Arterial Oxyhemoglobin Desaturation Research Articles

P-022: THERAPEUTIC EFFECTS OF GBT1118 ON SKELETAL MUSCLE ENERGETICS AND FUNCTION IN SICKLE CELL MICE

Purpose: Sickle cell disease (SCD) is an hemoglobinopathy ultimately resulting red blood cells sickling. SCD patients suffer from anemia, arterial oxyhemoglobin desaturation, hematologic and hemodynamic abnormalities, all of which disrupt oxygen supply and can reduce exercise capacity and quality of life. Strenuous exercise in SCD patients may induce hemolysis, an early lactate accumulation, an intracellular acidosis, all of which are potential triggering factors for sickling and vaso-occlusive crises. GBT1118 is a HbS polymerization inhibitor which can increase hemoglobin affinity for oxygen and the corresponding supply to tissues. On that basis, we hypothesized that GBT1118 could dampen skeletal muscle energetics and function. Materials and methods: Skeletal muscle energetics and function of sixteen Townes mice (2 ± 0.5 month-old) were assessed in response to a standardized Rest-Stimulation(1Hz)-Recovery protocol before and after an 8-week period (8WP). Investigations were conducted using a setup designed to be operational inside a 7T horizontal MRI scanner (PharmaScan-Bruker). The setup allows (i) magnetic resonance imaging, (ii) muscle force measurements and (iii) 31P-magnetic resonance spectroscopy. Assessments conducted before and after the 8WP were identified with number 1 (SCDGBT1) and two (SCDGBT2). Ten mice received a chronic supplementation of GBT1118 (4g/kg in chow) during the 8WP (SCDGBT), whereas six mice had access to not supplemented chow (SCDCON). Results: The specific peak force (sPf) measured at the beginning of stimulation significantly increased over the 8WP (SCDCON2 +68%, p < 0.05). This increased initial sPf was also present in SCDGBT2 as compared to SCDGBT1 (+ 30%, p < 0.05). Over the entire stimulation session, the overall specific [TM1] force production (sTFP) significantly increased over the 8WP (SCDCON2 +32%, p < 0.05, Figure 1). The increased sTFP was also present in SCDGBT2 as compared to SCDGBT1 (+ 25 %, p < 0.05). However, the sTFP-normalized pHi reduction and sTFP-normalized phosphocreatine (PCr) breakdown significantly decreased in SCDGBT2 as compared to SCDGBT1 (p < 0.05, Table 1). Conclusion: In the control condition, the 8-week period was accompanied by a significant increase in specific total force production. Such an increase has been previously reported from 3 to 10 weeks of age (+ 33%). Overall, the increased specific total force production we reported was related to time and cannot be accounted for by GBT supplementation. In SCDGBT, the expected increased force production related to time was associated to a reduced acidosis and PCr breakdown which were not found in the control condition. For a given amount of force, SCDGBT mice muscle would experience a lower net proton accumulation and a reduced net PCr consumption. This reduction of both acidosis and PCr consumption could illustrate a diminished cost of contraction in response to GBT1118 supplementation which could be related to an improved contractile efficiency as previously described in humans. SCD mice treated with GBT1118 exhibit a reduced acidosis for a given force. Given that acidosis is a potential triggering factor of sickling, GBT would protect SCD muscle against the consequences of sickling. One could speculate that SCD patients receiving GBT1118 might be able to perform exercise with a reduced exposure to sickling.Specific total force production in SCDCON and SCDGBT before and after the 8-week period. Each point represents a single measurement and lines are linking consecutive points. p-values are mentioned on the top of the figure.Metabolic indices in SCDCON and SCDGBT before and after the 8-week period. The authors do not declare any conflict of interest

Upper-airway flow limitation and transcutaneous carbon dioxide during sleep in normal pregnancy

