End Of Apnea Research Articles

Con: can physiological risk factors for obstructive sleep apnea be determined by analysis of data obtained from routine polysomnography?

The following argument was prepared in response to the question without the knowledge of the contents of the opposing argument. The answer is CLEARLY NO. The mechanisms of ventilatory instability in obstructive sleep apnea (OSA) are complex [1, 2], and defining them with confidence requires interventions that are not practical in routine polysomnography [3–5]. If it is not possible to measure instability traits from routine polysomnograms (PSGs), how is it that since 2015 papers and reviews are being published at an impressive rate in top-rated journals using an approach that claims to estimate all the stability factors from standard clinical PSGs? All these papers are based on a method proposed by Terrill et al. in 2015 to measure loop gain (LG) [6], and subsequently “improved” to provide more and more traits [7]. The basic approach is to measure ventilation in the hyperpneic phase between obstructive events (Vdrive). Without arousal, Vdrive is assumed to reflect chemical drive at the end of apnea. Arousal, if present, is assumed to contribute a fraction of Vdrive. A model with four variables (LG, time constant of chemical responses, circulatory delay, and the arousal contribution) is used to partition Vdrive into the components related to arousal (a constant predicted from the model; Varousal) and that related to the chemical drive (Vchem). The model is then used to estimate the time course of the chemical drive during the obstructed phase. From this LG, the chemical drive preceding arousal (arousal threshold), airway collapsibility, and pharyngeal muscle compensation are derived [8]. In our view, this model is based on untenable assumptions and does not identify the traits that are truly relevant to ventilatory instability in OSA:

Combined Analysis of Myocardial Deformation and Oxygenation Detects Inducible Ischemia Unmasked by Breathing Maneuvers in Chronic Coronary Syndrome.

IntroductionIn patients with chronic coronary syndromes, hyperventilation followed by apnea has been shown to unmask myocardium susceptible to inducible deoxygenation. The aim of this study was to assess whether such a provoked response is co-localized with myocardial dysfunction.MethodsA group of twenty-six CAD patients with a defined stenosis (quantitative coronary angiography > 50%) underwent a cardiovascular magnetic resonance (CMR) exam prior to revascularization. Healthy volunteers older than 50 years served as controls (n = 12). Participants hyperventilated for 60s followed by brief apnea. Oxygenation-sensitive images were analyzed for changes in myocardial oxygenation and strain.ResultsIn healthy subjects, hyperventilation resulted in global myocardial deoxygenation (-10.2 ± 8.2%, p < 0.001) and augmented peak circumferential systolic strain (-3.3 ± 1.6%, p < 0.001). At the end of apnea, myocardial signal intensity had increased (+9.1 ± 5.3%, p < 0.001) and strain had normalized to baseline. CAD patients had a similar global oxygenation response to hyperventilation (−5.8 ± 9.6%, p = 0.085) but showed no change in peak strain from their resting state (-1.3 ± 1.6%), which was significantly attenuated in comparison the strain response observed in controls (p = 0.008). With apnea, the CAD patients showed an attenuated global oxygenation response to apnea compared to controls (+2.7 ± 6.2%, p < 0.001). This was accompanied by a significant depression of peak strain (3.0 ± 1.7%, p < 0.001), which also differed from the control response (p = 0.025). Regional analysis demonstrated that post-stenotic myocardium was most susceptible to de-oxygenation and systolic strain abnormalities during respiratory maneuvers. CMR measures at rest were unable to discriminate post-stenotic territory (p > 0.05), yet this was significant for both myocardial oxygenation [area under the curve (AUC): 0.88, p > 0.001] and peak strain (AUC: 0.73, p = 0.023) measured with apnea. A combined analysis of myocardial oxygenation and peak strain resulted in an incrementally higher AUC of 0.91, p < 0.001 than strain alone.ConclusionIn myocardium of patients with chronic coronary syndromes and primarily intermediate coronary stenoses, cine oxygenation-sensitive CMR can identify an impaired vascular and functional response to a vasoactive breathing maneuver stimulus indicative of inducible ischemia.

Cardiovascular Responses to Simultaneous Diving and Muscle Metaboreflex Activation.

