition to conventional heart failure treatment on clinical status, neurohumoral and immune profile in patients with mild-to-moderate congestive heart failure

97 Influence of pentoxifilline in addition to conventional heart failure treatment on clinical status, neurohumoral and immune profile in patients with mild-to-moderate congestive heart failure

Effect of exercise training on skeletal muscle fibre characteristics in men with chronic heart failure. Correlation between skeletal muscle alterations, cytokines and exercise capacity

Background: In patients with congestive heart failure (CHF) there is a shift from aerobic type I muscle fibres to less aerobic type II fibres. Exercise training has been shown to have beneficial effects on exercise performance, peripheral pathology and the neurohumoral profile in stable patients with CHF. This study evaluated the effect of a 3 month exercise training program on skeletal muscle characteristics and the correlation of these to cytokines and exercise capacity in CHF patients. Methods: Skeletal muscle biopsies for enzyme-histochemical analysis were performed in 15 CHF patients in New York Heart Association classes II–III, with a mean ejection fraction of 33±5% before and after a 12 week training period. The patients were trained for 30 min, five times a week at 80% of the peak heart rate achieved at baseline ergometer cycle test. Fifteen healthy men were used as controls. Plasma samples were examined by enzyme immunoassays for levels of pro-inflammatory cytokines. Results: (a) At baseline we found muscle atrophy in five of the patients. The percent area of type I fibres (40.7±12.0 vs. 56.4±11.0%, P<0.05) and the thickness of type IIA (56.10±7.8 vs. 71.6±11.9 μm, P<0.001) and B-fibres (49.0±8.9 vs. 63.9±10.6 μm, P<0.001) were reduced, whereas the percent area of type IIA fibres (52.1±13.3 vs. 36.4±9.9%, P<0.05) was increased in heart failure patients compared to healthy controls. There was a modest correlation between fibre thickness and the level of interleukin 6 ( r=−0.657, P=0.008). (b) After exercise training there was a reduction in muscle area examined by light-microscopy, measured as a percentage of field (−2.7, P=0.003) with an concomitant increase in interstitium. This reduction correlated to the increase in the 6-min walk test ( r=−0.558, P=0.031). The thickness of type IIB fibres increased (+5.6 μm, P=0.068) and the area of type I fibres decreased (−6.1%, P=0.062). Conclusions: Patients with CHF have a relatively increased area of type IIA fibres and a relatively decreased area of type I fibres compared to healthy individuals. The thickness of type IIA and type IIB fibres is decreased compared to normal individuals. A modest negative correlation between the level of interleukin 6 and fibre thickness at baseline, suggests that inflammatory cytokines may be involved in the pathogenesis of the CHF related myopathy. A significant correlation between the reduction of muscle area, with increased interstitum, and the increase in the 6-min walk test may indicate that the improvement is due to increased capillary density permitting better flow reserve to exercising muscles.

Effects of Increasing Maintenance Dose of Digoxin on Left Ventricular Function and Neurohormones in Patients With Chronic Heart Failure Treated With Diuretics and Angiotensin-Converting Enzyme Inhibitors

Despite almost three centuries of use, the appropriate dosage of digitalis in patients with chronic heart failure and normal sinus rhythm has not been well studied. We studied 22 patients with heart failure who were receiving constant daily doses of digoxin, diuretics, and angiotensin-converting enzyme (ACE) inhibitors. In 18 patients, the oral daily dose of digoxin was increased from a mean of 0.20 +/- 0.07 to 0.39 +/- 0.11 mg/day corresponding to an increase in the serum digoxin concentration from 0.67 +/- 0.22 to 1.22 +/- 0.35 ng/mL. Radionuclide and echocardiographic left ventricular ejection fraction; maximal treadmill time; heart failure score; serum concentrations of norepinephrine, aldosterone, atrial natriuretic factor, and antidiuretic hormone; and plasma renin activity were obtained before and after the increase in digoxin dose. Subsequently, 9 patients were randomized to receive digoxin and 9 to receive placebo and radionuclide ejection fraction measured after 12 weeks. With the higher dose of digoxin compared with the lower dose, there was a significant increase in radionuclide ejection fraction from 23.7 +/- 9.6% to 27.1 +/- 11.8% (P = .007). No significant changes were noted in heart failure score; exercise tolerance; serum concentrations of norepinephrine, atrial natriuretic factor, and antidiuretic hormone; and plasma renin activity. There was, however, an increase in serum aldosterone concentration. Twelve weeks after the patients were randomized to receive digoxin or placebo, there was a significant decrease in ejection fraction (from 29.4 +/- 10.4% to 23.7 +/- 8.9%) in the placebo group but not in patients who continued to receive digoxin (P = .002). The increase in maintenance digoxin dose, while maintaining serum concentrations within therapeutic range, resulted in a significant increase in left ventricular ejection fraction that was not associated with significant changes in heart failure score, exercise tolerance, and neurohumoral profile.