Genioglossal length and EMG responses to static upper airway pressures during hypercapnia in goats.

Mechanoreflexes that activate genioglossus electromyogram (EMGgg) in response to negative upper airway pressure (UAP) may help defend airway patency in obstructive sleep apnea. Hypercapnia may affect mechanoreflexes by increasing EMGgg response to actively reduce genioglossus length (Lgg, measured by sonomicrometry). We hypothesized that during normocapnia, Lgg would be reduced at positive, and increased at negative UAP but hypercapnia would increase EMGgg responses to negative pressures and cause Lgg reductions. At 0, 3.5 and 7% inhaled CO2 (balance O2), Lgg and EMGgg were measured during static negative and positive UAP applied to the isolated upper airway in four unanesthetized goats. At 3.5 and 7% CO2 EMGgg was significantly increased and Lgg decreased with negative pressure while EMGgg was also greater at 7 than 0% CO2 (P<0.05). Non-significant pressure related Lgg changes were observed during normocapnia. These results suggest that hypercapnia may stimulate greater mechanoreflex EMGgg activation and consequent Lgg reduction in response to negative UAP application.

Serotonergic stimulation of the genioglossus and the response to nasal continuous positive airway pressure.

In obstructive sleep apnea (OSA), abnormal pharyngeal collapsibility may be offset by increased mechanoreflex-mediated activity of dilator muscles while awake, but this reflex is inhibited during sleep and during application of nasal continuous positive airway pressure (CPAP). Direct activation of upper airway (UA) motor neurons in the hypoglossal nucleus by a selective serotonin reuptake inhibitor (SSRI), paroxetine hydrochloride, may increase genioglossal electromyographic (EMG) activity (EMGgg) in a manner resistant to mechanoreflex inhibition. We studied the effects of paroxetine on EMGgg using an intraoral surface electrode during eupnea or room air breathing (RA), hypercapnia (HYP), and CPAP application in the presence of hypercapnia (CPAP + HYP) in 11 normal volunteers, using a double-blind, placebo-controlled crossover design. After 5 d of paroxetine, EMGgg activity increased significantly within each condition (p = 0.02). EMGgg during the conditions of HYP and HYP + CPAP were significantly greater than during RA for both placebo and paroxetine treatments (p = 0.006). EMGgg activity in HYP persisted during HYP + CPAP on paroxetine (183% versus 182% of placebo, respectively). We conclude that paroxetine produces an augmentation in EMGgg in normal subjects during wakefulness and that this effect persists during mechanoreflex inhibition. This is consistent with a central serotonergic effect.

Force production of the genioglossus as a function of muscle length in normal humans.

Resting muscle length affects both maximum force production and force maintenance. The strength and force maintenance characteristics of the genioglossus as a function of resting muscle length have not been described. We hypothesized that genioglossus optimum length (L(o)) could be defined in vivo and that the ability of the genioglossus to sustain a given workload would decrease as resting length deviated from L(o). To test this, 11 normal men repeated maximal isometric genioglossus protrusions at different muscle lengths to determine L(o). L(o) was also obtained by using submaximal efforts while simultaneously recording electromyographic activity of the genioglossus, with L(o) defined as the length at which the force-to-genioglossus electromyographic activity ratio was maximum. Both methods provided similar results. Force maintenance was measured at four muscle lengths on separate days. Target efforts representing 60% of each subject's maximum at L(o) and lasting 5 s were performed at 12-s intervals. Time limit of endurance of the genioglossus was defined as the time from trial onset at which 90% of the target could not be maintained for three consecutive efforts. Time limit of endurance was greatest at L(o) and fell to 47.5% at L(o) + 1 cm, 53.8% at L(o) - 1 cm, and 47.4% at L(o) - 1.5 cm. We conclude that L(o) of the genioglossus can be determined in vivo and that force maintenance of the genioglossus is decreased when operating length deviates from L(o).

Strategic decision making on shifting sands.