ObjectiveSleep during pregnancy involves a physiological challenge to provide sufficient gas exchange to the fetus. Enhanced ventilatory responses to hypercapnia and hypoxia may protect from deficient gas exchange, but sleep-disordered breathing (SDB) may predispose to adverse events. The aim of this study was to analyze sleep and breathing in healthy pregnant women compared to non-pregnant controls, with a focus on CO2 changes and upper-airway flow limitation. MethodsHealthy women in the third trimester and healthy non-pregnant women with normal body mass index (BMI) were recruited for polysomnography. Conventional analysis of sleep and breathing was performed. Transcutaneous carbon dioxide (TcCO2) was determined for each sleep stage. Flow-limitation was analyzed using the flattening index and TcCO2 values were recorded for every inspiration. ResultsEighteen pregnant women and 12 controls were studied. Pregnancy was associated with shorter sleep duration and more superficial sleep. Apnea–hypopnea index, arterial oxyhemoglobin desaturation, flow-limitation, snoring or periodic leg movements were similar in the two groups. Mean SaO2 and minimum SaO2 were lower and average heart rate was higher in the pregnant group. TcCO2 levels did not differ between groups but variance of TcCO2 was smaller in pregnant women during non-rapid eye movement (NREM). TcCO2 profiles showed transient TcCO2 peaks, which seem specific to pregnancy. ConclusionsHealthy pregnancy does not predispose to SDB. Enhanced ventilatory control manifests as narrowing threshold of TcCO2 between wakefulness and sleep. Pregnant women have a tendency for rapid CO2 increases during sleep which might have harmful consequences if not properly compensated.

Repeated exercise-induced arterial hypoxemia in a healthy untrained woman

A healthy 36-year-old untrained (maximal oxygen consumption (V˙O2max): 39mL/kg/min) woman completed multiple graded exercise tests on a treadmill. Temperature-corrected arterial blood samples were obtained in addition to esophageal pressure. Significant hypoxemia (−13mmHg arterial oxygen tension decrease) and arterial oxyhemoglobin desaturation (−6% decrease) was observed relative to rest and occurred during submaximal exercise and worsened at maximal intensities. Expiratory flow limitation (28–40% intersection of tidal volume) was present at near-maximal intensities. Relieving mechanical ventilatory constraints with a helium inspirate (79% He:21% O2) partially reversed the hypoxemia. Conversely, increasing chemical ventilatory stimuli, with hypercapnia (3.5% CO2), failed to increase ventilation. Maintaining oxyhemoglobin saturation, via a mildly hyperoxic (26% O2) inspirate, increased exercise duration (+45s) and V˙O2max (+5mL/kg/min). We attribute the hypoxemia to an excessive A–aO2 resulting from ventilation–perfusion mismatch and secondarily to mechanical ventilatory constraints. We conclude that a healthy untrained woman can develop EIAH and this remains stable over a period of 6 months.

The current clinical research of preoxygenation before emergency tracheal intubation in ICU

Background Preoxygenation is one of the necessary procedures before tracheal intubation,but hadn't been emphasized and popularized in ICU because of lacking of clinical evidences.Much work of preoxygenation before elective general anesthesia,has been done,but the study in ICU has just begun. Objective The summary discussed the relevant techniques,practice,problems and future development of preoxygenation in ICU. Content Preoxygenation in critically ill patients requiring emergency tracheal intubation increases oxygen reserves and duration of apnea without desaturation(DAWD) in the hopes of delaying the onset of arterial desaturation, thus prevents hypoxia during a planned or unexpected period of apnea.Side effects of preoxygenation such as stomach inflation should be prevented.Traditional manner of preoxygenation (bag-valve-mask ventilation) is less effective at reducing arterial oxyhemoglobin desaturation than other methods.Lacking of adequate clinical evidences,those effective metoods of preoxygenation weren't widely used in clinical practice Trend In order to explore a optimal preoxygenation method in ICU,further clinical studies is needed. Key words: ICU; Emergency tracheal intubation; Preoxygenation

Impairment of 3000-m Run Time at Altitude Is Influenced by Arterial Oxyhemoglobin Saturation

