Intrathoracic Pressure Fluctuations Research Articles

Obstructive sleep apnea induced bilateral tonic- clonic seizure of unknown origin: A case series of a novel association

BackgroundObstructive sleep apnea is a highly prevalent disorder, characterized by recurrent events of upper airway obstruction during sleep and associated with recurrent cycles of desaturation and re-oxygenation, sympathetic hyperactivity, and intra-thoracic pressure fluctuations, resulting in fragmentation of sleep and subsequent daytime fatigue with excessive sleepiness. Obstructive sleep apnea-induced bilateral tonic–clonic seizures are unheard of. We aimed to report 3 patients with previously undiagnosed obstructive sleep apnea who presented to the emergency department with new onset bilateral tonic–clonic seizure without any evidential neurological or metabolic cause. MethodsPatient data were obtained from medical records from the Department of Internal Medicine, IPGMER and SSKM Hospital, Kolkata, and Belle Vue Clinic, Kolkata, India. ResultsThree male patients (67, 58, and 44 years old) presented with bilateral tonic–clonic seizure disorder without any underlying cause of seizures after rigorous investigations except for moderate to severe obstructive sleep apnea on polysomnography. All 2 patients were seizure-free after being treated with levetiracetam, chronic continuous positive airway pressure therapy in 2, and only continuous positive airway pressure in the other. The patients remained seizure-free on continuous positive airway pressure, even when levetiracetam was withdrawn, suggesting obstructive sleep apnea's causality in their new-onset acute seizures. ConclusionAlthough further investigation is required to clarify this association, underlying obstructive sleep apnea should be ruled out in patients with a first-ever bilateral tonic–clonic seizure. Whether or not continuous positive airway pressure alone could effectively treat hypoxia and deranged cortical excitability, which may lead to seizures in cases with long-standing obstructive sleep apnea, is yet to be explored.

Abstract 14663: The Impact of Continuous Positive Airway Pressure for Sleep Apnea on Left Atrial Dilatation in Patients Receiving Catheter Ablation of Atrial Fibrillation

Background Sleep apnea (SA) and left atrial dilatation (LA) are both risk factors for an arrhythmia recurrence after catheter ablation (CA) of atrial fibrillation (AF). Negative intrathoracic pressure fluctuations during an obstructive apnea episode may cause the left atrium to distend and stretch its wall. However, the impact of continuous positive airway pressure (CPAP) for SA on the reverse LA remodeling has not been elucidated. Methods This study was conducted under a retrospective, single-center, observational design. Data was derived from screening tests for sleep apnea, which were routinely performed in patients scheduled to receive CA of AF in our institution. The severity of the sleep apnea was evaluated by the apnea-hypopnea index (AHI). After excluding patients who were already diagnosed with sleep apnea, we enrolled 1232 consecutive patients who underwent multidetector computed tomography (MDCT) both before and 3-months after the CA of AF. The left atrial dilatation and volume reduction were evaluated by the left atrial minimum volume (LA min V) using 256-slice MDCT. Results The age was 65±11 years, 27.8% were females, and 46.0% had non-paroxysmal AF. The mean AHI was 20.2±15.2 and LA min V 79.1± 37.8ml (r=0.31, p<0.0001) before CA. LA dilatation was defined as an LA min V≥79.1ml. After an adjustment by an advanced age (≥65 years), non-paroxysmal AF, male sex, obesity, hypertension, diabetes, and congestive heart failure, SA (AHI≥5) was a significant predictor of LA dilatation before CA (odds ratio 2.83, 95% confidence interval 1.55-5.16, p=0.0007). After CA, 206 out of 1092 patients (18.9%) with SA started CPAP. SA patients with CPAPs had a greater LA min V reduction rate on the postprocedural CT than those without CPAP (26.2% vs. 20.5%, p=0.013). Conclusion Among the patients scheduled to receive catheter ablation of AF, SA was independently associated with left atrial dilatation. Patients who started CPAP treatment for SA had greater LA reverse remodeling at 3 months after the CA.

