RESUMEN
The goal of our study was to develop a simple and practical method for simulating diving in humans using facial cold exposure and apnea stimuli to measure neural and circulatory responses during the stimulated diving reflex. We hypothesized that responses to simultaneous facial cold exposure and apnea (simulated diving) would be synergistic, exceeding the sum of responses to individual stimuli. We studied 56 volunteers (24 female and 32 male), average age of 39 years. All subjects were healthy, free of cardiovascular and other diseases, and on no medications. Although muscle sympathetic nerve activity (MSNA), blood pressure, and vascular resistance increased markedly during both early and late phases of simulated diving, significant reductions in heart rate were observed only during the late phase. Total MSNA during simulated diving was greater than combined MSNA responses to the individual stimuli. We found that simulated diving is a powerful stimulus to sympathetic nerve traffic with significant bradycardia evident in the late phase of diving and eliciting synergistic sympathetic and parasympathetic responses. Our data provide insight into autonomic triggers that could help explain catastrophic cardiovascular events that may occur during asphyxia or swimming, such as in patients with obstructive sleep apnea or congenital long QT syndrome.
Asunto(s)
Apnea/fisiopatología , Frío , Buceo/fisiología , Sistema Nervioso Simpático/fisiología , Adulto , Presión Sanguínea/fisiología , Bradicardia/etiología , Bradicardia/fisiopatología , Electrocardiografía , Cara , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Músculo Esquelético/fisiología , Estimulación Física , Factores de TiempoRESUMEN
OBJECTIVE: We tested the hypothesis that repetitive severe hypoxemia resulting from obstructive sleep apnea would increase serum erythropoietin, and that this increase would be attenuated by effective treatment of obstructive sleep apnea. METHODS: We studied healthy untreated patients with obstructive sleep apnea (18 severe and 10 very mild) before and after acute treatment with continuous positive airway pressure, and 12 healthy control subjects free of obstructive sleep apnea. RESULTS: Baseline erythropoietin levels before sleep were similar in the obstructive sleep apnea and control groups. However, erythropoietin levels increased (by 20%, P =.037) in patients with severe obstructive sleep apnea after 3.5 hours untreated (lowest O2, 77% +/- 3%), and decreased after 4 hours of continuous positive airway pressure treatment (P =.001). Erythropoietin responses in patients with severe obstructive sleep apnea were different (F = 4.0, P =.03) from controls, in whom erythropoietin levels remained stable throughout the night (P =.94). Erythropoietin responses were similar in very mild obstructive sleep apnea and controls (P =.58). CONCLUSIONS: Our results indicate that untreated severe obstructive sleep apnea results in increased erythropoietin, which decreases after continuous positive airway pressure treatment. Increased erythropoietin may be a potential reversible mechanism to explain the association between obstructive sleep apnea and cardiovascular disease.
Asunto(s)
Eritropoyetina/sangre , Apnea Obstructiva del Sueño/sangre , Adulto , Enfermedades Cardiovasculares/sangre , Presión de las Vías Aéreas Positiva Contínua , Femenino , Humanos , Hipoxia/sangre , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Apnea Obstructiva del Sueño/terapiaRESUMEN
It has been suggested that the insertion(I) allele of the I/deletion(D) polymorphism of the angiotensin converting enzyme (ACE) gene is associated with endurance exercise and increased physical conditioning in response to this type of exercise. To investigate the association between the ACE I/D polymorphism and physical activity status in 355 never treated, stage I hypertensives (265 men, 90 women, mean age: 33 +/- 9 years), in whom power exercise is contraindicated, participants of the HARVEST study. Physical activity was assessed using a standardized questionnaire. BMI and age did not vary among genotypes. None of active subjects performed power oriented exercises. ACE I/D frequencies (II-18%, ID-55%, DD-27%) were in Hardy-Weinberg equilibrium. Sedentary lifestyle was more common among DD than II hypertensives (76% in DD, and 48% in II, Chi(2) = 13.9, P = 0.001). In stepwise MANOVA using age, marital status, profession, sex, and ACE genotype as predictors of physical activity, marital status (F = 24.4, P < 0.0001) and ACE genotype (F = 16.03, P < 0.0001) contributed to more than 50% of the variance in physical activity status of the population. Our results suggest that the ACE I/D polymorphism may be a specific genetic factor associated with physical activity levels in free-living borderline and mild hypertensive subjects.
