Arousal and ventilatory responses during sleep in children with obstructive sleep apnea

Abnormal centralregulation of upper airway muscles may contribute to thepathophysiology of the childhood obstructive sleep apnea syndrome(OSAS). We hypothesized that this was secondary to global abnormalitiesof ventilatory control during sleep. We therefore compared the responseto chemical stimuli during sleep between prepubertal children with OSASand controls. Patients with OSAS aroused at a higherPCO₂ (58 ± 2 vs. 60 ± 5 Torr,P < 0.05); those with the highestapnea index had the highest arousal threshold(r = 0.52, P < 0.05). The hypercapnic arousal threshold decreased after treatment. For all subjects, hypoxia was apoor stimulus to arousal, whereas hypercapnia and, particularly, hypoxic hypercapnia were potent stimuli to arousal. Hypercapnia resulted in decreased airway obstruction in OSAS. Ventilatory responseswere similar between patients with OSAS and controls; however, thesample size was small. We conclude that children with OSAS haveslightly blunted arousal responses to hypercapnia. However, the overallventilatory and arousal responses are normal in children with OSAS,indicating that a global deficit in respiratory drive is not a majorfactor in the etiology of childhood OSAS. Nevertheless, subtleabnormalities in ventilatory control may exist.

     

Effects of inhaled CO2 and added dead space on idiopathic central sleep apnea

Xie, Ailiang, Fiona Rankin, Ruth Rutherford, and T. DouglasBradley. Effects of inhaledCO₂ and added dead space on idiopathic central sleep apnea. J. Appl.Physiol. 82(3): 918-926, 1997.We hypothesizedthat reductions in arterial PCO₂ (Pa_CO2) below the apnea threshold play akey role in the pathogenesis of idiopathic central sleep apnea syndrome(ICSAS). If so, we reasoned that raisingPa_CO2 would abolish apneas in thesepatients. Accordingly, patients with ICSAS were studied overnight onfour occasions during which the fraction of end-tidalCO₂ and transcutaneous PCO₂ were measured: during room airbreathing (N1), alternating room airand CO₂ breathing(N2),CO₂ breathing all night(N3), and addition of dead space viaa face mask all night (N4).Central apneas were invariably preceded by reductions infraction of end-tidal CO₂. Bothadministration of a CO₂-enrichedgas mixture and addition of dead space induced 1- to 3-Torr increasesin transcutaneous PCO₂, whichvirtually eliminated apneas and hypopneas; they decreased from43.7 ± 7.3 apneas and hypopneas/h onN1 to 5.8 ± 0.9 apneas andhypopneas/h during N3(P < 0.005), from 43.8 ± 6.9 apneas and hypopneas/h during room air breathing to 5.9 ± 2.5 apneas and hypopneas/h of sleep duringCO₂ inhalation during N2 (P < 0.01), and to 11.6% of the room air level while the patients werebreathing through added dead space duringN4 (P < 0.005). Because raisingPa_CO2 through two different meansvirtually eliminated central sleep apneas, we conclude that centralapneas during sleep in ICSA are due to reductions inPa_CO2 below the apnea threshold.

     

Sleep apnea in obese miniature pigs

Lonergan, Robert P., III, J. Catsby Ware, Richard L. Atkinson, W. Christopher Winter, and Paul M. Suratt. Sleep apnea in obese miniature pigs. J. Appl.Physiol. 84(2): 531-536, 1998.We postulated thatthree extremely obese Yucatan miniature pigs would have more sleepapnea than three nonobese Yucatan miniature pigs. Pigs were studiedwith the use of electroencephalograms, inductance plethysmography,oximetry, expired nasal CO₂, orthermistors. All of the obese pigs, but none of the nonobese pigs, hadboth sleep apnea (8.5, 10.3, and 97.0 in obese pigs vs. 0 apnea + hypopnea/h in all nonobese pigs; P < 0.05) and oxyhemoglobin desaturation episodes during sleep [9.4 ± 3.0 vs. 0 + 0.53 (SD) mean desaturation episodes/h in obese pigsvs. nonobese pigs, respectively; P < 0.05]. Two of the extremely obese pigs had obstructive sleepapnea, whereas the third obese pig had central sleep apnea. We conclude that sleep apnea occurs in extremely obese Yucatan minipigs and suggestthat this animal can be used as a model for sleep apnea in obesity.

