Effects of acute and chronic sleep deprivation on cardiovascular regulation.

Sleep is a fundamental physiological process, characterized by the activation of several cortical and subcortical neural networks. The relation between sleep and cardiovascular system is complex and bidirectional: sleep disorders may alter cardiovascular system, leading to an increased cardiovascular risk, while, on the contrary, cardio- vascular diseases are characterized by an alteration of physiological sleep. Autonomic nervous system (ANS) plays a key role in the regulation of cardiovascular functions during different sleep stages, with sympatho-vagal balance dynamically shifting towards sympathetic or vagal predominance across different sleep stages. Sleep deprivation (SD) has becoming one of the most relevant health problem in modern societies. SD can be related to aging, which is associated with increased sleep fragmentation, and to sleep disorders, such as sleep disordered breathing and neurological disorders. Experimental studies in animals showed that SD significantly affects cardiovascular functions, altering heart rate and blood pressure responses, and increasing sympathetic activity and neuroendocrine response to stressor stimuli. Clinical studies in humans have shown that SD, either due to experimental sleep loss and to sleep disorders, can affect different biological pathways, such as cardiovascular autonomic control, inflammation, immunity responses and metabolism. All these alterations may predispose subjects with SD to an increased cardiovascular risk. Hence, it is fundamental to identify the presence of a sleep disorder, which could be per se responsible for sleep loss, or the presence of sleep deprivation due to other factors, such as social life, habits etc., in order to identify subjects at high risk for cardiovascular events.

Possible relationships between headache-allodynia and nocturnal sleep breathing.

Sleep and headache are linked in a bidirectional way. Breathing quality during sleep may be a possible link between them. The objective of this study were to evaluate the prevalence of headache--and of allodynia--in a population of subjects who underwent cardiopulmonary monitoring during sleep for presumed respiratory problems; to evaluate the possible relationships between the presence of headaches--and of allodynia--and respiratory parameters. We studied 181 subjects, 112 without headache (mean age 59.4 ± 13.1 years, 97 men and 15 women); 69 with history of headache (42 men and 27 women; 41 migraineurs and 28 with tension type headache). Headache diagnosis was made according to ICHD-II criteria. A semi-structured ad hoc questionnaire was used to evaluate the presence of allodynia. Full cardiopulmonary monitoring was performed by SOMNO check(®) effort (WEINMANN) with SaO(2), T90 and AHI determination. Headache and headache-associated allodynia were particularly frequent in this population, suggesting a positive correlation between breathing problems during sleep and head pain, and allodynia. The observation that better respiratory parameters were found among headache sufferers with respect to those without headache, even in allodynic subjects, seems to reverse this point of view: headache and allodynia may possibly have an allostatic function preventing deep sleep and, in turn, avoiding prolonged apneas.

Hypersomnolence in fibromyalgia syndrome.

OBJECTIVE: To evaluate hypersomnolence in patients affected by fibromyalgia syndrome. METHODS: Thirty consecutive patients affected by fibromyalgia syndrome (FMS) (28 F) completed a sleep questionnaire and underwent the following evaluations: lung function tests; polysomnography; the Epworth sleepiness scale (ESS), which measures sleep complaints and daytime hypersomnolence; and the visual analogical scale (VAS) to detect subjective pain, fatigue, anxiety and depression. RESULTS: The FMS patients were divided into two groups based on their ESS score. Patients complaining of daytime hypersomnolence had a higher number of tender points (15 +/- 2 vs. 12 +/- 1, p < 0.01), a higher subjective pain score (72 +/- 15 vs. 52 +/- 13, p < 0.05), and more fatigue (p < 0.05). The diffusing capacity of the lung (Tlco) was more impaired and the occurrence of periodic breathing was higher. FMS patients complaining of daytime somnolence had significantly less efficient sleep than the FMS patients with no daytime somnolence (p < 0.05), i.e. a lower proportion of stage 3 sleep (5 +/- 2% vs. 12 +/- 3%; p < 0.001), stage 4 sleep (1 +/- 0.5% vs. 4 +/- 1%; p < 0.001), and twice as many arousals per hour of sleep (p < 0.01). The respiratory pattern of FMS patients with hypersomnolence showed a higher occurrence of periodic breathing (p < 0.05). The short length of apneas and hypopnoeas did not affect the apnea/hypopnea index (5.1 +/- 3 vs. 7 +/- 4; ns), but FMS patients with daytime hypersomnolence had a greater number of desaturations per hour of sleep (11 +/- 6 vs. 6 +/- 5; p < 0.05). Pulmonary volumes did not differ between the two groups. The EES score was significantly correlated in FMS patients, and even more markedly in the FMS patients with hypersomnolence, TLco, A/I, and disease duration. The ESS score was correlated significantly with the number of tender points only in FMS patients with daytime hypersomnolence. CONCLUSION: The occurrence of daytime hypersomnolence in FMS patients is linked to a greater severity of fibromyalgia symptoms and to more severe polysomnographic alterations.

