RESUMEN
BACKGROUND: Periodic measurement of glycated hemoglobin (HbA1c) is highly recommended for people with diabetes to determine whether their blood glucose is adequately controlled. Quality improvement programs initiated by health plans often focus on ensuring that HbA1c is being monitored in members with diabetes. To focus improvement efforts on members with poor blood glucose control, health plans need to know which members have high HbA1c levels. Recent development of home test kits provides another opportunity for health plans to help members measure their HbA1c and to identify members with high levels. METHODS: A sample of members from two health plans who were sent HbA1c self-test kits in January 2000 participated in a telephone interview. To understand why members did or did not use self-test kits sent by their health plans, the survey focused on perceived ease of use, outcomes, and normative beliefs. RESULTS: In the group of 380 members who were interviewed, 170 (45%) used the kit. HbA1c values were > 8 mg/dl in 43%. Among the 170 who used the kit, 160 said that they would use the kit. Their most common reason for using the kit was to find out how well their blood glucose was being controlled (48%). Convenience (12%) was the next most frequent reason for using the kit. Among the 210 members who did not use the kit, 81 members said that they would not or were not sure if they would when interviewed. Their most frequent reason for not using the kit was duplication of tests done by physicians (34%). Others were too busy (12%), wanted to talk with their physician (11%), or had difficulty using the kit (11%). CONCLUSIONS: Because the majority of health plan members did not use the kit and the majority who did use the kit had HbA1c levels < 8 mg/dl, sending home test kits to members did not result in a high yield of members with elevated HbA1c levels. Physicians' support for use of the kits and efforts to make kits easier to use might increase use. Efforts to avoid duplication of physicians' measurements could make this strategy to identify members with poorly controlled levels of blood glucose more cost-effective, although health plans would not know which monitored members might benefit most from programs to improve care of diabetes.
Asunto(s)
Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/prevención & control , Hemoglobina Glucada/metabolismo , Sistemas Prepagos de Salud/normas , Indicadores de Calidad de la Atención de Salud , Juego de Reactivos para Diagnóstico/estadística & datos numéricos , Gestión de la Calidad Total/organización & administración , Actitud Frente a la Salud , Diabetes Mellitus Tipo 1/psicología , Conocimientos, Actitudes y Práctica en Salud , Humanos , Minnesota , Motivación , Evaluación de Programas y Proyectos de Salud/métodos , Muestreo , Autocuidado/métodos , Autocuidado/psicología , Autocuidado/normas , Encuestas y CuestionariosRESUMEN
CONTEXT: Many Medicare beneficiaries enroll in managed care health plans to obtain outpatient drug benefits. Increasing pharmaceutical utilization and costs and decreasing drug benefits increase the likelihood that medication use by such enrollees will exceed drug benefits, which may lead to health plan disenrollment. OBJECTIVE: To test the hypothesis that exhaustion of managed care drug benefits by Medicare beneficiaries is associated with disenrollment from the health plan. DESIGN: Retrospective cohort study followed up for 1 year (1998) using an enrollment/claims database. SETTING: Four geographically diverse network-model health plans that had annual drug benefits of $300, $500, $600, or $1000. PARTICIPANTS: A total of 61,412 elderly Medicare beneficiaries. MAIN OUTCOME MEASURE: Voluntary disenrollment from health plans by members who did or did not exhaust their drug benefits. RESULTS: The likelihood of exhausting 1998 drug benefits ranged from 17% to 25% across health plans (P<.001). The relative hazards of disenrollment from the 4 plans when drug benefits had been exhausted were 2.5 (95% confidence interval [CI], 2.3-2.8), 1.9 (95% CI, 1.7-2.1), 2.7 (95% CI, 2.0-3.6), and 2.1 (95% CI, 1.9-2.4). Statistical adjustments for age, sex, prior enrollment, hospital admissions, physician visits, and county of residence did not alter these estimates. CONCLUSIONS: Exhaustion of drug benefits was associated with a significant increase in the likelihood of disenrollment of Medicare beneficiaries. This finding arouses concern that Medicare beneficiaries must change plans to have financial access to medications, which can lead to discontinuity in care and diversion of resources from care to administrative matters. Policymakers should strive to avoid fragmented systems of providing drug benefits.
