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1.
Adv Exp Med Biol ; 1232: 85-90, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31893398

RESUMO

Delayed orthostatic hypotension (OH) is a minor subset of orthostatic dysregulation (OD). Cerebral blood oxygenation in juvenile patients with delayed OH has not been studied. We investigated the bilateral changes in cerebral oxygenation in the prefrontal cortex during an active standing test in 23 juvenile patients with delayed OH using near-infrared spectroscopy (NIRS). We measured the oxy-Hb, deoxy-Hb, and total-Hb during the active standing test. Four observations were made during the test: t1 in a resting supine position, t2 when maintaining blood pressure, and the remaining two (t3, t4) during hypotension. The concentration of oxy-Hb significantly decreased prior to satisfying the diagnostic criteria of delayed OH after standing and did not change thereafter. The concentration of deoxy-Hb increased gradually during the measurement periods. In addition, total-Hb increased from t2 to t3. There was no significant difference in the change in each Hb parameter between the left and right cerebral hemispheres. Our results indicate that NIRS parameters are more sensitive than blood pressure for the interpretation of cerebral autoregulation in juvenile patients with delayed OH.


Assuntos
Sistema Cardiovascular , Circulação Cerebrovascular , Hipotensão Ortostática , Oxigênio , Posição Ortostática , Adolescente , Pressão Sanguínea , Circulação Cerebrovascular/fisiologia , Humanos , Hipotensão Ortostática/sangue , Hipotensão Ortostática/diagnóstico , Oxigênio/sangue , Espectroscopia de Luz Próxima ao Infravermelho
2.
Neurology ; 91(16): e1539-e1544, 2018 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-30232253

RESUMO

OBJECTIVE: To test whether the plasma levels of norepinephrine (NE) in patients with neurogenic orthostatic hypotension (nOH) predict their pressor response to droxidopa. METHODS: This was an observational study, which included patients with nOH. All patients had standardized autonomic function testing including determination of venous plasma catecholamine levels drawn through an indwelling catheter while resting supine. This was followed by a droxidopa titration with 100 mg increments in successive days until relief of symptoms, side effects, or the maximum dose of 600 mg was reached. No response was defined as an increase of <10 mm Hg in systolic blood pressure (BP) after 3-minute standing 1 hour after droxidopa administration. Nonlinear regression models were used to determine the relationship between BP response and plasma NE levels. RESULTS: We studied 20 patients with nOH due to Parkinson disease, pure autonomic failure, multiple system atrophy, or autoimmune autonomic neuropathies. Their supine plasma NE levels ranged from 44 to 850 pg/mL. Lower supine plasma NE levels were associated with greater pressor effect 1 hour after dose (R2 = 0.49) and higher standing BP (R2 = 0.45). Patients with no pressor response to droxidopa had higher NE levels (382 ± 100 vs 115 ± 20 pg/mL, p = 0.0014). A supine NE level of <219.5 pg/mL had 83% sensitivity and 93% specificity to predict a pressor response (area under the curve = 0.95, p = 0.0023). CONCLUSIONS: In patients with nOH, lower supine resting plasma NE levels are associated with a greater pressor effect of droxidopa treatment. This finding should help identify patients with nOH most likely to respond to standard doses of droxidopa. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that lower supine plasma NE levels accurately identify patients with nOH more likely to have a greater pressor effect from droxidopa.


Assuntos
Antiparkinsonianos/uso terapêutico , Droxidopa/uso terapêutico , Hipotensão Ortostática/sangue , Hipotensão Ortostática/tratamento farmacológico , Norepinefrina/sangue , Decúbito Dorsal , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiparkinsonianos/administração & dosagem , Pressão Sanguínea , Criança , Droxidopa/administração & dosagem , Feminino , Humanos , Hipotensão Ortostática/etiologia , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Resultado do Tratamento , Adulto Jovem
3.
Parkinsonism Relat Disord ; 55: 97-102, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29880316

