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OBJECTIVE: To review the clinical presentation, causes, and diagnostic approach to spontaneous hypoglycemia in adults without diabetes mellitus. METHODS: A literature review was performed using the PubMed and Google Scholar databases. RESULTS: Hypoglycemia is uncommon in people who are not on glucose-lowering medications. Under normal physiologic conditions, multiple neural and hormonal counterregulatory mechanisms prevent the development of abnormally low levels of plasma glucose. If spontaneous hypoglycemia is suspected, the Whipple triad should be used to confirm hypoglycemia before pursuing further diagnostic workup. The Whipple criteria include the following: (1) low levels of plasma glucose, (2) signs or symptoms that would be expected with low levels of plasma glucose, and (3) improvement in those signs or symptoms when the level of plasma glucose increases. Spontaneous hypoglycemia can be caused by conditions that cause endogenous hyperinsulinism, including insulinoma, postbariatric hypoglycemia, and noninsulinoma pancreatogenous hypoglycemia. Spontaneous hypoglycemia can also be seen with critical illness, hepatic or renal dysfunction, hormonal deficiency, non-diabetes-related medications, and non-islet cell tumors. The initial diagnostic approach should begin by obtaining a detailed history of the nature and timing of the patient's symptoms, medications, underlying comorbid conditions, and any acute illness. A laboratory evaluation should be conducted at the time of the spontaneous symptomatic episode. Supervised tests such as a 72-hour fast or mixed-meal test may be needed to recreate the situation under which the patient is likely to experience symptoms. CONCLUSION: We provide an overview of the physiology of counterregulatory response to hypoglycemia, its causes, and diagnostic approaches to spontaneous hypoglycemia in adults.
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Hipoglicemia , Adulto , Humanos , Glicemia , Diabetes Mellitus , Hipoglicemia/diagnóstico , Hipoglicemia/etiologia , Insulinoma/complicações , Insulinoma/diagnóstico , Neoplasias Pancreáticas/diagnósticoRESUMO
BACKGROUND: Regadenoson (REG), a selective adenosine A2a receptor agonist, is becoming the preferred pharmacologic agent for stress myocardial perfusion imaging (MPI). Hemodynamic and stress variables, immediate safety and use of aminophylline when using REG combined with low-level exercise (REG WALK MPI) compared with REG MPI, have not been well studied and formed the basis of our study. METHODS: Retrospective evaluation of patients who underwent REG MPI (n = 887) was compared to patients undergoing REG WALK MPI (n = 485) from January to November 2009. Patient demographics, hemodynamic parameters, REG MPI data, side effects, immediate major clinical events, and use of aminophylline were evaluated. RESULTS: Patients in REG WALK MPI group tended to be younger, male and obese compared to patients in REG MPI group. REG WALK MPI patients had higher stress heart rate (103 ± 20.5 vs 84 ± 19 bpm, P = .001), higher heart rate reserve (36.3 ± 19 vs 14.7 ± 15.5 bpm, P < .001), and greater systolic blood pressure rise (4.8 ± 21.3 vs -8.9 ± 19.8 mm Hg, P < .001), compared to REG MPI patients. No major adverse events were reported immediately after REG WALK MPI. There were no differences in drug-related side effects in between the two groups; however, the use of aminophylline was lower in REG WALK MPI Group (5.6% vs 11.4%, P = .001). CONCLUSION: REG WALK MPI gives more favorable hemodynamic response with lesser use of aminophylline and no increase in adverse events when compared with REG MPI.
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Agonistas do Receptor A2 de Adenosina , Teste de Esforço/métodos , Imagem de Perfusão do Miocárdio/métodos , Purinas , Pirazóis , Idoso , Aminofilina , Pressão Sanguínea , Eletrocardiografia/métodos , Exercício Físico , Feminino , Frequência Cardíaca , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Pheochromocytomas are neuroendocrine tumors that arise from chromaffin cells in the adrenal medulla. Giant pheochromocytomas commonly measure greater than 7 to 10â cm, and their incidence and presentation is not well known. We present a case of a 62-year-old female with a giant 15.9â cm cystic pheochromocytoma. The patient was medically managed with oral phenoxybenzamine solution dose 4 times greater than average and was treated with a radical left nephrectomy and adrenalectomy. This case offers insight into the clinical presentation of giant pheochromocytomas and the unique challenges they present both medically and surgically.
