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.

     

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.

     

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.

     

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.

     

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.

     

Respiratory changes associated with rapid eye movements in normo- and hypercapnia during sleep

Rapid eyemovements during rapid-eye-movement (REM) sleep are associated withrapid, shallow breathing. We wanted to know whether thiseffect persisted during increased respiratory drive byCO₂. In eight healthy subjects, werecorded electroencephalographic, electrooculographic, andelectromyographic signals, ventilation, and end-tidalPCO₂ during the night. InspiratoryPCO₂ was changed to increaseend-tidal PCO₂ by 3 and 6 Torr. During normocapnia, rapid eye movements were associated with a decreasein total breath time by 0.71 ± 0.19 (SE) s(P < 0.05) because of shortenedexpiratory time (0.52 ± 0.08 s,P < 0.001) and with a reduced tidalvolume (89 ± 27 ml, P < 0.05) because of decreased rib cage contribution (75 ± 18 ml, P < 0.05). Abdominal (11 ± 16 ml, P = 0.52) and minuteventilation (0.09 ± 0.21 ml/min, P = 0.66) did not change. Inhypercapnia, however, rapid eye movements were associated with afurther shortening of total breath time. Abdominal breathing was alsoinhibited (79 ± 23 ml, P < 0.05), leading to a stronger inhibition of tidal volume and minuteventilation (1.84 ± 0.54 l/min,P < 0.05). We conclude thatREM-associated respiratory changes are even more pronounced duringhypercapnia because of additional inhibition of abdominal breathing.This may contribute to the reduction of the hypercapnic ventilatory response during REM sleep.

     

Time course of sympathovagal imbalance and left ventricular dysfunction in conscious dogs with heart failure

To elucidate thetime course of sympathovagal balance and its relationship to leftventricular function in heart failure, we serially evaluated leftventricular contractility and relaxation and autonomic tone in 11 conscious dogs with tachycardia-induced heart failure. We determined adynamic map of sympathetic and parasympathetic modulation by powerspectral analysis of heart rate variability. The left ventricular peak+dP/dt substantially fell from 3,364 ± 338 to 1,959 ± 318 mmHg/s (P < 0.05) on the third day and declined gradually to 1,783 ± 312 mmHg/s at 2 wk of rapid ventricular pacing. In contrast, the timeconstant of left ventricular pressure decay and end-diastolic pressureincreased gradually from 25 ± 4 to 47 ± 5 ms(P < 0.05) and from 10 ± 2 to21 ± 3 mmHg (P < 0.05), respectively, at 2 wk of pacing. The high-frequency component(0.15-1.0 Hz), a marker of parasympathetic modulation, decreasedfrom 1,928 ± 1,914 to 62 ± 68 × 10³ms²(P < 0.05) on the third day andfurther to 9 ± 12 × 10³ms²(P < 0.05) at 2 wk. Similar to thetime course of left ventricular diastolic dysfunction, plasmanorepinephrine levels and the ratio of low (0.05- to 0.15-Hz)- tohigh-frequency component increased progressively from 135 ± 50 to 532 ± 186 pg/ml (P < 0.05) and from 0.06 ± 0.06 to 1.12 ± 1.01 (P < 0.05), respectively, at 2 wk ofpacing. These cardiac and autonomic dysfunctions recovered graduallytoward the normal values at 2 wk after cessation of pacing. Thus aparallel decline in left ventricular contractility with parasympatheticinfluence and a parallel progression in left ventricular diastolicdysfunction with sympathoexcitation suggest a close relationshipbetween cardiac dysfunction and autonomic dysregulation duringdevelopment of heart failure.

     

Contribution of abdomen and legs to central blood volume expansion in humans during immersion

