Décio Mion

Effects of Alcohol on Sympathetic Activity, Hemodynamics, and Chemoreflex Sensitivity

Alcohol intake has been shown to worsen obstructive sleep apnea and increase nocturnal hypoxemia. The mechanisms of this action are unclear. Animal studies suggest that a reduction in chemoreflex sensitivity may be implicated. Using a double-blind, randomized, vehicle-controlled design, we tested the hypothesis that oral alcohol intake depresses chemoreflex sensitivity in humans. We examined the effects of oral alcohol intake (1.0 g/kg body wt) on blood pressure, heart rate, heart rate variability, muscle sympathetic nerve activity, forearm vascular resistance, and minute ventilation in 16 normal male subjects. Peripheral and central chemoreflex sensitivity were measured in response to hypoxia (n = 10) and hypercapnia (n = 6), respectively. Plasma alcohol increased from 0 to 23.2 +/- 1.5 mmol/L (107 +/- 7 mg/dL) at 60 minutes and 20.2 +/- 1 mmol/L (93 +/- 4 mg/dL) at 85 minutes after alcohol intake (P < .0001). Alcohol induced an increase in heart rate from 59 +/- 2 to 66 +/- 2 beats per minute (P < .01) and increased the ratio of low- to high-frequency variability of heart rate (P < .05). Although alcohol increased sympathetic nerve activity by up to 239 +/- 22% of baseline values (P < .01), forearm vascular resistance after alcohol was lower than that after vehicle (P < .05). Blood pressure did not increase compared with the vehicle session. Oxygen saturation during hypoxia after alcohol was 4 +/- 1% lower than it was during hypoxia after vehicle (P < .05) although arterial blood PO2 was unchanged. Alcohol did not affect the cardiovascular, sympathetic, or ventilatory responses to either hypoxia or hypercapnia. Acute increases in plasma alcohol increase heart rate and sympathetic nerve activity; blood pressure is not increased, probably because of vasodilator effects of alcohol. Alcohol does not alter chemoreflex responses to hypoxia or hypercapnia; thus, alterations in chemoreflex sensitivity are unlikely to explain the effects of alcohol on sleep apnea. Alcohol may reduce the affinity of hemoglobin for oxygen.

Factors affecting post-exercise hypotension in normotensive and hypertensive humans.

BackgroundPost-exercise hypotension has been extensively described under laboratory conditions. However, studies investigating the persistence of this post-exercise decrease in blood pressure for longer periods have produced controversial results. The present investigation was conducted to verify the effect of a single bout of exercise on ambulatory blood pressure and to identify potential factors that might influence this post-exercise ambulatory blood pressure fall. DesignThe study was a randomized controlled clinical trial. MethodsThirty normotensive and 23 hypertensive subjects were submitted to two ambulatory blood pressure monitorings (using the SpaceLabs 90207, SpaceLabs, Redmond, Washington, USA), which were performed after 45 min of seated rest (control session) or cycling exercise at 50% peak oxygen uptake (exercise session). ResultsNormotensive subjects demonstrated a lower 24 h blood pressure level in the exercise session. Hypertensive patients showed no significant difference in ambulatory blood pressure level between the two experimental sessions. Further data analysis revealed that approximately 65% of the subjects in both groups experienced a fall in blood pressure after exercise. Moreover, in the normotensive subjects, this blood pressure fall was significantly and positively correlated with clinic and ambulatory blood pressure, and negatively correlated with weight and body mass index. The blood pressure response to exercise was also greater in women. In the hypertensive patients, the post-exercise blood pressure decrease was significantly and positively correlated with clinic and ambulatory blood pressure as well as with the peak oxygen uptake, and negatively correlated with age and body mass index. ConclusionsThe post-exercise ambulatory blood pressure fall observed in normotensive and hypertensive humans depends on individual characteristics. Moreover, in both normotensive and hypertensive humans, post-exercise ambulatory hypotension is greater in subjects with a higher initial blood pressure level.

Sympathetic nerve activity is decreased during device-guided slow breathing.