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American Thyroid Association guidelines recommend to follow athyreotic differentiated thyroid cancer patients with measurement of serum thyroglobulin and thyroglobulin antibody as tumor markers. The guidelines recommend that rising thyroglobulin or thyroglobulin antibody should prompt additional investigations and potentially additional therapies. Two patients with differentiated thyroid cancer who also received intravenous immunoglobulin are presented. Their cancer history, serial thyroglobulin and thyroglobulin antibody measurements and imaging findings relative to the time course of intravenous immunoglobulin treatment are illustrated. Acute rise in thyroglobulin antibody led to further imaging which did not show cancer progression. Additional history documented an intravenous immunoglobulin treatment exposure had occurred within the past one to two months before the increased thyroglobulin antibody measurement. Follow-up serial thyroglobulin antibody levels declined over time after the intravenous immunoglobulin exposure. Intravenous immunoglobulin, which is a pooled human serum product, contains thyroglobulin antibody. Commercially available thyroglobulin antibody assays may detect the thyroglobulin antibody contained within the administered intravenous immunoglobulin, leading to alarm and further imaging to exclude progressive malignancy. Thyroglobulin antibody rise and fall can be demonstrated in relationship to intravenous immunoglobulin time of administration. Thyroglobulin antibody is higher at time-points sooner than at later time-points following intravenous immunoglobulin treatments. Intravenous immunoglobulin may be a benign source of transiently high thyroglobulin antibody measured in the follow-up of differentiated thyroid cancer patients. Repeat thyroglobulin and thyroglobulin antibody testing one to two months following a higher level in a patient treated with intravenous immunoglobulin may avoid unnecessary imaging to look for progressive malignancy.
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Background: Cystic fibrosis-related diabetes (CFRD) is associated with pulmonary decline, compromised nutritional status, and earlier mortality. Although diabetes technology is increasingly being used in individuals with CFRD, there is a paucity of data investigating the impact of hybrid closed loop (HCL) technology on glycemia in this patient population. Materials and Methods: In this multicenter retrospective study of 13 adults and adolescents with CFRD, 14 days of continuous glucose monitor data were analyzed at baseline, 1 and 3 months after transition to the Tandem t:slim X2 pump with Control IQ™ technology, a HCL system. Results: Control IQ initiation was associated with a significant increase in % time in target range (70-180 mg/dL), as well as decreases in average glucose, % time in hyperglycemic ranges (% time >180 mg/dL, % time >250 mg/dL), and glycemic variability (standard deviation, coefficient of variation). There was no significant change in % time in hypoglycemia ranges (% time <54 mg/dL, % time <70 mg/dL). Conclusions: To our knowledge, this is the first study to report a beneficial effect of Food and Drug Administration (FDA)-approved HCL technology on glycemia in adults and adolescents with CFRD to date. Future studies are needed to understand the potential long-term glycemic benefits of HCL devices and to explore the impact of this technology on heath-related quality of life, pulmonary function, nutritional status, and mortality.
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Fibrose Cística , Diabetes Mellitus Tipo 1 , Adolescente , Adulto , Glicemia , Automonitorização da Glicemia , Fibrose Cística/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Controle Glicêmico , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Sistemas de Infusão de Insulina , Qualidade de Vida , Estudos Retrospectivos , TecnologiaRESUMO
BACKGROUND: Pharmacokinetic studies suggest delayed clearance of Regadenoson (REG), a new selective A2A receptor agonist in chronic kidney disease (CKD). The safety of REG in large series of CKD patients in daily clinical practice remains unstudied. METHODS: Retrospective study of patients with eGFR < 60 mL/min (n = 411, Grp 1, CKD) were compared to patients with eGFR ≥ 60 mL/min (n = 638, Grp 2, Control) undergoing REG-SPECT from Jan to Nov 2009. Patient demographics, REG-SPECT data, side effects, and arrhythmia occurrences were evaluated. RESULTS: No major adverse events were noted immediately after REG-SPECT or at 1 week of follow-up. There were no differences in any arrhythmias in between the two groups (Grp 1, 47.2% vs Grp 2, 42.9%, P = ns). Ninety-nine percent of arrhythmias in CKD patients were PACs or PVCs. Transient junctional rhythm was observed in one CKD patient. There were no occurrences of second degree or higher degree AV block. Grp 1 had a blunted heart rate response (16.6 ± 16.1 vs 24.9 ± 20.3 bpm, P ≤ .001) and greater systolic blood pressure drop response (-7.4 ± 21.1 vs -1.4 ± 20.9 mm Hg, P ≤ .001) compared to Grp 2. Transient headache was more in Grp 2 (15.8% vs 22.6%, P ≤ .007). Aminophylline use to ward-off the side effects was comparable (9.5% vs 9.9%, P = ns). CONCLUSION: REG-SPECT can be safely performed in CKD non-dialysis patients with excellent tolerability, minimal side effects, and favorable hemodynamic responses compared to control group.