Background: The aim of study was to assess hemodynamic changes during the simultaneous activation of muscle metaboreflex (MM) and diving reflex (DR) in a laboratory setting. We hypothesized that as long as the exercise intensity is mild DR can overwhelm the MM.Methods: Ten trained divers underwent all four phases (randomly assigned) of the following protocol. (A) Postexercise muscle ischemia session (PEMI): 3 min of resting followed by 3 min of handgrip at 30% of maximum force, followed immediately by 3 min of PEMI on the same arm induced by inflating a sphygmomanometer. Three minutes of recovery was further allowed after the cuff was deflated for a total of 6 min of recovery. (B) Control exercise recovery session: the same rest-exercise protocol used for A followed by 6 min of recovery without inflation. (C) DR session: the same rest-exercise protocol used for A followed by 1 min of breath-hold (BH) with face immersion in cold water. (D) PEMI-DR session: the same protocol used for A with 60 s of BH with face immersion in cold water during the first minute of PEMI. Stroke volume (SV), heart rate (HR), and cardiac output (CO) were collected by means of an impedance method.Results: At the end of apnea, HR was decreased in condition C and D with respect to A (−40.8 and −40.3%, respectively vs. −9.1%; p < 0.05). Since SV increase was less pronounced at the same time point (C = +32.4 and D = +21.7% vs. A = +6.0; p < 0.05), CO significantly decreased during C and D with respect to A (−23 and −29.0 vs. −1.4%, respectively; p < 0.05).Conclusion: Results addressed the hypothesis that DR overcame the MM in our setting.

Impact of rapid versus gradual changes in arterial partial pressure of carbon dioxide on blood flow and myocardial oxygenation in an experimental anaesthetized model

Introduction Hyper- and hypocapnia have known vaso-modulatory effects in the coronary circulation. Oxygenation-sensitive cardiovascular magnetic resonance (OS-CMR) detects changes in tissue oxygenation and can provide a comprehensive assessment of the impact of systemic blood gas changes on the myocardium. The purpose of this study was to compare the physiological responses to rapid blood gas changes induced by hyperventilation followed by apnea in comparison to steady-state levels of hypocapnia and hypercapnia in an experimental animal model. Methods Eighteen anaesthetized female swine were used in this study. A blood flow probe was attached to the left descending coronary artery (LAD) after a left-sided thoracotomy. In ten animals a hemodynamically significant LAD stenosis was induced, while eight animals served as controls. In a 3 Tesla MRI, paCO2 was modulated from a pre-set baseline (paO2=100mmHg/paCO2=40mmHg) to 30mmHg and subsequently 50mmHg by minor changes in ventilation rate. Rapid changes in paCO2 were achieved by 60s of hyperventilating (30/min) from baseline followed by an apnea of up to 90 seconds. OS-CMR images, coronary blood flow (CBF) of the LAD and arterial blood gases were recorded at each state. Results Targeting stable hypocapnia of 30mmHg from baseline did not alter CBF or myocardial oxygenation. Subsequent stable hypercapnia (paCO2=50mmHg) increased CBF significantly in control (5±5%, p=0.007) and stenosed (4±6%, p=0.036) animals, and myocardial oxygenation rose in both post-stenotic territories (4.2±6.2%, p=0.036) and in control subjects (6.2±6.2%, p=0.011). Rapid hyperventilation induced a similar degree of hypocapnia (control: paCO2=25±7mmHg, stenosed: 27±3mmHg) and showed a significant decrease of CBF by -34±23% (p=0.012) in healthy animals, and a significant decrease of -10±6% (p=0.010) in stenosed animals. This had no effect on tissue oxygenation. Apnea resulted in a similar paCO2 (control: paCO2=52±9mmHg, stenosed: 47±7mmHg) compared to steady-state blood gas levels, which increased CBF significantly in controls 346±327% (p=0.008) and stenosed 82±110 (p=0.039) animals markedly. By the end of apnea, a rise in tissue oxygenation of 2.9±2.2% was observed in controls (p=0.008), -2.7±5.1 (0.125) was observed in the stenosed group (Figure). Significant difference in myocardial oxygenation responses observed between control and stenosed subject was exclusively observed with apnea (p=0.011). Discussion Rapid hyperventilation followed by apnea results in more pronounced changes in myocardial blood flow than similar steady state deflections in paCO2. Only apnea after hyperventilation induced deoxygenation in the stenotic myocardium, which is in agreement with the concept of hypercapnia induced intercoronary steal, while steady state deviation did not compromise myocardial oxygenation. Similar breathing maneuvers may be seen in the induction phase of anaesthesia, which could potentially be a harbinger of perioperative ischemic myocardial events.

Hold your breath: peripheral and cerebral oxygenation during dry static apnea.

