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Students are challenged in transitioning from acquiring knowledge and understanding through reading textbooks to their learning to select, read, evaluate, and synthesize the primary literature. A customary approach to teaching this transition to beginning graduate students is for a faculty member to assign "readings" from the recent literature that promise to become key publications; such assignments generally underscore recent, novel scientific content. We advocate here an alternative approach for coaching students very early in their training: first, to read, analyze, and discuss a paper that highlights critically important features of effective and valid experimental design; and, second, to study a paper that can be shown historically to have fundamentally changed the way in which physiological function is understood. We consider as an example of the first goal a study that purports to demonstrate a principle of thermoregulation, but that interaction between students and instructor reveals the study's lack of an essential control. The second goal requires sufficient time for the publication to concretely validate its contribution(s). The purpose is to identify those essential properties of the selected paper that contributed to its having become a truly exemplary study. We present a 1957 paper by Dr. A. C. Burton ( Am Heart J 54: 801-810, 1957) as an illustration and analyze the study with respect to those attributes that contributed to its lasting importance. These alternative approaches to introduce inexperienced students to the original literature can produce critical insight into the process and can help students inculcate essential practices, guiding them to more productive careers.
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Educación de Postgrado/métodos , Fisiología/educación , Lectura , Ciencia en la Literatura , HumanosRESUMEN
OBJECTIVES: To describe self-reported stress level, cognitive appraisal and coping among patients with heart failure (HF), and to examine the association of cognitive appraisal and coping strategies with event-free survival. METHODS: This was a prospective, longitudinal, descriptive study of patients with chronic HF. Assessment of stress, cognitive appraisal, and coping was performed using Perceived Stress Scale, Cognitive Appraisal Health Scale, and Brief COPE scale, respectively. The event-free survival was defined as cardiac rehospitalization and all-cause death. RESULTS: A total of 88 HF patients (mean age 58 ± 13 years and 53.4% male) participated. Linear and cox regression showed that harm/loss cognitive appraisal was associated with avoidant emotional coping (ß = -0.28; 95% CI: -0.21 - 0.02; p = 0.02) and event free survival (HR = 0.53; 95% CI: 0.28 - 1.02; p = 0.05). CONCLUSIONS: The cognitive appraisal of the stressors related to HF may lead to negative coping strategies that are associated with worse event-free survival.
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Adaptación Psicológica , Insuficiencia Cardíaca , Supervivencia sin Progresión , Estrés Psicológico , Adulto , Anciano , Femenino , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/psicología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Pruebas PsicológicasAsunto(s)
Barorreflejo , Frecuencia Cardíaca , Presión Sanguínea , Humanos , Traumatismos de la Médula EspinalRESUMEN
OBJECTIVE: To evaluate the effects of pressure threshold respiratory training (RT) on heart rate variability and baroreflex sensitivity in persons with chronic spinal cord injury (SCI). DESIGN: Before-after intervention case-controlled clinical study. SETTING: SCI research center and outpatient rehabilitation unit. PARTICIPANTS: Participants (N=44) consisted of persons with chronic SCI ranging from C2 to T11 who participated in RT (n=24), and untrained control subjects with chronic SCI ranging from C2 to T9 (n=20). INTERVENTIONS: A total of 21±2 RT sessions performed 5 days a week during a 4-week period using a combination of pressure threshold inspiratory and expiratory devices. MAIN OUTCOME MEASURES: Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and beat-to-beat arterial blood pressure and heart rate changes during the 5-second-long maximum expiratory pressure maneuver (5s MEP) and the sit-up orthostatic stress test, acquired before and after the RT program. RESULTS: In contrast to the untrained controls, individuals in the RT group experienced significantly increased FVC and FEV1 (both P<.01) in association with improved quality of sleep, cough, and speech. Sympathetically (phase II) and parasympathetically (phase IV) mediated baroreflex sensitivity both significantly (P<.05) increased during the 5s MEP. During the orthostatic stress test, improved autonomic control over heart rate was associated with significantly increased sympathetic and parasympathetic modulation (low- and high-frequency change: P<.01 and P<.05, respectively). CONCLUSIONS: Inspiratory-expiratory pressure threshold RT is a promising technique to positively affect both respiratory and cardiovascular dysregulation observed in persons with chronic SCI.
