Sympathetic chemoreflex responses in obstructive sleep apnea and effects of continuous positive airway pressure therapy

BACKGROUND: Sympathetic nerve activity is increased in awake and regularly breathing patients with obstructive sleep apnea (OSA). Over time, repetitive hypoxic stress could alter sympathetic chemoreflex function in OSA. METHODS: We determined the responses to acute hypoxia (fraction of inspired oxygen of 0.1, for 5 min), static handgrip exercise, and the cold pressor test (CPT) in 24 patients with OSA (age, 50 +/- 3 years [mean +/- SEM]; apnea-hypopnea index, 47 +/- 6 events per hour) and in 14 age- and weight-matched nonapneic control subjects. Muscle sympathetic nerve activity (MSNA) [peroneal microneurography], BP, and ventilation were monitored. RESULTS: Basal MSNA was higher in OSA patients compared to control subjects (45 +/- 4 bursts per minute vs 33 +/- 4 bursts per minute, respectively; p < 0.05). Furthermore, compared to control subjects, the MSNA responses to hypoxia were markedly enhanced in OSA (p < 0.001). Whereas the ventilatory responses to hypoxia tended to be increased in OSA (p = 0.06), the BP responses did not differ between the groups (p = 0.45). The neurocirculatory reflex responses to handgrip exercise and to the CPT were similar in the two groups (p = not significant). In OSA patients who were retested after 1 to 24 months of continuous positive airway pressure (CPAP) therapy (n = 11), basal MSNA (p < 0.01) and the responses of MSNA to hypoxia (p < 0.01) decreased significantly, whereas the ventilatory responses remained unchanged (p = 0.82). CONCLUSION: These data suggest that the sympathetic responses to hypoxic chemoreflex stimulation are enhanced in OSA and may normalize in part following CPAP therapy.     

Muscle sympathetic nerve activity during wakefulness in heart failure patients with and without sleep apnea

Sympathetic activation and sleep apnea are present in most patients with symptomatic systolic heart failure (HF). Acutely, obstructive and central apneas increase muscle sympathetic activity (MSNA) during sleep by eliciting recurrent hypoxia, hypercapnia, and arousal. In obstructive sleep apnea patients with normal systolic function, this increase persists after waking. Whether coexisting sleep apnea augments daytime MSNA in HF is unknown. We tested the hypothesis that its presence exerts additive effects on MSNA during wakefulness. Overnight sleep studies and morning MSNA recordings were performed on 60 subjects with ejection fraction <45%. Of these, 43 had an apnea-hypopnea index > or =15 per hour. Subjects with and subjects without sleep apnea were similar for age, ejection fraction, HF etiology, body mass index, blood pressure, and heart rate. Daytime MSNA was significantly higher in those with sleep apnea (76+/-2 versus 63+/-4 bursts per 100 heartbeats [mean+/-SEM], P=0.005; 58+/-2 versus 50+/-3 bursts/min, P=0.037), irrespective of its etiology (the mean difference for central sleep apnea was 17 bursts per 100 heartbeats; n=14; P=0.006; and for obstructive sleep apnea, 11 bursts per 100 heartbeats; n=29; P=0.032). In a subgroup (n=8), treatment of obstructive sleep apnea lowered MSNA by 12 bursts per 100 heartbeats (P=0.003). Convergence of independent excitatory influences of HF and sleep apnea on central sympathetic neurons results in higher MSNA during wakefulness in HF patients with coexisting sleep apnea. This additional stimulus to central sympathetic outflow may accelerate the progression of HF; its attenuation by treatment of sleep apnea represents a novel nonpharmacological opportunity.     

Atrial septostomy decreases sympathetic overactivity in pulmonary arterial hypertension