RESUMO

INTRODUCTION: Plasma norepinephrine concentration reflects lesions causing OH. We investigate whether patients with high norepinephrinergic orthostatic hypotension (OH) whose supine plasma norepinephrine concentration (NEsupine) is above the mean value in all patients with Parkinson's disease (PD) have central sympathetic denervation. METHODS: We analyzed data from 110 non-demented patients with early de novo PD who underwent cardiovascular examinations. We divided the patients into three groups according to the presence or absence of orthostatic hypotension and NEsupine: patients without OH, patients with OH+high NEsupine, and patients with OH+low NEsupine. RESULTS: The mean NEsupine in all patients was 251.6 pg/ml. Twelve patients (10.9%) had OH+high NEsupine (≥251.6 pg/ml), and 45 patients (40.9%) had OH+low NEsupine (<251.6 pg/ml). OH was more pronounced in patients with OH+high NEsupine than in those with OH+low NEsupine (p = 0.024). Vasopressin release and percent increase of NE after orthostatic stress were well preserved in patients with OH+low NEsupine, but not in patients with OH+high NEsupine. Cognition was lower in patients with OH+high NEsupine than in patients with OH+low NEsupine (p = 0.019) and was associated with vasopressin release during orthostatic stress on multiple regression analysis. The degree of cardiac sympathetic denervation did not differ between two groups with OH. CONCLUSIONS: Patient with PD and high norepinephrinergic OH are a subset of patients who have early cognitive decline and impaired vasopressin release. Vasopressin release after orthostatic stress was closely related to global cognition in PD.


Assuntos
Hipotensão Ortostática/sangue , Hipotensão Ortostática/etiologia , Doença de Parkinson/complicações , Sesquiterpenos/sangue , 3-Iodobenzilguanidina/farmacocinética , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Transtornos Cognitivos/etiologia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Hipotensão Ortostática/diagnóstico , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Cintilografia , Teste da Mesa Inclinada/métodos , Vasopressinas/metabolismo
5.
Hypertension ; 71(3): 465-472, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29295851

RESUMO

Orthostatic hypotension (OH) has been linked with higher incidence of cardiovascular disease, but little is known about the mechanisms behind this association. We aimed to identify cardiovascular disease biomarkers associated with OH through a proteomic profiling approach. Seven hundred seventy-eight patients with unexplained syncope or orthostatic intolerance underwent head-up tilt test and supine blood samples. Of these, 220 met diagnostic criteria of OH, and 179 demonstrated normal hemodynamic response during head-up tilt test. Blood samples were analyzed by antibody-based Proximity Extension Assay technique simultaneously measuring 92 cardiovascular disease-related human protein biomarkers. The discovery algorithm was a sequential 2-step process of biomarker signature identification by supervised, multivariate, principal component analysis and verification by univariate ANOVA with Bonferroni correction. Patients with OH were older (67 versus 60 years; P<0.001) and more likely to be women (48% versus 41%; P>0.001) but did not differ from OH-negative patients in medical history. Principal component analysis identified MMP-7 (matrix metalloproteinase-7), TM (thrombomodulin), MB (myoglobin), TIM-1 (T-cell immunoglobulin and mucin domain-1), CASP-8 (caspase-8), CXCL-1 (C-X-C motif chemokine-1), Dkk-1 (dickkopf-related protein-1), lectin-like LOX-1 (oxidized low-density lipoprotein receptor-1), PlGF (placenta growth factor), PAR-1 (proteinase-activated receptor-1), and MCP-1 (monocyte chemotactic protein-1) as the most robust proteomic signature for OH. From this proteomic feature selection, MMP-7 and TIM-1 met Bonferroni-adjusted significance criteria in univariate and multivariate regression analyses. Proteomic profiling in OH reveals a biomarker signature of atherothrombosis and inflammation. Circulating levels of MMP-7 and TIM-1 are independently associated with OH and may be involved in cardiovascular disease promotion.


Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Hipotensão Ortostática/sangue , Metaloproteinase 7 da Matriz/sangue , Proteômica/métodos , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Biomarcadores/análise , Doenças Cardiovasculares/etiologia , Estudos Transversais , Feminino , Receptor Celular 1 do Vírus da Hepatite A/sangue , Humanos , Hipotensão Ortostática/complicações , Hipotensão Ortostática/diagnóstico , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valores de Referência , Análise de Regressão , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida , Teste da Mesa Inclinada
6.
J Dermatol ; 44(10): 1160-1163, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28620980

RESUMO

Autoimmune autonomic ganglionopathy (AAG), clinically characterized by gastrointestinal dysmotility, orthostatic hypotension and tonic pupils, is an idiopathic acquired disorder of the autonomic nervous system elicited by antibodies against ganglionic acetylcholine receptor (gAChR). We encountered a 60-year-old man who presented with severe anhidrosis, difficulty in thermoregulation, orthostatic hypotension, gastrointestinal dysmotility, tonic pupils and ptosis. Histologically, an anhidrotic skin sample was normal. Routine laboratory examinations of blood, urine and cerebrospinal fluid returned no abnormal findings. Serological examination revealed antibodies against α3 and ß4 subunits of gAChR. The diagnosis was AAG. As sudomotor dysfunction reflects ganglionic neuropathy in AAG, we concluded that his anhidrosis was attributable to AAG. Anhidrosis is an important clue for the diagnosis of AAG, a rare neurological disorder.