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Barorreflejo/fisiología , Frecuencia Cardíaca/fisiología , Terapia Respiratoria/métodos , Traumatismos de la Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/terapia , Adulto , Sistema Nervioso Autónomo/fisiopatología , Estudios de Casos y Controles , Enfermedad Crónica , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Persona de Mediana Edad , Mecánica Respiratoria/fisiología , Resultado del Tratamiento , Capacidad Vital , Adulto JovenRESUMEN
Key Points Summary We report how blood pressure, cardiac output and vascular resistance are related to height, weight, body surface area (BSA), and body mass index (BMI) in healthy young adults at supine rest and standing.Much inter-subject variability in young adult's blood pressure, currently attributed to health status, may actually result from inter-individual body size differences.Each cardiovascular variable is linearly related to height, weight and/or BSA (more than to BMI).When supine, cardiac output is positively related, while vascular resistance is negatively related, to body size. Upon standing, the change in vascular resistance is positively related to size.The height/weight relationships of cardiac output and vascular resistance to body size are responsible for blood pressure relationships to body size.These basic components of blood pressure could help distinguish normal from abnormal blood pressures in young adults by providing a more effective scaling mechanism. Introduction: Effects of body size on inter-subject blood pressure (BP) variability are not well established in adults. We hypothesized that relationships linking stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR) with body size would account for a significant fraction of inter-subject BP variability. Methods: Thirty-four young, healthy adults (19 men, 15 women) participated in 38 stand tests during which brachial artery BP, heart rate, SV, CO, TPR, and indexes of body size were measured/calculated. Results: Steady state diastolic arterial BP was not significantly correlated with any index of body size when subjects were supine. However, upon standing, the more the subject weighed, or the taller s/he was, the greater the increase in diastolic pressure. Systolic pressure strongly correlated with body weight and height both supine and standing. Diastolic and systolic BP were more strongly related to height, weight and body surface area than to body mass index. When supine: lack of correlation between diastolic pressure and body size, resulted from the combination of positive SV correlation and negative TPR correlation with body size. The positive systolic pressure vs. body size relationship resulted from a positive SV vs. height relationship. In response to standing: the positive diastolic blood pressure vs. body size relationship resulted from the standing-induced, positive increase in TPR vs. body size relationship. The relationships between body weight or height with SV and TPR contribute new insight into mechanisms of BP regulation that may aid in the prediction of health in young adults by providing a more effective way to scale BP with body size.
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Pulmonary and cardiovascular dysfunctions are leading causes of morbidity and mortality in patients with chronic Spinal Cord Injury (SCI). Impaired respiratory motor function and decreased Baroreflex Sensitivity (BS) are predictors for the development of cardiopulmonary disease. This observational case-controlled clinical study was undertaken to investigate if respiratory motor control deficits in individuals with SCI affect their ability to perform the Valsalva maneuver, and to determine if a sustained Maximum Expiratory Pressure (MEP) effort can serve as an acceptable maneuver for determination of the BS in the event that the Valsalva maneuver cannot be performed. The BS outcomes (ms/mmHg) were obtained using continuous beat-to-beat arterial blood pressure (BP) and heart rate (HR) recordings during Valsalva or MEP maneuvers in thirty nine individuals with chronic C3-T12 SCI. Twenty one participants (54%) reported signs of intolerance during the Valsalva maneuver and only 15 individuals (39%) were able to complete this task. Cervical level of injury was a significant risk factor (p=0.001) for failing to complete the Valsalva maneuver, and motor-complete injury was a significant risk factor for symptoms of intolerance (p=0.04). Twenty eight participants (72%) were able to perform the MEP maneuver; the other 11 participants failed to exceed the standard airway pressure threshold of 27cm H2O. Neither level nor completeness of injury were significant risk factors for failure of MEP maneuver. When the required airway pressure was sustained, there were no significant differences between BS outcomes obtained during Valsalva and MEP maneuvers. The results of this study indicate that individuals with high-level and motor-complete SCI are at increased risk of not completing the Valsalva maneuver and that baroreflex-mediated responses can be evaluated by using sustained MEP maneuver when the Valsalva maneuver cannot be performed.