Acute breath-holding deprives the human body from oxygen. In an effort to protect the brain, the diving response is initiated, coupling several physiological responses. The aim of this study was to describe the physiological responses to apnea at the cardiac, peripheral and cerebral level. 31 physically active subjects (17 male, 14 female, 23.3 ± 1.8years old) performed a maximal static breath-hold in a seated position. Heart rate (HR), muscle and cerebral oxygenation (by means of near-infrared spectroscopy, NIRS) were continuously measured. RM MANOVA's were used to identify changes in HR, peripheral (mTOI) and cerebral (cTOI) tissue oxygenation and oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin during apnea. Average apnea duration was 157 ± 41s. HR started decreasing after 10s (p < 0.001) and dropped on average by 27 ± 14bpm from baseline (p < 0.001). mTOI started decreasing 10s after apnea (p < 0.001) and fell by 8.6 ± 4.0% (p < 0.001). Following an immediate drop after 5s (p < 0.001), cTOI increased continuously, reaching a maximal increase of 3.7 ± 2.4% followed by a steady decrease until the end of apnea. cTOI fell on average 5.4 ± 8.3% below baseline (p < 0.001). During apnea, the human body elicits several protective mechanisms to protect itself against the deprivation of oxygen. HR slows down, decreasing O2 demand of the cardiac muscle. The decrease in mTOI and increase in cTOI imply a redistribution of blood flow prioritizing the brain. However, this mechanism is not sufficient to maintain cTOI until the end of apnea.

S1-03 SESSION 1: NEUROSURGERY INTRACRANIAL HYPERTENSION AND SLEEP-DISORDERED BREATHING IN CHILDREN WITH CRANIOSYNOSTOSIS

Introduction: Sleep-disordered breathing (SDB), by means of hypercapnia-related vasodilatation, or raised intrathoracic pressures at the end of apnea, can be a contributor to raised intracranial pressure (rICP). Many children with craniosynostosis have SDB – either obstructive sleep apnoea (OSA) related to midface hypoplasia and airway problems, and/or due to central causes such as Chiari I- in addition to rICP. In our institution, children who have unequivocal findings of rICP such as frank papilloedema progress directly to treatment (usually vault expansion). We use ICP monitoring for “borderline” cases such as subtle disc changes or in the presence of concerning radiological or clinical features. Methods: Since 2015, we have routinely carried out simultaneous sleep studies (SS) for children undergoing ICP monitoring to assess the physiological relationship between these phenomena. We report data from all children with craniosynostosis who underwent combined SS/ICP monitoring in this period. Results: 27 consecutive patients were identified (19 males), with a mean age of 6 years (range 1–18 years). Diagnoses were Apert (8), sagittal (6), multisuture non-syndromic (5), Crouzon (5), Muenke (2) and Pfeiffer (1). Indications for undertaking ICP/SS were: ophthalmic examination findings (13), clinical symptoms e.g. headache (11) and deteriorating visual electrophysiology (7). 10 patients were found to have normal ICP, of which 8 had normal SS and 2 had mild OSA. 14 had rICP, of which 12 had normal SS and 2 had moderately severe OSA. 2 children had low ICP, both with normal SS, and 1 child had borderline ICP, and mild OSA. 10 patients had undergone previous airway interventions. In the high ICP group, physiological rises in pCO2 caused significant ICP spikes. All children with raised or borderline ICP and obstructive airway pathology (3) went on to have either continuous positive airway pressure or surgical airway management. All others with raised ICP (12) went on to have vault expansion. At last follow-up following surgical airway management, headaches had since resolved. Conclusions: There appears to be a relationship between OSA and raised pressure in a proportion of children with craniosynostosis. Understanding this relationship may aid monitoring and decision making in these patients.

Occurrence of cardiac output decrease (via stroke volume) is more pronounced in women than in men during prolonged dry static apnea.