Strategic decision making in today's health care marketplace is very challenging. In the past, strategic plans were written for five to ten years. With the rapidly changing environment, planning for more than two years is difficult. It is critical for organizations to set a pathway for success. However, the organization needs to be able to respond quickly to environmental changes and take advantage of opportunities. The article presents a case study on a relatively new organization that has ambitious strategic goals. It discusses the decision-making process on the ways to enter a new marketplace, including the key factors assessed by the organization and their implications.

Joint NASA-ESA-DARA Study. Part three: characterization of sleep under ambient CO2-levels of 0.7% and 1.2%.

An experiment was conducted to study sleep quality and sleep architecture in volunteers living in a closed system under elevated ambient CO2 levels of 0.7% and 1.2%. In a closed system, human life is possible only if the CO2 level is permanently adjusted. For the Russian space station MIR, for example, the CO2 levels of the present study are actual upper limits for the adjustment. Sleep architecture was found to be altered in astronauts on the orbiting MIR station. Sleep quantity and quality were reduced. The latency to the first REM sleep was shorter in space and slow wave sleep was redistributed from the first to the second sleep cycle. The elevated CO2 concentration in the atmosphere on MIR may be one of the reasons for those observations regarding sleep in space. Thus, this experiment was also conducted in order to clarify the interpretation of data obtained from astronauts on MIR. In this study sleep polygraphies could be recorded in 4 subjects who lived for 23 d under 0.7% and then for the same period of time under 1.2% CO2. Findings suggest that these levels of ambient CO2 do not reduce sleep quality. Sleep architecture, however, was slightly changed and showed that the amount of slow wave sleep increased with the duration of the exposure to CO2. But it can be excluded that findings on MIR were caused by elevated CO2-levels.

Influence of preload and afterload on genioglossus muscle length in awake goats.

The genioglossus is an upper airway dilator muscle, the length of which is directly related to patency in the oropharyngeal region. We hypothesized that genioglossal length (Lgg) is dynamically influenced by the afterload exerted by negative upper airway pressure during inspiration and by the intrinsic length-tension characteristics of the muscle (preload). Seven awake goats were chronically instrumented with electrodes for EMGgg and sonomicrometry for Lgg. We examined the Lgg-EMGgg relationship during hypercapnia and inspiratory resistive loading (18 cm H2O/L/s). The goats breathed through the upper airway (TC) or airflow was diverted through a tracheostomy (TO). We found that: (1) passive inspiratory lengthening was observed with negative upper airway pressure (UAP) but not when UAP = 0 (TO breathing), (2) Lgg shortening for a given EMGgg was significantly decreased with negative inspiratory UAP, and (3) phasic Lgg shortening per unit EMGgg was greatest when Lgg was near optimal length (Lo). We conclude that genioglossal length is substantially influenced by afterload exerted by negative UAP and that genioglossal active shortening may be limited if the muscle operates at a length significantly greater or less than the optimal length.

Central respiratory carbon dioxide chemosensitivity does not decrease during sleep.

The ventilatory response to CO2 decreases during slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep compared with awake levels. However, it is not known to what extent this can be attributed to decreased sensitivity of the CO2 chemoreflex. Mechanical factors during sleep may decrease ventilatory output, or PCO2 at the central chemoreceptor may not increase to the same degree as PaCO2, particularly during REM sleep when brain blood flow (BBF) is increased. In 10 goats, we measured the ventilatory (VI), diaphragmatic electromyogram (EMGdI), and BBF responses to CO2 rebreathing during each sleep-wake state. delta VI/delta PaCO2 decreased from wakefulness to SWS (p less than 0.05) and REM sleep (p less than 0.05). In contrast, delta EMGdI/delta PaCO2 was decreased only during REM sleep (p less than 0.05). Concurrently, delta BBF/delta PaCO2 increased during REM sleep (p less than 0.05) compared with the awake state or SWS. A significant reciprocal correlation existed between delta EMGdI/delta PaCO2 and delta BBF/delta PaCO2 across sleep states (r = -0.786). When EMGdI was related to directly measured cerebral venous PCO2 (n = 4), a single linear function (r = 0.894) was found, independent of sleep-wake state. Similar results were obtained during quasi-steady-state hypercapnia. We conclude that central CO2 chemosensitivity is intact during sleep.