Untreated sleep apnea and left atrial dilatation in patients with atrial fibrillation prior to catheter ablation

Abstract Background Sleep apnea and left atrial dilatation are both risk factors for an arrhythmia recurrence after catheter ablation (CA) of atrial fibrillation (AF). Negative intrathoracic pressure fluctuations during an obstructive apnea episode may cause the left atrium to distend and stretch its wall. Whether sleep apnea is associated with left atrial dilatation in patients receiving CA of AF remains unknown. Purpose We sought to elucidate whether moderate or severe untreated sleep apnea was associated with left atrial dilatation in patients with AF before CA. Methods This study was conducted under a retrospective, single-center, observational design. The data were derived from screening tests for sleep apnea, which were routinely performed in patients scheduled to receive CA of AF in our institution. After excluding patients who were already diagnosed with sleep apnea, we enrolled 1265 consecutive patients (age 65±11 years, 27.8% females, and 46.2% of non-paroxysmal AF) who underwent both home sleep apnea testing and multidetector computed tomography (MDCT) before the CA of AF. The severity of the sleep apnea was evaluated by the apnea-hypopnea index (AHI) using a watch-type peripheral arterial tonometry. Left atrial dilatation was evaluated by the left atrial maximum volume (LA max V) using 256-slice MDCT. Results The age was 65±11 years, 27.8% were females, and 46.2% had non-paroxysmal AF. The mean AHI was 20.3±15.3 and LA max V 105±34 ml (R2=0.075, p<0.0001). LA dilatation was defined by larger than mean LA max V (LA max V≥105 ml). We examined an LA max V≥105 ml as a predictor. After an adjustment by an advanced age (≥65 years), non-paroxysmal AF, male sex, obesity, hypertension, and congestive heart failure, all of which were significant predictors of an LA max V≥105ml in the univariate analysis, moderate or severe sleep apnea (AHI≥15) was a significant predictor of an LA max V≥105 ml (odds ratio 1.63, 95% confidence interval 1.24–2.14, p=0.0005). Conclusion Among the patients scheduled to receive catheter ablation of AF, moderate or severe sleep apnea was independently associated with left atrial dilatation. Funding Acknowledgement Type of funding sources: None.

Pathogenetic links between ischemic stroke and sleep-disordered breathing

The paper reviews the pathophysiological links between ischemic stroke and sleep-disordered breathing. We discuss well-known mechanisms, such as intermittent hypoxemia, disturbed sleep structure and fluctuations in intrathoracic pressure, autonomic imbalance, oxidative stress, as well as genetic factors and the role of glymphatic system. The impact of sleep-disordered breathing on the development of various subtypes of stroke (according to the TOAST classification) and the so-called “wake-up stroke” is presented.

Pharmacological inhibition of acetylcholine-regulated potassium current (I K,ACh) prevents atrial arrhythmogenic changes in a rat model of repetitive obstructive respiratory events.

BackgroundIn obstructive sleep apnea (OSA), intermittent hypoxemia and intrathoracic pressure fluctuations may increase atrial fibrillation (AF) susceptibility by cholinergic activation.ObjectiveTo investigate short-term atrial electrophysiological consequences of obstructive respiratory events, simulated by intermittent negative upper airway pressure (INAP), and the role of atrial acetylcholine-regulated potassium current (IK,ACh) activated by the M2 receptor.MethodsIn sedated (2% isoflurane), spontaneously breathing rats, INAP was applied noninvasively by a negative pressure device for 1 minute, followed by a resting period of 4 minutes. INAP was applied repeatedly throughout 70 minutes, followed by a 2-hour recovery period. Atrial effective refractory period (AERP) and AF inducibility were determined throughout the protocol. To study INAP-induced IK,ACh activation, protein levels of protein kinase C (PKCƐ) were determined in membrane and cytosolic fractions of left atrial (LA) tissue by Western blotting. Moreover, an IK,ACh inhibitor (XAF-1407: 1 mg/kg) and a muscarinic receptor inhibitor (atropine: 1 μg/kg) were investigated.ResultsIn vehicle-treated rats, repetitive INAP shortened AERP (37 ± 3 ms vs baseline 44 ± 3 ms; P = .001) and increased LA membrane PKCƐ content relative to cytosolic levels. Upon INAP recovery, ratio of PKCƐ membrane to cytosol content normalized and INAP-induced AERP shortening reversed. Both XAF-1407 and atropine increased baseline AERP (control vs XAF-1407: 61 ± 4 ms; P > .001 and control vs atropine: 58 ± 3 ms; P = .011) and abolished INAP-associated AERP shortening.ConclusionShort-term simulated OSA is associated with a progressive, but transient, AERP shortening and a PKCƐ translocation to LA membrane. Pharmacological IK,ACh and muscarinic receptor inhibition prevented transient INAP-induced AERP shortening, suggesting an involvement of IK,ACh in the transient arrhythmogenic AF substrate in OSA.