Little is known about sex differences in autonomic cardiovascular regulation of the diving response, and the few available studies of these differences were conducted on subjects with limited or no diving experience. We examined the influence of sex on hemodynamics during dry static apnea (SA) in eight male and eight female elite divers matched for their breath hold (BH) ability. Hemodynamics was assessed by means of simultaneous echocardiography and impedance cardiography measurements, and arterial pressure and oxygen saturation ([Formula: see text]) were also collected. In the first quarter (AP25%) and half (AP50%) of apnea duration cardiac output (CO) showed a more rapid and intense decrease in women than in men (-43% vs. -17% during AP25% and -40% vs. -19% during AP50%, respectively, P < 0.05). At the same time points, systemic vascular resistance (SVR) increased more in women than in men (+22% vs. +100% at AP25% and +48% vs. +107% at AP50%, respectively, P < 0.05). [Formula: see text] progressively declined in both groups, but men showed a more pronounced decrease than women at the end of apneas (-13% vs. -5%, respectively, P < 0.05). In men the higher the body surface area values the longer the apnea, while in women the higher the SVR response the longer the apnea. In elite female divers, the magnitude of CO decrease during dry SA was larger than in male divers. The capacities to store oxygen and to reduce O2 consumption play a pivotal role in BH performance, but their extent seems to be different in the sexes. NEW & NOTEWORTHY This is the first study in which the influence of sex on hemodynamics during dry static apnea has been investigated in two groups of elite divers matched for their breath hold ability. We also show the correlation between the performances obtained by divers during a real competition and their anthropometric, respiratory, and cardiovascular characteristics.

Influence of lung volume on the interaction between cardiac output and cerebrovascular regulation during extreme apnoea

What is the central question of this study? Does the reduction in cardiac output observed during extreme voluntary apnoea, secondary to high lung volume, result in a reduction in cerebral blood flow, perfusion pressure and oxygen delivery in a group of elite free divers? What is the main finding and its importance? High lung volumes reduce cardiac output and ventricular filling during extreme apnoea, but changes in cerebral blood flow are observed only transiently during the early stages of apnoea. This reveals that whilst cardiac output is important in regulating cerebral haemodynamics, the role of mean arterial pressure in restoring cerebral perfusion pressure is of greater significance to the regulation of cerebral blood flow. We investigated the role of lung volume-induced changes in cardiac output (Q̇) on cerebrovascular regulation during prolonged apnoea. Fifteen elite apnoea divers (one female; 185±7cm, 82±12kg, 29±7years old) attended the laboratory on two separate occasions and completed maximal breath-holds at total lung capacity (TLC) and functional residual capacity (FRC) to elicit disparate cardiovascular responses. Mean arterial pressure (MAP), internal jugular venous pressure and arterial blood gases were measured via cannulation. Global cerebral blood flow was quantified by ultrasound and cardiac output was quantified by via photoplethysmography. At FRC, stroke volume and Q̇ did not change from baseline (P>0.05). In contrast, during the TLC trial stroke volume and Q̇ were decreased until 80 and 40% of apnoea, respectively (P<0.05). During the TLC trial, global cerebral blood flow was significantly lower at 20%, but subsequently increased so that cerebral oxygen delivery was comparable to that during the FRC trial. Internal jugular venous pressure was significantly higher throughout the TLC trial in comparison to FRC. The MAP increased progressively in both trials but to a greater extent at TLC, resulting in a comparable cerebral perfusion pressure between trials by the end of apnoea. In summary, although lung volume has a profound effect on Q̇ during prolonged breath-holding, these changes do not translate to the cerebrovasculature owing to the greater sensitivity of cerebral blood flow to arterial blood gases and MAP; regulatory mechanisms that facilitate the maintenance of cerebral oxygen delivery.

Sustained apnea induces endothelial activation.

Apnea diving has gained worldwide popularity, even though the pathophysiological consequences of this challenging sport on the human body are poorly investigated and understood. This study aims to assess the influence of sustained apnea in healthy volunteers on circulating microparticles (MPs) and microRNAs (miRs), which are established biomarkers reflecting vascular function. Short intermittent hypoxia due to voluntary breath-holding affects circulating levels of endothelial cell-derived MPs (EMPs) and endothelial cell-derived miRs. Under dry laboratory conditions, 10 trained apneic divers performed maximal breath-hold. Venous blood samples were taken, once before and at 4 defined points in time after apnea. Samples were analyzed for circulating EMPs and endothelial miRs. Average apnea time was 329 seconds (±103), and SpO2 at the end of apnea was 79% (±12). Apnea was associated with a time-dependent increase of circulating endothelial cell-derived EMPs and endothelial miRs. Levels of circulating EMPs in the bloodstream reached a peak 4 hours after the apnea period and returned to baseline levels after 24 hours. Circulating miR-126 levels were elevated at all time points after a single voluntary maximal apnea, whereas miR-26 levels were elevated significantly only after 30 minutes and 4 hours. Also miR-21 and miR-92 levels increased, but did not reach the level of significance. Even a single maximal breath-hold induces acute endothelial activation and should be performed with great caution by subjects with preexisting vascular diseases. Voluntary apnea might be used as a model to simulate changes in endothelial function caused by hypoxia in humans.

