Effects of sleep-disordered breathing and hypertension on cognitive function in elderly adults.

Purpose: The prevalence of sleep-disordered breathing (SDB) increases with aging. SDB is a risk of hypertension, and both might lead to cognitive decline. However, the role of SDB and hypertension on the pathogenesis of age-related cognitive decline remains unclear. We examined the effects of these two diseases on cognitive function in elderly adults.Methods: Fifty-two elderly individuals (mean age, 69.6 ± 4.0 years) free from impairment in daily living activities participated in this study. Apnea/hypopnea index (AHI) and minimum oxygen saturation (SpO2) were assessed using a portable home monitoring device. We evaluated excessive daytime sleepiness with the Epworth sleepiness scale (ESS). Cognitive performance was assessed using the Wisconsin card sorting test (WCST), continuous performance test-Identical pairs (CPT-IP), and N-back task. Hypertension and diabetes mellitus were evaluated via questionnaire and blood pressure value.Results: The WCST category achievement was significantly lower in participants with minimum SpO2 <90% than those with minimum SpO2 ≥90%. The percentage of correct answer on the 0- and 1-back tasks was significantly lower in the hypertensives than normotensives. Minimum SpO2 was correlated with category achievement on the WCST. Multiple regression analysis including age, sex, body mass index, AHI, minimum SpO2, ESS, hypertension, and diabetes mellitus revealed that hypertension was the most significant factor for percentage correct answers on the 0- and 1-back tasks. There were no significant correlations between body mass index, ESS or diabetes mellitus and the parameters of WCST, CPT-IP, or N-back tasks.Conclusion: In elderly adults, nocturnal hypoxia and hypertension had a negative effect on cognitive function.

Very low frequency component of heart rate variability as a marker for therapeutic efficacy in patients with obstructive sleep apnea: Preliminary study.

BACKGROUND: Although positive airway pressure (PAP) therapy is effective for treating obstructive sleep apnea (OSA), some patients with severe OSA are intolerable to this treatment, which may lead to an increase in the mortality and morbidity of cardiovascular diseases. We investigated the relationship between heart rate variability (HRV) and sleep parameters during natural sleep and treatment of patients with OSA. MATERIALS AND METHODS: This was the cross-sectional observation study. Patients were 17 males with severe OSA who were unable to accept continuous PAP. Standard polysomnography was performed for two consecutive nights, i.e., during natural sleep and following night with bilevel PAP (BiPAP) treatment. Time-dependent responses of the amplitudes of low frequency (LF), very low frequency (VLF), and high frequency components of HRV were assessed with the technique of complex demodulation. RESULTS: Apnea-hypopnea index, oxygen desaturation time, and percentage of stage 1 sleep were significantly reduced, whereas the percentages of rapid eye movement and stages 3 + 4 sleep were increased, by BiPAP treatment. Therapy also reduced the amplitudes of VLF and LF components of HRV. Difference in amplitudes of VLF during natural sleep and treatment with BiPAP was significantly correlated with difference in percentages of stage 1 and stages 3 + 4 sleep. CONCLUSION: Therapy-induced amelioration of OSA and sleep quality was accompanied by decrease in the amplitudes of VLF components of HRV. The VLF component may thus reflect physiological changes in both autonomic activity and sleep structure and serve as an objective marker for therapeutic efficacy in patients with severe OSA.

Blunted cyclic variation of heart rate predicts mortality risk in post-myocardial infarction, end-stage renal disease, and chronic heart failure patients.

