Mechanical effects of pharyngeal constrictor activation on pharyngeal airway function

The mechanicaleffects of pharyngeal constrictor (PC) muscle activation on pharyngealairway function were determined in 20 decerebrate, tracheotomized cats.In 10 cats, a high-compliance balloon attached to a pressure transducerwas partially inflated to just occlude the pharyngeal airway. Duringprogressive hyperoxic hypercapnia, changes in pharyngeal balloonpressure were directly related to phasic expiratory hyopharyngeus(middle PC) activity. In two separate protocols in 10 additional cats,the following measurements were obtained with and without bilateralelectrical stimulation (0.2-ms duration, threshold voltage) of thedistal cut end of the vagus nerve's pharyngeal branch supplying PCmotor output: 1) pressure-volumerelationships in an isolated, sealed upper airway at a stimulationfrequency of 30 Hz and 2) rostrally directed axial force over a stimulation frequency range of 0-40 Hz. Airway compliance determined from the pressure-volume relationships decreased with PC stimulation at and below resting airway volume. Compared with the unstimulated condition, PC stimulation increased airway pressure at airway volumes at and above resting volume. Thisconstrictor effect progressively diminished as airway volume wasbrought below resting volume. At relatively low airway volumes belowresting volume, PC stimulation decreased airway pressure compared withthat without stimulation. PC stimulation generated a rostrally directedaxial force that was directly related to stimulation frequency. Theresults indicate that PC activation stiffens the pharyngeal airway,exerting both radial and axial effects. The radial effects aredependent on airway volume: constriction of the airway at relativelyhigh airway volumes, and dilation of the airway at relatively lowairway volumes. The results imply that, under certain conditions, PCmuscle activation may promote pharyngeal airway patency.

     

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.

     

Gender differences in airway resistance during sleep

Trinder, John, Amanda Kay, Jan Kleiman, and Judith Dunai.Gender differences in airway resistance during sleep.J. Appl. Physiol. 83(6):1986-1997, 1997.At the onset of non-rapid-eye-movement (NREM)sleep there is a fall in ventilation and an increase in upper airwayresistance (UAR). In healthy men there is a progressive increase in UARas NREM sleep deepens. This study compared the pattern of change in UARand ventilation in 14 men and 14 women (aged 18-25 yr) both duringsleep onset and over the NREM phase of a sleep cycle (from wakefulnessto slow-wave sleep). During sleep onset, fluctuations betweenelectroencephalographic alpha and theta activity were associated withmean alterations in inspiratory minute ventilation and UAR of between 1 and 4.5 l/min and between 0.70 and 5.0 cmH₂O · l¹ · s,respectively, with no significant effect of gender on either change(P > 0.05). During NREM sleep,however, the increment in UAR was larger in men than in women(P < 0.01), such that the meanlevels of UAR at peak flow reached during slow-wave sleep were ~25and 10 cmH₂O · l¹ · sin men and women, respectively. We speculate that the greater increasein UAR in healthy young men may represent a gender-related susceptibility to sleep-disordered breathing that, in conjunction withother predisposing factors, may contribute to the development ofobstructive sleep apnea.

     

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.

     

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.

     

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.

     

Within-night variation in respiratory effort preceding apnea termination and EEG delta power in sleep apnea

We studied the within-night variability of themaximum esophageal pressure deflection before apnea termination(DP_max) in nine patients withsevere obstructive sleep apnea as an index of the arousal threshold andthe mean electroencephalogram (EEG) delta power for each 30 s as anindex of the timing of sleep cycles. Periodicity in the time variationof delta power and DP_max was analyzed by determining their power spectral density and their relationship determined by cross correlation.DP_max and delta power variedcyclically and in phase with a major periodicity (major peak in powerspectral density) of 117.6 ± 8.8 (SE) min. The correlation betweenthe values of DP_max and deltapower was significant (P < 0.001) ineach subject (mean r = 0.47 ± 0.03), and the coherence betweenDP_max and delta power at theirdominant frequency was high. Within cycles of non-rapid-eye-movementsleep, DP_max and delta powerincreased, reaching peak values on average at or after midcycle. Thesefindings suggest that the arousal threshold to airway occlusion inpatients with obstructive sleep apnea varies cyclically during thenight synchronous to the underlying cycles of sleep.

