RESUMO
Recently, it has been proposed, that the blood pressure (BP) lowering effect of gastric bypass surgery not only is explained by the obtained weight loss, but that the anatomical rearrangement of the gut after 'malabsorptive' surgical techniques, such as the laparoscopic Roux-en-Y gastric bypass (LRYGB), may affect BP through a change in a putative 'entero-renal' axis. If so one could anticipate a reduction in BP even before a noticeable weight loss was obtained. The purpose of the present study was to investigate the very early BP response to LRYGB surgery. Ten severely obese hypertensive (mean BMI 40.8 kg/m2) and 10 severely obese normotensive (mean BMI 41.7 kg/m2) patients underwent 24-h ambulatory blood pressure measurements (24 h ABPMs) before LRYGB and again day 1 and day 10 after LRYGB. No change in 24 h BP was observed day 1 after LRYGB. Day 10 after surgery both hypertensive and normotensive patients demonstrated a significant 12.6 mmHg and 9.5 reduction in systolic BP (SBP), respectively. Mean arterial pressure (MAP) decreased by 8.3 and 5.4 mmHg. At day 10 postoperatively, a weight loss of 7.9 kg in the hypertensive patients and 7.0 kg in the normotensive patients was observed. The reduction in BP after LRYGB takes place before any substantial weight loss has occurred. The reason for this remains speculative, but obese hypertensive patients may clearly benefit from the operation even if the goal of achieving 'normoweight' is not obtained.
Assuntos
Pressão Sanguínea , Derivação Gástrica , Hipertensão/cirurgia , Obesidade Mórbida/cirurgia , Adulto , Monitorização Ambulatorial da Pressão Arterial , Índice de Massa Corporal , Feminino , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/complicações , Obesidade Mórbida/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Redução de PesoRESUMO
OBJECTIVES: Hypothermia is still unproven as beneficial treatment in human stroke, although in animal models, conditioning the brain with hypothermia has induced tolerance to insults. Here, we delineate the feasibility of drug-induced mild hypothermia in reducing ischemic brain damage when conditioning before (preconditioning) and after (postconditioning) experimental stroke. METHODS: Hypothermia was induced in rats with a bolus of 6 mg/kg talipexole followed by 20 h continuous talipexole infusion of 6 mg/kg in total. Controls received similar treatment with saline. The core body temperature was continuously monitored. In preconditioning, hypothermia was terminated before either reversible occlusion of the middle cerebral artery (MCAO) for 60 min or global ischemia for 10 min with 2-vessel occlusion and hypotension. In postconditioning, rats experienced 60 min of MCAO before hypothermia was induced either immediately or with 3 h delay. Rats survived ischemia for 2, 7 or 90 days. Infarct volumes were quantified by stereology. Additional experiments of methodological relevance were included in the study. RESULTS: Talipexole induced mild hypothermia (35.1±1.1 to 36.0±0.5°C) for <20 h. Hypothermic pre- and postconditioning reduced infarct sizes by more than 60% as monitored during the first 90 days after experimental stroke (p<0.05). CONCLUSION: Talipexole is registered for use as a dopamine substitute in humans with Parkinson's disease. Although dosages cannot be directly translated to patients, our study exemplifies in an animal model that drug-induced hypothermia in a clinical setting might reduce cerebral ischemic damage before neuro- and cardiac surgical procedures and after stroke.
Assuntos
Azepinas/farmacologia , Isquemia Encefálica/patologia , Agonistas de Dopamina/farmacologia , Hipotermia Induzida/métodos , Pós-Condicionamento Isquêmico/métodos , Precondicionamento Isquêmico/métodos , Animais , Western Blotting , Isquemia Encefálica/metabolismo , Modelos Animais de Doenças , Ratos , Fator A de Crescimento do Endotélio Vascular/biossínteseRESUMO
OBJECTIVE: Plasma volume assessment may be of importance in several disorders. The purpose of the present study was to compare the reliability of plasma volume measurements by technetium-labeled human serum albumin ((99m)Tc-HSA) with a simultaneously performed plasma volume determination with iodine-labeled human serum albumin ((125)I-HSA). MATERIALS AND METHODS: In 15 healthy volunteers, simultaneous plasma volume measurements with (99m)Tc-HSA and (125)I-HSA were performed after ½ hour in the supine position. Blood samples were obtained 10, 15, 20, and 30 minutes after the injection for accurate retropolation from the plasma counts to time zero to correct for leakage of the isotopes from the circulation. RESULTS: The mean difference (bias) between plasma volume measured with (125)I-albumin and (99m)Tc-albumin was 8 ml (0.1 ml/kg) with limits of agreement (bias ±1.96 SD) ranging from -181-196 ml (-2.3-2.5 ml/kg). The tracer disappearance rate was significantly higher with (99m)Tc-albumin (-23.1±7.1%/h) than with (125)I-albumin (-6.7±3.6%/h) (p <0.001). CONCLUSION: This study demonstrates that (99m)Tc-HSA can replace (125)I-HSA for single measurements of plasma volume in healthy volunteers. It needs to be emphasized however, that repeated blood sampling for 1/2 hour after injection of the tracer is required to correct for the disappearance of (99m)Tc and (99m)Tc-HSA from the circulation.