Abstract 14347: Sleep Apnea and Left Atrial Dilatation in Patients With Atrial Fibrillation Prior to Catheter Ablation

Introduction: Sleep apnea and left atrial dilatation are both risk factors for an arrhythmia recurrence after catheter ablation (CA) of atrial fibrillation (AF). Negative intrathoracic pressure fluctuations during an obstructive apnea episode may cause the left atrium to distend and stretch its wall. Whether sleep apnea is associated with left atrial dilatation in patients receiving CA of AF remains unknown. Methods: This study was conducted under a retrospective, single-center, observational design. The data were derived from screening tests for sleep apnea, which were routinely performed in patients scheduled to receive CA of AF in our institution. After excluding patients who were already diagnosed with sleep apnea, we enrolled 1265 consecutive patients (age 65±11 years, 27.8% females, and 46.2% of non-paroxysmal AF) who underwent both home sleep apnea testing and multidetector computed tomography (MDCT) before the CA of AF. The severity of the sleep apnea was evaluated by the apnea-hypopnea index (AHI) using a watch-type peripheral arterial tonometry. Left atrial dilatation was evaluated by the left atrial maximum volume (LA max V) using 256-slice MDCT. Results: The age was 65±11 years, 27.8% were females, and 46.2% had non-paroxysmal AF. The mean AHI was 20.3±15.3 and LA max V 104.9±33.9 ml (R 2 =0.075, p<0.0001). LA dilatation, defined by an LA max V≥100 ml, was more frequently observed in patients with an AHI≥15 than those with an AHI<15 (62.5% vs. 40.2%, p<0.0001). We examined an LA max V≥100 ml as a predictor. After an adjustment by an advanced age (≥65 years), non-paroxysmal AF, male sex, obesity, hypertension, and congestive heart failure, all of which were significant predictors of an LA max V≥100ml in the univariate analysis, moderate or severe sleep apnea (AHI≥15) was a significant predictor of an LA max V≥100 ml (odds ratio 1.49, 95% confidence interval 1.13-1.97, p=0.0049). Conclusion: Among the patients scheduled to receive catheter ablation of AF, moderate or severe sleep apnea was independently associated with left atrial dilatation.

Obstructive Sleep Apnea Syndrome as a Trigger of Cardiac Arrhythmias.

Obstructive sleep apnea syndrome (OSAS) has a high prevalence in western countries. Many papers have been published with the purpose of demonstrating that OSAS acts as an arrhythmia trigger and is responsible for an increase in cardiovascular morbidity and mortality. The aim of this study was to review our knowledge on this topic. There is a lot of evidence demonstrating the relationship between OSAS and arrhythmias, but there remains a lack of an interventional randomized trial to demonstrate that by treating OSAS we can reduce arrhythmia burden. OSAS is a highly prevalent illness in western countries and is clearly related to an increase in cardiovascular mortality and morbidity. Cardiac arrhythmias are triggered by a repetitive hypoxemia, hypercapnia, acidosis, intrathoracic pressure fluctuations, reoxygenation, and arousals during apnea and hypopnea episodes. Early diagnosis and treatment of these patients can reduce further cardiovascular morbidity and mortality.