BACKGROUND: We have reported previously that the sympathetic nervous system is activated in patients with pulmonary arterial hypertension (PAH), and that this is only partly explained by a decrease in arterial oxygenation. Possible causes for increased muscle sympathetic nerve activity (MSNA) in patients with PAH include right atrial distension and decreased cardiac output. Both may be improved by atrial septostomy, but this intervention also further decreases arterial oxygenation. In the present study, we wanted to investigate the effect of atrial septostomy on MSNA in patients with PAH. METHODS: We recorded BP, heart rate (HR), arterial O2 saturation (SaO2), and MSNA before and after atrial septostomy in PAH patients (mean [+/- SE] age, 48 +/- 5 years) and in closely matched control subjects. Measurements were also performed after septostomy, while SaO2 was brought to the preprocedure level by supplemental O2 therapy. RESULTS: Compared to the control subjects (n = 10), the PAH patients (n = 11) had a lower mean BP (75 +/- 2 vs 96 +/- 3 mm Hg, respectively; p < 0.001), lower mean SaO2 (92 +/- 1% vs 97 +/- 0%, respectively; p < 0.001), increased mean HR (84 +/- 4 vs 68 +/- 3 beats/min; p < 0.01), and markedly increased mean MSNA (76 +/- 5 vs 29 +/- 2 bursts per minute; p < 0.001). Atrial septostomy decreased mean SaO2 (to 85 +/- 2%; p < 0.001) and mean MSNA (to 69 +/- 4 bursts per minute; p < 0.01), but did not affect HR or BP. Therapy with supplemental O2 did not affect MSNA, BP, or HR. The decrease in MSNA was correlated to the decrease in right atrial pressure (r = 0.62; p < 0.05). CONCLUSIONS: Atrial septostomy in PAH patients decreases sympathetic hyperactivity despite an associated decrease in arterial oxygenation, and this appears to be related to decreased right atrial distension.     

Cigarette smoking augments sympathetic nerve activity in patients with coronary heart disease

It has been shown that cigarette smoking increases blood pressure (BP) and heart rate (HR), and decreases muscle sympathetic nerve activity (MSNA) in healthy young smokers. The decrease in MSNA might be secondary to baroreflex responses to the pressor effect. We tested the hypothesis that cigarette smoking increases MSNA in smokers with impaired baroreflex function. The effects of cigarette smoking on BP, HR, forearm blood flow (FBF), forearm vascular resistance (FVR), and MSNA were examined in 14 patients with stable effort angina (59+/-3 years, group CAD) and 10 healthy smokers (23+/-1 years, group C). In group CAD, the arterial baroreflex sensitivity (BRS) was significantly lower than in group C (4.7+/-0.8 versus 15.1+/-2.2 msec/mmHg, P<0.01). In both groups, cigarette smoking increased the plasma concentration of nicotine, systolic and diastolic BP, HR, and FVR significantly (P<0.01), but decreased FBF significantly (P<0.01). After smoking, MSNA was decreased significantly in group C (from 35.2+/-3.5 to 23.5+/-3.2 bursts/100 beats, P<0.01), but increased significantly in group CAD (from 48.8+/-5.4 to 57.3+/-5.5 bursts/100 beats, P<0.01). There was significant correlation between BRS and changes in MSNA (r= -0.62, P<0.01). Cigarette smoking increased MSNA in smokers with impaired baroreflex function. This demonstrates that cigarette smoking stimulates sympathetic nerve activity by both a direct peripheral effect and a centrally mediated effect.     

Abnormal muscle metaboreflex control of sympathetic activity in never-treated hypertensive subjects

BACKGROUND: Muscle metaboreflex control in hypertensive subjects has not been described yet. We investigated the integrity of muscle metaboreflex control of muscle sympathetic nerve activity (MSNA) and blood pressure (BP) in never-treated hypertensive subjects. METHODS: Eighteen hypertensive (42+/-1 years) and 22 normotensive subjects (38+/-1 years) were studied. The MSNA was measured by microneurography and forearm blood flow (FBF) by venous occlusion plethysmography. The BP was noninvasively monitored. RESULTS: Baseline MSNA was significantly increased in hypertensive subjects when compared with normal subjects (34+/-2 v 22+/-2 bursts/min, P<.001). Baseline FBF was significantly decreased in hypertensive subjects (2.66+/-0.2 v 2.05+/-0.1 mL/min/100 mL, P=.04). During moderate handgrip exercise (30% maximal voluntary contraction), MSNA levels were significantly higher in hypertensive subjects. However, MSNA responses were significantly lower in hypertensive subjects (1+/-3 v 10+/-2 bursts/100 heart beats, P = .001). Similarly, FBF responses were significantly lower in hypertensive subjects when compared with normotensive subjects (0.70+/-0.19 v 1.60+/-0.36 mL/min/100 mL, P=.04). During the postexercise circulatory arrest, when the metaboreflex control is isolated, MSNA levels returned toward baseline in hypertensive subjects (58+/-4 v 55+/-3 bursts/100 heart beats, P=.98). In contrast, in normotensive subjects, MSNA levels remained significantly elevated when compared with baseline (48+/-3 v 35+/-1 bursts/100 heart beats, P<.001). CONCLUSIONS: These findings suggest an association between hypertension and decreased muscle metaboreflex control of MSNA.     