Responses of diaphragm and external oblique muscles to flow-resistive loads during sleep.

Although it is generally agreed that rapid respiratory compensation for externally applied inspiratory loads is impaired or absent during sleep, the individual components of the "load-compensating reflex" may not be inhibited by sleep to the same degree. We studied the effect of inspiratory flow-resistive loading (18 cm H2O/L/s) for two consecutive breaths on inspiratory (diaphragm) and expiratory (external oblique) muscle activity, and respiratory timing, in six awake and sleeping goats. During the first loaded breath in the awake state, peak integrated diaphragmatic electromyogram activity (EMGdi) increased 16.7 +/- 3.9% (p less than 0.01), peak integrated external oblique EMG activity (EMGeo) increased 21.0 +/- 7.5% (p less than 0.001), and electrical inspiratory time (Ti) increased 18.1 +/- 2.1% (p less than 0.01). In contrast, loading did not significantly change peak EMGdi or EMGeo on the first or second breaths in any sleep state. However, Ti was significantly increased during loading in all sleep states (p less than 0.01) to a similar degree seen during wakefulness. Loading did not significantly alter electrical expiratory time. No significant differences were noted between the first and second loaded breaths. We conclude that the reflex increases in peak EMG of both inspiratory and expiratory muscles in response to inspiratory flow-resistive loading during the awake state are absent during all stages of sleep; however, one aspect of load compensation, prolongation of Ti, is preserved during sleep and aids in maintaining tidal volume.

The role of vascular tone in the control of upper airway collapsibility.

Upper airway collapsibility may be influenced by both muscular and nonmuscular factors. Because mucosal blood volume (and therefore vascular tone) is an important determinant of nasal airway patency, vascular tone may be an important nonmuscular determinant of pharyngeal collapsibility. This hypothesis was tested in two experimental models. First, upper airway closing (CP) and opening (OP) pressures and static compliance were measured in nine anesthetized, sinoaortic-denervated, paralyzed cats with isolated upper airways. Vascular tone was decreased with either papaverine or sodium nitroprusside (NTP), and increased with phenylephrine (PE), whereas blood pressure and end-tidal CO2 were maintained constant. Vasodilation increased CP (control = -10.4 +/- 1.3, NTP = -7.3 +/- 1.2 cm H2O; p less than 0.05) and OP (control = -7.9 +/- 1.5, NTP = -3.3 +/- 1.8 cm H2O; p less than 0.05). In contrast, vasoconstriction tended to decrease CP (control = -10.7 +/- 1.5, PE = -11.7 +/- 1.4 cm H2O; p less than 0.09) and OP (control = -8.1 +/- 1.2, PE = -9.9 +/- 1.9 cm H2O; p less than 0.1). Thus, vasodilation increased and vasoconstriction tended to decrease upper airway collapsibility. Upper airway static compliance was unchanged during either drug infusion. In order to assess changes in pharyngeal cross-sectional area (CSA) that occurred during vasodilation, magnetic resonance imaging was utilized in seven cats. During vasodilation with NTP, pharyngeal CSA was reduced from 0.44 +/- 0.10 to 0.30 +/- 0.09 cm2 (p less than 0.05), and pharyngeal volume was reduced from 15.3 +/- 2.4 to 13.9 +/- 2.7 cm3 (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Brain hypoxia preferentially stimulates genioglossal EMG responses to CO2.