Assuntos
Autoanticorpos/sangue , Doenças Autoimunes do Sistema Nervoso/complicações , Gânglios Autônomos/imunologia , Hipo-Hidrose/etiologia , Proteínas do Tecido Nervoso/imunologia , Receptores Nicotínicos/imunologia , Autoanticorpos/imunologia , Doenças Autoimunes do Sistema Nervoso/sangue , Doenças Autoimunes do Sistema Nervoso/imunologia , Doenças Autoimunes do Sistema Nervoso/terapia , Blefaroptose/sangue , Blefaroptose/etiologia , Blefaroptose/terapia , Gânglios Autônomos/efeitos dos fármacos , Gânglios Autônomos/patologia , Gastroenteropatias/sangue , Gastroenteropatias/etiologia , Gastroenteropatias/terapia , Motilidade Gastrointestinal/efeitos dos fármacos , Glucocorticoides/uso terapêutico , Humanos , Hipo-Hidrose/sangue , Hipo-Hidrose/terapia , Hipotensão Ortostática/sangue , Hipotensão Ortostática/etiologia , Hipotensão Ortostática/terapia , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Pessoa de Meia-Idade , Plasmaferese , Prednisolona/uso terapêutico , Pele/inervação , Pele/patologia , Falha de Tratamento
10.
Mov Disord ; 31(9): 1417-21, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27270501

RESUMO

INTRODUCTION: Leptin is involved in the regulation of blood pressure; however, no studies have evaluated the role of leptin in blood pressure changes during orthostatic stress in PD patients. The aim of this study was to determine whether plasma leptin levels influence orthostatic blood pressure changes in PD patients. METHODS: We enrolled 55 patients and 25 age-matched healthy controls in this study. Associations between head-up tilt test measurements and leptin levels were evaluated. RESULTS: Systolic blood pressure changes during the head-up tilt tests were strongly correlated with leptin levels at baseline and at a 60-degree head-up tilt in PD patients, but not in control subjects. Multiple regression analysis also demonstrated that leptin levels were associated with orthostatic blood pressure changes. CONCLUSION: These observations suggest that low leptin levels may be associated with orthostatic hypotension during the head-up tilt test in patients with PD. © 2016 International Parkinson and Movement Disorder Society.


Assuntos
Pressão Sanguínea/fisiologia , Hipotensão Ortostática/sangue , Leptina/sangue , Doença de Parkinson/sangue , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
11.
J Hypertens ; 34(6): 1036-43, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27027426

RESUMO

OBJECTIVES: Orthostatic hypotension is a common condition among older adults and is associated with a range of deleterious outcomes. Recently, interest has developed in hypovitaminosis D (defined as low 25 hydroxiyvitamin D levels) as a potential risk factor for orthostatic hypotension. We conducted a systematic review and meta-analysis examining the association of orthostatic hypotension between study participants with and without hypovitaminosis D, including the adjustment of potential confounders (age, sex, BMI, renal function, comorbidities, seasonality, use of antihypertensive medications, and supplementation with cholecalciferol). METHODS: A systematic literature search of major electronic databases from inception until 09/2015 was made for articles providing data on orthostatic hypotension and hypovitaminosis D. A random effects meta-analysis of cross-sectional studies investigating orthostatic hypotension prevalence comparing participants with vs. those without hypovitaminosis D was undertaken, calculating the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Of 317 initial hits, five cross-sectional studies were meta-analysed including 3646 participants (1270 with hypovitaminosis D and 2376 without). The participants with hypovitaminosis D had a higher prevalence of orthostatic hypotension (OR = 1.88; 95% CI: 1.25-2.84; I = 68%) that was not affected by adjusting for a median of five potential confounders (OR = 2.03; 95% CI: 1.13-3.68; I = 73%). People with orthostatic hypotension had significantly reduced serum vitamin D concentrations (standardized mean difference = -0.42; 95% CI: -0.72 to -0.12). One longitudinal study confirmed the association between hypovitaminosis D and orthostatic hypotension. CONCLUSION: Our meta-analysis highlights that hypovitaminosis D is associated with orthostatic hypotension, independent of potential confounders. Further longitudinal studies and clinical trials are required to confirm these findings.