Pharmacological inhibition of acetylcholine-regulated potassium current (IK,ACh) and associated A1- and M2-pathways prevent atrial arrhythmogenic changes in a rat model for obstructive sleep apnea

Abstract Background In obstructive sleep apnea (OSA), intermittent hypoxemia and intrathoracic pressure fluctuations may increase vagal tone and adenosine release, potentially resulting in an increased acetylcholine-regulated potassium current (IK,ACh). Here we elucidated acute atrial electrophysiological effects of obstructive respiratory events simulated by intermittent negative upper airway pressure (INAP) and the role of atrial IKACh activation by A1-receptor and M2-receptor activation. Methods In sedated spontaneously breathing rats (2% isoflurane), either IK,ACh-inhibitor (XAF-1407: 1mg/kg), M2-receptor inhibitor (atropine; 1μg/kg), A1-receptor inhibitor (Rolofylline; 1μg/kg) or a buffer-based vehicle was perfused (Control). INAP was applied non-invasively by a negative pressure device 14 times throughout 70 minutes. Simulated apneas were maintained for one minute with a four minute resting period. Atrial effective refractory period (AERP) and atrial activation time were acquired by a programmed atrial pacing protocol before, during and after applied INAP throughout the study. Results Independent of IK,Ach-inhibition, single INAP applications prolonged transiently atrial activation times (Control: INAP vs. pre-INAP p=0.034; XAF-1407: INAP vs. pre-INAP p=0.039). In control-rats, seventy minutes of repetitive INAP decreased AERP by 15.45±0.06% (vs. baseline p=0.0015), which was reversible upon 1 hour of recovery. AERP shortening correlated with the cumulative pressure applied per body weight (Pearson r=−0.773; p=0.025). Whilst only XAF-1407 and atropine increased baseline AERP, all drug interventions, XAF-1407, atropine and Rolofylline could prevent INAP-associated AERP shortening (end INAP-protocol vs. respective baseline XAF-1407 p=0.994; atropine p=0.984; Rolofylline p=0.951). Drops in oxygen saturation and applied INAP were comparable in all groups. Conclusion Short-term simulated OSA is associated with progressive AERP shortening, which was determined by the cumulative negative airway pressure applied. This potentially represents an important insight in future OSA treatment. Pharmacological IK,ACh inhibition prevented INAP-associated AERP-shortening suggesting an involvement in acute atrial arrhythmogenesis in OSA. However, if IK,Ach and its potential upstream activating A1- and M2-pathway pose a pharmacological treatment target for OSA-patients with AF, requires further investigation. Funding Acknowledgement Type of funding source: None

741Pharmacological inhibition of the acetylcholine-regulated potassium channel (IK,ACh) prevents atrial arrhythmogenic changes in a rat model for obstructive sleep apnea

Abstract Background In obstructive sleep apnea (OSA), intermittent hypoxemia and intrathoracic pressure fluctuations may increase vagal tone, resulting in an increased acetylcholine-regulated potassium current (IK,ACh). Here we elucidated acute atrial electrophysiological effects of obstructive respiratory events simulated by intermittent negative upper airway pressure (INAP) and the role of atrial IKACh activation. Methods In sedated spontaneously breathing rats (2% isoflurane), either IK,ACh-inhibitor (XAF-1407: 1mg/kg) or a buffer-based vehicle was perfused (Control). INAP was applied non-invasively by a negative pressure device 14 times throughout 70 minutes. Simulated apneas were maintained for one minute with a four minute resting period. Atrial effective refractory period (AERP), inducible atrial fibrillation (AF)-durations and atrial activation time were acquired by a programmed atrial pacing protocol before, during and after applied INAP throughout the study. Results During single INAP applications atrial activation times prolonged transiently in both groups (Control: INAP vs. pre-INAP p = 0.034; XAF-1407: INAP vs. pre-INAP p = 0.039). In control-rats, seventy minutes of repetitive INAP prolonged P-wave duration (+10.8 ± 2.7% vs. baseline, p = 0.008) and decreased AERP by 14.6 ± 3.1% (vs. baseline p = 0.001). AERP shortening correlated with the cumulative pressure applied per body weight (Pearson r= -0.773; p= 0.025). XAF-1407 could prevent P-wave prolongation and AERP shortening. Inducible AF-durations (CTR 0.94 ± 0.34s vs. XAF-1407 0.1 ± 0.09s p = 0.049) were shorter in XAF-1407 treated rats. Drops in oxygen saturation or applied INAP were comparable in control and XAF-1407 rats. Conclusion Short-term simulated OSA is associated with AF-related arrhythmogenic changes, which could be prevented by pharmacological IK,ACh inhibition. Moreover, the cumulative negative airway pressure applied determined aERP shortening and may represent a target for OSA treatment. These findings have important implications for the antiarrhythmic management of AF patients with OSA.