     

Effect of topical upper airway anesthesia on apnea duration through the night in obstructive sleep apnea

Cala, S. J., P. Sliwinski, M. G. Cosio, and R. J. Kimoff.Effect of topical upper airway anesthesia on apnea duration through the night in obstructive sleep apnea. J. Appl.Physiol. 81(6): 2618-2626, 1996.It haspreviously been reported that the duration of obstructive apneasincreases from the beginning to the end of the night (M. Charbonneau,J. M. Marin, A. Olha, R. J. Kimoff, R. D. Levy, and M. Cosio.Chest 106: 1695-1701, 1994). The purpose of this study wasto test the hypothesis that stimulation of upper airway (UA) sensoryreceptors during obstructed inspiratory efforts contributes to arousaland apnea termination and that a progressive attenuation of thismechanism through the night contributes to apnea lengthening. Westudied seven patients (six men, one woman) with severe obstructivesleep apnea (apnea-hypopnea index = 93 ± 26 events/h) during twoconsecutive nights of polysomnographic monitoring. On one night (randomorder), we performed topical UA anesthesia with 0.2% tetracaine and onthe control night, sham anesthesia. We measured apnea duration,esophageal pressure (Pes) during apneas, and apneicO₂ desaturation. Consistent withprevious findings, apnea duration, number of efforts per apnea, andpeak Pes at end apnea increased from the beginning to the end of the control nights. UA anesthesia produced a significant increase in apneaduration at the beginning of the night but no change in apnea length atthe end of the night. Peak Pes and the rate of increase in Pes duringthe anesthesia nights were greater than during control nights, but therate of increase in Pes was similar for the beginning and end of thecontrol and anesthesia nights. These findings suggest that UA sensoryreceptors play a role in mediating apnea termination at the beginningof the night but that the contribution of these receptors diminishes asthe night progresses such that greater inspiratory efforts arerequired to trigger arousal, leading to apnea prolongation.

     

Anatomy of pharynx in patients with obstructive sleep apnea and in normal subjects

Isono, Shiroh, John E Remmers, Atsuko Tanaka, Yasuhide Sho,Jiro Sato, and Takashi Nishino. Anatomy of pharynx in patients with obstructive sleep apnea and in normal subjects.J. Appl. Physiol. 82(4):1319-1326, 1997.Anatomic abnormalities of the pharynx arethought to play a role in the pathogenesis of obstructive sleep apnea(OSA), but their contribution has never been conclusively proven. Thepresent study tested this anatomic hypothesis by comparing themechanics of the paralyzed pharynx in OSA patients and in normalsubjects. According to evaluation of sleep-disordered breathing (SDB)by nocturnal oximetry, subjects were divided into three groups: normalgroup (n = 17), SDB-1(n = 18), and SDB-2(n = 22). The static pressure-arearelationship of the passive pharynx was quantified under generalanesthesia with complete paralysis. Age and body mass index werematched among the three groups. The site of the primary closure was thevelopharynx in 49 subjects and the oropharynx in only 8 subjects.Distribution of the location of the primary closure did not differamong the groups. Closing pressure(PC) of the velopharynx forSDB-1 and SDB-2 groups (0.90 ± 1.34 and 2.78 ± 2.78 cmH₂O, respectively) wassignificantly higher than that for the normal group (3.77 ± 3.44 cmH₂O;P < 0.01). Maximal velopharyngealarea for the normal group (2.10 ± 0.85 cm²) was significantly greaterthan for SDB-1 and SDB-2 groups (1.15 ± 0.46 and 1.06 ± 0.75 cm², respectively). Theshape of the pressure-area curve for the velopharynx differed betweennormal subjects and patients with SDB, being steeper in slope nearPC in patients with SDB.Multivariate analysis of mechanical parameters and oxygen desaturationindex (ODI) revealed that velopharyngealPC was the only variable highly correlated with ODI. VelopharyngealPC was associated withoropharyngeal PC, suggestingmechanical interdependence of these segments. We conclude that thepassive pharynx is more narrow and collapsible in sleep-apneic patientsthan in matched controls and that velopharyngeal PC is the principal correlate ofthe frequency of nocturnal desaturations.