Although the dominant respiratory response to hypoxia is stimulation of breathing via the peripheral chemoreflex, brain hypoxia may inhibit respiration. We studied the effects of two levels of brain hypoxia without carotid body stimulation, produced by inhalation of CO, on ventilatory (VI) and genioglossal (EMGgg) and diaphragmatic (EMGdi) responses to CO2 rebreathing in awake, unanesthetized goats. Neither delta VI/delta PCO2 nor VI at a PCO2 of 60 Torr was significantly different between the three conditions studied (0%, 25%, and 50% carboxyhemoglobin, HbCO). There were also no significant changes in delta EMGdi/delta PCO2 or EMGdi at a PCO2 of 60 Torr during progressive brain hypoxia. In contrast, delta EMGgg/delta PCO2 and EMGgg at a PCO2 of 60 Torr were significantly increased at 50% HbCO compared with either normoxia or 25% HbCO (P less than 0.05). The PCO2 threshold at which inspiratory EMGgg appeared was also decreased at 50% HbCO (45.6 +/- 2.6 Torr) compared with normoxia (55.0 +/- 1.4 Torr, P less than 0.02) or 25% HbCO (53.4 +/- 1.6 Torr, P less than 0.02). We conclude that moderate brain hypoxia (50% HbCO) in awake, unanesthetized animals results in disproportionate augmentation of EMGgg relative to EMGdi during CO2 rebreathing. This finding is most likely due to hypoxic cortical depression with consequent withdrawal of tonic inhibition of hypoglossal inspiratory activity.

Arterial oxygen saturation during Nd:YAG laser photoresection of endobronchial tumors under local anesthesia. Use of intermittent supplemental oxygen with pulse oximetry guidance.

Although Nd:YAG laser photoresection of endobronchial lung tumor can result in significant arterial oxygen desaturation, oxygen supplementation during procedures is often limited due to fear of intrabronchial combustion. We gave intermittent pulse supplemental oxygen to ten patients during 26 laser procedures performed under local anesthesia using SaO2 measured by a pulse oximeter as a guide. In four procedures (15.4 percent), severe oxygen desaturation contraindicated performing or completing laser phototherapy. In the remaining 22 procedures (84.6 percent), laser photoresection was safely and successfully performed without incident. Thus, pulse oximetry is a valuable tool and intermittent oxygen supplementation with pulse oximeter guidance an effective technique for maintaining adequate oxygenation during laser photoresection.

Genioglossal and diaphragmatic EMG responses to hypoxia during sleep.

Activation of pharyngeal dilator muscles, such as the genioglossus, during hypoxia must be sufficient to overcome the increased subatmospheric pressure generated by the diaphragm. This is particularly important during sleep, when upper airway resistance is greater. We measured ventilatory, genioglossal (EMGgg) and diaphragmatic (EMGdi) electromyogram responses to isocapnic hypoxia during wakefulness (W), slow-wave sleep (SWS), and rapid eye movement (REM) sleep in seven chronically instrumented adult goats. We also compared the EMG responses to hypoxia to response to CO2 during W. delta EMGdi/delta SaO2 decreased progressively from W to SWS (p less than 0.05) to REM sleep (p less than 0.05 versus SWS), paralleling the corresponding ventilatory responses. EMGgg was activated only below an SaO2 threshold, similar during W (69.8 +/- 6.3%) and SWS (67.2 +/- 4.3%), beyond which there was a brisk linear increase. During REM sleep, arousal preceded activation of EMGgg in each animal, although SaO2 at arousal (61.3 +/- 4.4%) was less than the SaO2 threshold for EMGgg activation during W or SWS (p less than 0.05). Despite state-related differences in the individual muscle responses, simultaneous EMGgg and EMGdi during hypoxia or hypercapnia in W, and during hypoxia in SWS and REM sleep, were linked in a constant manner. This suggests common integration of central and peripheral chemoreceptor inputs. Furthermore, these relationships are unaffected by either SWS or REM sleep.

Linkage between brain blood flow and respiratory drive during rapid-eye-movement sleep.

The correlation between brain blood flow (BBF) and respiratory neuromotor output, as reflected by diaphragmatic electromyogram (EMG) activity (EMGdi), was studied during wakefulness, rapid-eye-movement (REM) sleep, and non-REM sleep (NREM). Compared with the awake state, mean BBF increased by 4.7% during NREM and by 32.6% during REM (P less than 0.001). Also, surges of BBF during REM occurred during periods of intense phasic activity. EMGdi [peak and peak/inspiratory time (TI)] was highly variable within REM periods but fluctuated as a reciprocal function of simultaneously measured BBf (r = -0.49, P less than 0.001). Furthermore, mean EMGdipeak decreased from NREM to REM in a manner reciprocally related to the corresponding change in BBF (r = -0.77, P = 0.015). These findings suggest that a component of the reduction of respiratory neuromotor output during REM is attributable to increased BBF with consequent relative hypocapnia in the central chemoreceptor environment.