Asunto(s)
Prescripciones de Medicamentos/economía , Programas Controlados de Atención en Salud/economía , Medicare/economía , Costos de los Medicamentos , Prescripciones de Medicamentos/estadística & datos numéricos , Programas Controlados de Atención en Salud/estadística & datos numéricos , Medicare/estadística & datos numéricos , Formulación de Políticas , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Estados UnidosAsunto(s)
Planificación en Salud Comunitaria , Manejo de la Enfermedad , Insuficiencia Cardíaca , Evaluación de Programas y Proyectos de Salud , Anciano , Análisis Costo-Beneficio , Costos de la Atención en Salud , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/economía , Humanos , Persona de Mediana Edad , Admisión del Paciente , Educación del Paciente como Asunto , Ensayos Clínicos Controlados Aleatorios como AsuntoAsunto(s)
Programas Controlados de Atención en Salud/estadística & datos numéricos , Medicaid/estadística & datos numéricos , Satisfacción del Paciente/estadística & datos numéricos , Adulto , Recolección de Datos , Atención a la Salud/normas , Estudios de Evaluación como Asunto , Femenino , Accesibilidad a los Servicios de Salud/economía , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Necesidades y Demandas de Servicios de Salud/estadística & datos numéricos , Humanos , Programas Controlados de Atención en Salud/normas , Medicaid/normas , Estados UnidosRESUMEN
CONTEXT: Emergency department services may be used more appropriately if laypeople's knowledge of managing minor medical problems could be enhanced, especially since Medicaid applies a "prudent layperson" standard for providing access to emergency care. OBJECTIVE: To investigate the effect of mailing a booklet, First Look, that informed Medicaid beneficiaries about care of common nonurgent conditions and encouraged use of alternatives to emergency care including care by office-based physicians, telephonic nursing assistance, and self-care. STUDY DESIGN: A randomized, parallel group study. PATIENTS AND METHODS: Administrative data from 2 health plans serving urban Medicaid populations were used to identify households with a history of emergency department utilization (n = 3101 and n = 3822). Within each health plan, households were randomly assigned to receive First Look. The number of emergency department visits during 6.5 months of follow-up was the primary study endpoint. RESULTS: Compared with controls, 1% fewer members of households that were mailed First Look visited an emergency department in each health plan (23% versus 24% in Plan A; 27% versus 28% in Plan B). The 95% confidence intervals on the observed differences were -3% to 1% and -4% to 1% in Plans A and B, respectively. The proportion of emergency department visits for conditions discussed in First Look was not significantly reduced in households that were mailed the booklet (62% versus 60% in Plan A and 51% versus 48% in Plan B). CONCLUSION: Mailing First Look to Medicaid beneficiaries did not have a significant effect on use of emergency departments. Medicaid programs need to evaluate other, perhaps more multifaceted, interventions to promote appropriate use of emergency departments.
Asunto(s)
Servicio de Urgencia en Hospital/estadística & datos numéricos , Programas Controlados de Atención en Salud/organización & administración , Medicaid/organización & administración , Visita a Consultorio Médico/estadística & datos numéricos , Educación del Paciente como Asunto/métodos , Adolescente , Adulto , Anciano , Niño , Enfermedad/clasificación , Accesibilidad a los Servicios de Salud , Investigación sobre Servicios de Salud , Humanos , Programas Controlados de Atención en Salud/estadística & datos numéricos , Medicaid/estadística & datos numéricos , Persona de Mediana Edad , Folletos , Estados UnidosAsunto(s)
Antagonistas Adrenérgicos/uso terapéutico , Carbazoles/uso terapéutico , Ensayos Clínicos como Asunto/métodos , Insuficiencia Cardíaca/tratamiento farmacológico , Propanolaminas/uso terapéutico , Índice de Severidad de la Enfermedad , Antagonistas Adrenérgicos/efectos adversos , Carbazoles/efectos adversos , Carvedilol , Mareo/inducido químicamente , Insuficiencia Cardíaca/clasificación , Insuficiencia Cardíaca/psicología , Humanos , Variaciones Dependientes del Observador , Satisfacción del Paciente , Pacientes/psicología , Propanolaminas/efectos adversos , Calidad de Vida , Resultado del TratamientoRESUMEN
Patients with syncope underwent head-up tilt testing at 60 degrees and 80 degrees followed by edrophonium or isoproterenol challenge when indicated. The 80 degrees tilt protocol and edrophonium provocation were found to be as effective or more effective in eliciting neurally mediated syncope in susceptible patients.