     

Interaction of cross-sectional area, driving pressure, and airflow of passive velopharynx

Isono, Shiroh, Thom R. Feroah, Eric A. Hajduk, Rollin Brant,William A. Whitelaw, and John E. Remmers. Interaction ofcross-sectional area, driving pressure, and airflow of passive velopharynx. J. Appl. Physiol. 83(3):851-859, 1997.Previous studies have shown that, when thepharyngeal muscles are relaxed, the velopharynx is a highly compliantsegment of the pharynx. Thus, under these circumstances,cross-sectional area of the velopharynx (A_VP), drivingpressure across the velopharynx (P), and inspiratory airflow(I) willbe mutually interdependent variables. The purpose of the presentinvestigation was to describe the interrelation among these threevariables during inspiration. We studied 15 sleeping patients withobstructive sleep apnea/hypopnea when the pharyngeal muscles wererendered hypotonic by applying continuous positive airway pressure tothe nasal airway.A_VP, determined by endoscopic imaging, was significantly greater at onset ofI limitationthan at minimum oropharyngeal pressure(P < 0.01). Snoring was neverobserved duringIlimitation. In a subgroup of six patients, values for P,I, andA_VP were obtainedat 0.1-s intervals at various levels of mask pressure. For these sixpatients, the mathematical expressionI = 0.657(A_VP/A_max) · P^0.332,where A_max ismaximal A_VP,described the relationship among the three variables(R² = 0.962) forflow-limited and non-flow-limited inspirations. The impedance of thepassive velopharynx, defined asP^0.33/,was inversely related toA_VP and increaseddramatically when A_VP was <0.3cm². In summary, we observed aprogressive decrease inA_VP during flow-limited inspiration in patients with obstructive sleep apnea. Thisconstriction of the velopharynx contributes to an increase invelopharyngeal impedance that, in turn, counterbalances the increase inP during flow limitation.

     

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.

     

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.

     

Upper airway neuromuscular compensation during sleep is defective in obstructive sleep apnea

Obstructive sleep apnea is the result of repeated episodes of upper airway obstruction during sleep. Recent evidence indicates that alterations in upper airway anatomy and disturbances in neuromuscular control both play a role in the pathogenesis of obstructive sleep apnea. We hypothesized that subjects without sleep apnea are more capable of mounting vigorous neuromuscular responses to upper airway obstruction than subjects with sleep apnea. To address this hypothesis we lowered nasal pressure to induce upper airway obstruction to the verge of periodic obstructive hypopneas (cycling threshold). Ten patients with obstructive sleep apnea and nine weight-, age-, and sex-matched controls were studied during sleep. Responses in genioglossal electromyography (EMG(GG)) activity (tonic, peak phasic, and phasic EMG(GG)), maximal inspiratory airflow (V(I)max), and pharyngeal transmural pressure (P(TM)) were assessed during similar degrees of sustained conditions of upper airway obstruction and compared with those obtained at a similar nasal pressure under transient conditions. Control compared with sleep apnea subjects demonstrated greater EMG(GG), V(I)max, and P(TM) responses at comparable levels of mechanical and ventilatory stimuli at the cycling threshold, during sustained compared with transient periods of upper airway obstruction. Furthermore, the increases in EMG(GG) activity in control compared with sleep apnea subjects were observed in the tonic but not the phasic component of the EMG response. We conclude that sustained periods of upper airway obstruction induce greater increases in tonic EMG(GG), V(I)max, and P(TM) in control subjects. Our findings suggest that neuromuscular responses protect individuals without sleep apnea from developing upper airway obstruction during sleep.     

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.

     

Neuromechanical control of upper airway patency during sleep.