Assuntos
Agonistas do Receptor A2 de Adenosina/efeitos adversos , Nefropatias/fisiopatologia , Imagem de Perfusão do Miocárdio/efeitos adversos , Purinas/efeitos adversos , Pirazóis/efeitos adversos , Tomografia Computadorizada de Emissão de Fóton Único/efeitos adversos , Idoso , Doença Crônica , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Renal , Estudos RetrospectivosRESUMO
The Cardiac Arrhythmia Suppression Trial demonstrated that antiarrhythmic drugs not only fail to prevent sudden cardiac death, but actually increase overall mortality. These findings have been confirmed in additional trials. The "proarrhythmic" effects of most currently available antiarrhythmic drugs makes it essential that we investigate novel strategies for the prevention of sudden cardiac death. Targeted ablation of cardiac sympathetic neurons may become a therapeutic option by reducing sympathetic activity. Thus cholera toxin B subunit (CTB) conjugated to saporin (a ribosomal inactivating protein that binds to and inactivates ribosomes; CTB-SAP) was injected into both stellate ganglia to test the hypothesis that targeted ablation of cardiac sympathetic neurons reduces the susceptibility to ischemia-induced, sustained ventricular tachycardia in conscious rats. Rats were randomly divided into three groups: 1) control (no injection); 2) bilateral stellate ganglia injection of CTB; and 3) bilateral stellate ganglia injection of CTB-SAP. CTB-SAP rats had a reduced susceptibility to ischemia-induced, sustained ventricular tachycardia. Associated with the reduced susceptibility to ventricular arrhythmias were a reduced number of stained neurons in the stellate ganglia and spinal cord (segments T(1)-T(4)), as well as a reduced left ventricular norepinephrine content and sympathetic innervation density. Thus CTB-SAP retrogradely transported from the stellate ganglia is effective at ablating cardiac sympathetic neurons and reducing the susceptibility to ventricular arrhythmias.
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Coração/inervação , Isquemia Miocárdica/fisiopatologia , Neurônios/fisiologia , Sistema Nervoso Simpático/fisiologia , Taquicardia Ventricular/fisiopatologia , Animais , Fibras Autônomas Pré-Ganglionares/efeitos dos fármacos , Fibras Autônomas Pré-Ganglionares/fisiologia , Vias Autônomas/citologia , Vias Autônomas/fisiologia , Pressão Sanguínea/fisiologia , Toxina da Cólera/farmacologia , Estimulação Elétrica , Frequência Cardíaca/fisiologia , Imuno-Histoquímica , Masculino , Infarto do Miocárdio/patologia , Norepinefrina/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas Inativadoras de Ribossomos Tipo 1/farmacologia , Saporinas , Medula Espinal/citologia , Gânglio Estrelado/citologia , Gânglio Estrelado/fisiologia , Sistema Nervoso Simpático/citologiaRESUMO
When the spinal cord is injured at or below thoracic level 5 (T5), cardiovascular control is markedly unbalanced as the heart and blood vessels innervated by upper thoracic segments remain under brain stem control, whereas the vasculature of the lower body is affected by unregulated spinal reflexes. Importantly, the regulation of heart rate and cardiac function is abnormal after spinal cord injury (SCI) at T5 because sympathetic outflow to the heart is increased. An increase in tonic sympathetic outflow may be attributable to multiple mechanisms, such as increases in cardiac sympathetic innervation density, altered morphology of stellate ganglia neurons, and/or structural neuroplasticity of cardiac sympathetic preganglionic neurons (SPNs). Furthermore, these neuroplastic changes associated with SCI may be mediated by nerve growth factor (NGF). NGF is a neurotrophin that supports the survival and differentiation of sympathetic neurons and enhances target innervation. Therefore, we tested the hypothesis that T5 spinal cord transection (T5X) is associated with an increased left ventricular (LV) NGF content, LV sympathetic innervation density, and cardiac SPN arborization. In intact and paraplegic (9 wk posttransection) rats, LV NGF content (ELISA), LV sympathetic innervation density (tyrosine hydroxylase immunohistochemistry), and cardiac SPN arborization (cholera toxin B immunohistochemistry and Sholl Analysis) were determined. Paraplegia, compared with intact, significantly increased LV NGF content, LV sympathetic innervation density, and cardiac SPN arborization. Thus, altered autonomic behavior following SCI is associated with structural neuroplastic modifications.