Peripheral sympathetic control during dobutamine infusion: effects of aging and heart failure

OBJECTIVES: We assessed the effects of beta-adrenergic agonism on muscle sympathetic nerve activity (MSNA) in patients with congestive heart failure (CHF) and young and matched controls. BACKGROUND: Myocardial response to beta-adrenergic stimulation decreases with aging and with CHF. METHODS: In CHF patients, we measured cardiac hemodynamics and MSNA (microneurography) before, with short-term (n = 5), and after 48-h (n = 9) of dobutamine infusion (10 microg/kg/min). In eight young controls and nine controls matched to the CHF patients, we measured cardiac hemodynamics and MSNA during randomized short-term dobutamine (10 microg/kg/min) and placebo infusions. RESULTS: In CHF patients, short-term dobutamine infusion did not modify mean blood pressure (MBP), MSNA, or heart rate (HR). Moreover, 48-h dobutamine infusion increased cardiac index (3.1 +/- 0.2 vs. 2.2 +/- 0.2 l/min/m(2), p = 0.006), decreased mean pulmonary pressure (28 +/- 7 vs. 38 +/- 7 mm Hg, p = 0.0001) and peripheral resistance (1,099 +/- 112 vs. 1,759 +/- 263, p = 0.03), but did not change MBP, HR, or MSNA in the patients. In matched controls, dobutamine increased HR (87 +/- 5 vs. 65 +/- 2 beats/min, p = 0.0009) but did not change MBP or MSNA. In young controls, dobutamine increased MBP (102 +/- 2 vs. 90 +/- 2 mm Hg, p = 0.0003) and decreased MSNA (28 +/- 5 vs. 35 +/- 3 bursts/min, p = 0.03) but did not change HR (p = 0.054). In the controls, the largest increases in MBP with dobutamine were associated with the most marked reductions in MSNA (r = -0.49, p = 0.04) and the smallest increases in HR (r = -0.70, p = 0.001). CONCLUSIONS: Arterial baroreceptor activation during increases in MBP inhibits MSNA and limits the HR response to dobutamine in controls. This mechanism, together with peripheral vasodilation, probably contributes to the absence of peripheral sympathetic withdrawal despite substantial hemodynamic improvements in CHF patients.     

Acupuncture inhibits sympathetic activation during mental stress in advanced heart failure patients

BACKGROUND: In heart failure (HF) patients, muscle sympathetic nerve activity is increased, and HF patients with the greatest sympathetic activation have the poorest prognosis. In animals, acupuncture is sympathoinhibitory, and the most profound sympathoinhibition occurs in animals with the highest resting sympathetic nerve activity. The purpose of this study was to test the hypothesis that acupuncture is sympathoinhibitory in humans with HF. METHODS AND RESULTS: Fifteen advanced HF patients underwent acute mental stress testing before and during (1) "real" acupuncture (n = 10), (2) non-acupoint acupuncture (n = 10), and (3) no-needle acupuncture control (n = 10). Muscle sympathetic nerve activity (MSNA) was recorded using peroneal microneurography. Resting MSNA was not different before and after acupuncture (52 +/- 22 versus 50 +/- 21 bursts/min, P = NS). During mental stress, SNA increased significantly. This increase was eliminated following real acupuncture (mean delta MSNA pre-acupuncture versus post-acupuncture: 149 +/- 171 versus -169 +/- 130, P =.03), but not after non-acupoint or no-needle acupuncture controls. The changes in blood pressure and heart rate during mental stress were not attenuated by real or control acupuncture. CONCLUSION: Acute acupuncture attenuates sympathoexcitation during mental stress in advanced HF patients.     