Hypercapnia is essential to reduce the cerebral oxidative metabolism during extreme apnea in humans

The cerebral metabolic rate of oxygen (CMRO2) is reduced during apnea that yields profound hypoxia and hypercapnia. In this study, to dissociate the impact of hypoxia and hypercapnia on the reduction in CMRO2, 11 breath-hold competitors completed three apneas under: (a) normal conditions (NM), yielding severe hypercapnia and hypoxemia, (b) with prior hyperventilation (HV), yielding severe hypoxemia only, and (c) with prior 100% oxygen breathing (HX), yielding the greatest level of hypercapnia, but in the absence of hypoxemia. The CMRO2 was calculated from the product of cerebral blood flow (ultrasound) and the radial artery-jugular venous oxygen content difference (cannulation). Secondary measures included net-cerebral glucose/lactate exchange and nonoxidative metabolism. Reductions in CMRO2 were largest in the HX condition (−44 ± 15%, p < 0.05), with the most severe hypercapnia (PaCO2 = 58 ± 5 mmHg) but maintained oxygen saturation. The CMRO2 was reduced by 24 ± 27% in NM (p = 0.05), but unchanged in the HV apnea where hypercapnia was absent. A net-cerebral lactate release was observed at the end of apnea in the HV and NM condition, but not in the HX apnea (main effect p < 0.05). These novel data support hypercapnia/pH as a key mechanism mediating reductions in CMRO2 during apnea, and show that severe hypoxemia stimulates lactate release from the brain.

The impact of hematocrit on oxygenation-sensitive cardiovascular magnetic resonance.

BackgroundOxygenation-sensitive (OS) Cardiovascular Magnetic Resonance (CMR) is a promising utility in the diagnosis of heart disease. Contrast in OS-CMR images is generated through deoxyhemoglobin in the tissue, which is negatively correlated with the signal intensity (SI). Thus, changing hematocrit levels may be a confounder in the interpretation of OS-CMR results. We hypothesized that hemodilution confounds the observed signal intensity in OS-CMR images.MethodsVenous and arterial blood from five pigs was diluted with lactated Ringer solution in 10 % increments to 50 %. The changes in signal intensity (SI) were compared to changes in blood gases and hemoglobin concentration. We performed an OS-CMR scan in 21 healthy volunteers using vasoactive breathing stimuli at baseline, which was then repeated after rapid infusion of 1 L of lactated Ringer’s solution within 5–8 min. Changes of SI were measured and compared between the hydration states.ResultsThe % change in SI from baseline for arterial (r = -0.67, p < 0.0001) and venous blood (r = -0.55, p = 0.002) were negatively correlated with the changes in hemoglobin (Hb). SI changes in venous blood were also associated with SO2 (r = 0.68, p < 0.0001) and deoxyHb concentration (-0.65, p < 0.0001). In healthy volunteers, rapid infusion resulted in a significant drop in the hemoglobin concentration (142.5 ± 15.2 g/L vs. 128.8 ± 15.2 g/L; p < 0.0001). Baseline myocardial SI increased by 3.0 ± 5.7 % (p = 0.026) following rapid infusion, and in males there was a strong association between the change in hemoglobin concentration and % changes in SI (r = 0.82, p = 0.002). After hyperhydration, the SI response after hyperventilation was attenuated (HV, p = 0.037), as was the maximum SI increase during apnea (p = 0.012). The extent of SI attenuation was correlated with the reduction in hemoglobin concentration at the end of apnea (r = 0.55, p = 0.012) for all subjects and at maximal SI (r = 0.63, p = 0.037) and the end of breath-hold (r = 0.68, p = 0.016) for males only.ConclusionIn dynamic studies using oxygenation-sensitive CMR, the hematocrit level affects baseline signal intensity and the observed signal intensity response. Thus, the hydration status of the patient may be a confounder for OS-CMR image analysis.

Dynamic diaphragmatic MRI during apnea struggle phase in breath-hold divers

The purpose of the study was to provide insight in diaphragmatic involuntary breathing movements (IBM) during struggle phase of apnea at total lung capacity (TLC) and functional residual capacity (FRC) using magnetic resonance imaging along with measurements of hemodynamics and arterial oxygenation. The study was performed in eight elite breath-hold divers. There was a similar increase in diaphragmatic cranio-caudal excursions towards the end of TLC and FRC apnea. The greatest diaphragmatic excursion in both apneas and during tidal breathing was in the middle and posterior part of the diaphragm. Diaphragm thickness in elite BHD was within the reference range of normal values suggesting no diaphragmatic hypertrophy in this population. We found that the range of diaphragmatic excursions increases toward the end of apneas. Additionally, our data suggest that the diaphragm participates in IBM occurrence and that various segments of the diaphragm behave nonhomogenously both in tidal breathing and IBMs.