It is known that slow breathing (<10 breaths min–1) reduces blood pressure (BP), but the mechanisms involved in this phenomenon are not completely clear. The aim of this study was to evaluate the acute responses of the muscle sympathetic nerve activity, BP and heart rate (HR), using device-guided slow breathing (breathe with interactive music (BIM)) or calm music. In all, 27 treated mild hypertensives were enrolled. Muscle sympathetic nerve activity, BP and HR were measured for 5 min before the use of the device (n=14) or while subjects listened to calm music (n=13), it was measured again for 15 min while in use and finally, 5 min after the interventions. BIM device reduced respiratory rate from 16±3 beats per minute (b.p.m) to 5.5±1.8 b.p.m (P<0.05), calm music did not affect this variable. Both interventions reduced systolic (−6 and −4 mm Hg for both) and diastolic BPs (−4 mm Hg and −3 mm Hg, respectively) and did not affect the HR (−1 and −2  b.p.m respectively). Only the BIM device reduced the sympathetic nerve activity of the sample (−8 bursts min–1). In conclusion, both device-guided slow breathing and listening to calm music have decreased BP but only the device-guided slow breathing was able to reduce the peripheral sympathetic nerve activity.

A randomized, placebo-controlled trial of the effects of physical exercises and estrogen therapy on health-related quality of life in postmenopausal women

Objective:The purpose of this study was to evaluate the isolated and associated effects of estrogen therapy (estradiol valerate 1 mg/d orally) and physical exercise (moderate aerobic exercise, 3 h/wk) on health-related quality of life (HRQOL) and menopausal symptoms among women who had undergone hysterectomy. Design:A 6-month, randomized, double-blind, placebo-controlled clinical trial with 44 postmenopausal women who had undergone hysterectomy. The interventions were physical exercise and hormone therapy (n = 9), being sedentary and hormone therapy (n = 14), physical exercise and placebo (n = 11), and being sedentary and placebo (n = 10). HRQOL was assessed by a Brazilian standard version of the Medical Outcome Study Short-Form Health Survey and symptoms by Kupperman Index at baseline and after 6 months. Results:There was a decrease in symptoms in all groups, but only groups who performed physical exercise showed an increase in quality of life. Analysis of variance showed that changes in physical functioning (P = 0.001) and bodily pain (P = 0.012) scores over the 6-month period differed significantly between women who exercised and women who were sedentary, regardless of hormone therapy. Hormone therapy had no effect, and there was also no significant association between physical exercise and hormone therapy in HRQOL. Conclusions:Physical exercises can reduce menopausal symptoms and enhance HRQOL, independent of whether hormone therapy is taken.

Comparação dos perfis dos pacientes hipertensos atendidos em Pronto-Socorro e em tratamento ambulatorial

: This study compares 100 hypertensive patients in emergency units with those who were seen in outpatient clinics. Hypertensive patients seen at the emergency unit showed to be different (p < 0.05) from those seen at the outpatient clinic regarding: higher blood pressure; lower income; not belonging to the hospital community; greater alcohol intake; became aware of their hypertension because felt bad; measured blood pressure less often; did not take the medicine more often. In conclusion, unfavorable characteristics can contribute to hypertensive patients who do not follow antihypertension treatment adequately, leading to care in emergency units.O estudo comparou 100 hipertensos atendidos no Pronto-socorro com 100 pacientes do Ambulatorio. Os hipertensos do Pronto-Socorro foram diferentes (p < 0,05) em relacao a: maior pressao arterial; menor renda salarial; maior consumo de bebida alcoolica; nao pertenciam a comunidade do hospital; descobriram ser hipertensos por sentirem-se mal; mediram menos a pressao; e deixaram de tomar mais medicamentos. A analise multivariada revelou diferencas significativas entre os dois grupos quanto a renda, ao local onde e medida a pressao e nao tomar os medicamentos. Concluiu-se que caracteristicas desfavoraveis podem contribuir para nao realizar o tratamento anti-hipertensivo, levando a atendimentos em unidades de emergencia.This study compares 100 hypertensive patients in emergency units with those who were seen in outpatient clinics. Hypertensive patients seen at the emergency unit showed to be different (p < 0.05) from those seen at the outpatient clinic regarding: higher blood pressure; lower income; not belonging to the hospital community; greater alcohol intake; became aware of their hypertension because felt bad; measured blood pressure less often; did not take the medicine more often. In conclusion, unfavorable characteristics can contribute to hypertensive patients who do not follow antihypertension treatment adequately, leading to care in emergency units.