The decline in maximal oxygen uptake (ΔVO(2)max) with acute exposure to moderate altitude is dependent on the ability to maintain arterial oxyhemoglobin saturation (SaO2). This study examined if factors related to ΔVO(2)max at altitude are also related to the decline in race performance of elite athletes at altitude. Twenty-seven elite distance runners (18 men and 9 women, VO(2)max = 71.8 ± 7.2 mL·kg(-1)·min(-1)) performed a treadmill exercise at a constant speed that simulated their 3000-m race pace, both in normoxia and in 16.3% O2 (∼2100 m). Separate 3000-m time trials were completed at sea level (18 h before altitude exposure) and at 2100 m (48 h after arrival at altitude). Statistical significance was set at P ≤ 0.05. Group 3000-m performance was significantly slower at altitude versus sea level (48.5 ± 12.7 s), and the declines were significant in men (48.4 ± 14.6 s) and women (48.6 ± 8.9 s). Athletes grouped by low SaO2 during race pace in normoxia (SaO2 < 91%, n = 7) had a significantly larger ΔVO(2) in hypoxia (-9.2 ± 2.1 mL·kg(-1)·min(-1)) and Δ3000-m time at altitude (54.0 ± 13.7 s) compared with athletes with high SaO2 in normoxia (SaO2 > 93%, n = 7, ΔVO(2) = -3.5 ± 2.0 mL·kg(-1)·min(-1), Δ3000-m time = 38.9 ± 9.7 s). For all athletes, SaO2 during normoxic race pace running was significantly correlated with both ΔVO(2) (r = -0.68) and Δ3000-m time (r = -0.38). These results indicate that the degree of arterial oxyhemoglobin desaturation, already known to influence ΔVO(2)max at altitude, also contributes to the magnitude of decline in race performance at altitude.

Impairment Of 3000m Racing Performance At Moderate Altitude Is Influenced By VO2 And SaO2 Maintenance

Athletic competitions involving endurance exercise at moderate altitude are characterized by impaired performances compared to sea level. The decline in maximal oxygen uptake (VO2max) with acute exposure to moderate altitude has been shown to be dependent on both the magnitude of VO2max at sea level, as well as the ability to maintain arterial oxyhemoglobin saturation (SaO2) during exercise. Whether these relationships extend to influence racing performance with acute altitude exposure is unknown. PURPOSE: This study examined if SaO2 and VO2 maintenance during heavy exercise in acute hypoxia are related to the acute decline in racing performance of elite athletes at altitude. METHODS: Twenty-seven elite distance runners (18 M, 9 F, VO2max = 71.8 + 7.2 ml/kg/min) performed a treadmill exercise bout at a constant speed which simulated their 3000m race pace, both in normoxia (elevation 230m) and breathing 16.3 % O2 (simulating 2100m). Separate 3000m time trials were completed on 400m all-weather outdoor tracks at elevations of 230m (SL), 18 hrs prior to exposure to altitude, and 2100m (ALT), 48 hrs after arrival at altitude. Statistical significance was set at P < 0.05. RESULTS: Group 3000m time trial performance was significantly slower at ALT versus SL (D3000m race time = +48.5 + 12.7 s or 9.2%), and the declines in performances were similar in men (+48.4 + 14.6 s) and women (+48.6 + 8.9 s). Athletes grouped as low SaO2 during race pace treadmill running in normoxia (SaO2 < 91%, n = 7) had a significantly larger decline in race pace VO2 in hypoxia (-9.2 + 2.1 ml/kg/min) and slowing of 3000m race time at altitude (+54.0 + 13.7 s) compared to athletes grouped with high SaO2 during race pace running in normoxia (SaO2 > 93%, n = 7, DVO2 = -3.5 + 2.0 ml/kg/min, D3000m race time = +38.9 + 9.7 s). SaO2 during normoxic race pace running was significantly correlated with both the decline in VO2 from normoxia to hypoxia during race pace running (r = -0.68), as well as the decline in 3000m race time at ALT (r = -0.38). CONCLUSION: These results indicate that the degree of arterial oxyhemoglobin desaturation during heavy exercise, already known to influence the decline in VO2max at altitude, also contributes to the magnitude of the decline in racing performance with acute altitude exposure. Supported by a grant from the US Olympic Committee and USA Track and Field

Diagnostic and therapeutic approach to coexistent chronic obstructive pulmonary disease and obstructive sleep apnea

The high prevalence of both obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) in Western societies is well documented. However, OSA frequently remains unrecognized and untreated among patients with COPD. Patients with both conditions have a greater risk for fatal and nonfatal cardiovascular events compared with patients with COPD or OSA alone. Efficacious treatment with continuous positive airway pressure reduces the risk of cardiovascular complications in patients with OSA. The aim of the present review is to discuss the diagnostic approach to patients with both conditions and to delineate the benefits of timely recognition and treatment of OSA in patients with COPD.