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Barorreflejo/fisiología , Traumatismos de la Médula Espinal/fisiopatología , Maniobra de Valsalva/fisiología , Adolescente , Adulto , Presión Sanguínea/fisiología , Enfermedad Crónica , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Modelos Lineales , Modelos Logísticos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVE: To investigate the effects of respiratory motor training (RMT) on pulmonary function and orthostatic stress-mediated cardiovascular and autonomic responses in individuals with chronic spinal cord injury (SCI). DESIGN: Before-after intervention case-controlled clinical study. SETTING: SCI research center and outpatient rehabilitation unit. PARTICIPANTS: A sample of (N=21) individuals with chronic SCI ranging from C3 to T2 diagnosed with orthostatic hypotension (OH) (n=11) and healthy, noninjured controls (n=10). INTERVENTIONS: A total of 21±2 sessions of pressure threshold inspiratory-expiratory RMT performed 5d/wk during a 1-month period. MAIN OUTCOME MEASURES: Standard pulmonary function test: forced vital capacity, forced expiratory volume in one second, maximal inspiratory pressure, maximal expiratory pressure, beat-to-beat arterial blood pressure, heart rate, and respiratory rate were acquired during the orthostatic sit-up stress test before and after the RMT program. RESULTS: Completion of RMT intervention abolished OH in 7 of 11 individuals. Forced vital capacity, low-frequency component of power spectral density of blood pressure and heart rate oscillations, baroreflex effectiveness, and cross-correlations between blood pressure, heart rate, and respiratory rate during the orthostatic challenge were significantly improved, approaching levels observed in noninjured individuals. These findings indicate increased sympathetic activation and baroreflex effectiveness in association with improved respiratory-cardiovascular interactions in response to the sudden decrease in blood pressure. CONCLUSIONS: Respiratory training increases respiratory capacity and improves orthostatic stress-mediated respiratory, cardiovascular, and autonomic responses, suggesting that this intervention can be an efficacious therapy for managing OH after SCI.
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Ejercicios Respiratorios/métodos , Hipotensión Ortostática/rehabilitación , Traumatismos de la Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/rehabilitación , Adulto , Sistema Nervioso Autónomo/fisiopatología , Presión Sanguínea/fisiología , Enfermedad Crónica , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Pruebas de Función RespiratoriaRESUMEN
Significant drops in arterial blood pressure and cerebral hemodynamics have been previously observed during vasovagal syncope (VVS). Continuous and simultaneous monitoring of these physiological variables during VVS is rare, but critical for determining which variable is the most sensitive parameter to predict VVS. The present study used a novel custom-designed diffuse correlation spectroscopy flow-oximeter and a finger plethysmograph to simultaneously monitor relative changes of cerebral blood flow (rCBF), cerebral oxygenation (i.e., oxygenated/deoxygenated/total hemoglobin concentration: r[HbO2]/r[Hb]/rTHC), and mean arterial pressure (rMAP) during 70 deg head-up tilt (HUT) in 14 healthy adults. Six subjects developed presyncope during HUT. Two-stage physiological responses during HUT were observed in the presyncopal group: slow and small changes in measured variables (i.e., Stage I), followed by rapid and dramatic decreases in rMAP, rCBF, r[HbO2], and rTHC (i.e., Stage II). Compared to other physiological variables, rCBF reached its breakpoint between the two stages earliest and had the largest decrease (76±8%) during presyncope. Our results suggest that rCBF has the best sensitivity for the assessment of VVS. Most importantly, a threshold of â¼50% rCBF decline completely separated the subjects from those without presyncope, suggesting its potential for predicting VVS.
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Circulación Cerebrovascular , Oxígeno/análisis , Síncope Vasovagal/diagnóstico , Adulto , Presión Arterial , Velocidad del Flujo Sanguíneo , Encéfalo/irrigación sanguínea , Femenino , Hemodinámica , Hemoglobinas/análisis , Humanos , Hipoxia , Masculino , Persona de Mediana Edad , Óptica y Fotónica , Oximetría , Pletismografía , Recurrencia , Espectroscopía Infrarroja Corta , Síncope Vasovagal/fisiopatologíaRESUMEN
OBJECTIVES: The high mortality and morbidity rates associated with heart failure are still not well explained. A few psychosocial factors have been studied and explain some of this risk, but other factors, like stress, remain largely unexplored in heart failure. This study aimed to (1) examine the association of stress with 6-month cardiac event-free survival, (2) examine the relationship of stress with salivary cortisol, and (3) examine the association of salivary cortisol level with 6-month cardiac event-free survival. METHOD: A total of 81 heart failure patients participated. Stress was measured using the brief Perceived Stress Scale. Cortisol was measured from unstimulated whole expectorated saliva. Cox regression analyses were used to determine whether stress predicted event-free survival, and if salivary cortisol predicted event-free survival. Linear and multiple regressions were used to determine the association of stress with salivary cortisol. RESULTS: Stress was not a significant predictor of event-free survival in heart failure (heart rate = 1.06; 95% confidence interval = 0.95-1.81; p = 0.32). Salivary cortisol was a significant predictor of event-free survival in the unadjusted model (heart rate = 2.30; 95% confidence interval = 0.99-5.927; p = 0.05), but not in the adjusted model. Stress (ß 1.06; 95% confidence interval = 0.95-1.18; p = 0.32) was not a significant predictor of salivary cortisol level. CONCLUSION: Stress is a complex phenomenon, and our measure of stress may not have captured it well. Alternatively, the physical stressors acting in heart failure produce levels of neurohormonal activation that mask the effects of psychosocial stressors or an indirect association of stress with outcomes that is mediated through another construct. Future studies are needed to investigate stress in patients with heart failure to provide definitive answers.