     

Intracerebroventricular propranolol prevented vascular resistance increases on arousal from sleep apnea

Zinkovska, Sophia, and Debra A. Kirby.Intracerebroventricular propranolol prevented vascular resistanceincreases on arousal from sleep apnea. J. Appl.Physiol. 82(5): 1637-1643, 1997.Despite theincreased risk of sudden cardiac death associated with sleep apnea,little is known about mechanisms controlling cardiovascular responsesto sleep apnea and arousal. Chronically instrumented pigs were used toinvestigate the effects of airway obstruction (AO) duringrapid-eye-movement (REM) and non-REM (NREM) sleep and arousal on meanarterial pressure (MAP), heart rate (HR), cardiac output (CO), andtotal peripheral resistance (TPR). A stainless steelcannula was implanted in the lateral cerebral ventricle. During REMsleep, HR was 133 ± 10 beats/min, MAP was 65 ± 3 mmHg, CO was1,435 ± 69 ml/min, and TPR was 0.046 ± 0.004 mmHg · ml¹ · min.During AO, CO decreased by 90 ± 17 ml/min(P < 0.05). On arousal from AO, MAPincreased by 15 ± 3 mmHg, HR increased by 10 ± 3 beats/min, andTPR increased by 0.008 ± 0.001 mmHg · ml¹ · min(all P < 0.05). Changes during NREMwere similar but were more modest during AO. After theintracerebroventricular administration of propranolol (50 µg/kg; a-adrenoreceptor blocking agent), decreases in CO during AO andincreases in HR during arousal were intact, but increases in MAP andTPR were no longer significant. These data suggest thatvascular responses to AO during sleep may be regulated in part by-adrenergic receptors in the central nervous system.

     

Perinatal nicotine exposure impairs ability of newborn rats to autoresuscitate from apnea during hypoxia

Failure toautoresuscitate by hypoxic gasping during prolonged sleep apnea hasbeen suggested to play a role in sudden infant death. Furthermore,maternal smoking has been repeatedly shown to be a risk factor forsudden infant death. The present experiments were carried out onnewborn rat pups to investigate the influence of perinatal exposure tonicotine (the primary pharmacological and addictive agent in tobacco)on their time to last gasp during a single hypoxic exposure and ontheir ability to autoresuscitate during repeated exposure to hypoxia.Pregnant rats received either nicotine (6 mg · kg¹ · 24 h¹) or vehiclecontinuously from day 6 of gestationto days 5 or 6 postpartum via an osmotic minipump.On days 5 or6 postpartum, pups were exposed eitherto a single period of hypoxia (97%N₂-3% CO₂) and their time to last gaspwas determined, or they were exposed repeatedly to hypoxia and theirability to autoresuscitate from primary apnea was determined. Perinatalexposure to nicotine did not alter the time to last gasp, but it didimpair the ability of pups to autoresuscitate from primary apnea. Aftervehicle, the pups were able to autoresuscitate from 18 ± 1 (SD)periods of hypoxia, whereas, after nicotine, the pups were able toautoresuscitate from only 12 ± 2 periods(P < 0.001) of hypoxia. Thus ourdata provide evidence that perinatal exposure to nicotine impairs the ability of newborn rats to autoresuscitate from primary apnea duringrepeated exposure to hypoxia, such as may occur during episodes ofprolonged sleep apnea.

     

Systemic and myocardial hemodynamics during periodic obstructive apneas in sedated pigs

The effects of periodic obstructive apneas onsystemic and myocardial hemodynamics were studied in ninepreinstrumented sedated pigs under four conditions: breathing room air(RA), breathing 100% O₂,breathing RA after critical coronary stenosis (CS) of the left anteriordescending coronary artery, and breathing RA after autonomic blockadewith hexamethonium (Hex). Apneas with RA increased mean arterialpressure (MAP; from baseline 103.0 ± 3.5 to late apnea 123.6 ± 7.0 Torr, P < 0.001) and coronary blood flow (CBF; late apnea 193.9 ± 22.9% of baseline,P < 0.001) but decreased cardiacoutput (CO; from baseline 2.97 ± 0.15 to late apnea 2.39 ± 0.19 l/min, P < 0.001). Apneas withO₂ increased MAP (from baseline105.1 ± 4.6 to late apnea 110.7 ± 4.8 Torr, P < 0.001). Apneas with CS producedsimilar increases in MAP as apneas with RA but greater decreases in CO(from baseline 3.03 ± 0.19 to late apnea 2.1 ± 0.15 l/min,P < 0.001). In LAD-perfused myocardium, there was decreased segmental shortening (baseline 11.0 ± 1.5 to late apnea 7.6 ± 2.0%,P < 0.01) and regionalintramyocardial pH (baseline 7.05 ± 0.03 to late apnea 6.72 ± 0.11, P < 0.001) during apneas withCS but under no other conditions. Apneas with Hex increased to the sameextent as apneas with RA. Myocardial O₂ demand remained unchangedduring apnea relative to baseline. We conclude that obstructiveapnea-induced changes in left ventricular afterload and CO aresecondary to autonomic-mediated responses to hypoxemia. Increased CBFduring apneas is related to regional metabolic effects of hypoxia andnot to autonomic factors. In the presence of limited coronary flowreserve, decreased O₂ supply during apneas can lead to myocardial ischemia, which in turnadversely affects left ventricular function.