Respiratory System Determinants of Peripheral Fatigue and Endurance Performance

We briefly summarize recent evidence pertaining to how mechanisms primarily under the control of the respiratory system-namely, arterial oxyhemoglobin desaturation, respiratory muscle work and fatigue, and cyclical fluctuations in intrathoracic pressure-may contribute to exercise limitation. Respiratory influences on cardiac output and on sympathetic vasoconstrictor activity and blood flow distribution are shown to be important determinants of performance. We also address how a compromised O2 transport exacerbates the rate of development of peripheral muscle fatigue and, in turn, precipitates central fatigue and exercise limitation.

Cerebral oximetry improves detection of sickle cell patients at risk for nocturnal cerebral hypoxia

We previously used cerebral oximetry to identify low cerebral venous oxygen saturation in waking children with sickle cell disease (SCD). Because arterial oxyhemoglobin desaturation is common during sleep in SCD patients, this study compared both waking and sleeping systemic arterial and cerebral venous oxygenation dynamics in children with and without SCD. Seventeen African-American (AA) children with homozygous SCD [8 (4-15) years; 29% male; normal transcranial Doppler velocities] were compared with a control cohort (CON) comprised of six healthy AA children [9 (4-16) years, 33% male]. Standard all-night polysomnographic recordings were performed, including measurement of arterial oxygen saturation by pulse oximetry (SpO(2)). Regional cerebral oxygen saturation (rSO(2)) was measured non-invasively with cerebral oximetry. Intra-cohort comparisons examined the influence of sleep on SpO(2) and rSO(2) in the subjects. Inter-cohort comparisons of SpO(2), rSO(2,) and the rSO(2)/SpO(2) ratio assessed the impact of SCD on systemic and cerebral oxygenation during wakefulness and sleep. Cohort differences in SpO(2) were not statistically significant in either wakefulness or sleep. However, only in the SCD cohort was the magnitude of SpO(2) change statistically significant (P = 0.002). In contrast, both waking and sleep rSO(2) cohort median values did differ significantly [awake: CON 76 (67-86) vs. SCD 62 (58-71), P = 0.01; sleep: CON 65 (60-77) vs. SCD 55 (48-61), P = 0.01)]. The waking rSO(2)/SpO(2) ratio was also significantly lower in the SCD group [CON 0.78 (0.68-0.88) vs. SCD of 0.66 (0.61-0.72); P = 0.015]. During sleep, the ratio was also significantly lower in the SCD group [CON 0.71 (0.66-0.81) vs. SCD 0.59 (0.52-0.65); P = 0.011]. Our findings suggest that SCD patients may be at increased risk of cerebral hypoxia during both wakefulness and sleep.

Noninvasive Ventilation Improves Preoxygenation before Intubation of Hypoxic Patients

Critically ill patients are predisposed to oxyhemoglobin desaturation during intubation. To find out whether noninvasive ventilation (NIV), as a preoxygenation method, is more effective at reducing arterial oxyhemoglobin desaturation than usual preoxygenation during orotracheal intubation in hypoxemic, critically ill patients. Prospective randomized study performed in two surgical/medical intensive care units (ICUs). Preoxygenation was performed, before a rapid sequence intubation, for a 3-min period using a nonrebreather bag-valve mask (control group) or pressure support ventilation delivered by an ICU ventilator through a face mask (NIV group) according to the randomization. The control (n = 26) and NIV (n = 27) groups were similar in terms of age, disease severity, diagnosis at admission, and pulse oxymetry values (Sp(O(2))) before preoxygenation. At the end of preoxygenation, Sp(O(2)) was higher in the NIV group as compared with the control group (98 +/- 2 vs. 93 +/- 6%, p < 0.001). During the intubation procedure, the lower Sp(O(2)) values were observed in the control group (81 +/- 15 vs. 93 +/- 8%, p < 0.001). Twelve (46%) patients in the control group and two (7%) in the NIV group had an Sp(O(2)) below 80% (p < 0.01). Five minutes after intubation, Sp(O(2)) values were still better in the NIV group as compared with the control group (98 +/- 2 vs. 94 +/- 6%, p < 0.01). Regurgitations (n = 3; 6%) and new infiltrates on post-procedure chest X ray (n = 4; 8%) were observed with no significant difference between groups. For the intubation of hypoxemic patients, preoxygenation using NIV is more effective at reducing arterial oxyhemoglobin desaturation than the usual method.

Evidence of exercise-induced O2 arterial desaturation in non-elite sportsmen and sportswomen following high-intensity interval-training.