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Fibras Autônomas Pré-Ganglionares/fisiologia , Coração/inervação , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia , Traumatismos da Medula Espinal/fisiopatologia , Sistema Nervoso Simpático/fisiologia , Animais , Toxina da Cólera/farmacologia , Corantes , Dendritos/fisiologia , Dendritos/ultraestrutura , Ensaio de Imunoadsorção Enzimática , Imuno-Histoquímica , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Fator de Crescimento Neural/metabolismo , Vias Neurais/patologia , Vias Neurais/fisiologia , Neurônios/ultraestrutura , Ratos , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/patologia , Gânglio Estrelado/patologia , Gânglio Estrelado/fisiologia , Tirosina 3-Mono-Oxigenase/metabolismo , Função Ventricular Esquerda/fisiologiaRESUMO
Individuals with spinal cord injuries above thoracic level 6 (T(6)) experience episodic bouts of life-threatening hypertension as part of a condition termed autonomic dysreflexia. The paroxysmal hypertension can be caused by a painful stimulus below the level of the injury. Targeted ablation of mesenteric projecting sympathetic neurons may reduce the severity of autonomic dysreflexia by reducing sympathetic activity. Therefore, cholera toxin B subunit (CTB) conjugated to saporin (SAP; a ribosomal inactivating protein that binds to and inactivates ribosomes) was injected into the celiac ganglion to test the hypothesis that targeted ablation of mesenteric projecting sympathetic neurons reduces the pressor response to pain in conscious, spinal cord-transected rats. Nine Sprague-Dawley male rats underwent a spinal cord transection between thoracic vertebrae 4 and 5. Following recovery (5 wk), all rats were instrumented with a radio telemetry device for recording arterial pressure and bilateral catheters in the gluteus maximus muscles for the infusion of hypertonic saline (hNa(+)Cl(-)). Subsequently, the hemodynamic responses to intramuscular injection of hNa(+)Cl(-) (100 microl and 250 microl, in random order) were determined. Following the experiments in the no celiac ganglia injected condition (NGI), rats received injections of CTB-SAP (n = 5) or CTB (n = 3) into the celiac ganglia. CTB-SAP rats, compared with NGI and CTB rats, had reduced pressor responses to hNa(+)Cl(-). Furthermore, the number of stained neurons in the celiac ganglia and spinal cord (segments T(6)-T(12)), was reduced in CTB-SAP rats. Thus, CTB-SAP retrogradely transported from the celiac ganglia is effective at ablating mesenteric projecting sympathetic neurons and reducing the pressor response to pain in spinal cord-transected rats.
Assuntos
Disreflexia Autonômica , Toxina da Cólera/farmacologia , Gânglios Simpáticos/efeitos dos fármacos , Dor/complicações , Proteínas Inativadoras de Ribossomos Tipo 1/farmacologia , Traumatismos da Medula Espinal/complicações , Simpatectomia Química , Animais , Disreflexia Autonômica/etiologia , Disreflexia Autonômica/fisiopatologia , Disreflexia Autonômica/terapia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Estado de Consciência , Modelos Animais de Doenças , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/fisiologia , Gânglios Simpáticos/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Injeções Intramusculares , Masculino , Dor/fisiopatologia , Ratos , Ratos Sprague-Dawley , Solução Salina Hipertônica/farmacologia , Saporinas , Traumatismos da Medula Espinal/fisiopatologia , Vértebras Torácicas , Fibras Aferentes Viscerais/efeitos dos fármacos , Fibras Aferentes Viscerais/fisiologiaRESUMO
Students generally approach topics in physiology as a series of unrelated phenomena that share few underlying principles. However, if students recognized that the same underlying principles can be used to explain many physiological phenomena, they may gain a more unified understanding of physiological systems. To address this concern, we developed a simple, inexpensive, and easy to build model to demonstrate the underlying principles regarding Starling's Law of the Heart as well as lung and arterial elastic recoil. A model was chosen because models significantly enhance student understanding. Working with models also encourages research-oriented learning and helps our students understand complex ideas. Students are drawn into discussion by the power of learning that is associated with manipulating and thinking about objects. Recognizing that the same underlying principles can be used to explain many physiological phenomena may help students gain a more complete understanding of physiological systems.