Hyperventilation and seizures in an adolescent female

A 16 year-old girl was admitted after suffering from recurrent episodes of dyspnea and stridor, cyanosis, loss of contact, stiffening of all four limbs, clenching of the jaw and eye retroversion that lasted for a few seconds to a minute, followed by slow recovery of consciousness without any loss of sphincter control. These symptoms began at the age of 11 and worsened over time. Prolonged rate corrected QT intervals was observed with an ECG. Two cardio-respiratory monitorings were performed (one during daytime hours while the patient was awake, and one at night time while the patient slept). Daytime recordings showed 17 central apnoeas and 97 central hypopneas, with an apnea-hypopnea index (AHI) of 13.2 events/hour, that were associated with severe oxyhemoglobin desaturation. In contrast, night time recordings were normal (AHI=1.1 events/hour). The patient underwent diurnal monitoring of transcutaneous pCO2(PtcCO2), transcutaneous O2(PtcO2), SpO2 and end tidal CO2 (PETCO2), with simultaneous monitoring of regional cerebral oxymetry (rSO2) which showed values of PtcCO2 between 8 and 15 mmHg, suggesting several episodes of marked hyperventilation. Twenty-nine episodes of severe arterial desaturation (SpO2<50%) were registered, all after the same number of apnea events, with ascent of PtcO2 up to 28 mmHg at the end of apnea. During the final phase of apnea, the patient showed cyanosis, contact disturbance, grimaces, oral movements of rhyme, and, on three occasions, partial seizures. A mask was packaged and applied daytime to the face of the patient during episodes of hyperventilation to prevent, together with a psychiatric follow up, rapid falls of PaCO2 levels determining central apnoeas.

Cardiovascular responses to dry resting apnoeas in elite divers while breathing pure oxygen

PurposeWe hypothesized that the third dynamic phase (ϕ3) of the cardiovascular response to apnoea requires attainment of the physiological breaking point, so that the duration of the second steady phase (ϕ2) of the classical cardiovascular response to apnoea, though appearing in both air and oxygen, is longer in oxygen. MethodsNineteen divers performed maximal apnoeas in air and oxygen. We measured beat-by-beat arterial pressure, heart rate (fH), stroke volume (SV), cardiac output (Q˙). ResultsThe fH, SV and Q˙ changes during apnoea followed the same patterns in oxygen as in air. Duration of steady ϕ2 was 105±37 and 185±36s, in air and oxygen (p<0.05), respectively. At end of apnoea, arterial oxygen saturation was 1.00±0.00 in oxygen and 0.75±0.10 in air. ConclusionsThe results support the tested hypothesis. Lack of hypoxaemia during oxygen apnoeas suggests that, if chemoreflexes determine ϕ3, the increase in CO2 stores might play a central role in eliciting their activation.

Asynchrony of lingual muscle recruitment during sleep in obstructive sleep apnea.

Pharyngeal collapsibility during sleep increases primarily due to decline in dilator muscle activity. However, genioglossus EMG is known to increase during apneas and hypopneas, usually without reversing upper airway obstruction or inspiratory flow limitation. The present study was undertaken to test the hypothesis that intense activation of the genioglossus fails to prevent pharyngeal obstruction during sleep, and to evaluate if sleep-induced changes in tongue muscle coordination may be responsible for this phenomenon. We compared genioglossus and tongue retractors EMG activity in 13 obstructive sleep apnea (OSA) patients during wakefulness, while breathing through inspiratory resistors, to the activity observed at the end of apneas and hypopneas after 25 mg of brotizolam, before arousal, at equal esophageal pressure. During wakefulness, resistive breathing triggered increases in both genioglossus and retractor EMG. Activation of agonist tongue muscles differed considerably from that of the arm, as both genioglossus and retractors were activated similarly during all tongue movements. During sleep, flow limitation triggered increases in genioglossal EMG that could reach more than twofold the level observed while awake. In contrast, EMGs of the retractors reached less than half the wakefulness level. In sleeping OSA patients, genioglossal activity may increase during obstructed breathing to levels that exceed substantially those required to prevent pharyngeal collapse during wakefulness. In contrast, coactivation of retractors is deficient during sleep. These findings suggest that sleep-induced alteration in tongue muscle coordination may be responsible for the failure of high genioglossal EMG activity to alleviate flow limitation.