AIMS: Cyclic variation of heart rate (CVHR) associated with sleep-disordered breathing is thought to reflect cardiac autonomic responses to apnoeic/hypoxic stress. We examined whether blunted CVHR observed in ambulatory ECG could predict the mortality risk. METHODS AND RESULTS: CVHR in night-time Holter ECG was detected by an automated algorithm, and the prognostic relationships of the frequency (FCV) and amplitude (ACV) of CVHR were examined in 717 patients after myocardial infarction (post-MI 1, 6% mortality, median follow-up 25 months). The predictive power was prospectively validated in three independent cohorts: a second group of 220 post-MI patients (post-MI 2, 25.5% mortality, follow-up 45 months); 299 patients with end-stage renal disease on chronic haemodialysis (ESRD, 28.1% mortality, follow-up 85 months); and 100 patients with chronic heart failure (CHF, 35% mortality, follow-up 38 months). Although CVHR was observed in ≥96% of the patients in all cohorts, FCV did not predict mortality in any cohort. In contrast, decreased ACV was a powerful predictor of mortality in the post-MI 1 cohort (hazard ratio [95% CI] per 1 ln [ms] decrement, 2.9 [2.2-3.7], P < 0.001). This prognostic relationship was validated in the post-MI 2 (1.8 [1.4-2.2], P < 0.001), ESRD (1.5 [1.3-1.8], P < 0.001), and CHF (1.4 [1.1-1.8], P = 0.02) cohorts. The prognostic value of ACV was independent of age, gender, diabetes, ß-blocker therapy, left ventricular ejection fraction, sleep-time mean R-R interval, and FCV. CONCLUSION: Blunted CVHR detected by decreased ACV in a night-time Holter ECG predicts increased mortality risk in post-MI, ESRD, and CHF patients.

Influence of sleep duration on cortical oxygenation in elderly individuals.

AIM: Short sleep duration is a risk factor for cardiovascular diseases. Cerebral blood flow and its regulation are affected by pathological conditions commonly observed in the elderly population, such as dementia, atherosclerosis, diabetes mellitus (DM), stroke, and hypertension. The purpose of this study was to examine the influence of sleep duration on cortical oxygenated hemoglobin (OxyHb) using near-infrared spectroscopy (NIRS). METHODS: Seventy-three individuals (age, 70.1 ± 3.9 years, 51 men and 22 women) participated in this study. Cortical OxyHb levels were measured with NIRS. We evaluated age, body mass index (BMI), smoking status, alcohol intake, sleep duration, hypertension, DM, and hyperlipidemia using a questionnaire. Blood pressure was measured using plethysmography. RESULTS: Peak OxyHb and area under the NIRS curve significantly decreased in participants with sleep duration <7 h compared with those with sleep duration ≥7 h (0.136 ± 0.212 mM·mm vs 0.378 ± 0.342 mM·mm, P = 0.001; 112.0 ± 243.6 vs 331.7 ± 428.7, P = 0.012, respectively). Sleep duration was significantly correlated with peak OxyHb level and area under the NIRS curve (r = 0.378, P = 0.001; r = 0.285, P = 0.015, respectively). Multiple regression analysis, including age, BMI, sex, smoking status, alcohol intake, sleep duration, hypertension, DM, and hyperlipidemia revealed that sleep duration was the only significant independent factor associated with peak OxyHb and area under the NIRS curve (ß = 0.343, P = 0.004; ß = 0.244, P = 0.049, respectively), and smoking status was independently correlated with time to the peak OxyHb (ß = -0.319, P = 0.009). CONCLUSION: Sleep duration may be an important factor that influences cortical oxygenation in the elderly population.

Blood Pressure Regulation and Hypertension in Obstructive Sleep Apnea Syndrome: A Historical Perspective.

In obstructive sleep apnea syndrome (OSAS), an underlying disease of secondary hypertension, repeated episodes of asphyxia due to obstructive sleep apnea (OSA), followed by arousal, lead to various cardiovascular consequences. Using a canine model of OSAS, it was found that a single load of OSA caused an abrupt increase in blood pressure (BP) (Apnea Surge in seconds), while multiple OSA episodes occurring nightly for 1-3 months led to a sustained elevation of BP during both nighttime and daytime. Epidemiological studies on 24-hour ambulatory BP measurements revealed that some hypertensive patients experienced elevated BP in the early morning (Morning Surge), which could be intensified by OSAS. The resonance of Apnea Surge in seconds and Morning Surge increases the risk of organ damage, triggers the cardiovascular events, and adversely affects the prognosis of hypertensive patients with OSAS.For ameliorating these risks, OSA should be treated with positive airway pressure properly.