Assuntos
Hipotensão Ortostática/epidemiologia , Deficiência de Vitamina D/epidemiologia , Estudos de Casos e Controles , Estudos Transversais , Humanos , Hipotensão Ortostática/sangue , Prevalência , Fatores de Risco , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangue
12.
Hypertens Res ; 39(7): 543-7, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26911234

RESUMO

Long-chain omega-3 polyunsaturated fatty acids (PUFAs) from fish have been shown to lower blood pressure. However, there is little information about the association with orthostatic hypotension, for which hypertension is a risk factor. We investigated the associations between serum long-chain omega-3 PUFAs and orthostatic hypotension in 1666 middle-aged or older men and women free of cardiovascular disease (CVD), diabetes or hypertension in 1998-2001 in the Kuopio Ischemic Heart Disease Risk Factor Study (KIHD) in eastern Finland. We also investigated the associations with mercury exposure, a major source of which is fish, and which has been associated with higher CVD risk in KIHD. Orthostatic hypotension was defined as decrease in systolic blood pressure of at least 20 mm Hg or diastolic blood pressure of at least 10 mm Hg within 1 min of standing. Orthostatic hypotension was found in 146 participants (8.8%). The mean serum concentrations were 1.67% (s.d. 0.92) for eicosapentaenoic acid, 0.79% (s.d. 0.16) for docosapentaenoic acid (DPA) and 2.78 (s.d. 0.92) for docosahexaenoic acid of all serum fatty acids. The mean pubic hair mercury concentration was 1.5 µg g(-1) (s.d. 1.6). We did not find statistically significant associations between the serum long-chain omega-3 PUFAs or pubic hair mercury and risk of orthostatic hypotension, except for DPA. Those in the highest vs. the lowest serum DPA tertile had multivariate-adjusted 41% lower odds for orthostatic hypotension (95% confidence interval 7-63%, P-trend=0.02). Serum long-chain omega-3 PUFAs or mercury exposure were not associated with the risk of orthostatic hypotension, except for the inverse association with DPA.


Assuntos
Pressão Sanguínea , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-3/sangue , Hipotensão Ortostática/induzido quimicamente , Mercúrio/toxicidade , Adulto , Idoso , Ácidos Graxos Insaturados/sangue , Feminino , Finlândia , Humanos , Hipotensão Ortostática/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco
13.
Am J Physiol Heart Circ Physiol ; 310(3): H416-25, 2016 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-26608337

RESUMO

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.


Assuntos
Aldosterona/sangue , Angiotensinas/sangue , Pressão Arterial/fisiologia , Catecolaminas/sangue , Frequência Cardíaca/fisiologia , Hipotensão Ortostática/sangue , Síndrome da Taquicardia Postural Ortostática/sangue , Renina/sangue , Síncope/sangue , Vasopressinas/sangue , Adolescente , Angiotensina I/sangue , Angiotensina II/sangue , Pressão Sanguínea/fisiologia , Criança , Diástole , Dopamina/sangue , Epinefrina/sangue , Feminino , Humanos , Hipotensão Ortostática/fisiopatologia , Masculino , Norepinefrina/sangue , Intolerância Ortostática/sangue , Intolerância Ortostática/fisiopatologia , Síndrome da Taquicardia Postural Ortostática/fisiopatologia , Estudos Prospectivos , Síncope/fisiopatologia , Sístole , Teste da Mesa Inclinada
14.
J Hypertens ; 33(8): 1594-601, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26136066