Acute cardiovascular and sympathetic effects of nicotine replacement therapy

Sympathetic overactivity is implicated in the increased cardiovascular risk of cigarette smokers. Excitatory nicotinic receptors are present on peripheral chemoreceptor cells. Chemoreceptors located in the carotid and aortic bodies increase ventilation (Ve), blood pressure (BP), heart rate (HR), and sympathetic nerve activity to muscle circulation (MSNA) in response to hypoxia. We tested the hypothesis that nicotine replacement therapy (NRT) increases MSNA and chemoreceptor sensitivity to hypoxia. Sixteen young healthy smokers were included in the study (8 women). After a randomized and blinded sublingual administration of a 4-mg tablet of nicotine or placebo, we measured minute Ve, HR, mean BP, and MSNA during normoxia and 5 minutes of isocapnic hypoxia. Maximal voluntary end-expiratory apneas were performed at baseline and at the end of the fifth minute of hypoxia. Nicotine increased HR by 7+/-3 bpm, mean BP by 5+/-2 mm Hg, and MSNA by 4+/-1 bursts/min, whereas subjects breathed room air (all P<0.05). During hypoxia, nicotine also raised HR by 8+/-2 bpm, mean BP by 2+/-1 mm Hg, and MSNA by 7+/-2 bursts/min (all P<0.05). Nicotine increased MSNA during the apneas performed in normoxia and hypoxia (P<0.05). Nicotine also raised the product of systolic BP and HR, a marker of cardiac oxygen consumption, during normoxia, hypoxia, and the apneas (P<0.05). Ve, apnea duration, and O2 saturation during hypoxia and the apneas remained unaffected. In conclusion, sympathoexcitatory effects of NRT are not because of an increased chemoreflex sensitivity to hypoxia. NRT increases myocardial oxygen consumption in periods of reduced oxygen availability.     

Refractory hypertension and sleep apnoea: effect of CPAP on blood pressure and baroreflex.

This study was undertaken to determine whether abolition of obstructive sleep apnoea (OSA) by continuous positive airway pressure (CPAP) could reduce blood pressure (BP) in patients with refractory hypertension. In 11 refractory hypertensive patients with OSA, the acute effects of CPAP on nocturnal BP were studied during sleep and its longer term effects on 24-h ambulatory BP after 2 months. During a single night's application, CPAP abolished OSA and reduced systolic BP in stage 2 sleep from 138.3 +/- 6.8 to 126.0 +/- 6.3 mmHg. There was also a trend towards a reduction in average diastolic BP (from 77.7 +/- 4.5 to 72.9 +/- 4.5). CPAP usage for 2 months was accompanied by an 11.0 +/- 4.4 mmHg reduction in 24-h systolic BP. In addition, both the nocturnal and daytime components of systolic BP fell significantly by 14.4 +/- 4.4 and 9.3 +/- 3.9 mmHg, respectively. Diastolic BP was reduced significantly at night by 7.8 +/- 3.0 mmHg. In patients with refractory hypertension, acute abolition of obstructive sleep apnoea by continuous positive airway pressure reduces nocturnal blood pressure. These data also suggest that continuous positive airway pressure may reduce nocturnal and daytime systolic blood pressure chronically. Randomised trials are needed to confirm the latter results.     

Prognosis of patients with heart failure and obstructive sleep apnea treated with continuous positive airway pressure

BACKGROUND: Therapy with continuous positive airway pressure (CPAP) provides several benefits for patients with heart failure (HF) complicated by obstructive sleep apnea (OSA). However, the effect on the prognosis of such patients remains unknown. Aims: To determine whether CPAP therapy and compliance affects the prognosis of HF patients with OSA. METHODS: We classified 88 patients with HF and moderate-to-severe OSA into a CPAP-treated group (n = 65) and an untreated group (n = 23), and then those treated with CPAP were further subclassified according to CPAP therapy compliance. The frequency of death and hospitalization was analyzed using multivariate analysis. RESULTS: During a mean (+/- SD) period of 25.3 +/- 15.3 months, 44.3% of the patients died or were hospitalized. Multivariate analysis showed that the risk for death and hospitalization was increased in the untreated group (hazard ratio [HR], 2.03; 95% confidence interval [CI], 1.07 to 3.68; p = 0.030) and in less compliant CPAP-treated patients (HR, 4.02; 95% CI, 1.33 to 12.2; p = 0.014). CONCLUSION: Therapy with CPAP significantly reduced the risk of death and hospitalization among patients with HF and OSA. However, reduced compliance with CPAP therapy was significantly associated with an increased risk of death and hospitalization.     