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UNLABELLED: Oxycodone (OXY) is one of the most commonly abused opiates during pregnancy. Perinatal opiate exposure (POE) is associated with neurobehavioral and hormone changes. Little is known about the effects of perinatal OXY on the cardiovascular (CV) responses to stress. OBJECTIVES: to determine the effects of POE on: (1) CV responses to acute stress and ability to discriminate using a classical conditioning paradigm; (2) changes in CV response to the paradigm and retention of the ability to discriminate from postnatal day (PD) 40 to young adulthood. METHODS: Pregnant rats were given i.v. OXY or vehicle (CON) daily. OXY and CON males were fitted with BP telemetry units. Offspring were classically conditioned by following a pulsed tone (CS+) with tail shock. A steady tone (CS-) was not followed by shock. BP and HR were recorded during resting periods and conditioning. Changes in BP, HR from composite analysis were compared. The paradigm was repeated on PD 75. RESULTS: At PD 40, OXY rats had a lower baseline mean BP (OXY: 114.8 ± 1.0 vs. CON: 118.3 ± 1.0 mm Hg; mean ± SEM) but larger amplitude of the conditional BP increase during the stress response (OXY: +3.9 ± 0.4 vs. CON: +1.7 ± 0.4 mm Hg). Both OXY and CON rats were able to discriminate between CS+ and CS-. At PD 75, the effects of OXY on the increased amplitude of the conditional BP had dissipated (CON: +3.4 ± 2.3 vs. OXY: +4.5 ± 1.4 mm Hg). BP responses to the stress and non-stress stimuli did not differ in the OXY group, suggesting that OXY may have decreased the ability of the offspring to discriminate (OXY: CS+: 147.1 ± 1.6, CS-: 145.9 ± 1.6 mm Hg vs. CON: CS+: 155.4 ± 2.7, CS-: 147.8 ± 2.7 mm Hg). CONCLUSION: POE is associated with subtle alterations in stress CV responses in weanling rats which dissipate when the conditioning is repeated at an early adult age. Although POE effect on the ability to discriminate at weanling age could not be detected, POE may impair retention of this ability in adulthood.
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This study examined the effect of 2-week infusion of angiotensin-II (Ang-II; 175 ng/kg/min) via minipump in rats (n=7) upon the mean arterial blood pressure (mBP) and heart rate (HR) response to an acute stress as compared to rats infused with saline (n=7). The acute stress was produced by a classical aversive conditioning paradigm: a 15s tone (CS+) followed by a half second tail shock. Baseline mBP in Ang-II infused rats (167.7±21.3 mm Hg; mean±SD) significantly exceeded that of controls (127.6±13.5 mm Hg). Conversely, baseline HR in the Ang-II infused rats (348±33) was significantly lower than controls (384±19 bpm). The magnitude of the mBP increase during CS+ did not differ between groups, but the HR slowing during CS+ in the Ang-II infused rats (-13.2±8.9 bpm) was significantly greater than that seen in controls (-4.2±5.5 bpm). This augmented bradycardia may be inferentially attributed to an accentuated increase in cardiac parasympathetic activity during CS+ in the Ang-II infused rats. The mBP increased above baseline immediately post-shock delivery in controls, but fell in the Ang-II infused rats, perhaps because of a 'ceiling effect' in total vascular resistance. This classical conditioning model of 'acute stress' differs from most stress paradigms in rats in yielding a HR slowing concomitant with a pressor response, and this slowing is potentiated by Ang-II.