     

Neural mechanism of the pressor response to obstructive and nonobstructive apnea

Katragadda, Srinivas, Ailiang Xie, Dominic Puleo, James B. Skatrud, and Barbara J. Morgan. Neural mechanism of the pressorresponse to obstructive and nonobstructive apnea. J. Appl. Physiol. 83(6): 2048-2054, 1997.Obstructive and nonobstructive apneas elicitsubstantial increases in muscle sympathetic nerve activity and arterialpressure. The time course of change in these variables suggests acausal relationship; however, mechanical influences, such as release ofnegative intrathoracic pressure and reinflation of the lungs, arepotential contributors to the arterial pressure rise. To test thehypothesis that apnea-induced pressor responses are neurally mediated,we measured arterial pressure (photoelectric plethysmography), musclesympathetic nerve activity (peroneal microneurography), arterialO₂ saturation (pulse oximeter),and end-tidal CO₂ tension (gasanalyzer) during sustained Mueller maneuvers, intermittent Muellermaneuvers, and simple breath holds in six healthy humans before,during, and after ganglionic blockade with trimethaphan (3-4mg/min, titrated to produce complete disappearance of sympatheticbursts from the neurogram). Ganglionic blockade abolished the pressorresponses to sustained and intermittent Mueller maneuvers (4 ± 1 vs. +15 ± 3 and 0 ± 2 vs. +15 ± 5 mmHg) and breathholds (0 ± 3 vs. +11 ± 3, allP < 0.05). We conclude that theacute pressor response to obstructive and nonobstructive voluntaryapnea is sympathetically mediated.

     

Arousal pattern following central and obstructive breathing abnormalities in infants and children

McNamara, Frances, Faiq G. Issa, and Colin E. Sullivan.Arousal pattern following central and obstructive breathing abnormalities in infants and children. J. Appl.Physiol. 81(6): 2651-2657, 1996.We analyzed thepolysomnographic records of 15 children and 20 infants with obstructivesleep apnea (OSA) to examine the interaction between central andobstructive breathing abnormalities and arousal from sleep. Eachpatient was matched for age with an infant or child who had no OSA. Wefound that the majority of respiratory events in infants and childrenwas not terminated with arousal. In children, arousals terminated 39.3 ± 7.2% of respiratory events during quiet sleep and 37.8 ± 7.2% of events during active (rapid-eye-movement) sleep. In infants,arousals terminated 7.9 ± 1.0% of events during quiet sleep and7.9 ± 1.2% of events during active sleep. In both infants andchildren, however, respiratory-related arousals occurred more frequently after obstructive apneas and hypopneas than after central events. Spontaneous arousals occurred in all patients with OSA duringquiet and active sleep. The frequency of spontaneous arousals was notdifferent between children with OSA and their matched controls. Duringactive sleep, however, infants with OSA had significantly fewerspontaneous arousals than did control infants. We conclude that arousalis not an important mechanism in the termination of respiratory eventsin infants and children and that electroencephalographic criteria arenot essential to determine the clinical severity of OSA in thepediatric population.