RESUMO

OBJECTIVES: Orthostatic hypotension has been linked with increased mortality and cardiovascular morbidity; however, the underlying mechanisms are still unknown. The aim of the study was to assess markers of coagulability in patients with and without orthostatic hypotension who suffered transient loss of consciousness. METHODS: A total of 233 consecutive patients more than 15 years old, with unexplained transient loss of consciousness, underwent head-up tilt test (HUT, Italian protocol). Blood samples were collected during supine rest before and at 3 min of 70° HUT for determination of fibrinogen, von Willebrand factor antigen (vWF:Ag) and activity (vWF:GP1bA), factor VIII (FVIII:C), lupus anticoagulant, and functional activated protein C-resistance. Orthostatic hypotension was defined as persistent decrease in SBP and/or DBP of more than 20/10 mmHg or SBP lower than 90 mmHg during passive HUT. RESULTS: One hundred and seventy-eight patients (81 men, 45.5%) not treated with vitamin-K antagonists were analyzed. Those with orthostatic hypotension (n = 49) were older [61 ±â€Š18 vs. 47 ±â€Š21 years (mean ±â€ŠSD), P < 0.001], had increased FVIII: C-supine (1.2 ±â€Š0.39 vs. 1.0 ±â€Š0.35, P = 0.001), FVIII:C-standing (1.2 ±â€Š0.36 vs. 1.0 ±â€Š0.34, P = 0.001), vWF:Ag-supine (1.5 ±â€Š0.66 vs. 1.1 ±â€Š0.44, P < 0.001), vWF:Ag-standing (1.5 ±â€Š0.67 vs. 1.1 ±â€Š0.46, P < 0.001), vWF:GP1bA-supine (1.5 ±â€Š0.73 vs. 1.1 ±â€Š0.42, P < 0.001), vWF:GP1bA-standing (1.5 ±â€Š0.75 vs. 1.1 ±â€Š0.42 P < 0.001), fibrinogen-standing (2.9 ±â€Š0.53 vs. 2.7 ±â€Š0.61, P = 0.03) but not fibrinogen-supine (2.8 ±â€Š0.54 vs. 2.7 ±â€Š0.61, P = 0.078) compared with patients without orthostatic hypotension. However, after adjustment for age, sex, and comorbidity, only vWF:Ag and vWF:GP1bA levels remained significantly increased in orthostatic hypotension patients. CONCLUSION: Concentration of vWF is elevated in patients with orthostatic hypotension who suffered a syncopal event. This observation may be helpful in understanding the increased risk of cardiovascular events in orthostatic hypotension.


Assuntos
Hipotensão Ortostática/sangue , Síncope/sangue , Fator de von Willebrand/metabolismo , Adulto , Idoso , Biomarcadores/sangue , Pressão Sanguínea , Fator VIII/metabolismo , Feminino , Fibrinogênio/metabolismo , Humanos , Hipotensão Ortostática/complicações , Inibidor de Coagulação do Lúpus/sangue , Masculino , Pessoa de Meia-Idade , Decúbito Dorsal , Síncope/etiologia , Teste da Mesa Inclinada
15.
PLoS One ; 10(6): e0128962, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26053073

RESUMO

BACKGROUND: Impaired autonomic control of postural homeostasis results in orthostatic intolerance. However, the role of neurohormones in orthostatic intolerance has not been explained. METHODS: Six-hundred-and-seventy-one patients (299 males; 55 ± 22 years) with unexplained syncope underwent head-up tilt (HUT) with serial blood sampling. Systolic blood pressure (SBP) and heart rate (HR) supine, after 3 min, and lowest BP/highest HR during HUT were recorded. Plasma levels of epinephrine, norepinephrine, renin, C-terminal-pro-arginine-vasopressin (CT-proAVP), C-terminal- endothelin-1 (CT-proET-1), and mid-regional-fragment of pro-atrial-natriuretic-peptide (MR-proANP) were determined at supine and 3 min of HUT. Multivariate-adjusted logistic regression model was applied to compare 1st (reference) with 4th quartile of 3 min and maximal ΔSBP/ΔHR (i.e. pronounced hypotension or tachycardia) vs. changes in neuroendocrine biomarkers, respectively. RESULTS: Higher resting CT-proET-1 predicted BP fall at 3 min (Odds ratio (OR) per 1 SD: 1.62, 95%CI 1.18-2.22; p = 0.003), and max BP fall during HUT (1.82, 1.28-2.61; p = 0.001). Higher resting CT-proAVP predicted BP fall at 3 min (1.33, 1.03-1.73; p = 0.03), which was also associated with increase in CT-proAVP (1.86, 1.38-2.51; p = 0.00005) and epinephrine (1.47, 1.12-1.92; p = 0.05) during HUT. Lower resting MR-proANP predicted tachycardia at 3 min (0.37, 0.24-0.59; p = 0.00003), and max tachycardia during HUT (0.47, 0.29-0.77; p = 0.002). Further, tachycardia during HUT was associated with increase in epinephrine (1.60, 1.15-2.21; p = 0.005), and norepinephrine (1.87, 1.38-2.53; p = 0.005). CONCLUSIONS: Resting CT-proET-1 and CT-proAVP are increased in orthostatic hypotension, while resting MR-proANP is decreased in postural tachycardia. Moreover, early BP fall during orthostasis evokes increase in CT-proAVP and epinephrine, while postural tachycardia is associated with increase in norepinephrine and epinephrine.