The aim of this study was to investigate the development of exercise-induced hypoxemia (EIH defined as an exercise decrease > 4 % in oxygen arterial saturation, i. e. SaO (2) measured with a portable pulse oximeter) in twelve sportsmen and ten sportswomen (18.5 +/- 0.5 years) who were non-elite and not initially engaged in endurance sport or training. They followed a high-intensity interval-training program to improve V.O (2)max for eight weeks. The training running speeds were set at approximately 140 % V.O (2)max running speed up to 100 % 20-m maximal running speed. Pre- and post-training pulmonary gas exchanges and SaO (2) were measured during an incremental running field-test. After the training period, men and women increased their V.O (2)max (p < 0.001) by 10.0 % and 7.8 %, respectively. Nine subjects (seven men and two women) developed EIH. This phenomenon appeared even in sportsmen with low V.O (2)max from 45 ml x min (-1) x kg (-1) and seemed to be associated with inadequate hyperventilation induced by training: because only this hypoxemic group showed 1) a decrease in maximal ventilatory equivalent in O (2) (V.E/V.O (2), p < 0.01) although maximal ventilation increased (p < 0.01) with training, i. e. in EIH-subjects the ventilatory response increased less than the metabolic demand after the training program; 2) a significant relationship between SaO (2) at maximal workload and the matched V.E/V.O (2) (p < 0.05, r = 0.67) which strengthened a relative hypoventilation implication in EIH. In conclusion, in this field investigation the significant decrease in the minimum SaO (2) inducing the development of EIH after high-intensity interval-training indicates that changes in training conditions could be accompanied in approximately 40 % non-endurance sportive subjects by alterations in the degree of arterial oxyhemoglobin desaturation developing during exercise.

Relationship among the severity of sleep apnea syndrome, cardiac arrhythmias, and autonomic imbalance.

The relationship between obstructive sleep apnea syndrome (OSAS), cardiac arrhythmias, and conduction disturbances in adults remains controversial. Early studies showed a higher prevalence than more recent and designed epidemiological studies. To clarify the actual prevalence of cardiac arrhythmias and conduction disturbances in patients referred for assessment of OSAS, a prospective cohort study was conducted: 147 consecutive patients (103 men; mean age of 54.5 +/- 10.7 years) underwent time-synchronized polysomnography and ECG Holter monitoring. OSAS was diagnosed in 66 (44.9%) of them based on an apnea hypopnea index (AHI) > or = 10. Prevalence of heart failure, of prior myocardial infarction, of hypertension, and of ventricular arrhythmias were similar in patients with or without OSAS. Nocturnal paroxysmal asystole was significantly more prevalent in OSAS patients (10.6 vs 1.2%; P < 0.02) and the number of episodes of bradycardia and pauses increased with the severity of the syndrome. Almost all bradycardic events occurred in patients with severe OSAS (AHI > 30), prolonged periods of arterial oxyhemoglobin desaturation, and low diurnal awake PaO2. Moreover, using heart rate variability analysis, nocturnal sinusal dysfunction contrasted with a blunted diurnal parasympathetic modulation of the sinus node. Frequent nocturnal nonsustained supraventricular tachycardias were predominantly found in patients with severe sleep related breathing disorders; however, an increased risk of ventricular arrhythmias was not found. Under continuous positive airway pressure treatment, the 1-year follow-up of OSAS patients with nocturnal pauses did not reveal any arrhythmic event justifying a specific intervention.

Cerebral oxygenation during chronic obstructive pulmonary disease.

Cognitive dysfunction has been recognized in chronic obstructive pulmonary disease (COPD) patients who are hypoxic during wakefulness (1,2). COPD patients with acceptable arterial oxygen (Pa02) during wakefulness may experience arterial oxyhemoglobin desaturation to < 85% during sleep (3). It is unknown whether cerebral oxygenation is compromised in sleeping patients with COPD with or without arterial hypoxemia. Therefore, we studied the effect of spontaneous arterial desaturation in COPD patients during sleep on regional cerebral oxygenation (rSO2) to test the hypothesis that patients with COPD suffer decrements in rSO2 during sleep.KeywordsChronic Obstructive Pulmonary DiseaseChronic Obstructive Pulmonary Disease PatientCerebral OxygenationArterial HypoxemiaHypopnea IndexThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Effects of Nasal O2 on Sleep-Related Disordered Breathing in Ambulatory Patients with Stable Heart Failure