Assessment of cognitive function and sleep-wake rhythms in community-dwelling older adults.

Disruption of the circadian rhythm and sleep-wake cycles is a consequence of aging and is associated with the cognitive decline and many neurodegenerative conditions. We investigated the bedtime, wake-up time, sleep timing (midpoint between bedtime and wake-up time), and sleep timing standard deviation (SD) using the actigraphy among 80 consecutive volunteers aged ≥ 60 years. Global cognitive function and executive function of detailed cognitive domains were evaluated using the mini-mental state examination (MMSE) and Wisconsin card sorting test (WCST) and subjective daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS). The category achievement (CA), total errors (TE), perseverative errors of Nelson (PEN), non-perseverative errors (NPE), and difficulties in maintaining set (DMS) on the WCST were significantly correlated with sleep timing SD (CA: r = - 0.276, p = 0.013, TE: r = 0.311, p = 0.005, PEN: r = 0.241, p = 0.032, NPE: r = 0.250, p = 0.025, DMS: r = 0.235, p = 0.036), but not with the MMSE score. Multiple regression analyses with the stepwise forward selection method including age, ESS score, bedtime, sleep timing, and sleep timing SD, revealed that the ESS score, and sleep timing SD were significant factors related to CA on the WCST (ESS score: ß = - 0.322, p = 0.004; sleep timing SD: ß = - 0.250, p = 0.022). Assessment of sleep-wake rhythms, daytime sleepiness, and cognitive function using the MMSE and WCST is valuable for the prediction of cognitive decline in the geriatric population.

Continuous positive airway pressure intolerance associated with elevated nasal resistance is possible mechanism of complex sleep apnea syndrome.

PURPOSE: Complex sleep apnea syndrome (CompSAS) is diagnosed after an elimination of obstructive events with continuous positive airway pressure (CPAP), when a central apnea index ≥5/h or Cheyne-Stokes respiration pattern emerges in patients with obstructive sleep apnea syndrome (OSAS). However, the pathophysiology of CompSAS remains controversial. METHODS: Of the 281 patients with suspected OSAS, all of whom underwent polysomnography conducted at Nagoya University Hospital, we enrolled 52 patients with apnea-hypopnea index ≥15/h (age 51.4 ± 13.3 years). The polysomnographic findings, left ventricular ejection fraction (LVEF), and nasal resistance were compared between the CompSAS patients and OSAS patients. RESULTS: Forty-three patients were diagnosed with OSAS and nine patients with central sleep apnea syndrome by natural sleep PSG. Furthermore, 43 OSAS patients were classified into the OSAS patients (OSAS group, n = 38) and the CompSAS patients (CompSAS group, n = 5) by the night on CPAP PSG. The nasal resistance was significantly higher in CompSAS group than in OSAS group (0.30 ± 0.10 vs. 0.19 ± 0.07 Pa/cm(3)/s, P = 0.004). The arousal index, percentage of stage 1 sleep, and oxygen desaturation index were significantly decreased, and the percentage of stage REM sleep was significantly increased in the OSAS group with the initial CPAP treatment, but not in the CompSAS group. In addition, the patients with CompSAS showed normal LVEF. CONCLUSION: CPAP intolerance secondary to an elevated nasal resistance might relate to frequent arousals, which could presumably contribute to an increase in central sleep apnea. Further evaluation in a large study is needed to clarify the mechanism of CompSAS.

Association of sleep-wake rhythm and sleep quality with endothelial function in young adults.