Assuntos
Biomarcadores/sangue , Hemodinâmica , Hipotensão Ortostática/sangue , Hipotensão Ortostática/fisiopatologia , Disautonomias Primárias/sangue , Disautonomias Primárias/fisiopatologia , Pressão Sanguínea , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Sistemas Neurossecretores/fisiopatologia , Razão de Chances , Reflexo , Análise de Regressão , Síncope , Sístole , Taquicardia/sangue , Taquicardia/fisiopatologia , Teste da Mesa Inclinada
16.
Heart Rhythm ; 12(6): 1287-94, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25684232

RESUMO

BACKGROUND: The pathophysiology of orthostatic hypotension (OH) is multifactorial, with the most frequent causes being adverse effects of cardioactive drugs. In 20%-40% of cases, the etiology is unknown. In recent reports, altered levels of endogenous neuropeptides have been observed in noncardiac syncope, but B-type natriuretic peptide (BNP) and its amino-terminal cleavage fragment (NT-proBNP) have not been studied. OBJECTIVE: The purpose of this study was to assess the possibility that BNP with its diuretic and vasorelaxant properties could contribute to OH. METHODS: This prospective observational study comprised 85 consecutive OH subjects (58 women, age 49 ± 23 years) referred to a tertiary-care syncope clinic. All patients had normal left ventricular systolic and diastolic function, and clinical and laboratory findings consistent with euvolemia or modest hypovolemia. In 45 of 85 individuals (53%), an OH cause was determined. RESULTS: Among the remaining 40 patients (21 women, age 57 ± 16 years) with OH of unknown cause, 6 of 40 (15%) exhibited unexpectedly elevated plasma NT-proBNP levels (14000, 5210, 2570, 7990, 3480, and 6680 pg/mL). In contrast, NT-proBNP values were normal (ie, <300 pg/mL) in the remaining 34 patients with OH of unknown cause and 45 patients with OH of known etiology. At 8 to 12 months of follow-up, volume repletion therapy requirements in patients with initial increased NT-proBNP diminished in conjunction with gradual fall of NT-proBNP concentrations. CONCLUSION: In select patients, markedly elevated levels of BNP or NT-proBNP may be associated with and possibly contribute to symptomatic OH.


Assuntos
Hipotensão Ortostática/etiologia , Peptídeo Natriurético Encefálico/sangue , Idoso , Idoso de 80 Anos ou mais , Cateterismo Cardíaco , Feminino , Hemodinâmica , Humanos , Hipotensão Ortostática/sangue , Hipotensão Ortostática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/fisiologia , Estudos Prospectivos , Teste da Mesa Inclinada
17.
Clin Auton Res ; 25(1): 61-7, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25638582

RESUMO

BACKGROUND: Parkinson disease with orthostatic hypotension (PD + OH) and the parkinsonian form of multiple system atrophy (MSA-P) can be difficult to distinguish clinically. Recent studies indicate that PD entails a vesicular storage defect in catecholaminergic neurons. Although cardiac sympathetic neuroimaging by (18)F-dopamine positron emission tomography can identify decreased vesicular storage, this testing is not generally available. We assessed whether plasma biomarkers of a vesicular storage defect can separate PD + OH from MSA-P. METHODS: We conceptualized that after F-dopamine injection, augmented production of F-dihydroxyphenylacetic acid (F-DOPAC) indicates decreased vesicular storage, and we therefore predicted that arterial plasma F-DOPAC would be elevated in PD + OH but not in MSA-P. We measured arterial plasma F-DOPAC after (18)F-dopamine administration (infused i.v. over 3 min) in patients with PD + OH (N = 12) or MSA-P (N = 21) and in healthy control subjects (N = 26). Peak F-DOPAC:dihydroxyphenylglycol (DHPG) was also calculated to adjust for effects of denervation on F-DOPAC production. RESULTS: Plasma F-DOPAC accumulated rapidly after initiation of (18)F-dopamine infusion. Peak F-DOPAC (5-10 min) in PD + OH averaged three times that in MSA-P (P < 0.0001). Among MSA-P patients, none had peak F-DOPAC > 300 nCi-kg/cc-mCi, in contrast with 7 of 12 PD + OH patients (χ(2) = 16.6, P < 0.0001). DHPG was lower in PD + OH (3.83 ± 0.36 nmol/L) than in MSA-P (5.20 ± 0.29 nmol/L, P = 0.007). All MSA-P patients had peak F-DOPAC:DHPG < 60, in contrast with 9 of 12 PD + OH patients (χ(2) = 17.5, P < 0.0001). Adjustment of peak F-DOPAC for DHPG increased test sensitivity from 58 to 81% at similar high specificity. INTERPRETATION: After F-dopamine injection, plasma F-DOPAC and F-DOPAC:DHPG distinguish PD + OH from MSA-P.