The purpose of this study was 1) to determine the effects of nasal O2 on periodic breathing, arterial oxyhemoglobin desaturation and nocturnal ventricular arrhythmias in patients with heart failure and 2) determine the characteristics of patients whose periodic breathing will be reversed by O2 administration; our hypothesis was that patients with more severe periodic breathing and desaturation, will respond more favorably to oxygen. Prospective study. Referral sleep laboratory of a Department of Veterans Affairs Medical Center. 36 ambulatory male patients with heart failure whose initial polysomnograms showed periodic breathing with fifteen or more episodes of apnea (A) and hypopnea (H) per hour (AH index, AHI) were treated with nasal O2 during the subsequent full night polysomnography. Oxygen. Arterial blood gases and hydrogen ion concentrations were measured, and cardiac radionuclide ventriculography, Holter monitoring, and polysomnography were done. The studies were scored blindly. Treatment with O2 resulted in a significant reduction in AHI (49+/-19 vs 29+/-29, means+/-SD), central apnea index (28+/-23 vs 13+/-18 per hour), and the percent of total sleep time below an arterial oxyhemoglobin saturation of 90% (23+/-21% vs 0.8+/-2.3%). In spite of virtual normalization of saturation with O2 therapy, the number of ventricular arrhythmias during sleep did not change significantly. In 39% of the patients (14 out of 36), O2 therapy resulted in reversal of central sleep apnea (defined by a reduction in AHI to less than 15/hr). In this group, the AHI decreased by 78% which was significantly (p=0.0001) more than improved (22%) in AHI of the remaining patients (n=22). The main differences between baseline characteristics of the two groups was a significantly higher mean PaCO2 in patients who did respond fully to O2 (39.3+/-5.4 vs 36.1+/-4.2 mm Hg, p=0.03). In both groups, however, O2 administration resulted in significant and similar improvement in arterial oxyhemoglobin saturation (saturation <90%, percent total sleep time 0.1+/-0.3% vs 1+/-3%). In patients with stable heart failure, administration of nasal O2 significantly improves periodic breathing and virtually eliminates clinically significant arterial oxyhemoglobin desaturation. The beneficial effects of O2, however, may be modulated by the level of arterial PCO2. Acute O2 therapy has important benefits on sleep apnea and nocturnal arterial oxyhemoglobin desaturation in heart failure patients. Long term benefits of O2 therapy in heart failure and sleep apnea need to be determined.

Sleep apnea in 81 ambulatory male patients with stable heart failure. Types and their prevalences, consequences, and presentations.

Heart failure is a highly prevalent disorder that continues to be associated with repeated hospitalizations, high morbidity, and high mortality. Sleep-related breathing disorders with repetitive episodes of asphyxia may adversely affect heart function. The main aims of this study were to determine the prevalence, consequences, and differences in various sleep-related breathing disorders in ambulatory male patients with stable heart failure. This article reports the results of a prospective study of 81 of 92 eligible patients with heart failure and a left ventricular ejection fraction < 45%. There were 40 patients without (hourly rate of apnea/hypopnea, 4 +/- 4; group 1) and 41 patients with (51% of all patients; hourly rate of apnea/hypopnea, 44 +/- 19; group 2) sleep apnea. Sleep disruption and arterial oxyhemoglobin desaturation were significantly more severe and the prevalence of atrial fibrillation (22% versus 5%) and ventricular arrhythmias were greater in group 2 than in group 1. Forty percent of all patients had central sleep apnea, and 11% had obstructive sleep apnea. The latter patients had significantly greater mean body weight (112 +/- 30 versus 75 +/- 16 kg) and prevalence of habitual snoring (78% versus 28%). However, the hourly rate of episodes of apnea and hypopnea (36 +/- 10 versus 47 +/- 21), episodes of arousal (20 +/- 14 versus 23 +/- 11), and desaturation (lowest saturation, 72 +/- 11% versus 78 +/- 12%) were similar in patients with these different types of apnea. Fifty-one percent of male patients with stable heart failure suffer from sleep-related breathing disorders: 40% from central and 11% from obstructive sleep apnea. Both obstructive and central types of sleep apnea result in sleep disruption and arterial oxyhemoglobin desaturation. Patients with sleep apnea have a high prevalence of atrial fibrillation and ventricular arrhythmias.