O perfil de um grupo de pessoas hipertensas de acordo com conhecimento e gravidade da doença

Foram entrevistados 205 hipertensos em tratamento ambulatorial para avaliar o papel do perfil bio-social no conhecimento e grau de gravidade da doenca. As caracteristicas da populacao foram: 72% mulheres, 63% brancos, 78% com mais de 40 anos, 60% casados, 68% com baixa escolaridade, 41% com renda de 1 a 3 salarios, 75% com peso elevado, 76% nao fumantes, 89% sem atividade fisica regular, e das mulheres 48% ja tinham usado hormonios anticoncepcionais. A analise evidenciou que a ausencia de conhecimento se associou com sexo masculino, idade entre 20 e 40 anos, viuvo, nao branco e peso normal. Pressao arterial mais elevada (diastolica> 110 mm Hg) se associou com mais de 60 anos, nao casado, acima do peso, baixa escolaridade, baixa renda, com mais de 5 anos de hipertensao e ja ter feito tratamento anterior.

An 18-Week, Prospective, Randomized, Double-Blind, Multicenter Study of Amlodipine/Ramipril Combination Versus Amlodipine Monotherapy in the Treatment of Hypertension : The Assessment of Combination Therapy of Amlodipine/Ramipril (ATAR) Study

BACKGROUND A combination of antihypertensive agents of different drug classes in a fixed-dose combination (FDC) may offer advantages in terms of efficacy, tolerability, and treatment compliance. Combination of a calcium channel blocker with an angiotensin-converting enzyme inhibitor may act synergistically to reduce blood pressure (BP). OBJECTIVE The aim of this study was to compare the efficacy and tolerability of an amlodipine/ramipril FDC with those of amlodipine monotherapy. METHODS This 18-week, prospective, randomized, double-blind study was conducted at 8 centers across Brazil. Patients with stage 1 or 2 essential hypertension were enrolled. After a 2-week placebo run-in phase, patients received amlodipine/ramipril 2.5/2.5 mg or amlodipine 2.5 mg, after which the doses were titrated, based on BP, to 5/5 then 10/10 mg (amlodipine/ramipril) and 5 then 10 mg (amlodipine). The primary end point was BP measured in the intent-to-treat (ITT) population. Hematology and serum biochemistry were assessed at baseline and study end. Tolerability was assessed using patient interview, laboratory analysis, and physical examination, including measurement of ankle circumference to assess peripheral edema. RESULTS A total of 222 patients completed the study (age range, 40-79 years; FDC group, 117 patients [mean dose, 7.60/7.60 mg]; monotherapy, 105 patients [mean dose, 7.97 mg]). The mean (SD) changes in systolic BP (SBP) and diastolic BP (DBP), as measured using 24-hour ambulatory blood pressure monitoring (ABPM) and in the physicians office, were significantly greater with combination therapy than monotherapy, with the exception of office DBP (ABPM, -20.76 [1.25] vs -15.80 [1.18] mm Hg and -11.71 [0.78] vs -8.61 [0.74] mm Hg, respectively [both, P = 0.004]; office, -27.51 [1.40] vs -22.84 [1.33] mm Hg [P = 0.012] and -16.41 [0.79] vs -14.64 [0.75] mm Hg [P = NS], respectively). In the ITT analysis, the mean changes in ambulatory, but not office-based, BP were statistically significant (ABPM: SBP, -20.21 [1.14] vs -15.31 [1.12] mm Hg and DBP, -11.61 [0.72] vs -8.42 [0.70] mm Hg, respectively [both, P = 0.002]; office: SBP, -26.60 [1.34] vs -22.97 [1.30] mm Hg and DBP, -16.48 [0.78] vs -14.48 [0.75] mm Hg [both, P = NS]). Twenty-nine patients (22.1%) treated with combination therapy and 41 patients (30.6%) treated with monotherapy experienced > or =1 adverse event considered possibly related to study drug. The combination-therapy group had lower prevalence of edema (7.6% vs 18.7%; P = 0.011) and a similar prevalence of dry cough (3.8% vs 0.8%; P = NS). No clinically significant changes in laboratory values were found in either group. CONCLUSIONS In this population of patients with essential hypertension, the amlodipine/ramipril FDC was associated with significantly reduced ambulatory and office-measured BP compared with amlodipine monotherapy, with the exception of office DBP. Both treatments were well tolerated.