     

Systemic and pulmonary hemodynamic responses to normal and obstructed breathing during sleep

Schneider, H., C. D. Schaub, K. A. Andreoni, A. R. Schwartz,R. L. Smith, J. L. Robotham, and C. P. O'Donnell. Systemic andpulmonary hemodynamic responses to normal and obstructed breathing during sleep. J. Appl. Physiol. 83(5):1671-1680, 1997.We examined the hemodynamic responses to normalbreathing and induced upper airway obstructions during sleep in acanine model of obstructive sleep apnea. During normal breathing,cardiac output decreased (12.9 ± 3.5%,P < 0.025) from wakefulness tonon-rapid-eye-movement sleep (NREM) but did not change from NREM torapid-eye-movement (REM) sleep. There was a decrease(P < 0.05) in systemic (7.2 ± 2.1 mmHg) and pulmonary (2.0 ± 0.6 mmHg) arterial pressures fromwakefulness to NREM sleep. In contrast, systemic (8.1 ± 1.0 mmHg,P < 0.025), but not pulmonary,arterial pressures decreased from NREM to REM sleep. During repetitiveairway obstructions (56.0 ± 4.7 events/h) in NREM sleep, cardiacoutput (17.9 ± 3.1%) and heart rate (16.2 ± 2.5%) increased(P < 0.05), without a change instroke volume, compared with normal breathing during NREM sleep. Duringsingle obstructive events, left (7.8 ± 3.0%,P < 0.05) and right (7.1 ± 0.7%, P < 0.01)ventricular outputs decreased during the apneic period. However, left(20.7 ± 1.6%, P < 0.01) andright (24.0 ± 4.2%, P < 0.05)ventricular outputs increased in the postapneic period because of anincrease in heart rate. Thus 1) thesystemic, but not the pulmonary, circulation vasodilates during REMsleep with normal breathing; 2)heart rate, rather than stroke volume, is the dominant factormodulating ventricular output in response to apnea; and3) left and right ventricular outputs oscillate markedly and in phase throughout the apnea cycle.

     

Effects of microtubules and microfilaments on [Ca(2+)](i) and contractility in a reconstituted fibroblast fiber

We used a reconstituted fiber formed when 3T3fibroblasts are grown in collagen to characterize nonmusclecontractility and Ca²⁺ signaling. Calf serum (CS) andthrombin elicited reversible contractures repeatable for >8 h. CSelicited dose-dependent increases in isometric force; 30% produced thelargest forces of 106 ± 12 µN (n = 30), whichis estimated to be 0.5 mN/mm² cell cross-sectionalarea. Half times for contraction and relaxation were 4.7 ± 0.3 and 3.1 ± 0.3 min at 37°C. With imposition of constant shortening velocities, force declined with time, yieldingtime-dependent force-velocity relations. Forces at 5 s fit thehyperbolic Hill equation; maximum velocity(V_max) was 0.035 ± 0.002 L_o/s.Compliance averaged 0.0076 ± 0.0006 L_o/F_o. Disruption of microtubules with nocodazole in a CS-contracted fiber had no net effects on force, V_max, or stiffness; force increased in 8, butdecreased in 13, fibers. Nocodazole did not affect baselineintracellular Ca²⁺ concentration([Ca²⁺]_i) but reduced (~30%) the[Ca²⁺]_i response to CS. The force afternocodazole treatment was the primary determinant of stiffness andV_max, suggesting that microtubules were not amajor component of fiber internal mechanical resistance. Cytochalasin Dhad major inhibitory effects on all contractile parameters measured butlittle effect on [Ca²⁺]_i.

     

An induced blood pressure rise does not alter upper airway resistance in sleeping humans

Wilson, Christine R., Shalini Manchanda, David Crabtree,James B. Skatrud, and Jerome A. Dempsey. An induced blood pressurerise does not alter upper airway resistance in sleeping humans.J. Appl. Physiol. 84(1): 269-276, 1998.Sleep apnea is associated with episodic increases in systemicblood pressure. We investigated whether transient increases in arterialpressure altered upper airway resistance and/or breathingpattern in nine sleeping humans (snorers and nonsnorers). Apressure-tipped catheter was placed below the base of the tongue, andflow was measured from a nose or face mask. Duringnon-rapid-eye-movement sleep, we injected 40- to 200-µg iv boluses ofphenylephrine. Parasympathetic blockade was used if bradycardia wasexcessive. Mean arterial pressure (MAP) rose by 20 ± 5 (mean ± SD) mmHg (range 12-37 mmHg) within 12 s and remained elevated for105 s. There were no significant changes in inspiratory or expiratorypharyngeal resistance (measured at peak flow, peak pressure, 0.2 l/s orby evaluating the dynamic pressure-flow relationship). Atpeak MAP, end-tidal CO₂ pressure fell by 1.5 Torr and remained low for 20-25 s. At 26 s after peak MAP, tidal volume fell by 19%, consistent with hypocapnic ventilatory inhibition. We conclude that transient increases in MAP of a magnitude commonly observed during non-rapid-eye-movement sleep-disordered breathing do not increase upper airway resistance and, therefore, willnot perpetuate subsequent obstructive events.