Exercise-induced oxyhemoglobin desaturation and pulmonary diffusing capacity during high-intensity exercise.

The purpose of this investigation was to examine if exercise-induced arterial oxyhemoglobin desaturation selectively observed in highly trained endurance athletes could be related to differences in the pulmonary diffusing capacity (DL) measured during exercise. The DL of 24 male endurance athletes was measured using a 3-s breath-hold carbon monoxide procedure (to give DLCO) at rest as well as during cycling at 60% and 90% of these previously determined VO2max. Oxyhemoglobin saturation (SaO2%) was monitored throughout both exercise protocols using an Ohmeda Biox II oximeter. Exercise-induced oxyhemoglobin desaturation (DS) (SaO2% < 91% at VO2max) was observed in 13 subjects [88.2 (0.6)%] but not in the other 11 nondesaturation subjects [NDS: 92.9 (0.4)%] (P < or = 0.05), although VO2max was not significantly different between the groups [DS: 4.34 (0.65) l/min vs NDS: 4.1 (0.49) l/min]. At rest, no differences in either DLCO [ml CO.mmHg-1.min-1: 41.7 (1.7) (DS) vs 41.1 (1.8) (NDS)], DLCO/VA [8.2 (0.4) (DS) vs 7.3 (0.9) (NDS)], MVV [l/min: 196.0 (10.4) (DS) vs 182.0 (9.9) (NDS)] or FEV1/FVC [86.3 (2.2) (DS) vs 82.9 (4.7) (NDS)] were found between groups (P > or = 0.05). However, VE/VO2 at VO2max was lower in the DS group [33.0 (1.1)] compared to the NDS group [36.8 (1.5)] (P < or = 0.05). Exercise DLCO (ml CO.mmHg-1.min-1) was not different between groups at either 60% VO2max [DS: 55.1 (1.4) vs NDS: 57.2 (2.1)] or at 90% VO2max [DS: 61.0 (1.8) vs NDS: 61.4 (2.9)]. A significant relationship (r = 0.698) was calculated to occur between SaO2% and VE/VO2 during maximal exercise. The present findings indicate that the exercise-induced oxyhemoglobin desaturation seen during submaximal and near-maximal exercise is not related to differences in DL, although during maximal exercise SaO2 may be limited by a relatively lower exercise ventilation.

Central Sleep Apnea-Hypopnea Syndrome in Heart Failure: Prevalence, Impact, and Treatment

Despite recent advances in its treatment, congestive heart failure associated with depressed left ventricular function continues to be associated with excess morbidity and mortality. Multiple factors may contribute to the progressively declining course of heart failure. Nocturnal arterial oxyhemoglobin desaturation caused by sleep-disordered breathing could be a contributing factor, particularly because it has been associated with excess mortality in patients with chronic obstructive pulmonary disease. Cheyne and Stokes were the first to observe periodic breathing in patients with heart failure (Cheyne-Stokes respiration). However, relatively large-scale systematic studies have been performed only recently. We studied 42 patients with stable, optimally treated heart failure, without other co-morbid disorders: 19 patients (45%) had an apnea-hypopnea index of more than 20/hour. These episodes were associated with an excess number of arousals and arterial oxyhemoglobin desaturation. Treatment options include nocturnal administration of oxygen, continuous positive airway pressure (CPAP), and medications such as theophylline. Large-scale studies are needed to evaluate the efficacy of these treatment options on quality of life, morbidity, and mortality of patients with heart failure.

Sleep in multiple pregnancy: Breathing patterns, oxygenation, and periodic leg movements

OBJECTIVES: Our goal was to study whether multiple pregnancy at the third trimester predisposes to breathing disturbances and arterial oxyhemoglobin desaturation during sleep. STUDY DESIGN: Nocturnal breathing, oxygenation, and movement activity were studied in 10 mothers: 8 with twins, 1 with triplets, and 1 with quadruplets. RESULTS: No obstructive and few central sleep apnea episodes were observed. Four subjects had episodes of increased respiratory resistance, but only one, the mother with quadruplets, was significantly affected. Arterial oxyhemoglobin saturation was always maintained above 90%. Periodic leg movements were present in all mothers, with a frequency range of 3.7 to 49.7 movements per hour. CONCLUSIONS: In spite of the large uterus in multiple pregnancy, nocturnal breathing and oxygenation are well maintained. Increased motor activity and frequent awakenings suggest poor sleep quality, which may be further compromised by intensive periodic leg movements. (A M J O BSTET G YNECOL 1996;174:1622-5.)