Asunto(s)
Cardiotónicos , Inhibidores de la Colinesterasa , Edrofonio , Isoproterenol , Síncope Vasovagal/diagnóstico , Pruebas de Mesa Inclinada/métodos , Adulto , Anciano , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Síncope Vasovagal/inducido químicamenteRESUMEN
BACKGROUND: Dynamic cardiomyoplasty is an evolving treatment for heart failure that uses an electrically stimulated latissimus dorsi muscle wrapped around the heart to improve cardiac function. Preoperative patient characteristics and deaths after cardiomyoplasty have been recorded during the past 5 years in a cumulative database representing worldwide experience of 42 medical centers. METHODS: Statistical models of hazards (monthly death rates) were used to identify risk factors for transiently increased risk of cardiovascular mortality within 2 months after cardiomyoplasty. RESULTS: Actuarial survival (n = 261) was 88%, 80%, and 76% at 1, 3, and 6 months after cardiomyoplasty, respectively. The peak hazard of 6% dying per month occurred during the first month after the surgical procedure. Lower ejection fraction, increased number of major coronary arteries with > or = 70% stenotic lesions, and lower chronotropic responses during exercise were independent risk factors for the transient increase in early cardiovascular mortality. Early risk of cardiovascular mortality was significantly reduced as centers gained experience with more than 3 patients. CONCLUSION: Early survival after cardiomyoplasty has improved with experience and might be reduced further by preoperative assessments that identify patients at highest risk.
Asunto(s)
Cardiomioplastia/mortalidad , Análisis Actuarial , Causas de Muerte , Enfermedad Coronaria/epidemiología , Bases de Datos como Asunto , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/cirugía , Frecuencia Cardíaca/fisiología , Humanos , Funciones de Verosimilitud , Masculino , Persona de Mediana Edad , Análisis Multivariante , Consumo de Oxígeno/fisiología , Esfuerzo Físico/fisiología , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Volumen Sistólico/fisiología , Tasa de Supervivencia , Factores de Tiempo , Función Ventricular Izquierda/fisiologíaRESUMEN
BACKGROUND: Peripheral vasodilatation in response to muscarinic agonists has been shown to be subnormal during heart failure. However, a more recent study suggested that the abnormal muscarinic-induced vasodilatation was not due to abnormal nitric oxide synthase activity. This study was designed to show that nitric oxide synthase contributes to desmopressin-induced forearm vasodilatation and to determine whether vasodilatation mediated by nitric oxide synthase is abnormal during heart failure. METHODS: Desmopressin (10, 50, and 100 ng/min) was infused into the brachial artery of 10 healthy subjects and eight patients with heart failure, and forearm blood flow was measured by venous occlusion plethsymography. Desmopressin responses were then recorded during inhibition of nitric oxide synthase with L-monomethylarginine or after aspirin. RESULTS: In healthy subjects, desmopressin caused a significant (p < 0.001) dose-dependent increase in forearm blood flow of 0.9 +/- 0.6, 4.0 +/- 2.6, and 7.9 +/- 2.6 ml/min/dl, respectively. Desmopressin responses in heart failure of 0.8 +/- 0.6, 1.7 +/- 1.4, and 3.1 +/- 1.0 ml/min/dl were significantly less (p < 0.001) than normal. L-Monomethylarginine reduced desmopressin responses in normal subjects (p < 0.01), and this inhibitory effect was significantly (p < 0.01) greater than in patients with heart failure. Aspirin did not affect desmopressin-induced vasodilatation. CONCLUSION: Nitric oxide synthase contributes to desmopressin-induced forearm vasodilatation. In response to desmopressin, patients with heart failure have subnormal vasodilatation mediated through nitric oxide synthase.