Left ventricular diastolic dysfunction in patients with obesity hypoventilation syndrome.

Obesity hypoventilation syndrome (OHS) can be complicated by several cardiovascular conditions. We assessed the prevalence and factors associated with left ventricular diastolic dysfunction (LVDD) in patients with OHS. In this prospective observational study, all consecutive OHS patients referred to the sleep disorders clinic between January 2002 to December 2016 were included (n=113). Demographic data, echocardiography, sleep parameters, arterial blood gases (ABGs), and lung functions were recorded. Of 113 patients with OHS who participated, 76 patients (67%) had LVDD. More than two-thirds had grade 1 LVDD. Median body mass index (BMI) was 42.8 kg/m2. Median PaCO2 was 55.8 mmHg. Median apnea hypopnea index (AHI) was 52 (25-38.5). Eighty-four (75.7%) patients were hypertensive, and 60 (54.1%) were diabetic. To minimize the effect of fluctuations in intrathoracic pressure during the obstructive respiratory events on the cardiac function, 38 OHS patients with mild to moderate OSA (AHI <30) were identified. Twenty-seven (71%) had LVDD. When compared to OHS patients without LVDD, patients with LVDD had higher BMI (47.4±6.5 versus 41.5±4.5, P=0.009). Hypertension was more common in OHS patients with LVDD than without LVDD (89.3% versus 54.5%, P=0.03). Correlation analysis revealed that hypertension (r=-0.37, P=0.016) had significant correlations with LVDD. Diastolic left ventricular dysfunction is prevalent among OHS patients even in the absence of severe OSA. Hypertension and obesity were significantly more common in patients with LVDD. Assessment of diastolic dysfunction should be included in the initial evaluation of OHS patients to encourage the early institution of therapy.

CARDIOVASCULAR AND METABOLIC IMPAIRMENT IN PATIENTS WITH OBSTRUCTIVE SLEEP APNEA

Since the moment when the obstructive nature of sleep apnea was first revealed, many new in-formation on this disease have been obtained. Now obstructive sleep apnea (OSA) recognized as an independent predictor of the development of impaired glucose tolerance (insulin resistance, fasting hyperglycaemia), type 2 diabetes mellitus (DM2), resistant arterial hypertension, cardio- vascular death. The problem of identifying and treating patients with OSA is still actual. In real clinical practice, there is a need for an integrated approach to the diagnosis and therapy of comorbid OSA patients with metabolic impairment and cardiovascular diseases. The aim of this review is to assess the clinical and pathogenesis features of metabolic impaired, carbohydrate metabolism, basic metabolism, eating behavior, body weight fluctuations in patients with ob-structive sleep apnea syndrome. Methods. In our work, we used a retrospective analysis of pub-lished clinical research data of domestic and foreign authors over the past 20 years. The review included studies with adequate design from the standpoint of «good clinical practice» (GCP) and evidence-based medicine. The conclusion . According to modern interpretation, obstructive sleep apnea is considered as an independent disease that has its pathogenic mechanisms, clinical and functional manifestations. There are several main causes of the effect of OSA on the metabolic component and the work of the cardiovascular system. Among them, intermittent hypoxemia, endothelial dysfunction, fluctuations in intrathoracic pressure, increased activity of the sympathetic nervous system, disturbance of the structure of sleep are leading. OSA is considered as a disease capable of disabling patients of working age, dramatically changing the quality of life, leading to early mortality due to cardiovascular disasters. Timely detection of clinical symptoms of OSA and the strategy of early administration of CPAP therapy significantly improve the quality of treatment and prognosis of comorbid patients.

Central sleep apnoea in congestive heart failure

Central sleep apnoea in congestive heart failure

Inter-device differences in monitoring for goal-directed fluid therapy.