Adrenergic and reflex abnormalities in obesity-related hypertension

Previous studies have shown that essential hypertension and obesity are both characterized by sympathetic activation coupled with a baroreflex impairment. The present study was aimed at determining the effects of the concomitant presence of the 2 above-mentioned conditions on sympathetic activity as well as on baroreflex cardiovascular control. In 14 normotensive lean subjects (aged 33. 5+/-2.2 years, body mass index 22.8+/-0.7 kg/m(2) [mean+/-SEM]), 16 normotensive obese subjects (body mass index 37.2+/-1.3 kg/m(2)), 13 lean hypertensive subjects (body mass index 24.0+/-0.8 kg/m(2)), and 16 obese hypertensive subjects (body mass index 37.5+/-1.3 kg/m(2)), all age-matched, we measured beat-to-beat arterial blood pressure (by Finapres device), heart rate (HR, by ECG), and postganglionic muscle sympathetic nerve activity (MSNA, by microneurography) at rest and during baroreceptor stimulation and deactivation induced by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. Blood pressure values were higher in lean hypertensive and obese hypertensive subjects than in normotensive lean and obese subjects. MSNA was significantly (P:<0.01) greater in obese normotensive subjects (49.1+/-3.0 bursts per 100 heart beats) and in lean hypertensive subjects (44.5+/-3.3 bursts per 100 heart beats) than in lean normotensive control subjects (32.2+/-2.5 bursts per 100 heart beats); a further increase was detectable in individuals with the concomitant presence of obesity and hypertension (62.1+/-3. 4 bursts per 100 heart beats). Furthermore, whereas in lean hypertensive subjects, only baroreflex control of HR was impaired, in obese normotensive subjects, both HR and MSNA baroreflex changes were attenuated, with a further attenuation being observed in obese hypertensive patients. Thus, the association between obesity and hypertension triggers a sympathetic activation and an impairment in baroreflex cardiovascular control that are greater in magnitude than those found in either of the above-mentioned abnormal conditions alone.     

Exercise training reduces sympathetic nerve activity in heart failure patients treated with carvedilol

BACKGROUND: Evidence suggests that carvedilol decreases muscle sympathetic nerve activity (MSNA) in patients with heart failure (HF) but carvedilol fails to improve forearm vascular resistance and overall functional capacity. Exercise training in HF reduces MSNA and improves forearm vascular resistance and functional capacity. AIMS: To investigate whether the beneficial effects exercise training on MSNA are maintained in the presence of carvedilol. METHODS AND RESULTS: Twenty seven HF patients, NYHA Class II-III, EF <35%, peak VO(2) <20 ml/kg/min, treated with carvedilol were randomly divided into two groups: exercise training (n=15) and untrained (n=12). MSNA was recorded by microneurography. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. The four-month training program consisted of three 60-min exercise/week on a cycloergometer. Baseline parameters were similar between groups. Exercise training reduced MSNA (-14+/-3.3 bursts/100 HB, p=0.001) and increased forearm blood flow (0.6+/-0.1 mL/min/100 g, p<0.001) in HF patients on carvedilol. In addition, exercise training improved peak VO(2) in HF patients (20+/-6%, p=0.002). MSNA, FBF and peak VO(2) were unchanged in untrained HF patients on carvedilol. CONCLUSION: Exercise training reduces MSNA in heart failure patients treated with carvedilol. In addition, the beneficial effects of exercise training on muscle blood flow and functional capacity are still realized in patients on carvedilol.     

Reduced sympathoneural responses to the cold pressor test in individuals with essential hypertension and in those genetically predisposed to hypertension. No support for the "pressor reactor" hypothesis of hypertension development