Sleep-Disordered Breathing and Poor Functional Outcome After Stroke

We objectively evaluated patients with recent stroke to determine the prevalence of sleep-disordered breathing (SDB) and whether SDB was associated with unfavorable clinical outcomes. Forty-seven patients with recent ischemic stroke (median, 13 days) were studied with computerized overnight oximetry for evidence of arterial oxyhemoglobin desaturation (SaO2). Polysomnography was also performed on 19 patients. Medical history, sleep history, location of stroke, and severity of neurological deficit were recorded, and patients were observed by staff for evidence of snoring and excessive daytime sleepiness. Functional abilities were measured with the use of the Barthel Index (BI). Outcome variables included ability to return home at discharge, continued residence at home at 3 and 12 months, BI at discharge, BI at 3 and 12 months, and death from any cause at 12 months. Mean SaO2 during oximetry was 94.0 +/- 1.7%, and percentage of recording time spent at < 90% SaO2 was 4.3 +/- 5.7%. The number of desaturation events per hour of recording time (desaturation index [DI]) was 9.5 +/- 9.67, with 15 of 47 (32%) having DI > 10 and 6 of 47 (13%) having DI > 20. Oximetry measures of SDB correlated with lower BI scores at discharge and lower BI at 3- and 12-month follow-ups (P < or = .05, Pearson coefficients). Oximetry measures correlated with return home after discharge, but the association between oximetry measures and living at home was lost at 12 months. Two oximetry variables correlated with death at 1 year. Brain stem location correlated with higher DI and time at < 90% SaO2, but patients with hemispheric stroke and oximetry abnormalities also had worse functional outcome. No correlation was found between oximetry values and sex, age, preexisting medical conditions (except previous stroke), or severity of neurological deficit. Oximetry abnormalities were associated with a history of snoring. Polysomnography on 19 patients confirmed oximetry evidence of severe SDB. Eighteen of 19 patients (95%) had an apnea-hypopnea index (AHI) of > 10 events per hour of recording, 13 of 19 (68%) had an AHI > 20, and 10 of 19 (53%) had an AHI > 30. Desaturation events were largely due to obstructive apneas. SDB accompanied by arterial oxyhemoglobin desaturation is common in patients undergoing rehabilitation after stroke and is associated with higher mortality at 1 year and lower BI scores at discharge and at 3 and 12 months after stroke. SDB may be an independent predictor of worse functional outcome. Obstructive sleep apnea appeared to be the most common form of SDB, and the frequent history of snoring suggests that SDB preceded the stroke in most patients.

Obstructive sleep apnea: A multisystemic disorder

Obstructive sleep apnea is a multisystemic disorder with pathologic sequelae that become apparent after a number of years. Patients with obstructive sleep apnea generally present with hypersomnolence, and diagnosis is eventually established through observation of the patient during sleep. Patients with obstructive sleep apnea snore loudly and experience nocturnal oxygen desaturation and repetitive disruptions from sleep that eventually lead to daytime hypersomnolence. Numerous complex interactive pathophysiologic events occur during each obstructive episode, and it is important for the clinician to be aware of the cardiopulmonary, neurologic, and anatomic abnormalities associated with this condition. The anatomic configuration of the pharynx and the physiologic response to occlusion of the upper airway have a major role in the pathogenesis of this disorder. Alveolar ventilation during an apneic episode is immediately reduced to zero, and the metabolic demands for oxygen must be met by oxygen stores within the body. With repetitive episodes of obstruction, the oxygen stores within the lungs are diminished and the rate of arterial oxyhemoglobin desaturation increases. During apneic episodes, the systemic blood pressure increases while heart rate and cardiac output decrease. Bradydysrhythmias have been noted with the obstructive apneic episodes, and ventricular dysrhythmias are associated with episodes of severe oxyhemoglobin desaturation. Coexisting cardiopulmonary or neuromuscular disease in patients with obstructive sleep apnea contributes to the development of hypoventilation, serious gas exchange derangement, and general cardiovascular instability.