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Sistema Cardiovascular , Modelos Biológicos , Fisiologia/educação , Fisiologia/métodos , Educação de Graduação em Medicina/métodos , Humanos , Aprendizagem , Fisiologia/instrumentaçãoRESUMO
AIMS: Patients with chronic kidney disease (CKD) have worse cardiovascular outcomes. The prognostic value of the new pharmacological stressor regadenoson (REG) in patients with varying levels of kidney function is not known (REG-SPECT). Furthermore, the impact of varying levels of kidney dysfunction on cardiac outcomes in patients undergoing REG-SPECT has not been defined. Our objective was to evaluate the prognostic value of regadenoson stress imaging in patients with different levels of kidney dysfunction. METHODS AND RESULTS: We followed 1107 consecutive patients who underwent REG-SPECT for a mean duration of 1.8 ± 0.8 years. CKD was defined as estimated glomerular filtration rate (GFR) 60 mL/min/1.73 m(2). Kaplan-Meier survival analysis was performed to evaluate survival, free of major adverse cardiac events (MACE). CKD patients with GFR <60 (47% male, mean age 70 years) had a higher prevalence of cardiac risk factors and a history of coronary artery disease and were on significantly more cardiac medications (P < 0.001) than those with GFR >60. Patients with GFR <60 were significantly more likely to develop adverse cardiac outcomes including congestive heart failure (CHF) (P = 0.02), cardiac death (P < 0.001), all-cause death (P < 0.001), and MACE (P < 0.001) over the period of follow-up. Cardiac death increased with worsening levels of perfusion defects (SSS) across the entire spectrum of renal function (P < 0.001). GFR <60 was an independent predictor of MACE with a hazard ratio (HR) of 1.49 (95% CI: 1.06-2.08). The presence of transient ischaemic dilation (TID) was associated with an HR of 5.06 (95% CI: 1.43-17.90). CONCLUSIONS: Renal function is a powerful risk predictor in patients undergoing REG-SPECT. REG-SPECT provides robust prognostication across the entire spectrum of renal function.
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Agonistas do Receptor A2 de Adenosina , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/etiologia , Falência Renal Crônica/complicações , Compostos Organofosforados , Compostos de Organotecnécio , Purinas , Pirazóis , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/terapia , Eletrocardiografia , Determinação de Ponto Final , Feminino , Humanos , Falência Renal Crônica/fisiopatologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Prognóstico , Compostos Radiofarmacêuticos , Fatores de Risco , Taxa de SobrevidaRESUMO
Myocardial perfusion imaging is a well-established noninvasive modality for the diagnosis and prognosis of coronary artery disease. The pharmacologic stress agents adenosine and dipyridamole are widely used in imaging studies, but cause undesirable side effects, like atrioventricular block and bronchospasm, due to their nonselective adenosine receptor activation. Furthermore, the mode of administration of these agents as a bolus infusion is less preferred. Regadenoson, an A2A adenosine receptor selective pharmacologic stress agent was approved in 2008 and is widely used instead of adenosine and dipyridamole. This article reviews regadenosons structure, mechanism of action, advantages over adenosine and dipyridamole, and its role in various patient populations undergoing stress perfusion imaging. Emerging applications where regadenoson could be of potential use are also explored.