     

Enhanced ventilatory and exercise performance in athletes with slight expiratory resistive loading

Fee, Lawrence L., Richard M. Smith, and Michael B. English.Enhanced ventilatory and exercise performance in athletes withslight expiratory resistive loading. J. Appl.Physiol. 83(2): 503-510, 1997.We determined thecardiorespiratory and performance effects of slight (1.5-3.0cmH₂O) expiratory resistiveloading (ERL). Twenty-eight highly fit [peakO₂ uptake(O_{2 peak}) = 63.6 ± 1.3 ml · kg¹ · min¹]athletes (age = 33.5 ± 1.3 yr) performed pairedO_{2 peak} cycle ergometer tests (control vs. ERL). End-expiratory lung volume wasseparately determined in a subset of subjects(n = 12) at steady-state 75% maximumpower output (PO_max) and wasfound to increase (0.67 ± 0.29 liter) with ERL. In theO_{2 peak}tests, peak expiratory pressure at the mouth, mean inspiratory flow, minute ventilation, and O₂ pulsewere greater with ERL at every intensity level (i.e., 75, 80, 85, and90% PO_max). Increased minute ventilation was largely due to a trend toward increased tidal volume(P < 0.05 at 80%PO_max).O₂ uptake was greater at 90%PO_max with ERL. IncreasedO₂ pulse with ERL at comparativeworkloads suggests that stroke volume was augmented with ERL. Also,with ERL, athletes attained higherO_{2 peak} (63.0 ± 1.4 vs. 60.1 ± 1.3 ml · kg¹ · min¹)and greater PO_max (352.0 ± 9.9 vs. 345.7 ± 9.5 W). We conclude that elevated end-expiratory lungvolume in response to slight ERL during strenuous exercise served toattenuate both airflow and blood flow limitations, which enhancedexercise capacity.

     

Contraction-induced increase in Vmax of palmitate uptake and oxidation in perfused skeletal muscle

To evaluate the effects of contractions on thekinetics of uptake and oxidation of palmitate in a physiological musclepreparation, rat hindquarters were perfused with glucose (6 mmol/l),albumin-bound [1-¹⁴C]palmitate, andvarying amounts of albumin-bound palmitate (200-2,200 µmol/l) atrest and during muscle contractions. When plotted against the unboundpalmitate concentration, palmitate uptake and oxidation displayedsimple Michaelis-Menten kinetics with estimated maximal velocity(V_max)and Michaelis-Menten constant(K_m) values of42.8 ± 3.8 (SE)nmol · min¹ · g¹and 13.4 ± 3.4 nmol/l for palmitate uptake and 3.8 ± 0.4 nmol · min¹ · g¹and 8.1 ± 2.9 nmol/l for palmitate oxidation, respectively, at rest.Whereas muscle contractions increased theV_maxfor both palmitate uptake and oxidation to 91.6 ± 10.1 and 16.5 ± 2.3 nmol · min¹ · g¹,respectively, theK_m remainedunchanged.V_maxand K_m estimates obtained from Hanes-Woolf plots (substrate concentration/velocity vs.substrate concentration) were not significantly different. In theresting perfused hindquarter, an increase in palmitate delivery from31.9 ± 0.9 to 48.7 ± 1.2 µmol · g¹ · h¹by increasing perfusate flow was associated with a decrease in thefractional uptake of palmitate so that the rates of uptake andoxidation of palmitate remained unchanged. It is concluded that therates of uptake and oxidation of long-chain fatty acids (LCFA) saturatewith an increase in the concentration of unbound LCFA in perfusedskeletal muscle and that muscle contractions, but not an increase inplasma flow, increase theV_maxfor LCFA uptake and oxidation. The data are consistent with the notion that uptake of LCFA in muscle may be mediated in part by a transport system.