Asunto(s)
Desamino Arginina Vasopresina/farmacología , Antebrazo/irrigación sanguínea , Insuficiencia Cardíaca/fisiopatología , Óxido Nítrico Sintasa/metabolismo , Fármacos Renales/farmacología , Vasodilatación/efectos de los fármacos , Adulto , Aspirina/farmacología , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Femenino , Insuficiencia Cardíaca/enzimología , Humanos , Masculino , Persona de Mediana Edad , Óxido Nítrico Sintasa/antagonistas & inhibidores , Pletismografía , omega-N-Metilarginina/farmacologíaRESUMEN
Many studies have investigated the pathophysiologic contributions of abnormalities in the endothelial nitric oxide pathway to the heightened vasoconstrictor tone that is characteristic of the clinical syndrome of heart failure. The most consistent abnormality is a reduced vasodilator response to muscarinic stimulation with either acetylcholine or methacholine, a finding which has been identified in several animal models of heart failure as well as in forearm and leg resistance vessels in patients with heart failure. More recent studies with desmopressin, a vasopressin 2 receptor agonist that stimulates nitric oxide production independent of the muscarinic receptor, have demonstrated that the abnormality in endothelium-dependent vasodilation was not limited to the muscarinic pathway. At present, the mechanisms of the defect in the endothelial nitric oxide pathway are unknown. But, they appear not to be directly related to sympathetic stimulation. Finally, studies using transplant recipients have demonstrated that this defect is reversible. In addition, a pilot study has demonstrated that supplemental oral L-arginine, the precursor for nitric oxide, has beneficial effects on forearm blood flow responses to exercise, arterial compliance nad functional status as assessed by increased distances during a 6-minute walk test and lower scores on the Living with Heart Failure Questionnaire. These studies suggest that the endothelial nitric oxide pathway may be a target for therapeutic interventions in heart failure.
Asunto(s)
Vasos Sanguíneos/fisiopatología , Endotelio Vascular/metabolismo , Insuficiencia Cardíaca/fisiopatología , Óxido Nítrico/metabolismo , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/metabolismo , HumanosRESUMEN
BACKGROUND: Patients with heart failure have reduced peripheral blood flow at rest, during exercise, and in response to endothelium-dependent vasodilators. Nitric oxide formed from L-arginine metabolism in endothelial cells contributes to regulation of blood flow under these conditions. A randomized, double-blind crossover study design was used to determine whether supplemental oral L-arginine can augment peripheral blood flow and improve functional status in patients with moderate to severe heart failure. METHODS AND RESULTS: Fifteen subjects were given 6 weeks of oral L-arginine hydrochloride (5.6 to 12.6 g/d) and 6 weeks of matched placebo capsules in random sequence. Compared with placebo, supplemental oral L-arginine significantly increased forearm blood flow during forearm exercise, on average from 5.1 +/- 2.8 to 6.6 +/- 3.4 mL. min-1. dL-1 (P < .05). Furthermore, functional status was significantly better on L-arginine compared with placebo, as indicated by increased distances during a 6-minute walk test (390 +/- 91 versus 422 +/- 86 m, P < .05) and lower scores on the Living With Heart Failure questionnaire (55 +/- 28 versus 42 +/- 26, P < .05). Oral L-arginine also improved arterial compliance from 1.99 +/- 0.38 to 2.36 +/- 0.30 mL/mm Hg (P < .001) and reduced circulating levels of endothelin from 1.9 +/- 1.1 to 1.5 +/- 1.1 pmol/L (P < .05). CONCLUSIONS: Supplemental oral L-arginine had beneficial effects in patients with heart failure. Further studies are needed to confirm the therapeutic potential of supplemental oral L-arginine and to identify mechanisms of action in patients with heart failure.