Asunto(s)
Hipertensión/genética , Actividad Motora , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , Adulto , Análisis de Varianza , Presión Sanguínea/fisiología , Índice de Masa Corporal , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Hipertensión/fisiopatología , Masculino , Estado Civil , Mutagénesis Insercional , Resistencia Física , Eliminación de Secuencia , Encuestas y CuestionariosRESUMEN
OBJECTIVE: Left ventricular hypertrophy (LVH) is associated with an increased risk for cardiovascular morbidity and mortality. Epidemiological studies suggest that LVH may be influenced by genetic factors. However, the evidence associating individual genes with left ventricular (LV) mass is inconsistent and contradictory. METHODS: We investigated the association between angiotensin-converting enzyme insertion/deletion, angiotensinogen and alpha-adducin polymorphisms with LV mass and plasma renin activity (PRA) in 162 men with mild, never-treated hypertension who were recruited for the Hypertension and Ambulatory Recording Venetia Study. The effect of each polymorphism on LV mass and PRA was tested in one-way analysis of covariance using LV mass index or PRA as the dependent variable after adjusting for covariates. RESULTS: The alpha-adducin polymorphism was the only individual polymorphism independently associated with LV mass index (F = 7.78, P= 0.006). Patients homozygous for the allele of that polymorphism had a LV mass index (123.4 +/- 10.5 g/m(2) ) significantly higher compared with heterozygotes (90.8 +/- 2.5 g/m(2) , P<0.01) or homozygotes (94.7 +/- 1.7 g/m(2) , P<0.05). These subjects also have significantly lower PRA (F = 4.2, P= 0.017). Albeit uncommon, 40% of homozygotes of the alpha-adducin polymorphism had LVH (odds ratio, 15.1; 95% confidence interval, 3.0-82.1). CONCLUSIONS: The homozygotic state of the allele of alpha-adducin polymorphism is independently associated with increased LV mass and low PRA. These data suggest that genetic considerations may contribute importantly to risk stratification, and perhaps therapeutic interventions targeted at LVH and the renin-angiotensin system in hypertensive patients.
Asunto(s)
Proteínas de Unión a Calmodulina/genética , Hipertrofia Ventricular Izquierda/genética , Polimorfismo Genético , Renina/sangre , Adulto , Alelos , Angiotensinógeno/genética , Ecocardiografía , Homocigoto , Humanos , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Peptidil-Dipeptidasa A/genéticaRESUMEN
BACKGROUND: Leptin has been implicated in cardiovascular disease. A diet rich in fish has been associated with decreased cardiac and vascular risk. METHODS AND RESULTS: We examined the relationship between diet and leptin in 2 related homogeneous African tribal populations of Tanzania. One tribe consumes freshwater fish as their main diet component (n=279), and the other tribe consumes a primarily vegetarian diet (n=329). In multivariate analysis, plasma leptin levels were associated with type of diet (F=14.3, P<0.001), independent of age, body mass index, body fat, alcohol consumption, or insulin. Both male (2.5+/-2 [fish diet] versus 11.2+/-2.4 [vegetarian diet] ng/mL, P=0.017) and female (5.0+/-1.9 [fish diet] versus 11.8+/-1.4 [vegetarian diet] ng/mL, P=0.007) fish eaters had lower plasma leptin levels than did their vegetable diet counterparts, even though body mass index values were virtually identical. CONCLUSIONS: A diet rich in fish is associated with lower plasma leptin, independent of body fat. These findings may have implications for understanding the reduced cardiovascular risk in subjects on a high-fish diet.
Asunto(s)
Dieta , Peces , Leptina/sangre , Animales , Índice de Masa Corporal , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Estudios de Cohortes , Dieta Vegetariana , Femenino , Agua Dulce , Humanos , Masculino , Factores de Riesgo , TanzaníaRESUMEN
BACKGROUND: Obstructive sleep apnea (OSA) has been increasingly linked to cardiovascular and cerebrovascular disease. Inflammatory processes associated with OSA may contribute to cardiovascular morbidity in these patients. We tested the hypothesis that OSA patients have increased plasma C-reactive protein (CRP). METHODS AND RESULTS: We studied 22 patients (18 males and 4 females) with newly diagnosed OSA, who were free of other diseases, had never been treated for OSA, and were taking no medications. We compared CRP measurements in these patients to measurements obtained in 20 control subjects (15 males and 5 females) who were matched for age and body mass index, and in whom occult OSA was excluded. Plasma CRP levels were significantly higher in patients with OSA than in controls (median [range] 0.33 [0.09 to 2.73] versus 0.09 [0.02 to 0.9] mg/dL, P<0.0003). In multivariate analysis, CRP levels were independently associated with OSA severity (F=6.8, P=0.032). CONCLUSIONS: OSA is associated with elevated levels of CRP, a marker of inflammation and of cardiovascular risk. The severity of OSA is proportional to the CRP level.