Objective: The environment in modern society could disturb the sleep-wake rhythm. We aimed to study the association of sleep-wake rhythm with endothelial function and sleep quality. Material and Methods: Thirty-one healthy university students (mean age: 20.4±1.8 years) were enrolled. The endothelial function was evaluated with the percent endothelium-dependent flow-mediated dilation of the brachial artery [%FMD: (maximum diameter - baseline diameter)/baseline diameter x 100] using the high-resolution ultrasonography. We also measured the total sleep time (TST), sleep effciency, and the standard deviation (SD) of sleep timing (midpoint between bedtime and wake-up time) using the actigraphy. The irregular sleep-wake rhythm was defined as having the shift of bedtime or wake-up time for two hours or longer. Results: The %FMD and sleep efficiency were significantly lower in the irregular group than regular group (%FMD: 6.1±2.4 vs. 10.9±2.3, p<0.001, sleep effciency: 92.2±5.8 vs. 95.9±2.8%, p=0.027), whereas there was no significant difference in %FMD between the two groups of TST <6 hours and TST ≥6 hours. The %FMD was significantly correlated with SD of sleep timing (r=-0.481, p=0.006). Multiple regression analyses, including age, sex, TST, sleep effciency, and SD of sleep timing revealed that the SD of sleep timing was a significant factor associated with %FMD (ß=-0.454, p=0.017). Conclusion: Our findings suggest that the irregular sleep-wake rhythm and poor sleep quality could have adverse effects on endothelial function in young adults.

Sleep fragmentation and working memory in healthy adults.

INTRODUCTION: Sleep is essential for performing cognitive function in humans. We have hypothesized that sleep fragmentation compared to sleep efficiency may have a negative impact on the working memory. MATERIAL AND METHODS: Twenty-eight healthy adults (18 males and 10 females; mean age 27.8±15.5 years) were enrolled in this study. We measured the total sleep time (TST), sleep efficiency, %stage wakefulness (W), %stage rapid eye movement (REM), %stage N1, %stage N2, %stage N3, wake after sleep onset (WASO), and arousal index using polysomnography. Working memory, executive function, and sustained attention of three domains of cognitive function were evaluated with the number of back task (N-back task), Wisconsin card sorting test (WCST), and continuous performance test-identical pairs (CPT-IP), respectively. RESULTS: The percentage of correct answers on the 2-back task was significantly correlated with %stage REM, %stage N1, and %stage N2 (%stage REM: r=0.505, p=0.006; %stage N1: r=-0.637, p<0.001; %stage N2: r=0.670, p<0.001), and multiple regression analysis including the stepwise forward selection method revealed that %stage N2 was the most significant factor (%stage N2: ß=0.670, p<0.001). The percentage of correct answers on the 2-back task was also significantly correlated with TST, sleep efficiency, WASO, and arousal index (TST: r=0.492, p=0.008; sleep efficiency: r=0.622, p<0.001; WASO: r=-0.721, p<0.001; arousal index: r=-0.656, p<0.001), and WASO was the significant factor (ß=-2.086, p=0.007). The WCST category achievement and CPT-IP d-prime score were correlated with none of the sleep variables. CONCLUSION: Increased WASO and a decrease in %stage N2 were associated with worse working memory.

Effects of long sleep time and irregular sleep-wake rhythm on cognitive function in older people.

Sleep disturbances and cognitive decline are common in older adults. We aimed to investigate the effects of the total sleep time (TST) and sleep-wake rhythm on executive function and working memory in older adults. In 63 older participants, we measured the TST, wake after sleep onset (WASO), and sleep timing (midpoint between bedtime and wake-up time) using actigraphy. Executive function was evaluated with the trail making test B (TMT-B) and Wisconsin card sorting test (WCST). The number of back task (N-back task) was used to measure working memory. Participants with a TST ≥ 8 h had a significantly lower percentage of correct answers (% correct) on the 1-back task than those with a TST < 8 h. The % correct on the 1-back task was significantly correlated with the TST, WASO, and sleep timing. Multiple regression analyses revealed that the TST and sleep timing were significant factors of the % correct on the 1-back task. The TMT-B score was significantly correlated with the sleep timing. Category achievement on the WCST was significantly correlated with the standard deviation of the sleep timing. Therefore, a long sleep time and an irregular sleep-wake rhythm could have adverse effects on executive function and working memory in older people.

Clinical indication of nasal surgery for the CPAP intolerance in obstructive sleep apnea with nasal obstruction.