Obstructive sleep apnea is caused by pharyngeal occlusion due to alterations in upper airway mechanical properties and/or disturbances in neuromuscular control. The objective of the study was to determine the relative contribution of mechanical loads and dynamic neuromuscular responses to pharyngeal collapse during sleep. Sixteen obstructive sleep apnea patients and sixteen normal subjects were matched on age, sex, and body mass index. Pharyngeal collapsibility, defined by the critical pressure, was measured during sleep. The critical pressure was partitioned between its passive mechanical properties (passive critical pressure) and active dynamic responses to upper airway obstruction (active critical pressure). Compared with normal subjects, sleep apnea patients demonstrated elevated mechanical loads as demonstrated by higher passive critical pressures [-0.05 (SD 2.4) vs. -4.5 cmH2O (SD 3.0), P = 0.0003]. Dynamic responses were depressed in sleep apnea patients, as suggested by failure to lower their active critical pressures [-1.6 (SD 3.5) vs. -11.1 cmH2O (SD 5.3), P < 0.0001] in response to upper airway obstruction. Moreover, elevated mechanical loads placed some normal individuals at risk for sleep apnea. In this subset, dynamic responses to upper airway obstruction compensated for mechanical loads and maintained airway patency by lowering the active critical pressure. The present study suggests that increased mechanical loads and blunted neuromuscular responses are both required for the development of obstructive sleep apnea.     

Comparative hemodynamic effects of periodic obstructive and simulated central apneas in sedated pigs

Chen, Ling, and Steven M. Scharf. Comparativehemodynamic effects of periodic obstructive and simulated centralapneas in sedated pigs. J. Appl.Physiol. 83(2): 485-494, 1997.It has beenspeculated that because of increased left ventricular (LV) afterload,decreased intrathoracic pressure (ITP) is responsible for decreasedcardiac output (CO) in obstructive sleep apnea. If this were true, thenobstructive apnea (OA) should have a greater effect on CO than wouldcentral apnea (CA). To assess the importance of decreasedITP during OA, we studied seven preinstrumented sedated pigs with OAand simulated CA that were matched for blood gases and apneaperiodicities (with 15- or 30-s apnea duration). Compared with OA, CAwith 30-s apnea duration produced comparable decreases in heart rate(from baseline to end apnea: OA, 106.6 ± 4.8 to 93.4 ± 4.4 beats/min, P < 0.01; and CA, 111.1 ± 6.2 to 94.0 ± 5.2 beats/min,P < 0.01) and comparable increasesin LV end-diastolic pressure and LV end-diastolic myocardial segmentlength but greater increases in mean arterial pressure (97.1 ± 3.7 to 107.7 ± 4.3 Torr, P < 0.05;and 97.3 ± 4.8 to 119.3 ± 7.4 Torr,P < 0.01) and systemic vascularresistance (2,577 ± 224 to 3,346 ± 400 dyn · s · cm⁵,P < 0.01; and 2,738 ± 294 to5,111 ± 1,181 dyn · s · cm⁵,P < 0.01) and greater decreases inCO (3.18 ± 0.31 to 2.74 ± 0.26 l/min,P < 0.05; and 3.07 ± 0.38 to2.30 ± 0.36 l/min, P < 0.01) andstroke volume (32.2 ± 2.9 to 25.9 ± 2.4 ml,P < 0.05; and 31.5 ± 1.9 to 19.8 ± 3.1 ml, P < 0.01). Only CA increased LV end-systolic myocardialsegment length. Similar findings were observed with 15-s apneaduration. We conclude that CA produced greater depression of CO andgreater changes of afterload-related LV dysfunction than did OA.Therefore, decreased ITP was not the dominant factor determining LVfunction with apneas.

     

Measurement of pulmonary blood flow by fractal analysis of flow heterogeneity in isolated canine lungs