Johansen, Lars Bo, Thomas Ulrik Skram Jensen, Bettina Pump,and Peter Norsk. Contribution of abdomen and legs to central bloodvolume expansion in humans during immersion. J. Appl.Physiol. 83(3): 695-699, 1997.The hypothesis wastested that the abdominal area constitutes an important reservoir forcentral blood volume expansion (CBVE) during water immersion inhumans. Six men underwent 1) water immersion for 30 min (WI),2) water immersion for 30 min withthigh cuff inflation (250 mmHg) during initial 15 min to exclude legsfrom contributing to CBVE (WI+Occl), and3) a seated nonimmersed control with15 min of thigh cuff inflation (Occl). Plasma protein concentration andhematocrit decreased from 68 ± 1 to 64 ± 1 g/l and from 46.7 ± 0.3 to 45.5 ± 0.4%(P < 0.05), respectively, during WIbut were unchanged during WI+Occl. Left atrial diameter increased from27 ± 2 to 36 ± 1 mm (P < 0.05) during WI and increased similarly during WI+Occl from 27 ± 2 to 35 ± 1 mm (P < 0.05). Centralvenous pressure increased from 3.7 ± 1.0 to 10.4 ± 0.8 mmHg during WI (P < 0.05) butonly increased to 7.0 ± 0.8 mmHg during WI+Occl(P < 0.05). In conclusion, the dilution of blood induced by WI to the neck is caused by fluid from thelegs, whereas the CBVE is caused mainly by blood from theabdomen.

     

Effect of sleep/wake state on arterial blood pressure in genetically identical mice

Genetic determinants may contribute to the large variability inarterial blood pressure responses to changes in sleep/wake state inhumans. In this study, we developed techniques to examine therelationship between sleep/wake state and mean arterial pressure (MAP)in unrestrained, genetically identical mice (C57BL/6J;n = 9). The left common carotid arterywas catheterized, and arterial blood gases were analyzed 24-48 hpostsurgery to verify normal respiratory and metabolic function. Theanimals were then allowed to cycle naturally through sleep/wake statesover a 3- to 4-h period while continuous polysomnography and arterialpressure measurements were made. The MAP decreased fromquiet wakefulness to non-rapid-eye-movement sleep (9.8 ± 1.3 mmHg;P < 0.001) and further decreasedfrom non-rapid-eye-movement to rapid-eye-movement sleep (9.7 ± 1.8 mmHg; P < 0.001). We conclude thatthe inbred strain of C57BL/6J mice exhibits significant and consistentchanges in MAP related to sleep/wake state. Future studies can compare responses in this strain of mice with those in other inbred or transgenic mice to determine whether specific genes regulate arterial blood pressure responses to sleep/wake state.

     

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.

     

Atrial distension in humans during microgravity induced by parabolic flights

Videbaek, Regitze, and Peter Norsk. Atrialdistension in humans during microgravity induced by parabolic flights.J. Appl. Physiol. 83(6):1862-1866, 1997.The hypothesis was tested that human cardiacfilling pressures increase and the left atrium is distended during 20-speriods of microgravity (µG) created by parabolic flights, comparedwith values of the 1-G supine position. Left atrial diameter(n = 8, echocardiography) increasedsignificantly during µG from 26.8 ± 1.2 to 30.4 ± 0.7 mm(P < 0.05). Simultaneously, centralvenous pressure (CVP; n = 6, transducer-tipped catheter) decreased from 5.8 ± 1.5 to 4.5 ± 1.1 mmHg (P < 0.05), and esophageal pressure (EP; n = 6) decreased from1.5 ± 1.6 to 4.1 ± 1.7 mmHg (P < 0.05). Thus transmural CVP(TCVP = CVP  EP; n = 4)increased during µG from 6.1 ± 3.2 to 10.4 ± 2.7 mmHg(P < 0.05). It is concluded thatshort periods of µG during parabolic flights induce an increase inTCVP and left atrial diameter in humans, compared with the resultsobtained in the 1-G horizontal supine position, despite a decrease inCVP.

     

Magnitude and time course of hemodynamic responses to Mueller maneuvers in patients with congestive heart failure

