Apneic Duration Research Articles

The superior laryngeal nerve is involved in a brief apneic response to intralaryngeal, but not in the lethal ventilatory arrest to intravenous, administration of fentanyl (FNT) in rats

Rapid intravenous (IV) injection of FNT induces a sudden ventilatory arrest within a few minutes or even seconds, which is the major cause of overdose FNT‐induced death. Our previous studies have shown that right atrial or IV bolus injection of FNT in anesthetized rats produced a vagal‐mediated apnea or a lethal ventilatory arrest in a dose‐dependent manner (Zhuang et al, AJP 2012 and EB Meeting 2022). The superior laryngeal nerve (SLN) containing the laryngeal sensory afferents also travels in the vagus nerve and is capable of triggering the apneic response associated with hypertension and bradycardia upon activation. Here, we asked whether local administration of FNT into the larynx affected cardiorespiratory activities via acting on the SLN and to what extent the sudden ventilatory arrest induced by IV injection of FNT depended on the SLN integrity. FNT at 15 µg was either sprayed (5‐10 µl) into the larynx or bolus IV‐injected (50 µl) in the anesthetized rats with and without bilateral SLN transection. We found that FNT sprayed into the larynx induced an immediate brief apnea (~3.5‐fold of baseline TE) and laryngeal constriction (but not closure) associated with hypertension and bradycardia. The cardiorespiratory response disappeared after transection of SLN. Interestingly, the same dose of FNT given by IV injection induced a ventilatory arrest (apneic duration >8‐fold longer than that produced by the local administration) associated with laryngeal closure, hypotension and bradycardia. These responses to IV injection of FNT were not significantly affected by SLN transection. Our data suggest that the SLN is responsible for the brief apneic response to laryngeal application of FNT, but not for the lethal ventilatory arrest induced by rapid IV injection of FNT.

Apneic Oxygenation During Prolonged Laryngoscopy in Obese Patients: a Randomized, Double-Blinded, Controlled Trial of Nasal Cannula Oxygen Administration.

Obese patients have a propensity to desaturate during induction of general anesthesia secondary to their reduced functional residual capacity and increased oxygen consumption. Apneic oxygenation can provide supplemental oxygen to the alveoli, even in the absence of ventilation, during attempts to secure the airway. In this study, we hypothesized that oxygen administration through a nasopharyngeal airway and standard nasal cannula during a simulated prolonged laryngoscopy would significantly prolong the safe apneic duration in obese patients. One hundred thirty-five obese patients undergoing non-emergent surgery requiring general anesthesia were randomized to either the control group or to receive apneic oxygenation with air versus oxygen. All patients underwent a standard intravenous induction. For patients randomized to receive apneic oxygenation, a nasopharyngeal airway and standard nasal cannula were inserted. A simulated prolonged laryngoscopy was performed to determine the duration of the safe apneic period, defined as the beginning of laryngoscopy until the peripheral oxygen saturation (SpO2) reached 95%. The oxygen group had a median safe apneic duration that was 103s longer than the control group. The lowest mean SpO2 value during the induction period was 3.8% higher in the oxygen group compared to the control group. Following intubation, patients in the oxygen group had a mean end tidal carbon dioxide (ETCO2) level that was 3.0mmHg higher than patients in the control group. In obese patients, oxygen insufflation at 15L/min through a nasopharyngeal airway and standard nasal cannula can significantly increase the safe apneic duration during induction of anesthesia.

Blood lactate accumulation during competitive freediving and synchronized swimming

A number of competitive water sports are performed while breath-holding (apnea). Such performances put large demands on the anaerobic system, but the study of lactate accumulation in apneic sports is limited. We therefore aimed to determine and compare the net lactate accumulation (NLA) during competition events in six disciplines of competitive freediving (FD) and three disciplines of synchronized swimming (SSW). The FD disciplines were: static apnea (STA; n = 14); dynamic apnea (DYN; n = 19); dynamic apnea no fins (DNF; n = 16); constant weight (CWT; n = 12); constant weight no fins (CNF; n = 8); free immersion (FIM; n =10). The SSW disciplines were solo (n = 21), duet (n = 31) and team (n = 34). Capillary blood lactate concentration was measured before and three minutes after competition performances, and apneic duration and performance variables were recorded. In all nine disciplines NLA was observed. The highest mean (SD) NLA (mmol·L-1) was found in CNF at 6.3 (2.2), followed by CWT at 5.9 (2.3) and SSW solo at 5 (1.9). STA showed the lowest NLA 0.7 (0.7) mmol·L-1 compared to all other disciplines (P ⟨ 0.001). The NLA recorded shows that sports involving apnea involve high levels of anaerobic activity. The highest NLA was related to both work done by large muscle groups and long apneic periods, suggesting that NLA is influenced by both the type of work and apnea duration, with lower NLA in SSW due to shorter apneic episodes with intermittent breathing.