OBJECTIVE: The role of isolated nasal surgery for obstructive sleep apnea (OSA) patients with nasal obstruction, especially for an intolerance for continuous positive airway pressure (CPAP), is unclear. The aim of this study was to assess the effects of surgery for OSA patients with symptomatic nasal obstruction and CPAP intolerance. METHOD: Retrospectve comparative study.1037 OSA patients with apnea-hypopnea index (AHI) ≥ 20 were enrolled. Case-control study was performed between the male apnea patients undergoing nasal surgery: surgery group (n = 43) and the pair-matched apnea patients for age, sex, body mass index, and race: control group (n = 43). The surgery group suffering from nasal obstruction could not use continuous positive airway pressure, and the CPAP group free from nasal obstruction could use it successfully. RESULTS: In surgery group, surgery significantly decreased the nasal resistance and Epworth sleepiness scale scores without changing the AHI. Surgery significantly increased the nadir of oxygen saturation and shortened the apnea-hypopnea duration. Although all of the surgery group failed to use positive airway pressure preoperatively, the 40 patients of the 43 CPAP intolerance patients were able to use CPAP postoperatively. The resting three patients were cured OSA or changed the treatment to oral appliance(OA). For both groups, the cutoff nasal resistance for differentiating the failure of positive airway pressure and its success was 0.31 Pa/cm3/s. CONCLUSION: Isolated nasal surgery is effective for an intolerance of positive airway pressure in sleep apnea with nasal obstruction presumably by decreasing nasal resistance.

Aortic pressure augmentation as a marker of cardiovascular risk in obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) is associated with increases in cardiovascular morbidity and mortality. Vascular changes in individuals with OSAS have not been fully elucidated, however. The possible impact of OSAS on the extent of aortic pressure augmentation (AG), an indicator of cardiovascular risk, was investigated. Forty-five consecutive male patients aged 35 to 78 years (56.0+/-9.6 years) who were referred to the sleep clinic of Nagoya University Hospital for screening and treatment of OSAS and 71 age-matched healthy men were enrolled in the study. AG was derived from the pressure waveform measured at the radial artery by applanation tonometry. The number of apnea and hypopnea episodes per hour (apnea-hypopnea index [AHI]) was determined by standard polysomnography. AG was significantly greater in OSAS patients than in controls (9.0+/-4.1 vs. 6.4+/-3.4 mmHg, p<0.001), and it was significantly reduced in 19 OSAS patients treated with continuous positive airway pressure. AG was also significantly correlated with the AHI (r=0.562, p<0.001) and age (r=0.356, p=0.016) but not with the serum concentrations of low and high density lipoprotein-cholesterol, triglyceride, or glycosylated hemoglobin. Stepwise multiple regression analysis revealed that the AHI was the most significant contributing factor to the increased AG in OSAS patients (beta=0.109, r=0.530, p<0.001). OSAS may thus have an adverse effect on vascular function that can be ameliorated by appropriate treatment.

Nonsustained ventricular tachycardia does not affect the prognosis of neuromuscular diseases: A preliminary and retrospective study.

BACKGROUND: Nonsustained ventricular tachycardia (NSVT) is sometimes observed in patients with neuromuscular diseases (NMDs). The aim of this study was to assess the role of NSVT in the survival prognosis of NMD patients. METHODS: We retrospectively analyzed the patients with NMDs who had undergone Holter ECG recordings at a single center between February and August 2012. Sixty-eight patients were enrolled in this study. The 5 year follow-up was assessed according to the cumulative event-free rate. RESULTS: Twenty-one patients died during the follow-up, seven of whom died by cardiac death. The Kaplan-Meier survival curve that compared the patients with NSVT and those without NSVT indicated the NSVT was not related to the rate of all causes of death or cardiac death in those patients with NMDs. The survival curve was not significantly changed after the adjustment by age and ejection fraction. CONCLUSION: No significant correlations between NSVT and the prognosis in patients with NMDs were found.