BACKGROUND: The aim of this study was to examine the influences of genetic predisposition to hypertension and of age on the sympathetic nervous system response to the cold pressor test (CPT). METHODS: A total of 32 young subjects (aged 27 +/- 2 years) were studied: 11 normotensive subjects without a family history of hypertension (FH), 14 normotensive subjects with a strong family history of hypertension (FH+), and eight hypertensive subjects. In addition, 21 older subjects (aged 53 +/- 2 years) were studied: 13 hypertensive and eight normotensive subjects. Blood pressure (BP), heart rate (HR), and muscle sympathetic nerve activity (MSNA) were recorded at rest and during a 2-min period of a CPT. RESULTS: Both young and older hypertensive subjects had higher resting MSNA than did the normotensive ones (47 +/- 7 v 29 +/- 4 bursts per 100 heartbeats (P < .05) and 66 +/- 4 v 40 +/- 7 bursts per 100 heartbeats (P < .01), respectively). The CPT resulted in HR increases of similar magnitude in all groups of patients. The FH+ group displayed slightly less increase in systolic BP than that of the FH- group (P < .05). The MSNA increased to a far greater degree in FH- (103%) than in FH+ (32%) and in young hypertensive patients (12%) (P < .05). Similarly, MSNA change with the CPT was greater in older normotensive subjects than in older hypertensive patients (61% v 12%, P < .05). CONCLUSIONS: Our results show that a CPT induces sympathetic responses that are subnormal in hypertensive patients and those with a family history of hypertension, highlighting the importance of genetic factors in determining the sympathetic nervous reactivity to CPT.     

The effects of continuous positive airway pressure on myocardial energetics in patients with heart failure and obstructive sleep apnea.

OBJECTIVES: We sought to examine the short-term and longer term (6-week) effects of continuous positive airway pressure (CPAP) on myocardial energetics. BACKGROUND: Obstructive sleep apnea (OSA) and heart failure (HF) are both states of increased afterload and metabolic demand. Treatment with CPAP may initially reduce stroke volume but subsequently improves left ventricular function. However, it is not clear whether CPAP therapy favorably affects myocardial energetics and hence improves cardiac efficiency. METHODS: Twelve patients with HF were divided into two groups: 7 patients with OSA were treated with CPAP (group I), and 5 patients without OSA served as a control group (group II). Oxidative metabolism was measured using the mono-exponential fit of the myocardial [(11)C] acetate positron emission tomography time-activity curve (k-mono). Myocardial efficiency was derived using the work metabolic index (WMI = [heart rate x stroke volume index x systolic blood pressure]/k-mono) measured at baseline, during short-term CPAP, and after 6 +/- 3 weeks of CPAP. RESULTS: In group I, short-term CPAP tended to reduce SVI (p = 0.063) and reduced oxidative metabolism (p = 0.031). Work metabolic index did not change. However, longer term CPAP improved left ventricular ejection fraction (38.4 +/- 3.3% to 43.4 +/- 4.8%, p = 0.031), tended to reduce oxidative metabolism (0.047 +/- 0.012 to 0.040 +/- 0.008 min(-1), p = 0.078), and improved WMI (7.13 +/- 2.82 x 10(6) to 8.17 +/- 3.06 x 10(6) mm Hg.ml/m(2), p = 0.031). In group II (control), these parameters did not change. CONCLUSIONS: In this cohort of patients with HF and OSA, short-term CPAP decreased oxidative metabolism and tended to decrease SVI, but did not alter cardiac efficiency. Longer term CPAP improved cardiac efficiency, indicating an energy-sparing effect. These effects may contribute to the benefits of CPAP therapy.     

Blood pressure changes after automatic and fixed CPAP in obstructive sleep apnea: relationship with nocturnal sympathetic activity

Treatment of obstructive sleep apnea (OSA) by continuous positive airway pressure (CPAP) usually causes a reduction in blood pressure (BP), but several factors may interfere with its effects. In addition, although a high sympathetic activity is considered a major contributor to increased BP in OSA, a relationship between changes in BP and in sympathetic nervous system activity after OSA treatment is uncertain. This study was undertaken to assess if, in OSA subjects under no pharmacologic treatment, treatment by CPAP applied at variable levels by an automatic device (APAP) may be followed by a BP reduction, and if that treatment is associated with parallel changes in BP and catecholamine excretion during the sleep hours. Nine subjects underwent 24-h ambulatory BP monitoring and nocturnal urinary catecholamine determinations before OSA treatment and 2 months following OSA treatment by APAP (Somnosmart2, Weinmann, Hamburg, Germany). Eight control subjects were treated by CPAP at a fixed level. After APAP treatment, systolic blood pressure (SBP) decreased during sleep (p < 0.05), while diastolic blood pressure (DBP) decreased both during wakefulness (p < 0.05) and sleep (p < 0.02). Similar changes were observed in subjects receiving fixed CPAP. Nocturnal DBP changes were correlated with norepinephrine (in the whole sample: r = .61, p < 0.02) and normetanephrine (r = .71, p < 0.01) changes. In OSA subjects under no pharmacologic treatment, APAP reduces BP during wakefulness and sleep, similarly to CPAP. A reduction in nocturnal sympathetic activity could contribute to the reduction in DBP during sleep following OSA treatment.     