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Angiotensina II/metabolismo , Bradicardia/etiología , Sistema Cardiovascular/inervación , Modelos Animales de Enfermedad , Sistema Nervioso Parasimpático/metabolismo , Estrés Psicológico/fisiopatología , Angiotensina II/administración & dosificación , Angiotensina II/efectos adversos , Animales , Reacción de Prevención , Conducta Animal/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Bradicardia/inducido químicamente , Bradicardia/psicología , Sistema Cardiovascular/efectos de los fármacos , Sistema Cardiovascular/metabolismo , Implantes de Medicamentos , Frecuencia Cardíaca/efectos de los fármacos , Hipertensión/inducido químicamente , Hipertensión/etiología , Hipertensión/psicología , Masculino , Sistema Nervioso Parasimpático/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Reproducibilidad de los Resultados , Estrés Psicológico/metabolismoRESUMEN
We recorded arterial pressure (BP) and heart rate (HR) in type-1 diabetic rats vs. controls for >6 months. Diabetic rats (DIAB) were maintained on insulin from the day glucose >250 mg/dl ("Day 0"). Weight was similar between groups until ~3 weeks before Day 0 when the weight in DIAB transiently lagged the controls (CONT); this difference was maintained throughout the study, but both groups otherwise gained weight in parallel. Plasma glucose attained 371 ± 109 (SD) mg/dl by day 1 in DIAB. Mean BP was similar across groups, and declined through the initial 4-6 months in both the CONT (at -0.06 ± 0.04 mmHg/day) and in the DIAB (at -0.14 ± 0.21 mmHg/day; NS vs. CONT). HR in the CONT (Month 1: 341 ± 13 bpm) exceeded DIAB (325 ± 25 bpm) through ~6 months after Day 0, and also decreased progressively over this period in CONT (-0.19 ± 0.14 bpm/day) and DIAB (-0.29 ± 0.23 bpm/day; NS vs. CONT) before leveling. The BP power within 0.35-0.45 Hz changed during the 90 min before vs. after the transition from dark to light, and light to dark; there were no between group differences. The slope of the log-log linear portion of the BP power spectrum between 1.0/h and 1/min was similar across groups, and increased in both from month 1 to month 6. Regulatory mechanisms maintain similar profiles in BP and HR in diabetic vs. control animals through the initial half year of the disease.
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Presión Arterial/fisiología , Diabetes Mellitus Tipo 1/fisiopatología , Progresión de la Enfermedad , Frecuencia Cardíaca/fisiología , Animales , Glucemia/metabolismo , Peso Corporal/fisiología , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/complicaciones , Modelos Animales de Enfermedad , Dinámicas no Lineales , Disautonomías Primarias/sangre , Disautonomías Primarias/complicaciones , Disautonomías Primarias/fisiopatología , Ratas , Ratas Endogámicas BB , Telemetría/métodosRESUMEN
Cardiac and vascular dysfunctions resulting from autonomic neuropathy (AN) are complications of diabetes, often undiagnosed. Our objectives were to: 1) determine sympathetic and parasympathetic components of compromised blood pressure (BP) regulation in patients with peripheral neuropathy and 2) rank noninvasive indexes for their sensitivity in diagnosing AN. We continuously measured electrocardiogram, arterial BP, and respiration during supine rest and 70° head-up tilt in 12 able-bodied subjects, 7 diabetics without, 7 diabetics with possible, and 8 diabetics with definite, sensory, and/or motor neuropathy (D2). During the first 3 min of tilt, systolic BP (SBP) of D2 decreased [-10.9 ± 4.5 (SE) mmHg] but increased in able-bodied (+4.8 ± 5.4 mmHg). Compared with able-bodied, D2 had smaller low-frequency (0.04-0.15 Hz) spectral power of diastolic BP, lower baroreflex effectiveness index (BEI), and more SBP ramps. Except for low-frequency power of SBP, D2 had greater SBP and smaller RR interval harmonic and nonharmonic components at rest across the 0.003- to 0.45-Hz region. In addition, our results support previous findings of smaller HF RR interval power, smaller numbers of baroreflex sequences, and lower baroreflex sensitivity in D2. We conclude that diabetic peripheral neuropathy is accompanied by diminished parasympathetic and sympathetic control of heart rate and peripheral vasomotion and diminished baroreflex regulation. A novel finding of this study lies in the sensitivity of BEI to detect AN, presumably because of its combination of parameters that measure reductions in both sympathetic control of vasomotion and parasympathetic control of heart rate.