Ischaemia-modified albumin during experimental apnoea.

Ischaemia-modified albumin (IMA) is a marker of the release of reactive oxygen species (ROS) during hypoxaemia. In elite divers, breath-hold induces ROS production. Our aim was to evaluate the kinetics of IMA serum levels during apnea. Twenty breath-hold divers were instructed to perform a submaximal static breath-hold. Twenty non-diver subjects served as controls. Blood samples were collected at rest, every minute, at the end of breath-hold, and 10 min after recovery. The IMA level increased after 1 min of breath-hold (p < 0.003) and remained high until recovery. Divers were separated into 2 groups: subjects who held their breath for less than 4 min (G-4) and those who held it for more than 4 min (G+4). After 3 min of apnoea, the increase of IMA was higher in the G-4 group than in the G+4 group (p < 0.008). However, at the end of apnoea, the IMA level did not differ between groups. If IMA level was globally correlated with the apnoea duration, it is interesting to note that the higher IMA level was not found in the best divers. Similarly, if arterial blood oxygen saturation (SpO2) was globally inversely correlated with apnoea duration, the lowest SpO2 at the end of breath-hold was not found in the divers that performed the best apnoea. We concluded that these divers save their oxygen. The IMA level provides a useful measure of resistance to hypoxaemia.

The application of continuous positive airway pressure in association with obstructive sleep apnea syndrome and subconjunctival hemorrhage due to hypertensive attacks: case reports

Introduction Spontaneous subconjunctival hemorrhage associated with hypertension (HT) is common. Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for HT. Blood pressure during obstructive sleep apnea can increase up to 20% and reaches its highest level with the end of apnea. Materials and methods Case: 60-year-old male patient, BMI: 30.9 kg/m 2 , had complaints of subconjunctival hemorrhage in the morning after sleeping, repeated three times in the last two years. He described occasional complaints of snoring and daytime sleepiness. There was no history of trauma, antiplatelet therapy, and bleeding disorders. He was being taken regular medication for 5 years with a diagnosis of hypertension. In the color fundus imaging, hypertensive retinopathy was detected. Twice Holter monitoring was performed in patient with hypertension (Table 1). Day–night rates of the critical levels of systolic BP, day: 0%, 7%, and night: increased to 15%, 13%, diastolic BP, day: 0%, 0%, and night: increased to 0% to 13% were found. Oxygen saturation was monitored during sleep at night, and desaturation was observed. Then polysomnography test was performed. In polysomnography, apnea hypopnea index (AHI) was 45.8, and the patient was diagnosed with OSAS. Results Consequently, continuous positive airway pressure (CPAP) therapy was given. After the current antihypertensive treatment and CPAP treatment, systole: 2% at night, 1% critical level during the day was found significantly lower in the Holter monitoring. There was no recurrence of bleeding after CPAP treatment. Conclusion In our case, recurrence of subconjunctival hemorrhage due to hypertensive episodes caused by OSAS was observed. After CPAP treatment, subconjunctival hemorrhage due to hypertensive attacks did not relapse, because of regular course of blood pressure. The patients with complications of hypertension should be considered in terms of OSAS, because CPAP treatment prevents hypertensive episodes by night. Acknowledgements OSAS, subconjunctival hemorrhage due to hypertensive attacks.

Preinduction incentive spirometry versus deep breathing to improve apnea tolerance during induction of anesthesia in patients of abdominal sepsis

Abdominal sepsis is associated with varied degree of hypoxemia and atelactasis in the lung and can enhance the onset of desaturation of arterial blood during apnea. This study looked at methods to improve safety margin of apnea during induction of anesthesia in these high-risk patients. It was a randomized, single blind study on adult patients presenting for emergency laparotomy due to peritonitis in a university teaching hospital setting. In group 1 (IS) (n = 32), three sessions of incentive spirometry (IS) were performed within one hour before induction of anesthesia. In group 2 (DB) (n = 34), patients were subjected to deep breathing sessions in a similar manner. All patients received preoxygenation (100%) by mask for 3 min, followed by rapid-sequence induction of anesthesia using fentanyl, thiopental, and suxamethonium and endotracheal intubation. Patients were subjected to a period of apnea by keeping the end of the endotracheal tube open to air till they developed 95% hemoglobin saturation (SpO 2) by pulse oxymetry. Positive pressure ventilation was resumed at the end. We observed for hemodynamic changes, apnea time, and SpO 2 (100%) recovery time on resuming ventilation. Arterial blood gas samples were taken before intervention, after IS or DB, after preoxygenation, and at the end of apnea. One-way analysis of variance (ANOVA), X 2 test, Kaplan-Meier graph, and log-rank tests were applied to compare the two study groups. Oxygenation level in group 1 (265 ± 76.7 mmHg) patients was significantly (P < 0.001) higher than in group 2 (221 ± 61.8 mmHg)at the end of preoxygenation. The apnea time (median: lower bound - upper bound Confidence Interval apnea time) (272:240-279 s) in group 1 (IS) patients was significantly higher P < 0.05) than in group 2 (180:163-209 s) patients. Saturation recovery time (35:34-46 s) in group 1 (IS) patients was also quicker than in group 2 patients (48:44-58 s). IS in the preoperative period is superior to deep breathing sessions for improving apnea tolerance during induction of anesthesia in abdominal sepsis patients.