     

Upper airway muscle activity in normal women: influence of hormonal status

Obstructive sleep apnea is a disorder with astrong male predominance. One possible explanation could be an effectof female hormones on pharyngeal dilator muscle activity. Therefore, we determined the level of awake genioglossus electromyogram (EMGgg) andupper airway resistance in 12 pre- and 12 postmenopausal women underbasal conditions and during the application of an inspiratory resistiveload (25 cmH₂O · l¹ · s).In addition, a subgroup of eight postmenopausal women were studied asecond time after 2 wk of combined estrogen and progesterone replacement in standard doses. Peak phasic and tonic genioglossus activity, expressed as a percentage of maximum, were highest in theluteal phase of the menstrual cycle (phasic 23.9 ± 3.8%, tonic 10.2 ± 1.0%), followed by the follicular phase (phasic 15.5 ± 2.2%, tonic 7.3 ± 0.8%), and were lowest in the postmenopausal group (phasic 11.3 ± 1.6%, tonic of 5.0 ± 0.6), whereas upper airway resistance did not differ. There was a weak but significant positive correlation between progesterone levels and both peak phasic(P < 0.05) and tonic(P < 0.01) EMGgg. Finally, there was a significant increase in EMGgg in the postmenopausal group restudied after hormone therapy. In conclusion, female hormones (possibly progesterone) have a substantial impact on upper airway dilator muscleactivity.

     

Dehydration markedly impairs cardiovascular function in hyperthermic endurance athletes during exercise

González-Alonso, José, RicardoMora-Rodríguez, Paul R. Below, and Edward F. Coyle.Dehydration markedly impairs cardiovascular function inhyperthermic endurance athletes during exercise. J. Appl. Physiol. 82(4): 1229-1236, 1997.Weidentified the cardiovascular stress encountered by superimposingdehydration on hyperthermia during exercise in the heat and themechanisms contributing to the dehydration-mediated stroke volume (SV)reduction. Fifteen endurance-trained cyclists [maximalO₂ consumption(O_{2 max}) = 4.5 l/min] exercised in the heat for 100-120 min and either became dehydrated by 4% body weight or remained euhydrated by drinkingfluids. Measurements were made after they continued exercise at 71%O_{2 max} for 30 minwhile 1) euhydrated with anesophageal temperature (T_es) of38.1-38.3°C (control); 2)euhydrated and hyperthermic (39.3°C);3) dehydrated and hyperthermic withskin temperature (T_sk) of34°C; 4) dehydrated withT_es of 38.1°C and T_sk of 21°C; and5) condition4 followed by restored blood volume. Compared withcontrol, hyperthermia (1°C T_esincrease) and dehydration (4% body weight loss) each separatelylowered SV 7-8% (11 ± 3 ml/beat;P < 0.05) and increased heart ratesufficiently to prevent significant declines in cardiac output.However, when dehydration was superimposed on hyperthermia, thereductions in SV were significantly (P < 0.05) greater (26 ± 3 ml/beat), and cardiac output declined 13% (2.8 ± 0.3 l/min). Furthermore, mean arterialpressure declined 5 ± 2%, and systemic vascular resistanceincreased 10 ± 3% (both P < 0.05). When hyperthermia wasprevented, all of the decline in SV with dehydration was due to reducedblood volume (~200 ml). These results demonstrate that thesuperimposition of dehydration on hyperthermia during exercise in theheat causes an inability to maintain cardiac output and blood pressurethat makes the dehydrated athlete less able to cope with hyperthermia.

     