Asunto(s)
Arginina/uso terapéutico , Gasto Cardíaco Bajo/tratamiento farmacológico , Administración Oral , Adulto , Arginina/efectos adversos , Arginina/sangre , Gasto Cardíaco Bajo/fisiopatología , Estudios Cruzados , Método Doble Ciego , Femenino , Antebrazo/irrigación sanguínea , Antebrazo/fisiología , Humanos , Masculino , Persona de Mediana Edad , Óxido Nítrico Sintasa/antagonistas & inhibidores , Esfuerzo Físico , Calidad de Vida , Flujo Sanguíneo Regional/efectos de los fármacos , Vasoconstricción , omega-N-Metilarginina/farmacologíaAsunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/economía , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Captopril/economía , Captopril/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/economía , Análisis Costo-Beneficio , Humanos , Persona de Mediana Edad , Infarto del Miocardio/mortalidadRESUMEN
Treatments for heart failure, such as flosequinan, may have opposite effects on survival and quality of life. The Living With Heart Failure questionnaire was used to examine patients' willingness to risk drug-induced death for improved quality of life. In addition, patients' opinions concerning worthwhile improvements in the Living With Heart Failure score were described to provide a perspective for interpreting the results of clinical trials. A sample of 101 patients with heart failure were interviewed in cardiology clinics. Median (interquartile range) Living With Heart Failure questionnaire score were 54 (interquartile range, 34-74). Forty-nine percent of the patients would accept a1 in 100 risk of drug-induced death if the corresponding improvements in the Living With Heart Failure score were 20 (interquartile range, 10-25). In contrast, 40% were willing to accept a risk of drug-induced death equal to or greater than 5 in 100 for significantly (P < .001) smaller score improvements of 5 (interquartile range, 5-10). Living With Heart Failure scores that increase with perceived limitations secondary to heart failure tended to be higher, although not significantly (P = .22), in the subgroup that accepted greater risk of drug-induced death: 45 (interquartile range, 34-73) versus 58 (interquartile range, 42-77). A score improvement of 5, which has been commonly observed in clinical trials, would be sufficient reason for 72% of patients to take a medication that did not have side effects or significant costs. A 5-point improvement was less acceptable when costs or risks were associated with therapy: 52% would pay $60 per month and 38% would risk drug-induced death. These data suggest that many patients with heart failure would accept some risk of drug-induced death for improved quality of life. A 5-point improvement in the Living With Heart Failure score may be clinically significant depending on costs and adverse effects. The Living With Heart Failure questionnaire can be used to help patients evaluate the benefits versus risks of medical interventions.
Asunto(s)
Actitud Frente a la Salud , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/mortalidad , Calidad de Vida , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Aceptación de la Atención de Salud , Medición de Riesgo , Encuestas y CuestionariosRESUMEN
The physiologic effects of ACE inhibitors often result in symptomatic relief in patients with heart failure and prevention of episodes of decompensated heart failure and ischemic events in some patients. It is important to determine if these effects, in conjunction with all other aspects of ACE inhibitor treatment, favorably alter quality of life as judged by the patients. Questionnaires that allow patients to rate the effects of heart failure and treatments on their lives have been used in some controlled clinical trials. The available data suggest that symptomatic patients have a limited quality of life than can be improved by ACE inhibitors. In addition, it seems reasonable to assume that avoidance of episodes of decompensated heart failure and ischemic events would have some yet-to-be-defined effect on maintenance of patients' quality of life. However, the proportion of patients who experience these preventive effects during a few years of follow-up may be too small to document an effect on quality of life in the overall population with mild heart failure or asymptomatic left ventricular dysfunction. The high mortality rate associated with heart failure makes it difficult to study quality of life over prolonged periods of time. One investigation [18] has suggested that quality of life progressively deteriorates in survivors over 2 to 4 years despite administration of ACE inhibitors. This finding is consistent with the natural history of heart failure, although there are insufficient placebo-controlled data to determine whether ACE inhibitors can delay the long-term progressive decline in quality of life.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Calidad de Vida , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Ensayos Clínicos como Asunto , Insuficiencia Cardíaca/fisiopatología , HumanosRESUMEN
Studies of the mechanism of death in heart failure are dependent on the reliability and validity of classification of deaths as pump failure or arrhythmias (sudden). Two recent trials differed in that the Vasodilator Heart Failure Trial II (V-HeFT II) reported a higher incidence of sudden death than the Studies of Left Ventricular Dysfunction Treatment Trial (SOLVD) and an effect of enalapril on sudden death was not observed in SOLVD. A similar classification system was used in the two studies, but deaths in V-HeFT were classified centrally from a narrative summary, whereas deaths in SOLVD were classified in the field by individual investigators. To examine reliability, 10 narratives used to classify V-HeFT deaths were independently classified by 21 SOLVD investigators. In only 5 of 10 cases did 75% of SOLVD investigators agree with the V-HeFT classification. In no deaths were all SOLVD investigators in agreement on classification. Although V-HeFT classified 5 of 10 cases as sudden death, 16 of 21 SOLVD investigators classified less than 5 deaths as sudden and 1 classified none as sudden. The kappa statistic for interobserver agreement of 0.22 (P < or = .01) indicated interobserver agreement only slightly better than chance agreement. Therefore, the incidence of sudden death in heart failure is critically dependent on the bias of the investigator. Central classification will minimize inconsistencies, but it does not solve the problem that the mechanism of death is difficult to assign. Total mortality may be the only reliable endpoint in heart failure trials.