Autonomic dysfunction and urinary albumin excretion rate are associated with an abnormal blood pressure pattern in normotensive normoalbuminuric type 1 diabetic patients.

OBJECTIVE: To analyze the role of autonomic function and other possible factors associated with a blunted fall in nocturnal blood pressure. RESEARCH DESIGN AND METHODS: A total of 39 normotensive normnoalbuminuric type 1 diabetic patients were studied. Glomerular filtration rate (51Cr-EDTA technique), extracellular volume (51Cr-EDTA distribution volume), and urinary albumin excretion rate (UAER) (by radioimmunoassay) were measured. The subjects' 24-h ambulatory blood pressure and a 24-h electrocardiogram were recorded simultaneously Heart rate variability was calculated in the time domain for 24 h, in the frequency domain at night, at rest in the supine position, and during tilt. Patients were classified according to diastolic blood pressure (dBP) night/day ratio as dipper patients (< or =0.9) and nondipper patients (>0.9). RESULTS: Nondipper patients presented a higher low-frequency (LF) component (a sympathetic index) and higher LF/high-frequency (HF) ratio during sleep than dipper patients (0.29 +/- 0.12 vs. 0.19 +/- 0.10 normalized units [n.u.], P = 0.008; and 0.98 +/- 0.53 vs. 0.55 +/- 0.45 n.u., P = 0.007, respectively). At rest, the LF component in nondipper patients (0.38 +/- 0.13 n.u.) was higher than in dipper patients (0.27 +/- 0.12 n.u., P = 0.04). After the tilt, nondipper patients did not show an increase in the LF component (P = 0.32), but in dipper patients, the increase was significant (P = 0.001). In both groups, tilting promoted a decrease in the HF component (a parasympathetic index). In a stepwise multiple linear regression analysis, the LF component during sleep and the UAER accounted for 24% of the variability in the dBP night/day ratio. CONCLUSIONS: The predominance of sympathetic activity and increased levels of UAER, although within the normal range, are associated with a blunted fall in nocturnal dBP in normoalbuminuric normotensive type 1 diabetic patients.

Glomerular filtration rate, urinary albumin excretion rate, and blood pressure changes in normoalbuminuric normotensive type 1 diabetic patients: an 8-year follow-up study.

OBJECTIVE: To analyze the changes in glomerular filtration rate (GFR), urinary albumin excretion rate (UAER), and blood pressure (BP) levels in a cohort of normoalbuminuric and normotensive type 1 diabetic patients. RESEARCH DESIGN AND METHODS: This is an 8.4+/-2.1-year prospective study of 33 normotensive normoalbuminuric (24-h UAER <20 microg/min) type 1 diabetic patients. UAER (radioimmunoassay), GFR (51Cr-EDTA single-injection technique), and GHb (ion-exchange chromatography) were measured at baseline and at 1- to 2-year intervals. RESULTS: The GFR decreased (137.6+/-16.5 to 116.4+/-21.3 ml x min(-1) x 1.73 m(-2) P < 0.05) during the follow-up period. GFR reduction (-0.20+/-0.29 ml x min(-1) x month(-1); P < 0.05) was associated with baseline GFR and mean GHb (R2 = 0.30; beta = 0.072; F = 6.54; P = 0.004). UAER was higher at the end of the study (3.7-7.1 microg/min; P = 0.017). Microalbuminuria was observed in two patients, while macroalbuminuria was observed in one. No changes in UAER were observed when these three patients were excluded from the analysis. Mean blood pressure (MBP) increased during the study (85.8+/-9.7 to 99.6+/-11.6 mmHg; P < 0.001). MBP at the end of the study was associated with age and GFR at baseline (R2 = 0.39; beta = 0.074; F = 9.64; P = 0.001). CONCLUSIONS: In this cohort of normoalbuminuric normotensive type 1 diabetic patients, GFR decreased and BP levels increased during the follow-up period. The predictors for the GFR change were baseline GFR level and metabolic control. For end-of-study MBP, the predictor was baseline GFR level.