Barman, Scott A., Laryssa L. McCloud, John D. Catravas, andIna C. Ehrhart. Measurement of pulmonary blood flow by fractalanalysis of flow heterogeneity in isolated canine lungs. J. Appl. Physiol. 81(5):2039-2045, 1996.Regional heterogeneity of lung blood flow can bemeasured by analyzing the relative dispersion (RD) of mass(weight)-flow data. Numerous studies have shown that pulmonary bloodflow is fractal in nature, a phenomenon that can be characterized bythe fractal dimension and the RD for the smallest realizable volumeelement (piece size). Although information exists for theapplicability of fractal analysis to pulmonary blood flow in wholeanimal models, little is known in isolated organs. Therefore, thepresent study was done to determine the effect of blood flow rate onthe distribution of pulmonary blood flow in the isolated blood-perfusedcanine lung lobe by using fractal analysis. Four different radiolabeledmicrospheres (¹⁴¹Ce,⁹⁵Nb,⁸⁵Sr, and⁵¹Cr), each 15 µm in diameter,were injected into the pulmonary lobar artery of isolated canine lunglobes (n = 5) perfused at fourdifferent flow rates ( flow1 = 0.42 ± 0.02 l/min;flow2 = 1.12 ± 0.07 l/min;flow 3 = 2.25 ± 0.17 l/min; flow 4 = 2.59 ± 0.17 l/min), and the pulmonary blood flow distribution was measured. Theresults of the present study indicate that under isogravimetric bloodflow conditions, all regions of horizontally perfused isolated lunglobes received blood flow that was preferentially distributed to themost distal caudal regions of the lobe. Regional pulmonary blood flowin the isolated perfused canine lobe was heterogeneous and fractal innature, as measured by the RD. As flow rates increased, fractal dimension values (averaging 1.22 ± 0.08) remained constant, whereas RD decreased, reflecting more homogeneous blood flowdistribution. At any given blood flow rate, high-flow areas of the lobereceived a proportionally larger amount of regional flow, suggestingthat the degree of pulmonary vascular recruitment may also be spatially related.

     

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.

     

Soft palate muscle responses to negative upper airway pressure

The afferentpathways and upper airway receptor locations involved in negative upperairway pressure (NUAP) augmentation of soft palate muscle activity havenot been defined. We studied the electromyographic (EMG) response toNUAP for the palatinus, tensor veli palatini, and levator veli palatinimuscles in 11 adult, supine, tracheostomized, anesthetized dogs. NUAPwas applied to the nasal or laryngeal end of the isolated upper airwayin six dogs and to four to six serial upper airway sites from the nasalcavity to the subglottis in five dogs. When NUAP was applied at thelarynx, peak inspiratory EMG activity for the palatinus and tensorincreased significantly (P < 0.05) and plateaued at a NUAP of 10cmH₂O. Laryngeal NUAP failed toincrease levator activity consistently. Nasal NUAP did not increase EMGactivity for any muscle. Consistent NUAP reflex recruitment of softpalate muscle activity only occurred when the larynx was exposed to the stimulus and, furthermore, was abolished by bilateral section of theinternal branches of the superior laryngeal nerves. We conclude thatsoft palate muscle activity may be selectively modulated by afferentactivity originating in the laryngeal and hypopharyngeal airway.     

Cadaver validation of skeletal muscle measurement by magnetic resonance imaging and computerized tomography

Magnetic resonance imaging (MRI) and computerizedtomography (CT) are promising reference methods for quantifying wholebody and regional skeletal muscle mass. Earlier MRI and CTvalidation studies used data-acquisition techniques and data-analysisprocedures now outdated, evaluated anatomic rather than adiposetissue-free skeletal muscle (ATFSM), studied only the relatively largethigh, or found unduly large estimation errors. The aim ofthe present study was to compare arm and leg ATFSM cross-sectional areaestimates (cm²) by usingstandard MRI and CT acquisition and image-analysis methods withcorresponding cadaver estimates. A second objective was to validate MRIand CT measurements of adipose tissue embedded within muscle(interstitial adipose tissue) and surrounding muscle (subcutaneousadipose tissue). ATFSM area (n = 119)by MRI [38.9 ± 22.3 (SD)cm²], CT (39.7 ± 22.8 cm²), and cadaver (39.5 ± 23.0 cm²) were not different(P > 0.001), and both MRI and CTestimates of ATFSM were highly correlated with corresponding cadavervalues [MRI: r = 0.99, SE of estimate (SEE) 3.9 cm²,P < 0.001; and CT:r = 0.99, SEE = 3.8 cm²,P < 0.001].Similarly good results were observed between MRI- and CT-measured vs.cadaver-measured interstitial and subcutaneous adipose tissue. ForMRI-ATFSM the intraobserver correlation for duplicate measurements invivo was 0.99 [SEE = 8.7 cm²(2.9%), P < 0.001]. Thesefindings strongly support the use of MRI and CT as reference methodsfor appendicular skeletal muscle, interstitial and subcutaneous adiposetissue measurement in vivo.

     

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.