Continuous positive airway pressure improves daytime baroreflex sensitivity and nitric oxide production in patients with moderate to severe obstructive sleep apnea syndrome.

Individuals with obstructive sleep apnea syndrome (OSAS) are at high risk for cardiovascular morbidity and mortality. The effects of OSAS severity and nocturnal continuous positive airway pressure (CPAP) on daytime baroreflex sensitivity (BRS) and nitric oxide (NO) production were investigated in OSAS patients. Fifty-one consecutive males with OSAS and 29 age-matched healthy men underwent the Valsalva test and standard polysomnography. Patients with an apnea-hypopnea index (AHI) of >or=20 episodes per hour were randomized to receive CPAP treatment for 3 months (n=14) or no such treatment (n=19). The BRS index measured from the overshoot phase (phase IV) of the Valsalva maneuver and plasma NO concentration were significantly lower, whereas the AHI, oxygen desaturation time, arousal index, percentage of sleep stage 1, and systolic blood pressure were significantly greater, in patients with an AHI of >or=20/h than in those with an AHI of <20/h or in controls. The 24-h urinary excretion of norepinephrine was significantly reduced and the plasma NO concentration was significantly increased after one night of CPAP. The BRS index for phase IV and the Valsalva ratio were significantly increased in the CPAP group after the 3-month treatment period but remained unchanged in the non-CPAP group of OSAS patients. The daytime BRS index and NO production were thus inversely related to the severity of OSAS, and successful CPAP treatment improved these parameters in patients with moderate to severe OSAS. CPAP may therefore reduce the risk of cardiovascular complications due to endothelial dysfunction or increased sympathetic activity.

[Two cases of Duchenne muscular dystrophy complicated with dilated cardiomyopathy and cerebral infarction].

We report two cases of Duchenne muscular dystrophy (DMD) complicated with dilated cardiomyopathy (DCM), who were affected with cerebral infarction. Case 1 suddenly developed dysarthria and right facial weakness at age 21. Cranial CT study disclosed a low density area in the left basal ganglia and internal capsule. Case 2 had a history of transient ischemic attack (TIA) at age 21. Five months after the TIA, he developed right hemiplegia and dysarthria, and a low density area in the corona radiate in left cerebral hemisphere was observed in cranial CT. These two cases showed the radiographic cardiomegaly with cardio thoracic ratio (CTR) of 72.8% and 66.6%, the decreased echocardiographic left ventricular ejection fraction below 20%, and the elevated titer of thrombin-anti-thrombin III complex (TAT) and D-dimer. The autopsy of Case 2 at age 26 disclosed the remarkable degeneration and fibrosis of myocardium and old ischemic lesion in the left cerebral frontal cortex. Despite the negative finding of the emboli in the left heart, cardiogenic cerebral infarction secondary to DCM was strongly suspected in both cases.

Assessment of pulse rate variability by the method of pulse frequency demodulation.

BACKGROUND: Due to its easy applicability, pulse wave has been proposed as a surrogate of electrocardiogram (ECG) for the analysis of heart rate variability (HRV). However, its smoother waveform precludes accurate measurement of pulse-to-pulse interval by fiducial-point algorithms. Here we report a pulse frequency demodulation (PFDM) technique as a method for extracting instantaneous pulse rate function directly from pulse wave signal and its usefulness for assessing pulse rate variability (PRV). METHODS: Simulated pulse wave signals with known pulse interval functions and actual pulse wave signals obtained from 30 subjects with a trans-dermal pulse wave device were analyzed by PFDM. The results were compared with heart rate and HRV assessed from simultaneously recorded ECG. RESULTS: Analysis of simulated data revealed that the PFDM faithfully demodulates source interval function with preserving the frequency characteristics of the function, even when the intervals fluctuate rapidly over a wide range and when the signals include fluctuations in pulse height and baseline. Analysis of actual data revealed that individual means of low and high frequency components of PRV showed good agreement with those of HRV (intraclass correlation coefficient, 0.997 and 0.981, respectively). CONCLUSION: The PFDM of pulse wave signal provides a reliable assessment of PRV. Given the popularity of pulse wave equipments, PFDM may open new ways to the studies of long-term assessment of cardiovascular variability and dynamics.