Glomerular hyperfiltration is associated with blood pressure abnormalities in normotensive normoalbuminuric IDDM patients.

OBJECTIVE: To analyze the blood pressure patterns in normoalbuminuric IDDM patients with glomerular hyperfiltration. RESEARCH DESIGN AND METHODS: A controlled cross-sectional study of 38 normotensive normoalbuminuric (urinary albumin excretion rate < 20 micrograms/min) IDDM patients (18 hyperfiltering [glomerular filtration rate > 134 ml.min-1 1.73 m-2] and 20 normofiltering) and 20 normal individuals matched for age, sex, and BMI was performed. The 24-h ambulatory blood pressure was monitored using an auscultatory technique (Pressurometer IV, Del Mar Avionics), the glomerular filtration rate was measured by 51Cr-labeled EDTA method, extracellular volume by the distribution volume of 51Cr-labeled EDTA, and the 24-h urinary albumin excretion rate by radioimmunoassay. RESULTS: Mean nocturnal diastolic blood pressure was higher in hyperfiltering IDDM patients (70.4 +/- mmHg), when compared with the control group (65.1 +/- 5.3 mmHg, P = 0.04). Diastolic blood pressure night:day ratio was higher in hyperfiltering IDDM patients (92.0 +/- 8.6%), when compared with normofiltering IDDM patients (85.9 +/- 4.8%) and control subjects (87.0 +/- 6.8%, P = 0.02). In IDDM patients, the glomerular filtration rate significantly correlated with the diastolic blood pressure night:day ratio (r = 0.5, P = 0.002), extracellular volume (r = 0.04, P = 0.002), and HbA1 (r = 0.3, P = 0.03). In stepwise multiple regression analysis, factors associated with glomerular filtration rate were diastolic blood pressure night:day ratio, extracellular volume, and HbA1 (adjusted r2 = 0.27, P = 0.003). CONCLUSIONS: Glomerular hyperfiltration is associated with higher nocturnal diastolic blood pressure and with a blunted nocturnal decrease in diastolic blood pressure levels in normotensive and normoalbuminuric IDDM patients.

Abnormalities in gallbladder dynamics of type 1 (insulin-dependent) diabetic patients with autonomic neuropathy.

The aim of this study was to evaluate gallbladder dynamics in insulin-dependent diabetic patients with and without autonomic neuropathy. Gallbladder dynamics was studied by a scintigraphic method after a test meal in 26 insulin-dependent diabetic patients and 10 normal individuals. The presence and severity of autonomic neuropathy were defined according to the number of abnormal cardiovascular reflex tests: absent (no abnormal test), mild (1-3 abnormal tests), and severe (4-5 abnormal tests). The time from the moment when the patient started to take the test meal to the beginning of gallbladder emptying was longer (P = 0.01) in diabetic patients with mild (N = 11, 12.1 +/- 7.6 min) and severe neuropathy (N = 8, 11.0 +/- 10.6 min) than diabetic patients without autonomic neuropathy (N = 7, 3.9 +/- 4.4 min) and controls (N = 10, 4.8 +/- 4.2 min). The ejection rate was higher (P = 0.02) in the group with severe autonomic neuropathy (N = 8, 5.1 +/- 3.3%/min) than diabetic patients with mild (N = 11, 2.0 +/- 1.0%/min) or without autonomic neuropathy (N = 7, 1.8 +/- 0.8%/min) and controls (N = 10, 2.6 +/- 1%/min). Thirty-two percent of the diabetic patients with autonomic neuropathy presented increased perspiration, nausea and urgency to defecate after the ingestion of the test meal. A significant positive correlation of ejection rate with the presence of these symptoms (biserial point correlation test = 0.67, P < 0.01) was also observed. These data suggest that insulin-dependent diabetic patients with autonomic neuropathy present abnormalities of gallbladder emptying that could be related to specific gastrointestinal symptoms.