Obstructive sleep apnea following bilateral carotid body resection.

A patient who had undergone bilateral carotid body resection five years earlier for palliation of chronic airflow obstruction was found to have severe obstructive sleep apnea. He presented with hypercapnic respiratory failure, which improved after tracheostomy. A physiologic mechanism is proposed to explain this association. Previously reported studies of anesthetized animals suggest that loss of peripheral chemoreceptor activity could selectively decrease neural output to the genioglossus, the main protrusor muscle of the tongue, predisposing the upper airway to inspiratory occlusion.

Correlation between genioglossal and diaphragmatic responses to hypercapnia during sleep.

Oropharyngeal patency during sleep is dependent on the dilating force of the genioglossus, the main tongue protrusor muscle. We measured the ventilatory (Vl), diaphragmatic (EMGdi), and genioglossal (EMGgg) electromyographic responses to CO2 in awake and sleeping goats; delta Vl/delta PETCO2 decreased from awake (0.85 +/- 0.087 L/min/mm Hg) to NREM sleep (0.69 +/- 0.069) to REM sleep (0.57 +/- 0.078, p less than 0.005 versus awake). There were minimal decreases in delta EMGdi/delta PETCO2 and EMGdi at a PETCO2 of 55 mm Hg from awake to NREM, but a significant decrease in EMGdi at a PETCO2 of 55 mm Hg during REM sleep (p less than 0.025 versus NREM). Inspiratory EMGgg was only present above a PCO2 threshold, which was similar for each state (49.3 +/- 2.3 mm Hg PETCO2 awake, 48.8 +/- 2.4 during NREM, 49.5 +/- 2.5 during REM), and delta EMGgg/delta PETCO2 tended to be less during both sleep states compared with that while awake (p = 0.10). At any PCO2, inspiratory EMGgg was markedly inhibited during REM sleep when rapid eye movements were present (phasic REM). We conclude that there is disproportionate inhibition of the genioglossus relative to the diaphragm at low CO2 tensions and at any PCO2 during phasic REM sleep. This imbalance may predispose the upper airway to inspiratory occlusion during sleep.

The role of endogenous opioids in the ventilatory response to acute flow-resistive loads.

The ability of acute, short-term, inspiratory flow-resistive loading to generate endogenous opioids was studied in 6 unanesthetized goats. Endogenous opioid generation was assessed by measurement of immunoreactive beta-endorphin levels in the cisternal cerebrospinal fluid (CSF) after high (80 cm H2O/L/s) and moderate (50 cm H2O/L/s) resistive loading. The results show that CSF levels of beta-endorphin were significantly increased by both the high and moderate resistive loads (40 +/- 4 SEM pg/ml and 33.7 +/- 3.4 pg/ml, respectively) when compared with the same animals during unloaded control conditions (19.5 +/- 3.8 pg/ml). Both levels of loading also caused a significant progressive decline in tidal volume (to 82 +/- 8 and 89 +/- 8% of baseline tidal volume with the high and moderate loads, respectively). Naloxone administration (0.1 mg/kg) resulted in a transient but significant increase in tidal volume from the sixth through the twentieth minute (to 37 +/- 5 and 34 +/- 5% peak tidal volume increase with high and moderate loads, respectively). In addition, there was a significant correlation between the percent decline in tidal volume and mean inspiratory flow rate after loading and the level of beta-endorphin in the cisternal CSF. We conclude that relatively short-term, high-level, inspiratory flow-resistive loading results in elaboration of endogenous opioids within the central nervous system and that these opioids play a role in the progressive decline in tidal volume and mean inspiratory flow rate exhibited during these conditions.