Assuntos
Hipotensão Ortostática/sangue , Hipotensão Ortostática/diagnóstico , Atrofia de Múltiplos Sistemas/sangue , Atrofia de Múltiplos Sistemas/diagnóstico , Doença de Parkinson/sangue , Doença de Parkinson/diagnóstico , Ácido 3,4-Di-Hidroxifenilacético/sangue , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Comorbidade , Estudos Transversais , Diagnóstico Diferencial , Dopamina/farmacologia , Feminino , Radioisótopos de Flúor , Humanos , Masculino , Metoxi-Hidroxifenilglicol/análogos & derivados , Metoxi-Hidroxifenilglicol/sangue , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Vesículas Sinápticas/efeitos dos fármacos , Vesículas Sinápticas/fisiologia
18.
Clin Sci (Lond) ; 129(2): 107-16, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25706983

RESUMO

Patients with neurogenic orthostatic hypotension (OH) typically have impaired sympathetic nervous system tone and therefore low levels of upright plasma norepinephrine (NE) (noradrenaline). We report a subset of patients who clinically have typical neurogenic OH but who paradoxically have elevated upright levels of plasma NE. We retrospectively studied 83 OH patients evaluated at the Vanderbilt Autonomic Dysfunction Center between August 2007 and May 2013. Based on standing NE, patients were dichotomized into a hyperadrenergic OH group [hyperOH: upright NE ≥ 3.55 nmol/l (600 pg/ml), n=19] or a non-hyperadrenergic OH group [nOH: upright NE < 3.55 nmol/l (600 pg/ml), n=64]. Medical history and data from autonomic testing, including the Valsalva manoeuvre (VM), were analysed. HyperOH patients had profound orthostatic falls in blood pressure (BP), but less severe than in nOH [change in SBP (systolic blood pressure): -53 ± 31 mmHg compared with -68 ± 33 mmHg, P=0.050; change in DBP (diastolic blood pressure): -18 ± 23 mmHg compared with -30 ± 17 mmHg, P=0.01]. The expected compensatory increase in standing heart rate (HR) was similarly blunted in both hyperOH and nOH groups [84 ± 15 beats per minute (bpm) compared with 82 ± 14 bpm; P=0.6]. HyperOH patients had less severe sympathetic failure as evidenced by smaller falls in DBP during phase 2 of VM and a shorter VM phase 4 BP recovery time (16.5 ± 8.9 s compared with 31.6 ± 16.6 s; P<0.001) than nOH patients. Neurogenic hyperOH patients have severe neurogenic OH, but have less severe adrenergic dysfunction than nOH patients. Further work is required to understand whether hyperOH patients will progress to nOH or whether this represents a different disorder.


Assuntos
Sistema Nervoso Autônomo/metabolismo , Pressão Sanguínea , Hipotensão Ortostática/sangue , Norepinefrina/sangue , Idoso , Sistema Nervoso Autônomo/fisiopatologia , Biomarcadores/sangue , Feminino , Frequência Cardíaca , Humanos , Hipotensão Ortostática/classificação , Hipotensão Ortostática/diagnóstico , Hipotensão Ortostática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Postura , Estudos Retrospectivos , Tennessee , Regulação para Cima , Manobra de Valsalva
19.
Am J Med ; 128(2): 161-170.e1, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25447619