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Presión Sanguínea/fisiología , Diabetes Mellitus Tipo 1/fisiopatología , Diabetes Mellitus Tipo 2/fisiopatología , Neuropatías Diabéticas/fisiopatología , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Adulto , Barorreflejo/fisiología , Estudios de Casos y Controles , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Persona de Mediana Edad , Sistema Nervioso Parasimpático/fisiología , Caracteres Sexuales , Sistema Nervioso Simpático/fisiología , Sistema Vasomotor/fisiologíaRESUMEN
We recorded via telemetry the arterial blood pressure (BP) and heart rate (HR) response to classical conditioning following the spontaneous onset of autoimmune diabetes in BBDP/Wor rats vs. age-matched, diabetes-resistant control (BBDR/Wor) rats. Our purpose was to evaluate the autonomic regulatory responses to an acute stress in a diabetic state of up to 12 months duration. The stress was a 15-s pulsed tone (CS+) followed by a 0.5-s tail shock. The initial, transient increase in BP (i.e., the "first component," or C(1)), known to be derived from an orienting response and produced by a sympathetic increase in peripheral resistance, was similar in diabetic and control rats through â¼9 months of diabetes; it was smaller in diabetic rats 10 months after diabetes onset. Weakening of the C(1) BP increase in rats that were diabetic for >10 months is consistent with the effects of sympathetic neuropathy. A longer-latency, smaller, but sustained "second component" (C(2)) conditional increase in BP, that is acquired as a rat learns the association between CS+ and the shock, and which results from an increase in cardiac output, was smaller in the diabetic vs. control rats starting from the first month of diabetes. A concomitant HR slowing was also smaller in diabetic rats. The difference in the C(2) BP increase, as observed already during the first month of diabetes, is probably secondary to the effects of hyperglycemia upon myocardial metabolism and contractile function, but it may also result from effects on cognition. The small HR slowing concomitant with the C(2) pressor event is probably secondary to differences in baroreflex activation or function, though parasympathetic dysfunction may contribute later in the duration of diabetes. The nearly immediate deficit after disease onset in the C(2) response indicates that diabetes alters BP and HR responses to external challenges prior to the development of structural changes in the vasculature or autonomic nerves.
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Circadian changes in cardiovascular function during the progression of diabetes mellitus in the diabetes prone rat (BBDP) (n = 8) were studied. Age-matched diabetes-resistant rats (BBDR) served as controls. BP was recorded via telemetry in contiguous 4 hr time periods over 24 hours starting with 12 midnight to 4 am as period zero (P0). Prior to onset of diabetes BP was high at P0, peaked at P2, and then fell again at P3; BP and heart rate (HR) then increased gradually at P4 and leveled off at P5, thereby exhibiting a bipodal rhythm. These patterns changed during long-term diabetes. The cross-correlation coefficient of BP and HR was not significantly different across groups at onset, but it fell significantly at 9 months of duration of diabetes (BBDP: 0.39 ± 0.06; BBDR: 0.65 ± 0.03; P < .05). These results show that changes in circadian cardiovascular rhythms in diabetes mellitus became significant at the late stage of the disease.
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Previous reports indicate that prenatal cocaine exposure alters specific behaviors and hypothalamic-pituitary-adrenal axis (HPA) function in the offspring. In most previous studies, cocaine was given via subcutaneous injections. However intravenous administration more closely mimics human cocaine abuse during pregnancy. Therefore, we investigated the effects of prenatal cocaine exposure via intravenous injection to the mothers on open field behavior and HPA axis function of the offspring. We hypothesized that prenatal cocaine exposure decreases immobility in a novel environment, and enhances the HPA response to stress. Dams received cocaine (COC) or vehicle (control, CON) intravenously from gestation day 8 to postnatal day (PD) 5. Behaviors were recorded in the open field on PD 28 (weanlings). As expected, perinatally cocaine-exposed offspring spent less time immobile and had a longer latency to entering the center zone. No other behavioral activities were different between the groups. On PD 43-50, adolescent male and female offspring received either corticotropin releasing hormone (CRH) or saline intravenously. Plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels were determined before, and up to 60 min after injection. COC-exposed offspring of both sexes had higher basal CORT levels. Prenatal cocaine enhanced the CORT response to CRH/saline injections up to 60 min in males but not in females. These novel results show that perinatal administration of cocaine in a manner that most closely mimics human cocaine use has long-term effects on the offspring's behavioral response to stress and on HPA axis functions.