Abnormalities in gallbladder dynamics of type 1 (insulin-dependent) diabetic patients with autonomic neuropathy

The aim of this study was to evaluate gallbladder dynamics in insulin-dependent diabetic patients with and without autonomic neuropathy. Gallbladder dynamics was studied by a scintigraphicmethod after a test meal in 26 insulin-dependent diabetic patients and 10 normal individuals. The presence and severity of autonomic neuropathy were defined according to the number of abnormal cardiovascular reflex tests: absent (no abnormal test), mild (1-3 abnormal tests), and severe (4-5 abnormal tests). The time from the moment when the patient started to take the test meal to the begnning of gallbladder emptying was longer (P = 0.01) in diabetic patients with mild (N = 11,12.1 ñ 7.6 min) and severe neuropathy (N = 8,11.0 ñ 10.6 min) than diabetic patients without autonomic neuropathy (N = 7,3.9 ñ 4.4 min) and controls (N = 10,4.8 ñ 4.2 min). The ejection rate was higher (P = 0.02) in the group with severe autonomic neuropathy (N = 8,5.1 ñ 3.3 percent/min) than diabetic patients with mild (N = 11,2.) ñ 1.0 percent/min) or without autonomic neuropathy (N = 7,1.8 ñ 0.8 por cento/min) and controls (N = 10,2.6 ñ 1 percent/min). Thirty-two percent of the diabetic patients with autonomic neurpathy presented increased perspiration, nausea and urgency to defecate after the ingestion of the test meal. A significant positive correlation of ejection rate with the presence of these symptoms (biserial point correlation test = 0.67,P<0.01) was also observed. These data suggest that insulin-dependent diabetic patients with autonomic neuropathy present abnormalities of gallbladder emptying that could be related to specific gastrointestinal sumptoms

Chicken and fish diet reduces glomerular hyperfiltration in IDDM patients.

OBJECTIVE: To compare the effect of a normal protein diet (test diet) in which chicken and fish were substituted for red meat with a low-protein diet (LPD) on glomerular filtration rate (GFR) in normoalbuminuric insulin-dependent-diabetes mellitus (IDDM) patients. RESEARCH DESIGN AND METHODS: A crossover randomized clinical trial was performed in 15 normoalbuminuric IDDM patients, 9 normofiltering, and 6 hyperfiltering patients. They followed three diets for a 3-week period each: a usual diet (UD), an LPD (0.5 g.kg-1.day-1 of proteins, 7% calories as protein, 33% as fat, and 60% as carbohydrates), and a normoproteic isocaloric test diet in which white meat (chicken and fish) was substituted for red meat of the UD. At the end of each diet, a clinical evaluation and measurements of GFR (51Cr-ethylenediaminetetraacetate (EDTA) single injection technique), urinary albumin excretion (UAE), and plasma amino acids were performed. Dietary compliance was assessed by a 24-h urinary urea and weekly interviews with the dietitian. RESULTS: In all diabetic patients, GFR after the LPD (114.9 +/- 16.5 ml.min-1 x 1.73 m-2) and after the test diet (122.7 +/- 16.7 ml.min-1 x 1.73 m-2) was significantly lower than after the UD (132.0 +/- 27.7 ml.min-1 x 1.73 m-2) (P = 0.001). Similar results were found in the hyperfiltering group: after UD = 161.1 +/- 15.4 ml.min-1 x 1.73 m-2, after LPD = 129.8 +/- 9.0 ml.min-1 x 1.73 m-2, and after the test diet = 136.5 +/- 3.1 ml.min-1 x 1.73 m-2, (P < 0.001). In the normofiltering group, no significant changes in GFR were observed after the three diets. Metabolic control, nutritional indexes, blood pressure (BP), and UAE did not change after the three diets in all patients. CONCLUSIONS: A normoproteic diet with chicken and fish as the only meat protein source decreases the GFR in the hyperfiltering normoalbuminuric IDDM patients. The GFR reduction after this diet is similar to that observed after an LPD.

Effect of age and sex on glomerular filtration rate measured by 51Cr-EDTA.