To simulate theimmediate hemodynamic effect of negative intrathoracic pressure duringobstructive apneas in congestive heart failure (CHF), without inducingconfounding factors such as hypoxia and arousals from sleep, eightawake patients performed, at random, 15-s Mueller maneuvers (MM) attarget intrathoracic pressures of 20 (MM 20) and40 cmH₂O (MM 40),confirmed by esophageal pressure, and 15-s breath holds, as apneic timecontrols. Compared with quiet breathing, at baseline, before theseinterventions, the immediate effects [first 5 cardiac cycles(SD), P values refer to MM 40compared with breath holds] of apnea, MM 20, and MM 40 were, for left ventricular (LV) systolic transmural pressure (Ptm), 1.0 ± 1.9, 7.2 ± 3.5, and 11.3 ± 6.8 mmHg(P < 0.01); for systolic bloodpressure (SBP), 2.9 ± 2.6, 5.5 ± 3.4, and 12.1 ± 6.8 mmHg (P < 0.01); and forstroke volume (SV) index, 0.4 ± 2.8, 4.1 ± 2.8, and6.9 ± 2.3 ml/m²(P < 0.001), respectively.Corresponding values over the last five cardiac cycles were for LVPtm6.4 ± 4.4, 5.4 ± 6.6, and 4.5 ± 9.1 mmHg (P < 0.01); for SBP6.9 ± 4.2, 8.2 ± 7.7, and 24.2 ± 6.9 mmHg (P < 0.01); and for SVindex 0.4 ± 2.1, 5.2 ± 2.8, and 9.2 ± 4.8 ml/m²(P < 0.001), respectively.Thus, in CHF patients, the initial hemodynamic response to thegeneration of negative intrathoracic pressure includes an immediateincrease in LV afterload and an abrupt fall in SV. The magnitude ofresponse is proportional to the intensity of the MM stimulus. By theend of a 15-s MM 40, LVPtm falls below baseline values, yet SVand SBP do not recover. Thus, when 40cmH₂O intrathoracic pressure issustained, additional mechanisms, such as a drop in LV preload due toventricular interaction, are engaged, further reducing SV. The neteffect of MM 40 was a 33% reduction in SV index (from 27 to 18 ml/min²), and a 21% reductionin SBP (from 121 to 96 mmHg). Obstructive apneas can have adverseeffects on systemic and, possibly, coronary perfusion in CHF throughdynamic mechanisms that are both stimulus and timedependent.

     

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.

     

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.

     

Cardiopulmonary control in sleeping Sprague-Dawley rats treated with hydralazine

Carley, David W., Sinisa M. Trbovic, Alex Bozanich, andMiodrag Radulovacki. Cardiopulmonary control in sleepingSprague-Dawley rats treated with hydralazine. J. Appl.Physiol. 83(6): 1954-1961, 1997.To test thehypothesis that hydralazine can suppress spontaneous sleep-relatedcentral apnea, respiratory pattern, blood pressure, and heart periodwere monitored in Sprague-Dawley rats. In random order and on separatedays, rats were recorded after intraperitoneal injection of1) saline or2) 2 mg/kg hydralazine. Normalizedminute ventilation(NI)declined significantly with transitions from wake tonon-rapid-eye-movement (NREM) sleep (5.1%;P = 0.01) and rapid-eye-movement (REM)sleep (4.2%; P = 0.022).Hydralazine stimulated respiration(NIincreased by 21%; P < 0.03) andeliminated the effect of state onNI. Bloodpressure decreased by 17% after hydralazine, and the correlationbetween fluctuations in mean blood pressure andNI changedfrom strongly positive during control recordings to weakly negativeafter hydralazine (P < 0.0001 foreach). Postsigh and spontaneous apneas were reduced during NREM and REMsleep after hydralazine (P < 0.05 for each). This suppression was strongly correlated with the reductionin blood pressure and with the degree of respiratory stimulation. Weconclude that mild hydralazine-induced hypotension leads to respiratory stimulation and apnea suppression.

     

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.

     

Ventilatory response to exercise in subjects breathing CO2 or HeO2

Babb, T. G. Ventilatory response to exercise insubjects breathing CO₂ orHeO₂.J. Appl. Physiol. 82(3): 746-754, 1997.To investigate the effects of mechanical ventilatory limitationon the ventilatory response to exercise, eight older subjects with normal lung function were studied. Each subject performed graded cycleergometry to exhaustion once while breathing room air; once whilebreathing 3% CO₂-21%O₂-balanceN₂; and once while breathing HeO₂ (79% He and 21%O₂). Minute ventilation(E) and respiratory mechanics weremeasured continuously during each 1-min increment in work rate (10 or20 W). Data were analyzed at rest, at ventilatory threshold (VTh),and at maximal exercise. When the subjects were breathing 3%CO₂, there was an increase(P < 0.001) inE at rest and at VTh but not duringmaximal exercise. When the subjects were breathingHeO₂,E was increased(P < 0.05) only during maximalexercise (24 ± 11%). The ventilatory response to exercise belowVTh was greater only when the subjects were breathing 3% CO₂(P < 0.05). Above VTh, theventilatory response when the subjects were breathingHeO₂ was greater than whenbreathing 3% CO₂(P < 0.01). Flow limitation, aspercent of tidal volume, during maximal exercise was greater(P < 0.01) when the subjects werebreathing CO₂ (22 ± 12%) thanwhen breathing room air (12 ± 9%) or when breathingHeO₂ (10 ± 7%)(n = 7). End-expiratory lung volumeduring maximal exercise was lower when the subjects were breathingHeO₂ than when breathing room airor when breathing CO₂(P < 0.01). These data indicate thatolder subjects have little reserve for accommodating an increase inventilatory demand and suggest that mechanical ventilatory constraintsinfluence both the magnitude of Eduring maximal exercise and the regulation ofE and respiratory mechanics duringheavy-to-maximal exercise.