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Conducta Animal/efectos de los fármacos , Trastornos Relacionados con Cocaína/fisiopatología , Hormona Liberadora de Corticotropina/farmacología , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Estrés Psicológico/inducido químicamente , Animales , Animales Recién Nacidos , Conducta Animal/fisiología , Trastornos Relacionados con Cocaína/metabolismo , Trastornos Relacionados con Cocaína/psicología , Hormona Liberadora de Corticotropina/metabolismo , Femenino , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Efectos Tardíos de la Exposición Prenatal/psicología , Ratas , Ratas Sprague-Dawley , Estrés Psicológico/metabolismo , Estrés Psicológico/fisiopatologíaRESUMEN
Atomoxetine is a central norepinephrine reuptake inhibitor used to treat attention deficit hyperactivity disorder. We tested the effects of atomoxetine upon the heart rate (HR) and mean arterial blood pressure (mBP) response to aversive conditioning. In Protocol 1 the mBP and HR responses to a stress (15s tone followed by shock) were tested in 8 Sprague-Dawley rats given saline pretreatment for 3 days; the rats' responses were then tested for 3 additional days following atomoxetine (1mg/kg, sc). Atomoxetine decreased (p<0.05) baseline mBP from 128+/-11 mm Hg (mean+/-SD) to 117+/-19 mm Hg; baseline HR slowed from 380+/-23 bpm to 351+/-21 bpm. The mBP increase to acute stress was similar after saline vs. after drug, but the peak was attained more slowly. After atomoxetine HR tended to slow during stress rather than accelerate. In Protocol 2 the cardiovascular responses were tested (n=6) for 3 days post-saline and for 3 days after a higher dose of atomoxetine (2mg/kg, sc). The average HR acceleration during the last 10s of the stress after saline (+7.5+/-14.7 bpm) was replaced by a HR slowing (-6.2+/-10.5 bpm). We conclude that drug treatment (a) decreases baseline sympathetic tone and/or elevates cardiac parasympathetic tone; (b) slows sympathetic arousal to acute stress without changing its magnitude; and, (c) enables the emergence of elevated parasympathetic tone during the stress. These autonomic consequences are consistent with atomoxetine's anxiolytic and transient sedative effects.
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Inhibidores de Captación Adrenérgica/farmacología , Sistema Nervioso Autónomo/efectos de los fármacos , Bradicardia/tratamiento farmacológico , Frecuencia Cardíaca/efectos de los fármacos , Propilaminas/farmacología , Taquicardia/tratamiento farmacológico , Inhibidores de Captación Adrenérgica/uso terapéutico , Análisis de Varianza , Animales , Clorhidrato de Atomoxetina , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Bradicardia/etiología , Condicionamiento Clásico/fisiología , Modelos Animales de Enfermedad , Frecuencia Cardíaca/fisiología , Propilaminas/uso terapéutico , Ratas , Ratas Sprague-Dawley , Estrés Psicológico/complicaciones , Estrés Psicológico/etiología , Taquicardia/etiologíaRESUMEN
We compared arterial blood pressure (BP) and heart rate (HR) control in 9- to 11-week old obese Zucker rats (n=10; weight=452+/-45 g, average+/-SD) to age-matched, lean Zucker animals (n=13; weight=280+/-46 g). BP was measured by indwelling catheter. Baseline pressure was 113.1+/-7.0 mm Hg in the lean vs. 111.7+/-5.6 in the obese rats (NS). Baseline HR was 413+/-43 in the lean vs. 422+/-22 bpm in the obese animals (NS). Rats were classically conditioned by following a 15-second tone (CS+) with a 0.5-second tail shock. There were no between-group differences in the BP response to CS+. Conversely, heart rate (HR) decreased significantly (p<0.05) more during the last 10 s of the tone in the lean group (-46.0+/-21.5 bpm) vs. the obese (-17.8+/-21.7 bpm). This bradycardia was blocked by atropine. Finally, the change in HR divided by the change in arterial BP (DeltaHR/DeltaBP) following an intravenous bolus of phenylephrine (PE; 5 microg/kg) and following sodium nitroprusside (NP; 5 microg/kg) was determined. The DeltaHR/DeltaBP following PE was smaller in the obese (n=6; -1.36+/-0.60) vs. lean (n=5; -2.80+/-0.92); there was no difference in the response following NP. These data indicate that the BP response to a behavioral challenge did not differ in the obese rat vs. the lean animal, but that the obese subjects had an attenuated parasympathetic response to the stress, probably secondary to alterations in baroreflex function.