Asunto(s)
Muerte Súbita Cardíaca/etiología , Insuficiencia Cardíaca/mortalidad , Adulto , Ensayos Clínicos como Asunto , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Variaciones Dependientes del ObservadorRESUMEN
The purpose of this investigation was to determine whether vasodilator responses are attenuated and whether vasoconstriction is augmented with age in resistance vessels in the hindlimb of the dog. We examined blood flow (FAF) and pressure (FAP) responses in the femoral arterial system in older (109 +/- 8-mo-old) and younger mature (31 +/- 3-mo-old) female beagles during pentobarbital anesthesia. Vasodilator responses were evaluated during the intra-arterial administration of acetylcholine (ACh), which produces endothelium-dependent vasodilation, and albuterol, which mediates relaxation in vascular smooth muscle via beta-adrenoceptors. The vasoconstrictor response to phenylephrine (PE), an alpha-adrenergic agonist, was also examined. ACh and albuterol each induced dose-dependent vasodilation in the older and in the younger dogs. Resultant changes in neither FAF nor FAP were affected by age in response to either of these vasodilator substances. Likewise, reductions in femoral vascular resistance (FVR) in response to ACh or to albuterol were not age dependent. Vasodilation following induced hindlimb ischemia resulted in similar increases in FAF in both groups, but produced a greater reduction in FAP in older vs. younger dogs (P = 0.05). Similarly, FVR decreased more in the older beagles (P = 0.02). Vasoconstriction mediated by PE resulted in similar reductions in FAF in both age groups, but the increase in FAP was less at several PE doses in older vs. younger dogs (P < 0.05). However, increases in FVR in response to PE were not statistically different in the younger and older beagles.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Envejecimiento/fisiología , Presión Sanguínea/fisiología , Arteria Femoral/fisiología , Músculo Liso Vascular/fisiología , Músculos/irrigación sanguínea , Acetilcolina/farmacología , Albuterol/farmacología , Animales , Aorta/efectos de los fármacos , Aorta/crecimiento & desarrollo , Aorta/fisiología , Presión Sanguínea/efectos de los fármacos , Perros , Relación Dosis-Respuesta a Droga , Femenino , Arteria Femoral/efectos de los fármacos , Arteria Femoral/crecimiento & desarrollo , Miembro Posterior/irrigación sanguínea , Isquemia , Músculo Liso Vascular/irrigación sanguínea , Músculo Liso Vascular/efectos de los fármacos , Norepinefrina/sangre , Fenilefrina/farmacología , Flujo Sanguíneo Regional/efectos de los fármacos , Flujo Sanguíneo Regional/fisiología , Renina/sangre , Resistencia Vascular/efectos de los fármacos , Resistencia Vascular/fisiología , Vasoconstricción , VasodilataciónRESUMEN
Patients with heart failure have reduced forearm vasodilator responses when endothelial cell nitric oxide production is stimulated by muscarinic agonists. The aim of this study was to determine if activity of the nitric oxide pathway was also abnormal under basal conditions. Forearm blood flow (FBF) was measured with strain-gauge plethysmography in response to the intraarterial infusion of a subsystemic dose range of L-N-monomethylarginine (L-NMMA), a competitive inhibitor of nitric oxide synthase. In 18 normal subjects, the baseline FBF of 3.6 +/- 1.4 was decreased by 0.3 +/- 0.5 (p < 0.01), 1.0 +/- 0.7 (p < 0.01), 1.4 +/- 0.9 (p < 0.01), and 1.3 +/- 1.3 (p < 0.01) ml/min/100 ml forearm volume during infusions of 1, 4, 8, and 16 mumol/min of L-NMMA, respectively. In 10 patients with heart failure, the baseline FBF of 2.6 +/- 0.9 was decreased by 0.4 +/- 0.5 (p < 0.05), 0.4 +/- 0.5 (p < 0.05), 0.9 +/- 0.8 (p < 0.01), and 0.9 +/- 0.7 (p < 0.01) ml/min/100 ml forearm volume with the 4 doses of L-NMMA, respectively. There was no difference in the L-NMMA response between the 2 groups in terms of absolute flow, percent change, or with analysis of covariance to adjust for different baselines. The stable end products of nitric oxide (nitrite and nitrate) were measured in the forearm venous effluent. Nitrite and nitrate levels at baseline were not reduced in patients with heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Arginina/análogos & derivados , Antebrazo/irrigación sanguínea , Insuficiencia Cardíaca/fisiopatología , Óxido Nítrico/fisiología , Resistencia Vascular/efectos de los fármacos , Adulto , Anciano , Arginina/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Óxido Nítrico/antagonistas & inhibidores , Pletismografía/métodos , Flujo Sanguíneo Regional/efectos de los fármacos , omega-N-MetilargininaRESUMEN