[Effect of intermittent positive pressure ventilation on life-span and causes of death in Duchenne muscular dystrophy].

We have been introducing the intermittent positive pressure ventilation (IPPV) therapy in Duchenne muscular dystrophy (DMD) since 1990. Then, the changes of life-span and causes of mortality by IPPV were investigated in this study. The subjects were 157 patients of long-term followed up DMD in our hospital. The Kaplan-Meier's survival curve of 73 IPPV treated patients showed a median survival time of 31.0 years of age, whereas that of 20.4 years in 84 patients not treated by IPPV. The actual mean age of death in 29 IPPV treated patients was 25.68 +/- 5.18 years-old (M +/- SD), which was significantly higher than that in 74 patients with not-IPPV treated of 19.76 +/- 3.47. The IPPV treatment changed the major causes of death; 59.5% to 3.5% for respiratory failure, 12.2% to 37.9% for cardiac failure, and 0% to 10.3% for repiratory trouble. There were certain number of patients who died of repiratory infection, respiratory tract disorder, digestive organ disorders and sudden death. Thus, IPPV therapy is significantly effective for prolongation of life-span in DMD, and it seems to be necessary to establish the treatment strategy for cardiac failure and other potentially fatal complications.

Hypothesis: respiratory sinus arrhythmia is an intrinsic resting function of cardiopulmonary system.

A hypothesis is presented that explains the physiological reasons why the magnitude of respiratory sinus arrhythmia (RSA) appears to correlate with cardiac vagal tone. The hypothesis is that RSA is an intrinsic resting function of the cardiopulmonary system. Although RSA is mediated by respiratory modulation of cardiac vagal outflow and its magnitude is used as an index of cardiac vagal activity, RSA itself reflects cardiorespiratory interaction. RSA is universally observed among vertebrates throughout the evolution, suggesting that it may bear an intrinsic physiological role. Recent studies have shown that RSA improves pulmonary gas exchange efficiency by matching alveolar ventilation and capillary perfusion throughout respiration cycle. This suggests that in resting animals and humans, RSA could save cardiac and respiratory energy by suppressing unnecessary heartbeats during expiration and ineffective ventilation during waning phases of perfusion. Furthermore, evidence is accumulating for possible dissociation between the magnitude of RSA and vagal control of heart rate, suggesting separated and independent regulations for respiratory modulation of cardiac vagal outflow from those for cardiac vagal tone. By our hypothesis, the apparent associations between RSA and cardiac vagal tone are explained as indirect consequences; i.e., whenever the cardiac vagal tone changes in response to the resting level of the cardiopulmonary system, RSA appears to change parallel to it. Our hypothesis seems more consistent with both physiological and clinical evidence about RSA than that presuming RSA is an index of cardiac vagal activity.

Respiratory sinus arrhythmia: why does the heartbeat synchronize with respiratory rhythm?

Respiratory sinus arrhythmia (RSA) is heart rate variability in synchrony with respiration, by which the R-R interval on an ECG is shortened during inspiration and prolonged during expiration. Although RSA has been used as an index of cardiac vagal function, it is also a physiologic phenomenon reflecting respiratory-circulatory interactions universally observed among vertebrates. Previous studies have shown that the efficiency of pulmonary gas exchange is improved by RSA, suggesting that RSA may play an active physiologic role. The matched timing of alveolar ventilation and its perfusion with RSA within each respiratory cycle could save energy expenditure by suppressing unnecessary heartbeats during expiration and ineffective ventilation during the ebb of perfusion. Furthermore, evidence has accumulated of a possible dissociation between RSA and vagal control of that heart rate, suggesting differential controls between the respiratory modulation of cardiac vagal outflow and cardiac vagal tone. RSA or heart rate variability in synchrony with respiration is a biological phenomenon, which may have a positive influence on gas exchange at the level of the lung via efficient ventilation/perfusion matching.