Baseline plasma cGMP levels correlates with breath hold capacity in competitive breath hold divers

Breath‐hold (BH) duration depends on oxygen stores and consumption. Strong peripheral vasoconstriction and reduction in cardiac output (diving response) reduce oxygen consumption during apnea. A healthy reactive endothelium may be important for an efficient diving response. Endothelium‐derived nitric oxide (NO) is deeply involved in endothelial function and plasma cGMP is considered as a marker of endothelial NO synthase activity.ObjectiveTo evaluate the association between plasma cGMP and BH capacity in trained BH divers.MethodsNine BH divers performed BHs of maximal duration after inhalation to 80% of vital capacity. Oxygen consumption was evaluated with pulse oximetry (SpO2) and exhaled O2 fraction (EtFO2) at end of apnea. Baseline plasma cGMP was measured before and 10min after the apnea protocol.ResultsA strong positive correlation was found between baseline plasma cGMP levels and maximum BH duration (344±13 sec, R2=0.63, P=0.011), SpO2 at 4min (R2=0.53, P=0.026) and EtFO2 at breath‐holds aborted at 4min (R2=0.50, P=0.026). Mean plasma cGMP increased from 4.3±0.8 to 7,8±1.8nM as a result of the apnea protocol (P=0.024).ConlusionBaseline plasma cGMP predicts breath hold capacity and oxygen consumption during apnea in trained breath hold divers. This indicates that endothelial NOS activity could be important in the vascular part of the diving response.

Effect of Acute Ozone Induced Airway Inflammation on Human Sympathetic Nerve Traffic: A Randomized, Placebo Controlled, Crossover Study

BackgroundOzone concentrations in ambient air are related to cardiopulmonary perturbations in the aging population. Increased central sympathetic nerve activity induced by local airway inflammation may be one possible mechanism.Methodology/Principal FindingsTo elucidate this issue further, we performed a randomized, double-blind, cross-over study, including 14 healthy subjects (3 females, age 22–47 years), who underwent a 3 h exposure with intermittent exercise to either ozone (250 ppb) or clean air. Induced sputum was collected 3 h after exposure. Nineteen to 22 hours after exposure, we recorded ECG, finger blood pressure, brachial blood pressure, respiration, cardiac output, and muscle sympathetic nerve activity (MSNA) at rest, during deep breathing, maximum-inspiratory breath hold, and a Valsalva maneuver. While the ozone exposure induced the expected airway inflammation, as indicated by a significant increase in sputum neutrophils, we did not detect a significant estimated treatment effect adjusted for period on cardiovascular measurements. Resting heart rate (clean air: 59±2, ozone 60±2 bpm), blood pressure (clean air: 121±3/71±2 mmHg; ozone: 121±2/71±2 mmHg), cardiac output (clean air: 7.42±0.29 mmHg; ozone: 7.98±0.60 l/min), and plasma norepinephrine levels (clean air: 213±21 pg/ml; ozone: 202±16 pg/ml), were similar on both study days. No difference of resting MSNA was observed between ozone and air exposure (air: 23±2, ozone: 23±2 bursts/min). Maximum MSNA obtained at the end of apnea (air: 44±4, ozone: 48±4 bursts/min) and during the phase II of the Valsalva maneuver (air: 64±5, ozone: 57±6 bursts/min) was similar.Conclusions/SignificanceOur study suggests that acute ozone-induced airway inflammation does not increase resting sympathetic nerve traffic in healthy subjects, an observation that is relevant for environmental health. However, we can not exclude that chronic airway inflammation may contribute to sympathetic activation.