Endothelium-dependent vasodilation of peripheral resistance vessels is abnormal in patients with heart failure, but there are little in vivo data on endothelium-dependent vasodilation of peripheral conduit vessels. This study assessed endothelium-dependent vasodilation of forearm conduit and resistance vessels in normal subjects and patients with heart failure. The effects of intraarterial endothelium-dependent and endothelium-independent vasodilators on both forearm conduit (brachial artery) and resistance vessels were assessed in 9 patients with New York Heart Association class II-III heart failure and 11 normal subjects of similar age. Brachial artery diameter was measured by two-dimensional, moderate-frequency (8 MHz) ultrasound, and forearm blood flow was measured by strain gauge plethysmography. The endothelium-dependent vasodilator, methacholine (0.3 and 1.5 micrograms/min), increased brachial artery diameter by 7.6 +/- 1.3% and 12.2 +/- 1.5% in normal subjects as compared to 6.9 +/- 2.1% and 10.4 +/- 2.4% in patients with heart failure (P = NS, normal vs heart failure). The endothelium-independent vasodilator, nitroglycerin (0.15 microgram), also produced similar increases in brachial artery diameter in the two groups (8.2 +/- 1.3% in normal subjects vs 11.1 +/- 1.4% in patients with heart failure, P = NS). In contrast, forearm blood flow responses to methacholine were significantly (P < .05) greater in normal subjects (4.1 +/- 0.5 and 9.2 +/- 1.4 mL/min/100 mL forearm volume) than in patients with heart failure (2.0 +/- 0.8 and 5.1 +/- 1.3 mL/min/100 mL forearm volume). Forearm blood flow responses to the endothelium-independent vasodilator, sodium nitroprusside, were similar between the two groups. This study suggests that endothelium-dependent and endothelium-independent vasodilation of the brachial artery is not impaired in patients with class II-III heart failure. This finding contrasts with abnormal endothelium-dependent vasodilation of forearm resistance vessels. These data suggest that there are regional differences in endothelial function in patients with heart failure.
Asunto(s)
Arteria Braquial/fisiopatología , Endotelio Vascular/fisiopatología , Insuficiencia Cardíaca/fisiopatología , Vasodilatación/fisiología , Adulto , Anciano , Femenino , Antebrazo/irrigación sanguínea , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: The aim was to test the hypothesis that in normal humans angiotensin II would stimulate local release of noradrenaline under basal conditions or during a sympathetic stimulus provided by lower body negative pressure (LBNP). METHODS: Nine healthy volunteers received intra-arterial infusions of angiotensin II, 5 ng.min-1, into the non-dominant forearm. Forearm blood flow (strain gauge plethysmography) and regional noradrenaline spillover (using the tracer methodology of Esler) were measured during angiotensin II alone, LBNP alone, and LBNP plus angiotensin II. RESULTS: Angiotensin II and LBNP decreased forearm blood flow comparably: from 3.1(SD 1.5) to 2.4 (0.9) ml.100 g-1.min-1 during angiotensin II, p < 0.05; and from 3.3(1.5) to 2.5(1.0) ml.100 g-1.min-1 during LBNP, p < 0.05 (p = NS, A-II v LBNP). Angiotensin II had no effect on forearm venous noradrenaline or regional noradrenaline spillover. LBNP increased venous noradrenaline outflow from the forearm, from 1.6(0.40) to 2.1(0.6) nmol.min-1 (p < 0.05), while regional noradrenaline spillover tended to increase, rising from 1.5(0.8) to 2.0(1.0) nmol.100 ml-1.min-1. Angiotensin II did not enhance forearm blood flow or noradrenaline responses to LBNP. CONCLUSIONS: In the human forearm, mildly vasoconstrictor infusions of angiotensin II do not increase local release of noradrenaline, either alone or during mild LBNP. At least under these conditions, angiotensin II would not appear to be a potent influence on local sympathetic activity.