Assuntos
Volume Plasmático/fisiologia , Compostos Radiofarmacêuticos/sangue , Soroalbumina Radioiodada/química , Agregado de Albumina Marcado com Tecnécio Tc 99m/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/química , Reprodutibilidade dos Testes , Soroalbumina Radioiodada/análiseRESUMO
Cannabinoids have neuroprotective potentials, and the expression of endocannabinoids as well as cannabinoid receptors is induced after cerebral ischemia. They also induce hypothermia by lowering the hypothalamic set point. We have estimated the significance of such hypothermia in ischemic neuroprotection following systemic administration of WIN 55,212-2, a synthetic cannabinoid receptor agonist. Results showed that WIN 55,212-2 significantly reduced infarct volumes of rats subjected to focal cerebral ischemia (middle cerebral artery occlusion) and significantly decreased ischemic CA1 damage in rats subjected to global cerebral ischemia (two-vessel occlusion). A significant (approximately 50%) part of this neuroprotection was provided by WIN 55,212-2 induced hypothermia (33.7+/-1.1 degrees C/34.9+/-1.6 degrees C), because prevention of hypothermia by maintaining body core temperatures between 37.0 and 38.0 degrees C dissolved the neuroprotective effect into a hypothermic component and an unidentified component. Finally, the ability of WIN 55,212-2 to reduce levels of the proinflammatory cytokine IFNgamma in the infarcted hemisphere of rats subjected to focal cerebral ischemia required hypothermia. For the cannabinoid WIN 55,212-2, we have isolated and directly demonstrated that hypothermia is only part of, although significant, cannabinoid mediated neuroprotection in both global and focal cerebral ischemia. We conclude that cannabinoids are reliable candidates for drug-induced hypothermia and neuroprotection. These neuroprotective effects of cannabinoids could provide the basis for potential therapeutic uses of cannabinoids and/or endocannabinoids in stroke.
Assuntos
Isquemia Encefálica/prevenção & controle , Hipotermia , Morfolinas/uso terapêutico , Naftalenos/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Animais , Benzoxazinas , Ensaio de Imunoadsorção Enzimática , Masculino , Ratos , Ratos WistarRESUMO
OBJECTIVE: To examine 24-h blood pressure (24BP), systemic haemodynamics and the effect of sodium intake on 24BP in obese patients before and after gastric bypass surgery [laparoscopic Roux-en-Y gastric bypass (LRYGB)], and to determine whether weight loss from LRYGB might be related to an increase in plasma concentrations of atrial natriuretic peptide. METHODS: Twelve hypertensive and 12 normotensive morbidly obese patients underwent LRYGB: 24BP, systemic haemodynamics and mid-regional pro-atrial natriuretic peptide (MRproANP) were assessed before, 6 weeks and 12 months after surgery. The effect of high versus low sodium intake on 24BP was evaluated before and 12 months after LRYGB. RESULTS: Six weeks after LRYGB, the average weight loss was 20âkg, with a further 21âkg weight loss 1 year after surgery. In hypertensive patients, 24BP was significantly reduced at 6 weeks, but not 1 year after LRYGB. However, antihypertensive medications were successively reduced from baseline to 1 year after surgery. In normotensive patients, there was no change in 24BP 6 weeks after LRYGB, but a tendency towards a reduction 1 year after the operation. Plasma concentrations of MRproANP were subnormal prior to surgery in hypertensive patients and increased by 77% 1 year after the operation. In normotensive patients, preoperative concentrations were normal and increased only by 6%. High sodium intake induced plasma volume expansion, increased stroke volume and cardiac output, but no significant change in 24BP - neither before nor after LRYGB. CONCLUSIONS: LRYGB resulted in a significant 24BP reduction and a substantial increase in MRproANP plasma concentrations in hypertensive, obese patients 6 weeks after surgery, suggesting a causal link between obesity-hypertension and altered release/degradation of cardiac natriuretic peptides.