Controlled trial of continuous positive airway pressure in obstructive sleep apnea and heart failure

Obstructive sleep apnea (OSA) is highly prevalent among patients with congestive heart failure (CHF) and may contribute to progression of cardiac dysfunction via hypoxia, elevated sympathetic nervous system activity, and systemic hypertension. Our aim was to assess the long-term effect of OSA treatment with nocturnal continuous positive airway pressure (CPAP) on systolic heart function, sympathetic activity, blood pressure, and quality of life in patients with CHF. Fifty-five patients with CHF and OSA were randomized to 3 months of CPAP or control groups. End points were changes in left ventricular ejection fraction, overnight urinary norepinephrine excretion, blood pressure, and quality of life. Nineteen patients in the CPAP group and 21 control subjects completed the study. Compared with the control group, CPAP treatment was associated with significant improvements in left ventricular ejection fraction (delta 1.5 +/- 1.4% vs. 5.0 +/- 1.0%, respectively, p = 0.04), reductions in overnight urinary norepinephrine excretion (delta 1.6 +/- 3.7 vs. -9.9 +/- 3.6 nmol/mmol creatinine, p = 0.036), and improvements in quality of life. There were no significant changes in systemic blood pressure. In conclusion, treatment of OSA among patients with CHF leads to improvement in cardiac function, sympathetic activity, and quality of life.     

Obstructive sleep apnea syndrome: more insights on structural and functional cardiac alterations, and the effects of treatment with continuous positive airway pressure.

OBJECTIVES: We studied structural and functional cardiac alterations in obstructive sleep apnea (OSA), their relationship to the severity of OSA, and the effects of treatment with continuous positive airway pressure (CPAP). BACKGROUND: Obstructive sleep apnea may influence the cardiac function by several mechanisms in the awake patient. METHODS: Left and right ventricular morphology and function were studied using echocardiography before and after treatment with CPAP in symptomatic patients (Epworth sleepiness score, 10 +/- 4.8) with severe OSA (apnea-hypopnea index [AHI], 42 +/- 24). The patients (n = 43, 32 men) had no known cardiac disease and were obese (body mass index, 31.6 +/- 5.4 kg/m2). The same echocardiographic parameters were studied in age-matched overweight patients (n = 40; body mass index, 26.4 +/- 2.3 kg/m2). RESULTS: The patients were hypertensive (systolic blood pressure, 153 +/- 25 mm Hg), with a higher resting heart rate (77 +/- 10 beats/min, p = 0.008) compared with age-matched control patients (n = 40). There was right ventricular dilatation, hypertrophic interventricular septum, reduced left ventricular stroke volume, tissue Doppler-determined systolic and diastolic velocities of the left and right ventricle, and normal pulmonary artery pressure. The structural and functional parameters were significantly associated with AHI (p < 0.004). Multiple stepwise regression showed the interventricular septum thickness, right ventricular free wall, and mitral annulus tissue Doppler systolic velocities to be predictive of a higher AHI (p < 0.001). Six months after treatment with CPAP, significant improvements were observed in the symptoms and hemodynamics, as well as left and right ventricular morphology and function. CONCLUSIONS: The structural and functional consequences of OSA on the heart are influenced by the severity of AHI. These effects are reversible if the apneic episodes are abolished.     

The effects of exercise training on sympathetic neural activation in advanced heart failure: a randomized controlled trial