RESUMO

OBJECTIVE: We examined the diagnostic and predictive value of high-sensitivity cardiac troponin T (cTnThs) in patients with syncope. METHODS: We performed an analysis of consecutive patients with syncope presenting to the emergency department. The primary end point was the accuracy to diagnose a cardiac syncope. In addition, the study explored the prognostic relevance of cTnThs in patients with cardiac and noncardiac syncope. RESULTS: A total of 360 patients were enrolled (median age, 70.5 years; male, 55.8%; 23.9% aged >80 years). Cardiac syncope was present in 22% of patients, reflex syncope was present in 40% of patients, syncope due to orthostatic hypotension was present in 20% of patients, and unexplained syncope was present in 17.5% of patients. A total of 148 patients (41%) had cTnThs levels above the 99% confidence interval (CI) (cutoff point). The diagnostic accuracy for cTnThs levels to determine the diagnosis of cardiac syncope was quantified by the area under the curve (0.77; CI, 0.72-0.83; P < .001). A comparable area under the curve (0.78; CI, 0.73-0.83; P < .001) was obtained for the predictive value of cTnThs levels within 30 days: Patients with increased cTnThs levels had a 52% likelihood for adverse events, patients with cTnThs levels below the cutoff point had a low risk (negative predictive value, 83.5%). Increased cTnThs levels indicate adverse prognosis in patients with noncardiac causes of syncope, but not in patients with cardiac syncope being a risk factor for adverse outcome by itself. CONCLUSIONS: Patients with syncope presenting to the emergency department have a high proportion of life-threatening conditions. cTnThs levels show a limited diagnostic and predictive accuracy for the identification of patients with syncope at high risk.


Assuntos
Síncope/diagnóstico , Troponina T/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Serviço Hospitalar de Emergência , Feminino , Cardiopatias/sangue , Cardiopatias/complicações , Cardiopatias/diagnóstico , Humanos , Hipotensão Ortostática/sangue , Hipotensão Ortostática/complicações , Hipotensão Ortostática/diagnóstico , Masculino , Prognóstico , Estudos Prospectivos , Sensibilidade e Especificidade , Síncope/sangue , Síncope/etiologia
20.
World J Gastroenterol ; 20(30): 10553-63, 2014 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-25132775

RESUMO

AIM: To test the ability of adult-derived human liver stem/progenitor cells (ADHLSC) from large scale cultures to conjugate bilirubin in vitro and in bilirubin conjugation deficient rat. METHODS: ADHLSC from large scale cultures were tested for their phenotype and for their capacity to conjugate bilirubin in vitro after hepatogenic differentiation. In vivo, Gunn rats [uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) deficient animal] were injected with ADHLSC and cryopreserved hepatocytes (positive control). Two, 4, 13 and 27 wk post-transplantation, transplanted Gunn rat bilirubin serum levels were determined by high performance liquid chromatography. Human transplanted cell engraftment was assessed 27 wk post-transplantation using immunohistochemistry and RTqPCR. RESULTS: Large scale culture conditions do not modify ADHLSC phenotype, ADHLSC were able to specifically conjugate bilirubin. ADHLSC were intraportally injected into Gunn rats and blood UCB was measured at different times post-transplantation, infused-Gunn rats exhibited a metabolic effect 3 mo post-transplantation and maintained over a 6 mo period. ADHLSC engraftment into Gunn rat's liver was demonstrated by RTqPCR and immunohistochemistry against albumin and UGT1A1. CONCLUSION: ADHLSC from large scale cultures are efficient in conjugating bilirubin in vitro and in restoring a deficient metabolic function (reducing bilirubin level) in hyperbilirubinemic rats.


Assuntos
Bilirrubina/sangue , Hepatócitos/metabolismo , Hepatócitos/transplante , Hipotensão Ortostática/cirurgia , Transplante de Células-Tronco , Células-Tronco/metabolismo , Animais , Biomarcadores/sangue , Diferenciação Celular , Células Cultivadas , Criança , Modelos Animais de Doenças , Regulação para Baixo , Glucuronosiltransferase/deficiência , Glucuronosiltransferase/genética , Glucuronosiltransferase/metabolismo , Hepatócitos/enzimologia , Humanos , Hipotensão Ortostática/sangue , Hipotensão Ortostática/diagnóstico , Hipotensão Ortostática/enzimologia , Hipotensão Ortostática/genética , Masculino , Fenótipo , Ratos Gunn , Albumina Sérica/metabolismo , Células-Tronco/enzimologia , Fatores de Tempo
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