Goal-directed fluid therapy is an integral component of many Enhanced Recovery After Surgery (ERAS) protocols currently in use. The perioperative clinician is faced with a myriad of devices promising to deliver relevant physiologic data to better guide fluid therapy. The goal of this review is to provide concise information to enable the clinician to make an informed decision when choosing a device to guide goal-directed fluid therapy. The focus of many devices used for advanced hemodynamic monitoring is on providing measurements of cardiac output, while other, more recent, devices include estimates of fluid responsiveness based on dynamic indices that better predict an individual's response to a fluid bolus. Currently available technologies include the pulmonary artery catheter, esophageal Doppler, arterial waveform analysis, photoplethysmography, venous oxygen saturation, as well as bioimpedance and bioreactance. The underlying mechanistic principles for each device are presented as well as their performance in clinical trials relevant for goal-directed therapy in ERAS. The ERAS protocols typically involve a multipronged regimen to facilitate early recovery after surgery. Optimizing perioperative fluid therapy is a key component of these efforts. While no technology is without limitations, the majority of the currently available literature suggests esophageal Doppler and arterial waveform analysis to be the most desirable choices to guide fluid administration. Their performance is dependent, in part, on the interpretation of dynamic changes resulting from intrathoracic pressure fluctuations encountered during mechanical ventilation. Evolving practice patterns, such as low tidal volume ventilation as well as the necessity to guide fluid therapy in spontaneously breathing patients, will require further investigation.

Ontogeny and control of the heart rate power spectrum in the last third of gestation in fetal sheep

Power spectral analysis of fetal heart rate variability has been proposed to provide a non-invasive estimate of autonomic balance. However, there are few systematic data before birth. We therefore examined developmental changes in the frequency power spectrum at very low (0-0.04 Hz), low (0.04-0.15 Hz) and high frequencies (0.15-0.4 Hz), as well as the ratio of low- to high-frequency power (LF/HF), in chronically catheterized, healthy fetal sheep at 0.6 (n = 8), 0.7 (n = 7) and 0.8 gestational age (ga; n = 11). In a second study, 0.8 ga fetuses received either atropine (4.8 mg bolus, then 4.8 mg h(-1) for 30 min, n = 6) or 6-hydroxydopamine (20 mg ml(-1) at 2.5 ml h(-1) for 3 h; n = 9). Data were analysed by sleep state, defined by low-voltage-high-frequency (LV) or high-voltage-low-frequency (HV) EEG. Total spectral power increased with gestational age (P < 0.05), while LF/HF decreased from 0.6 to 0.7 ga. At 0.8 ga, heart rate and LF/HF were significantly higher during HV than LV sleep (P < 0.05). Consistent with this, although total spectral power was not significantly greater during HV sleep, there was a significant interaction between sleep state and frequency band (P = 0.02). Both atropine (P = 0.05) and 6-hydroxydopamine (P < 0.05) were associated with an overall reduction in spectral power but no significant effect on the LF/HF ratio. This study does not support substantial, consistent differences between the frequencies of sympathetic and parasympathetic activity in late-gestation fetal sheep.

Mechanismen der kardiovaskulären Komorbidität bei Patienten mit obstruktivem Schlafapnoesyndrom

The repetitive intermittent hypoxic episodes, central nervous arousal and intrathoracic pressure fluctuations that occur together with obstructive sleep apnoea are the primary pathophysiological mechanisms responsible for the cardiovascular co-morbidity. These phenomena lead to increased oxidative stress, systemic inflammation, disrupted vasomotor function, increased sympathetic activity and the development of arteriosclerosis in blood vessels. CPAP therapy lowers arterial blood pressure and has a positive effect on relevant specific aspects of cardiovascular co-morbidity. Until the results of current randomised studies have been published, it has to be decided on an individual basis whether the cardiovascular situation alone justifies CPAP therapy. This will usually be the case in severe OSA with daytime sleepiness, in young patients and patients with good compliance. Interventions that reduce cardiovascular risk and also have a positive effect on OSA, i. e., weight reduction, physical exercise and smoking cessation are always appropriate.

