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1.
Am J Hypertens ; 34(7): 744-752, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-33677553

RESUMO

BACKGROUND: Renal denervation (RDN) is effective at lowering blood pressure. However, it is unknown if ablative procedures elicit sympathetic denervation of the kidneys in humans. The aim of this investigation was to assess sympathetic innervation of the renal cortex following perivascular chemical RDN, which may be particularly effective at ablating perivascular efferent and afferent nerves. METHODS: Seven hypertensive patients (4F:3M; 50-65 years) completed PET-CT sympathetic neuroimaging of the renal cortex using 11C-methylreboxetine (11C-MRB, norepinephrine transporter ligand) and 6-[18F]-fluorodopamine (18F-FDA; substrate for the cell membrane norepinephrine transporter) before and 8 weeks after chemical RDN (Peregrine System Infusion Catheter, Ablative Solutions; n = 4; 2F:2M) or control renal angiography (n = 3; 2F:1M). Patients completed physiological phenotyping including 24-hour ambulatory blood pressure, hemodynamics, muscle sympathetic nerve activity, and 24-hour urine collection. RESULTS: RDN decreased 11C-MRB-derived radioactivity by ~30% (Δ  11C-MRB/chamber: -0.95 a.u. confidence interval (CI): -1.36 to -0.54, P = 0.0002), indicative of efferent RDN. In contrast, 18F-FDA-derived radioactivity increased (Δ  18F-FDA/chamber: 2.72 a.u. CI: 0.73-4.71, P = 0.009), consistent with reduced vesicular turnover. Controls showed no change in either marker. Ambulatory systolic pressure decreased in 3 of 4 patients (-9 mm Hg CI: -27 to 9, P = 0.058), and central systolic pressure decreased in all patients (-23 mm Hg CI: -51 to 5, P = 0.095). CONCLUSIONS: These results are the first to show efferent sympathetic denervation of the renal cortex following RDN in humans. Further studies of mechanisms underlying variable blood pressure lowering in the setting of documented RDN may provide insights into inconsistencies in clinical trial outcomes. CLINICAL TRIALS REGISTRATION: Trial Number NCT03465917.


Assuntos
Denervação , Hipertensão , Rim , Idoso , Denervação/métodos , Feminino , Humanos , Hipertensão/terapia , Rim/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Simpatectomia , Resultado do Tratamento
2.
Am J Physiol Regul Integr Comp Physiol ; 315(4): R587-R594, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-29897820

RESUMO

Women with a history of gestational hypertensive disorders (GHD) are at increased risk for developing perinatal cardiovascular complications (e.g., gestational hypertension, preeclampsia, etc.) in subsequent pregnancies. The underlying mechanisms remain uncertain, but impaired maternal left ventricular function may be one contributing factor for these complications. We evaluated the time course of changes in left ventricular function before, during, and after pregnancy in women with prior GHD. Sixteen women with a history of GHD (the high-risk group) and 25 women without such a history (controls) were enrolled. Resting hemodynamic and echocardiographic measurements were longitudinally performed before pregnancy, during early pregnancy (4-8 wk of gestation), during late pregnancy (32-36 wk of gestation), and postpartum (6-10 wk after delivery). Pregnancy outcomes were obtained after delivery. At prepregnancy, there was no difference in blood pressure and heart rate between the groups. Corrected isovolumic relaxation time was longer, E/ e' was larger, and Tei index was greater in the high-risk group than controls. Moreover, the rate of GHD during the study was significantly greater in the high-risk group than controls [odds ratio = 8.94 (95% confidence interval: 1.55-51.5), P = 0.007]. Multiple logistic regression analysis adjusted for age demonstrated that prepregnancy E/ e' was an independent predictor for GHD ( P = 0.017). Thus, women with a history of GHD have modestly impaired cardiac function prepregnancy compared with controls, which identifies an increased susceptibility to developing cardiovascular complications during a subsequent pregnancy.


Assuntos
Ventrículos do Coração/fisiopatologia , Hipertensão Induzida pela Gravidez/fisiopatologia , Contração Miocárdica , Função Ventricular Esquerda , Adulto , Estudos de Casos e Controles , Ecocardiografia Doppler , Feminino , Ventrículos do Coração/diagnóstico por imagem , Hemodinâmica , Humanos , Hipertensão Induzida pela Gravidez/diagnóstico por imagem , Hipertensão Induzida pela Gravidez/epidemiologia , Incidência , Paridade , Gravidez , Texas/epidemiologia , Fatores de Tempo
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