1. The effect of age and sex on glomerular filtration rate (GFR) was measured by the 51Cr-EDTA radioisotopic method in 76 normal individuals (43 women and 33 men). 2. Age has a significant effect on GFR. Subjects aged 41 to 60 years have GFR values [104.5 +/- 16.5 ml min-1 (1.73 m2)-1, N = 43] lower than younger individuals aged 20 to 40 years [116.6 +/- 11.2 ml min-1 (1.73 m2)-1, N = 33]. GFR decreases after 40 years of age by approximately 6.0 ml min-1 (1.73 m2)-1 per decade. 3. GFR values in women [105.9 +/- 16.0 ml min-1 (1.73 m2)-1, N = 43] were lower when compared to men [114.8 +/- 14.3 ml min-1 (1.73 m2)-1, N = 33]. 4. We conclude that the effect of sex and age must be taken into account when establishing reference values for GFR.

Effect of age and sex on glomerular filtration rate measured by 51Cr-EDTA

The effect of age and sex on glomerular filtration rate (GFR) was measured by the 51 Cr-EDTA radioisotopic method in 76 normal individuals (43 women and 33 men). Age has a significant effect on GFR. Subjects aged 41 to years have GFR values [104,5 ñ 16.5 ml min-1 (1.73 m2)-1, N=43] lower than younger individuals aged 20 to 40 years [116.6 ñ 11.2 ml min-1 (1.73 m2)-1, N=33]. GFR decreases after 40 years of age by approximately 6.0 ml min-1 (1.73 m2)-1 per decade. GFR values in women [105.9 ñ 16.0 ml min-1 (1.73 m2)-1, N=43] were lower when compared to men [114.8 ñ 14.3 ml min-1 (1.73 m2)-1, N=33]. We conclude that the effect of sex and age must be taken into account when establishing reference values for GFR

Altered pattern of circadian neural control of heart period in mild hypertension.

We addressed the problem of the circadian changes in neural control of heart period in ambulant hypertensive subjects. A running spectral analysis of R-R variability from Holter tapes provided markers of sympathetic, i.e. low-frequency component (LF) almost equal to 0.10 Hz, and vagal, i.e. high-frequency component (HF) almost equal to 0.25 Hz, controlling activities for the 24-h period of the recording. Significant circadian differences were observed in LF between the two groups of subjects: during night-time rest (0300-0400 h), LF was greater in hypertensives than in normotensives (56 +/- 2 and 48 +/- 2 nu, respectively; P less than 0.05). Furthermore, the difference between daytime and night-time LF values was progressively reduced with increasing severity of the hypertensive state, as assessed by resting arterial pressure levels. Spectral analysis of R-R variability suggests that essential hypertension may be characterized by a reduced day-night oscillation in sympathetic activity than can be quantified non-invasively using this approach.

Impaired heart rate variability in patients with chronic Chagas' disease.

Spectral analysis of heart rate variability was used to investigate the possible alteration in sympathovagal control of heart rate in patients with Chagas' disease. The study included 31 subjects, divided into three groups: controls, Chagas' 1 (subjects with only positive serology for Chagas' disease) and Chagas' 2 (subjects with positive serology and electrocardiographic abnormalities that are usually found in this disease). The subjects were studied during rest, while standing, and during handgrip exercise. With this approach, the low frequency (approximately 0.1 Hz) spectral component of R-R interval variability is considered to be a marker primarily of sympathetic activity, whereas the high frequency (approximately 0.25 Hz) component, which is related to respiration, seems mainly to reflect vagal activity. We observed significant (p less than 0.05) differences among the three groups during standing: although in the control subjects the low-frequency component increased (delta = 30 +/- 5 normalized units, nu), there was no increase in Chagas' 1 (delta = -1 +/- 8 nu) and Chagas' 2 (delta = -2 +/- 8 nu) patients. During handgrip exercise, another test that is capable of exciting sympathetic outflow, there was an increase of low frequency only in control subjects. These results confirm the occurrence of quantitative and assessable abnormalities in the neural control of heart rate variability in Argentinian patients with chronic Chagas' disease, even in the absence of heart failure.

Effects of sympathetic activation on heart rate variability in Chagas' patients.

To assess the alterations present in neural control of heart rate in patients with signs of Chagas' disease we studied the spectral components of heart rate variability in 10 Chagas' patients, without cardiac failure, and in 10 control subjects during supine and standing position. Chagas' patients during standing did not present the changes in the spectral components of heart rate variability which normally accompany sympathetic activation and vagal withdrawal.