Asunto(s)
Presión Sanguínea/fisiología , Frecuencia Cardíaca/fisiología , Obesidad/fisiopatología , Sistema Nervioso Parasimpático/fisiopatología , Estrés Fisiológico/fisiología , Antagonistas Adrenérgicos beta/administración & dosificación , Antagonistas Adrenérgicos beta/farmacología , Animales , Atropina/administración & dosificación , Atropina/farmacología , Presión Sanguínea/efectos de los fármacos , Peso Corporal/fisiología , Bradicardia/tratamiento farmacológico , Bradicardia/fisiopatología , Condicionamiento Clásico/fisiología , Estimulación Eléctrica/métodos , Frecuencia Cardíaca/efectos de los fármacos , Inyecciones Intravenosas , Antagonistas Muscarínicos/administración & dosificación , Antagonistas Muscarínicos/farmacología , Donantes de Óxido Nítrico/administración & dosificación , Donantes de Óxido Nítrico/farmacología , Nitroprusiato/administración & dosificación , Nitroprusiato/farmacología , Sistema Nervioso Parasimpático/efectos de los fármacos , Fenilefrina/administración & dosificación , Fenilefrina/farmacología , Propranolol/administración & dosificación , Propranolol/farmacología , Ratas , Ratas Zucker , Reflejo/efectos de los fármacos , Reflejo/fisiología , Simpatomiméticos/administración & dosificación , Simpatomiméticos/farmacologíaRESUMEN
Human Type 2 diabetes is associated with increased incidence of hypertension and disrupted blood pressure (BP) circadian rhythm. Db/db mice have been used extensively as a model of Type 2 diabetes, but their BP is not well characterized. In this study, we used radiotelemetry to define BP and the circadian rhythm in db/db mice. We found that the systolic, diastolic, and mean arterial pressures were each significantly increased by 11, 8, and 9 mmHg in db/db mice compared with controls. In contrast, no difference was observed in pulse pressure or heart rate. Interestingly, both the length of time db/db mice were active (locomotor) and the intensity of locomotor activity were significantly decreased in db/db mice. In contrast to controls, the 12-h light period average BP in db/db mice did not dip significantly from the 12-h dark period. A partial Fourier analysis of the continuous 72-h BP data revealed that the power and the amplitude of the 24-h period length rhythm were significantly decreased in db/db mice compared with the controls. The acrophase was centered at 0141 in control mice, but became scattered from 1805 to 0236 in db/db mice. In addition to BP, the circadian rhythms of heart rate and locomotor activity were also disrupted in db/db mice. The mean arterial pressure during the light period correlates with plasma glucose, insulin, and body weight. Moreover, the oscillations of the clock genes DBP and Bmal1 but not Per1 were significantly dampened in db/db mouse aorta compared with controls. In summary, our data show that db/db mice are hypertensive with a disrupted BP, heart rate, and locomotor circadian rhythm. Such changes are associated with dampened oscillations of clock genes DBP and Bmal1 in vasculature.
Asunto(s)
Presión Sanguínea , Ritmo Circadiano , Diabetes Mellitus Tipo 2/fisiopatología , Hipertensión/fisiopatología , Factores de Transcripción ARNTL , Animales , Aorta/metabolismo , Aorta/fisiopatología , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Glucemia/metabolismo , Monitoreo Ambulatorio de la Presión Arterial/métodos , Peso Corporal , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Modelos Animales de Enfermedad , Análisis de Fourier , Frecuencia Cardíaca , Hipertensión/metabolismo , Insulina/sangre , Masculino , Ratones , Ratones Endogámicos C57BL , Actividad Motora , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas Circadianas Period , ARN Mensajero/metabolismo , Telemetría , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
We hypothesized that prenatal oxycodone exposure suppresses the Hypothalamic-Pituitary-Adrenal (HPA) response to stress in late adolescence. Dark Agouti rats were given either intravenous oxycodone or vehicle (controls, CON) daily from gestation day 8 until postnatal day (PD) 5. At PD 45, the male and female offspring received intravenously either ovine corticotropin releasing hormone (CRH) or saline. Plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels were determined before, and 15, 30, and 60 min after injection. Prenatal oxycodone had no effect on baseline ACTH values; CRH elicited a greater ACTH response than saline. In males, prenatal oxycodone delayed and enhanced the peak ACTH response to CRH, but had no effect in females. The CORT response to CRH was not different between oxycodone and CON; however mean CORT levels in females were significantly higher than those in males at baseline and after stimulation. These results demonstrate that prenatal oxycodone increases pituitary response to CRH in late adolescent male rats, but not in females. The absence of an enhanced adrenal response in oxycodone-exposed males suggests either desensitization or maximal adrenal response to a high CRH dose. The mechanisms of postnatal sex-specific HPA dysregulation following prenatal oxycodone remain to be elucidated.