Assuntos
Fator Natriurético Atrial/metabolismo , Derivação Gástrica , Hipertensão/cirurgia , Obesidade Mórbida/cirurgia , Adulto , Fator Natriurético Atrial/sangue , Pressão Sanguínea , Feminino , Humanos , Hipertensão/epidemiologia , Laparoscopia , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/epidemiologia , Fatores de Tempo , Redução de PesoRESUMO
AIMS: Plasma volume (PV) expansion hallmarks worsening chronic heart failure (CHF) but no non-invasive means of quantifying volume status exists. Because weight and haematocrit are related to PV, they can be used to calculate relative PV status (PVS). We tested the validity and prognostic utility of calculated PVS in CHF patients. METHODS AND RESULTS: First, we evaluated the agreement between calculated actual PV (aPV) and aPV levels measured using (125)Iodine-human serum albumin. Second, we derived PVS as: [(calculated aPV - ideal PV)/ideal PV] × 100%. Third, we assessed the prognostic implications of PVS in 5002 patients from the Valsartan in Heart Failure Trial (Val-HeFT), and validated this in another 246 routine CHF outpatients. On analysis, calculated and measured aPV values correlated significantly in 119 normal subjects and 30 CHF patients. In the Val-HeFT cohort, mean (+SD) PVS was -9 ± 8% and related to volume biomarkers such as brain natriuretic peptide (BNP). Over 2 years, 977 (20%) patients died. Plasma volume status was associated with death and first morbid events in a 'J-shaped' fashion with the highest risk seen with a PVS > -4%. Stratification into PVS quartiles confirmed that a PVS > -4% was associated with increased mortality (unadjusted hazard ratio 1.65, 95% confidence interval 1.44-1.88, χ(2) = 54, P < 0.001) even after adjusting for 22 variables, including brain natriuretic peptide. These results were mirrored in the validation cohort. CONCLUSIONS: Relative PVS calculated from simple clinical indices reflects the degree to which patients have deviated from their ideal PV and independently relates to outcomes. The utility of PVS-driven CHF management needs further evaluation.
Assuntos
Insuficiência Cardíaca/fisiopatologia , Volume Plasmático , Idoso , Idoso de 80 Anos ou mais , Peso Corporal , Doença Crônica , Estudos de Coortes , Feminino , Insuficiência Cardíaca/diagnóstico , Hematócrito , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Técnica de Diluição de Radioisótopos , Reprodutibilidade dos Testes , Soroalbumina RadioiodadaRESUMO
BACKGROUND: Many patients with morbid obesity (BMIâ>â40âkg/m) have hypertension. The complex pathophysiological abnormalities linking hypertension to obesity have not been fully clarified, but abnormal sodium handling could be an important mechanism. METHOD: Therefore, we examined changes in body fluid compartments and haemodynamic responses (at rest and during exercise) after 5 days of a low-sodium diet (90âmmol/day) and 5 days of a high-sodium diet (250âmmol/day) in 12 morbidly obese, hypertensive patients; 12 morbidly obese, normotensive patients and 12 nonobese controls. RESULTS: High sodium intake as compared to low sodium intake was associated with an increase in plasma volume (obese, hypertensive patients: 5â±â4%; obese, normotensive patients: 10â±â11%; nonobese controls: 7â±â6%), cardiac output (CO) (obese, hypertensive patients: 17â±â12%; obese, normotensive patients: 20â±â16%; nonobese controls: 13â±â14%) and stroke volume (SV) (obese, hypertensive patients: 27â±â26%; obese, normotensive patients: 27â±â24%; nonobese controls: 18â±â27%) in all three groups with no differences between the groups. Despite an increase in CO during high salt intake, 24-h blood pressure (BP) was unchanged in patients and controls as a result of a reduction in total peripheral resistance (obese, hypertensive patients: -11â±â11%; obese, normotensive patients: -10â±â12%; nonobese controls: -5â±â14%). Similar changes were observed during an incremental bicycle exercise test wherein CO and SV were higher, whereas mean arterial BP was unchanged at each exercise level during high sodium intake. CONCLUSION: Despite substantial increases in CO and SV, we did not observe any significant change in BP during high sodium intake, neither in morbid obese patients nor in lean individuals.
Assuntos
Pressão Sanguínea/fisiologia , Obesidade Mórbida/fisiopatologia , Sódio na Dieta/administração & dosagem , Débito Cardíaco/fisiologia , Dieta Hipossódica , Exercício Físico/fisiologia , Feminino , Hemodinâmica/fisiologia , Humanos , Hipertensão/fisiopatologia , Masculino , Obesidade Mórbida/complicações , Descanso/fisiologia , Resistência Vascular/fisiologiaRESUMO
AIMS: In patients with heart failure (HF), the use of diuretics may be a double-edged sword that can alleviate symptoms of congestion, but also result in over-diuresis and intravascular volume depletion. The purpose of the present study was to examine plasma volume (PV) in HF patients receiving from 0 to 160 mg of furosemide and to investigate whether determination of plasma N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) concentrations can predict PV-status. METHODS AND RESULTS: Plasma volume, extracellular volume, glomerular filtration rate, NT-proBNP, and daily renal sodium excretion were measured in 18 patients with medically treated, compensated HF and in 27 healthy volunteers. Cardiac function was examined by non-invasive cardiac output determination and echocardiography. Exercise capacity was evaluated by 6 min walk test. There was a borderline significant difference in PV between patients with HF and control subjects (37.3 +/- 6.0 and 40.2 +/- 5.8 mL/kg, respectively, P = 0.092) with a significant tendency towards a contraction of PV with increasing use of diuretics (P = 0.031). There was no difference in extracellular volume between patients with HF and control subjects (P = 0.844). NT-proBNP plasma concentrations had no correlation to either sodium excretion (P = 0.193) or PV (P = 0.471) in patients with HF. CONCLUSION: Plasma volume in patients with HF was within normal limits, but patients treated with high doses of loop-diuretics tended to have subnormal PV. Single measurement of NT-proBNP plasma concentration could not be used to estimate intravascular volume status in patients with HF.