Effects of supplemental oxygen on forearm vasodilation in humans

Crawford, Paul, Peter A. Good, Eric Gutierrez, Joshua H. Feinberg, John P. Boehmer, David H. Silber, and Lawrence I. Sinoway. Effects of supplemental oxygen on forearm vasodilation in humans.J. Appl. Physiol. 82(5):1601-1606, 1997.Supplemental O₂ reduces cardiac output andraises systemic vascular resistance in congestive heart failure. Inthis study, 100% O₂ was given tonormal subjects and peak forearm flow was measured. Inexperiment 1, 100%O₂ reduced blood flow andincreased resistance after 10 min of forearm ischemia (flow 56.7 ± 7.9 vs. 47.8 ± 6.7 ml · min¹ · 100 ml¹;P < 0.02; vascular resistance 1.7 ± 0.2 vs. 2.4 ± 0.4 mmHg · min · 100 ml · ml¹;P < 0.03). Inexperiment 2, lower body negativepressure (LBNP; 30 mmHg) and venous congestion (VC) simulatedthe high sympathetic tone and edema of congestive heart failure.Postischemic forearm flow and resistance were measured under fourconditions: room air breathing (RA); LBNP+RA; RA+LBNP+VC; and 100%O₂+LBNP+VC. LBNP and VC did notlower peak flow. However, O₂raised minimal resistance (2.3 ± 0.4 RA; 2.8 ± 0.5 O₂+LBNP+VC,P < 0.04). When O₂ alone(experiment 1) was compared withO₂+LBNP+VC(experiment 2), no effect of LBNP+VCon peak flow or minimum resistance was noted, although the return rateof flow and resistance toward baseline was increased.O₂ reduces peak forearm flow evenin the presence of LBNP and VC.

     

Upper airway muscle activity and upper airway resistance in young adults during sleep

Henke, Kathe G. Upper airway muscle activity and upperairway resistance in young adults during sleep. J. Appl. Physiol. 84(2): 486-491, 1998.To determinethe relationship between upper airway muscle activity and upper airwayresistance in nonsnoring and snoring young adults, 17 subjects werestudied during sleep. Genioglossus and alae nasi electromyogramactivity were recorded. Inspiratory and expiratory supraglotticresistance (Rinsp and Rexp, respectively) were measured at peak flow,and the coefficients of resistance(K_insp andK_exp,respectively) were calculated. Data were recorded during control,with continuous positive airway pressure (CPAP), and on the breathimmediately after termination of CPAP. Rinsp during control averaged 7 ± 1 and 10 ± 2 cmH₂O · l¹ · sand K_inspaveraged 26 ± 5 and 80 ± 27 cmH₂O · l¹ · s²in the nonsnorers and snorers, respectively(P = not significant). Onthe breath immediately after CPAP,K_insp did notincrease over control in snorers (80 ± 27 for control vs. 46 ± 6 cmH₂O · l¹ · s²for the breath after CPAP) or nonsnorers (26 ± 5 vs. 29 ± 6 cmH₂O · l¹ · s²).These findings held true for Rinsp.K_exp did notincrease in either group on the breath immediately after termination ofCPAP. Therefore, 1) increases inupper airway resistance do not occur, despite reductions inelectromyogram activity in young snorers and nonsnorers, and2) increases in Rexp and expiratoryflow limitation are not observed in young snorers.

     

Mild sustained and intermittent hypoxia induce apoptosis in PC-12 cells via different mechanisms

Episodic hypoxia, a characteristic feature of obstructive sleep apnea, induces cellular changes and apoptosis in brain regions associated with neurocognitive function. To investigate whether mild, intermittent hypoxia would induce more extensive neuronal damage than would a similar degree of sustained hypoxia, rat pheochromocytoma PC-12 neuronal cells were subjected to either sustained (5% O₂) or intermittent (alternating 5% O₂ 35 min, 21% O₂ 25 min) hypoxia for 2 or 4 days. Quantitative assessment of apoptosis showed that while mild sustained hypoxia did not significantly increase cell apoptosis at 2 days (1.31 ± 0.29-fold, n = 8; P = NS), a significant increase in apoptosis occurred after 4 days (2.25 ± 0.4-fold, n = 8; P < 0.002), without increased caspase activation. Furthermore, caspase inhibition with the general caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (Z-VAD-FMK) did not modify sustained hypoxia-induced apoptosis. In contrast, mild, intermittent hypoxia induced significant increases in apoptosis at 2 days (3.72 ± 1.43-fold, n = 8; P < 0.03) and at 4 days (4.57 ± 0.82-fold, n = 8; P < 0.001) that was associated with enhanced caspase activity and attenuated by Z-VAD-FMK pretreatment. We conclude that intermittent hypoxia induces an earlier and more extensive apoptotic response than sustained hypoxia and that this response is at least partially dependent on caspase-mediated pathways. In contrast, caspases do not seem to play a role in sustained hypoxia-induced apoptosis. These findings suggest that different signaling pathways are involved in sustained and intermittent hypoxia-induced cell injury and may contribute to the understanding of differential brain susceptibility to sustained and intermittent hypoxia. episodic hypoxia; neuronal cell death; caspase; hypoxic adaptation