A Case Showing Close Relationship between the Pulse Instability and the Respiratory Instability Using Polysomnography Analysis

A 68-year-old man with paroxysmal atrial fibrillation (AF) was admitted due to sleep disordered breathing (SDB). Transthoracic echocardiography revealed left ventricular diastolic dysfunction (the ratio of early transmitral velocity to early diastolic velocity of the mitral annulus: E/E′=10.0) but well-preserved systolic function (left ventricular ejection fraction=64%). Overnight polysomnography (PSG) analysis was undergone for diagnosing SDB. Overnight PSG analysis revealed that this patient experienced severe SDB with an apnea-hypopnea index score of 47.3 events/h. Immediately after patient’s sleep, repetitive non-sustained AF was observed following sustained hypopnea events. Repetitive hypoxemia, autonomic nervous system imbalance and fluctuations in intrathoracic pressure may serve as a trigger for AF. Sustained AF was observed after non-sustained AF, indicating that AF begets AF. After sustained AF occurred, various kinds of repetitive SDB events were shown. These results suggest that AF causes respiratory instability. In summary, AF episodes of this patient could be induced by the respiratory instability and AF could induce respiratory instability. Sustained AF could cause circulation delay such as heart failure, resulting in the occurrence of various kinds of SDB. Therefore, both AF itself and respiratory instability could be a therapeutic target for improving patient’s morbidity. We report on a patient, showing the causative relationship between the pulse instability and the respiratory instability.

The Mechanism of Dead-in-Bed Syndrome and Other Sudden Unexplained Nocturnal Deaths

The mechanism of dead-in-bed syndrome (DBS), a rare but devastating condition that mainly affects young type 1 diabetes patients, remains mysterious. A new theory is proposed to explain this syndrome. This theory suggests that repeated episodes of hypoglycaemia-induced adaptation in orexin-A neurons cause (i) defective awakening and (ii) hypotonia of upper airway muscles during sleep. Consequently, due to the combined effect of these factors, long-term exposure of intermittent hypoxia occurs, leading to a combination of factors - such as depression of ventilation, increase in sympathetic tone, fluctuations in intrathoracic pressure and cardiac arrhythmias - these in conjunction with an underlying cardiovascular pathology (genetically inherited or acquired) cause cardio-respiratory failure and thus sudden death during sleep. This mechanism can be generalized to explain other cases of sudden unexplained nocturnal deaths including sudden infant deaths (SIDs).

Breathing strategy to preserve exercising cardiac function in patients with heart failure

The heart and lungs are closely linked as they lie in series, share a common surface area and compete for space within the thoracic cavity. The heart and lungs are exposed to the similar changes in intrathoracic pressure, and reflexes within one organ can influence the other (i.e. vagal influence of lung inflation on heart rate). In patients with heart failure, these cardiopulmonary interactions may be altered due to decreased lung and left ventricular compliance, increased cardiac size, high cardiac filling pressure and altered receptor sensitivity to neural activation. Exercise further affects the cardiopulmonary interactions by stimulating an increase in the depth and frequency of breathing which accentuates the fluctuations in intrathoracic pressure, and by requiring large increases in stroke volume and heart rate in order to respond to the increased metabolic demand. Previous work from our laboratory suggested that patients with heart failure avoid high lung volumes during exercise, often at the expense of unnecessary large positive expiratory intrathoracic pressures resulting in significant wasted effort. Moreover, we also observed that voluntarily increases in lung volume in patients with heart failure induced a mild relative bradycardia, a response not observed in similar aged healthy individuals. Thus, we hypothesized that the rapid shallow low lung volume breathing, in combination with positive expiratory intrathoracic pressure, often adopted by patients with heart failure during exercise is an attempt to preserve, or even enhance, the cardiac response to exercise.

Intermittent hypoxia: keeping it real

in this issue of the Journal of Applied Physiology , Tamisier and colleagues ([20][1]) describe a novel method for studying the effects of chronic intermittent hypoxia (CIH) in healthy human subjects. To investigate the effects of CIH on sleep, ventilatory control, and blood pressure, the authors

Point:Counterpoint: Respiratory sinus arrhythmia is due to a central mechanism vs. respiratory sinus arrhythmia is due to the baroreflex mechanism

Blood pressure and heart periods fluctuate at respiratory frequencies in healthy humans. Some researchers ([8][1], [23][2]) explain this as a cause-and-effect relation: blood pressure changes trigger baroreflex-mediated R-R interval changes. Here I make the case that respiratory sinus arrhythmia is