Amlodipine 2.5 mg once daily in older hypertensives: a brazilian multi-centre study

ObjectivesThe use of low-dose amlodipine has not yet been well established in the elderly. This study therefore aimed to evaluate the efficacy and tolerability of low-dose amlodipine in elderly patients with Joint National Committee VI stage I or II hypertension. Patients and methodsSixty-five hypertensive individuals (aged 66.3±5.3 years) received amlodipine 2.5 mg per day for 12 weeks before and after two periods of 4 weeks of placebo. At weeks 0, 12 and 16, patients were submitted to office, 24 h ambulatory blood pressure monitoring and home blood pressure measurement. ResultsOffice systolic and diastolic blood pressure showed decreases at weeks 8 (153±17, 90±9 mmHg) and 12 (152±16, 90±9 mmHg) compared with weeks 0 (164±16, 99±6 mmHg) and 16 (162±19, 95±9 mmHg). During ambulatory monitoring, a decrease was observed in the average 24 h systolic and diastolic pressure at week 12 (143±13, 86±7 mmHg) compared with weeks 0 (155±15, 93±6 mmHg) and 16 (152±16, 92±8 mmHg). A daytime and night-time reduction in systolic and diastolic pressure was observed on home blood pressure monitoring at week 12 (146±16/88±8, 144±16/93±8 mmHg) compared with weeks 0 (159±17/94±8, 161±19/93±8 mmHg) and 16 (153±16/93±8, 154±17/92±8 mmHg). Adverse reactions were infrequent. ConclusionsAmlodipine at a dose of 2.5 mg per day showed efficacy and good tolerability in elderly hypertensives.

Blood pressure regulation after deprivation of rapid-eye-movement sleep in rats.

We have shown previously that both sino-aortic denervation and high-renin hypertension in the rat produce a pronounced alteration in the pattern of blood pressure change during sleep; namely from unchanged to an increase in pressure during synchronized sleep, and from a slight increase to a marked decrease during desynchronized sleep. Since rapid-eye-movement sleep deprivation alters the pattern of sleep, we investigated the pattern of arterial pressure changes during sleep in rats submitted to a 48-h period of rapid-eye-movement sleep deprivation (platform technique). The deprived rats showed an increase in the number and length of desynchronized sleep episodes. Unexpectedly, they showed a blood pressure pattern change during synchronized and desynchronized sleep similar to that previously observed in sino-aortic denervated rats and in rats with high-renin hypertension: an increase in arterial pressure during synchronized sleep (+3.16 ± 0.4 versus +0.65 ± 0.65 mmHg in controls) and a decrease during desynchronized sleep (-6.24 ± 0.5 versus +4.22 ± 0.4 mmHg). These data suggest that deprivation of rapid-eye-movement sleep impairs the baroreceptor reflex function during sleep in rats.

The effect of siesta in parameters of cardiac structure and in interpretation of ambulatory arterial blood pressure monitoring

OBJECTIVE To evaluate the influence of the siesta in ambulatory blood pressure (BP) monitoring and in cardiac structure parameters. METHODS 1940 ambulatory arterial blood pressure monitoring tests were analyzed (Spacelabs 90207, 15/15 minutes from 7:00 to 22:00 hours and 20/20 minutes from 22:01 to 6.59hours) and 21% of the records indicated that the person had taken a siesta (263 woman, 52+/-14 years). The average duration of the siesta was 118+/-58 minutes. RESULTS (average +/- standard deviation) The average of systolic/diastolic pressures during wakefulness, including the napping period, was less than the average for the period not including the siesta (138+/-16/85+/-11 vs 139+/-16/86+/-11 mmHg, p<0. 05); 2) pressure loads during wakefulness including the siesta, were less than those observed without the siesta); 3) the averages of nocturnal sleep blood pressures were similar to those of the siesta, 4) nocturnal sleep pressure drops were similar to those in the siesta including wakefulness with and without the siesta; 5) the averages of BP in men were higher (p<0.05) during wakefulness with and without the siesta, during the siesta and nocturnal sleep in relation to the average obtained in women; 6) patients with a reduction of 0- 5% during the siesta had thickening of the interventricular septum and a larger posterior wall than those with a reduction during the siesta >5%. CONCLUSION The siesta influenced the heart structure parameters and from a statistical point of view the average of systolic and diastolic pressures and the respective pressure loads of the wakeful period.