OBJECTIVES: The goal of this study was to test the hypothesis that exercise training reduces resting sympathetic neural activation in patients with chronic advanced heart failure. BACKGROUND: Exercise training in heart failure has been shown to be beneficial, but its mechanisms of benefit remain unknown. METHODS: Sixteen New York Heart Association class II to III heart failure patients, age 35 to 60 years, ejection fraction < or =40% were divided into two groups: 1) exercise-trained (n = 7), and 2) sedentary control (n = 9). A normal control exercise-trained group was also studied (n = 8). The four-month supervised exercise training program consisted of three 60 min exercise sessions per week, at heart rate levels that corresponded up to 10% below the respiratory compensation point. Muscle sympathetic nerve activity (MSNA) was recorded directly from peroneal nerve using the technique of microneurography. Forearm blood flow was measured by venous plethysmography. RESULTS: Baseline MSNA was greater in heart failure patients compared with normal controls; MSNA was uniformly decreased after exercise training in heart failure patients (60 +/- 3 vs. 38 +/- 3 bursts/100 heart beats), and the mean difference in the change was significantly (p < 0.05) greater than the mean difference in the change in sedentary heart failure or trained normal controls. In fact, resting MSNA in trained heart failure patients was no longer significantly greater than in trained normal controls. In heart failure patients, peak VO(2) and forearm blood flow, but not left ventricular ejection fraction, increased after training. CONCLUSIONS: These findings demonstrate that exercise training in heart failure patients results in dramatic reductions in directly recorded resting sympathetic nerve activity. In fact, MSNA was no longer greater than in trained, healthy controls.     

Hypertensive left ventricular hypertrophy: relation to peripheral sympathetic drive.

OBJECTIVES: This study was designed to examine whether the occurrence of left ventricular hypertrophy (LVH) in moderate to severe essential hypertension (EHT) was associated with alteration in peripheral sympathetic drive. BACKGROUND: In hypertension, LVH is an independent predictor of increased morbidity and mortality. The reported mechanisms leading to LVH remain unclear but include hemodynamic and humoral factors. The sympathetic nervous system may be important, particularly as catecholamines have been shown to have trophic properties. We tested the hypothesis that sympathetic activity measured using microneurography could be different in patients with hypertension depending on the presence of LVH. METHODS: We examined 28 subjects with moderate to severe EHT (stages 2 to 3; Joint National Committee [JNC]-VI classification). Fourteen had echocardiographic evidence of LVH (EHT + LVH), while the other 14 subjects (EHT) did not. Subjects were matched in terms of age, body mass index and levels of arterial blood pressure. Peripheral muscle sympathetic nerve activity was measured from both multiunit bursts (MSNA) and single unit (s-MSNA) vasoconstrictor impulses via the peroneal nerve. RESULTS: The mean frequency of s-MSNA and MSNA was greater in the EHT + LVH group than it was in the EHT group (mean +/- SEM; 75.9 +/- 6.9 impulses/100 beats vs. 52.1 +/- 2.9 impulses/100 beats, p < 0.001 and 64.2 +/- 5.7 bursts/100 beats vs. 48.9 +/- 2.8 bursts/100 beats, p < 0.05). CONCLUSIONS: These results indicate that, in subjects with moderate to severe hypertension, the presence of LVH is associated with higher sympathetic discharge, evidenced by an increase in unitary firing frequency and also by fiber recruitment.     

Sympathetic rhythmicity in cardiac transplant recipients

BACKGROUND: Variability of R-R interval and muscle sympathetic nerve activity (MSNA) occurs predominantly at a low frequency (LF, +/-0.1 Hz) and a high frequency (HF, +/-0.25 Hz) in normal humans. Increased sympathetic drive in normal humans is associated with an increased LF component of the R-R interval and MSNA. Patients with severe heart failure have high sympathetic activity but decreased or absent LF power of both R-R and MSNA. We tested the hypothesis that this dysfunction in autonomic modulation in heart failure can be reversed by heart transplantation. METHODS AND RESULTS: We performed spectral analysis of resting MSNA, R-R interval, and respiration in 9 patients with heart transplants, 9 chronic heart failure patients, and 9 normal control subjects, all closely matched for age, sex, and body mass index. MSNA (bursts per minute) was higher in patients with heart transplants (74+/-3) than either patients with heart failure (56+/-6) or normal subjects (40+/-4) (P<0.001). LF variability in the R-R interval was reduced in both heart transplant recipients and heart failure patients compared with the control subjects (P<0.01). The LF variability in MSNA was also nearly absent in the heart failure patients (P<0.01). However, the LF and HF oscillations in MSNA in patients with heart transplants were comparable to those evident in the control subjects. CONCLUSIONS: Cardiac transplantation does not reduce MSNA. However, LF oscillations in sympathetic activity are restored after transplantation such that the MSNA oscillatory profile is similar to that observed in normal subjects.