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Agonistas do Receptor A2 de Adenosina , Doença da Artéria Coronariana/diagnóstico , Imagem de Perfusão do Miocárdio/métodos , Purinas , Pirazóis , Adenosina/farmacologia , Agonistas do Receptor A2 de Adenosina/química , Agonistas do Receptor A2 de Adenosina/farmacologia , Cafeína , Contraindicações , Dipiridamol/farmacologia , Ecocardiografia sob Estresse/métodos , Teste de Esforço/métodos , Reserva Fracionada de Fluxo Miocárdico/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Humanos , Antagonistas de Receptores Purinérgicos P1 , Purinas/química , Purinas/farmacologia , Pirazóis/química , Pirazóis/farmacologia , Vasodilatadores/farmacologiaRESUMO
Regadenoson (REG) is a A2a receptor selective pharmacologic SPECT imaging agent. Its safety in unselected chronic obstructive pulmonary disease (COPD) or asthma (AM) undergoing SPECT imaging has not been well evaluated. We retrospectively identified 228 patients (COPD n = 126 and AM n = 102, Grp 1) undergoing REG SPECT from Jan to Nov 2009 and compared to 1,142 patients without COPD and AM (control, Grp 2). A standard 400 µg REG bolus was used and gated Tc-99 m tetrofosmin SPECT done. Patient demographics, REG SPECT data, side effects, arrhythmia occurrences, and any exacerbation of COPD or AM leading to treatment, hospitalization or death were evaluated. The side effect profile of Grp 1 was also compared to a historical cohort who underwent intravenous dipyridamole thallium-201 imaging and adenosine SPECT. Both groups were comparable with regards to baseline characteristics. There was 0% incidence of clinical exacerbation of COPD or AM after REG. COPD patients had more non-significant arrhythmias (58.3% vs. Grp 2, 43%, P = 0.004). There was 0% incidence of any atrio-ventricular block and only 2 instances of brief supraventricular tachycardia. When compared to the historical cohort of COPD who underwent IV dipyridamole thallium imaging, COPD in Grp 1, had more dyspnea and flushing and when compared to COPD/AM patients who underwent adenosine SPECT, Grp 1 pts had more of flushing and headache (24.9% vs. 2.8%, P = <0.001) but less of bronchospasm (1.3% vs. 6.9%, P = 0.022) and AV block (0% vs. 4.2%, P = 0.014). REG SPECT can be safely performed in COPD and AM population.
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Antagonistas do Receptor A2 de Adenosina , Asma/complicações , Cardiopatias/diagnóstico por imagem , Hemodinâmica/efeitos dos fármacos , Imagem de Perfusão do Miocárdio/métodos , Doença Pulmonar Obstrutiva Crônica/complicações , Purinas , Pirazóis , Tomografia Computadorizada de Emissão de Fóton Único , Vasodilatadores , Antagonistas do Receptor A2 de Adenosina/efeitos adversos , Idoso , Asma/fisiopatologia , Bloqueio Atrioventricular/induzido quimicamente , Bloqueio Atrioventricular/diagnóstico , Broncoconstrição/efeitos dos fármacos , Distribuição de Qui-Quadrado , Feminino , Cardiopatias/complicações , Cardiopatias/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organofosforados , Compostos de Organotecnécio , Valor Preditivo dos Testes , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Purinas/efeitos adversos , Pirazóis/efeitos adversos , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Taquicardia Supraventricular/induzido quimicamente , Taquicardia Supraventricular/diagnóstico , Vasodilatadores/efeitos adversosRESUMO
Cholera toxin B subunit conjugated to saporin (SAP, a ribosomal inactivating protein that binds to and inactivates ribosomes) was injected in both stellate ganglia to evaluate the physiological response to targeted ablation of cardiac sympathetic neurons. Resting cardiac sympathetic activity (cardiac sympathetic tonus), exercise-induced sympathetic activity (heart rate responses to graded exercise), and reflex sympathetic activity (heart rate responses to graded doses of sodium nitroprusside, SNP) were determined in 18 adult conscious Sprague-Dawley male rats. Rats were randomly divided into the following three groups (n = 6/group): 1) control (no injection), 2) bilateral stellate ganglia injection of unconjugated cholera toxin B (CTB), and 3) bilateral stellate ganglia injection of cholera toxin B conjugated to SAP (CTB-SAP). CTB-SAP rats, compared with control and CTB rats, had reduced cardiac sympathetic tonus and reduced heart rate responses to graded exercise and graded doses of SNP. Furthermore, the number of stained neurons in the stellate ganglia and spinal cord (segments T(1)-T(4)) was reduced in CTB-SAP rats. Thus CTB-SAP retrogradely transported from the stellate ganglia is effective at ablating cardiac sympathetic neurons and reducing resting, exercise, and reflex sympathetic activity. Additional studies are required to further characterize the physiological responses to this procedure as well as determine if this new approach is safe and efficacious for the treatment of conditions associated with excess sympathetic activity (e.g., autonomic dysreflexia, hypertension, heart failure, and ventricular arrhythmias).