     

Neural-mechanical coupling of breathing in REM sleep

Smith, C. A., K. S. Henderson, L. Xi, C.-M. Chow, P. R. Eastwood, and J. A. Dempsey. Neural-mechanical coupling of breathing in REM sleep. J. Appl.Physiol. 83(6): 1923-1932, 1997.During rapid-eye-movement (REM) sleep theventilatory response to airway occlusion is reduced. Possiblemechanisms are reduced chemosensitivity, mechanical impairment of thechest wall secondary to the atonia of REM sleep, or phasic REM eventsthat interrupt or fractionate ongoing diaphragm electromyogram (EMG)activity. To differentiate between these possibilities, we studiedthree chronically instrumented dogs before, during, and after15-20 s of airway occlusion during non-REM (NREM) and phasic REMsleep. We found that 1) for a given inspiratory time the integrated diaphragm EMG(Di) was similar or reduced in REM sleep relativeto NREM sleep; 2) for a givenDi in response to airway occlusion and thehyperpnea following occlusion, the mechanical output (flow or pressure)was similar or reduced during REM sleep relative to NREM sleep;3) for comparable durations ofairway occlusion the Di and integratedinspiratory tracheal pressure tended to be smaller and more variable inREM than in NREM sleep, and 4)significant fractionations (caused visible changes in trachealpressure) of the diaphragm EMG during airway occlusion inREM sleep occurred in ~40% of breathing efforts. Thus reducedand/or erratic mechanical output during and after airwayocclusion in REM sleep in terms of flow rate, tidal volume, and/or pressure generation is attributable largely to reduced neural activity of the diaphragm, which in turn is likely attributable to REM effects, causing reduced chemosensitivity at the level of theperipheral chemoreceptors or, more likely, at the central integrator.Chest wall distortion secondary to the atonia of REM sleep maycontribute to the reduced mechanical output following airway occlusionwhen ventilatory drive is highest.

     

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.

     

Effect of upper airway negative pressure on inspiratory drive during sleep

To determine the effect of upper airway(UA) negative pressure and collapse during inspiration on regulation ofbreathing, we studied four unanesthetized female dogs duringwakefulness and sleep while they breathed via a fenestratedtracheostomy tube, which was sealed around the permanent trachealstoma. The snout was sealed with an airtight mask, thereby isolatingthe UA when the fenestration (Fen) was closed and exposing the UA tointrathoracic pressure changes, but not to flow changes, when Fen wasopen. During tracheal occlusion with Fen closed, inspiratory time(TI) increased duringwakefulness, non-rapid-eye-movement (NREM) sleep and rapid-eye-movement(REM) sleep (155 ± 8, 164 ± 11, and 161 ± 32%,respectively), reflecting the removal of inhibitory lung inflationreflexes. During tracheal occlusion with Fen open (vs. Fen closed):1) the UA remained patent;2)TI further increased duringwakefulness and NREM (215 ± 52 and 197 ± 28%, respectively) but nonsignificantly during REM sleep (196 ± 42%);3) mean rate of rise of diaphragmEMG (EMGdi/TI) and rate offall of tracheal pressure(Ptr/TI) were decreased,reflecting an additional inhibitory input from UA receptors; and4) bothEMGdi/TI andPtr/TI were decreasedproportionately more as inspiration proceeded, suggesting greaterreflex inhibition later in the effort. Similar inhibitory effects ofexposing the UA to negative pressure (via an open tracheal Fen) wereseen when an inspiratory resistive load was applied over severalbreaths during wakefulness and sleep. These inhibitory effectspersisted even in the face of rising chemical stimuli. This inhibitionof inspiratory motor output is alinear within an inspiration andreflects the activation of UA pressure-sensitive receptors by UAdistortion, with greater distortion possibly occurring later in theeffort.