Fasting improves static apnea performance in elite divers without enhanced risk of syncope

In competitive apnea divers, the nutritional demands may be essentially different from those of, for example, endurance athletes, where energy resources need to be maximised for successful performance. In competitive apnea, the goal is instead to limit metabolism, as the length of the sustainable apneic period will depend to a great extent on minimising oxygen consumption. Many but not all elite divers fast before performing static apnea in competition. This may increase oxygen consumption as mainly lipid stores are metabolised but could also have beneficial effects on apneic duration. Our aim was to determine the effect of over-night fasting on apnea performance. Six female and seven male divers performed a series of three apneas after eating and fasting, respectively. The series consisted of two 2-min apneas spaced by 3 min rest and, after 5 min rest, one maximal effort apnea. Apneas were performed at supine rest and preceded by normal respiration and maximal inspiration. Mean (±SD) time since eating was 13 h (±2 h 43 min) for the fasting and 1 h 34 min (±33 min) for the eating condition (P < 0.001). Mean blood glucose was 5.1 (±0.4) mmol/L after fasting and 5.9 (±0.7) mmol/L after eating (P<0.01). Lung volumes were similar in both conditions (NS). For the 2-min apneas, nadir SaO2 during fasting was 95 (±1)% and 92 (±2)% (P < 0.001) on eating and ETCO2 was lower in the fasting condition (P < 0.01) while heart rate (HR) during apnea was 74 (±10) bpm for fasting and 80 (±10) bpm for eating conditions (P < 0.01). Maximal apnea durations were 4 min 41 s (±43 s) during fasting and 3 min 51 s (±37 s) after eating (P < 0.001), and time without respiratory contractions was 31 s (25%) longer after fasting (P < 0.01). At maximal apnea termination, SaO2 and ETCO2 were similar in both conditions (NS) and apneic HR was 63 (±9) bpm for fasting and 70 (±10) bpm for eating (P < 0.01). The 22% longer apnea duration after fasting with analogous end apnea SaO2 levels suggests that fasting is beneficial for static apnea performance in elite divers, likely via metabolism-limiting mechanisms. The oxygen-conserving effect of the more pronounced diving response and possibly other metabolism-limiting mechanisms related to fasting apparently outweigh the enhanced oxygen consumption caused by lipid metabolism.

Acute dietary nitrate supplementation improves dry static apnea performance

Acute dietary nitrate (NO3−) supplementation has been reported to lower resting blood pressure, reduce the oxygen (O2) cost of sub-maximal exercise, and improve exercise tolerance. Given the proposed effects of NO3− on tissue oxygenation and metabolic rate, it is possible that NO3− supplementation might enhance the duration of resting apnea. If so, this might have important applications both in medicine and sport. We investigated the effects of acute NO3− supplementation on pre-apnea blood pressure, apneic duration, and the heart rate (HR) and arterial O2 saturation (SaO2) responses to sub-maximal and maximal apneas in twelve well-trained apnea divers. Subjects were assigned in a randomized, double blind, crossover design to receive 70ml of beetroot juice (BR; containing ∼5.0mmol of nitrate) and placebo juice (PL; ∼0.003mmol of nitrate) treatments. At 2.5h post-ingestion, the subjects completed a series of two 2-min (sub-maximal) static apneas separated by 3min of rest, followed by a maximal effort apnea. Relative to PL, BR reduced resting mean arterial pressure by 2% (PL: 86±7 vs. BR: 84±6mmHg; P=0.04). The mean nadir for SaO2 after the two sub-maximal apneas was 97.2±1.6% in PL and 98.5±0.9% in BR (P=0.03) while the reduction in HR from baseline was not significantly different between PL and BR. Importantly, BR increased maximal apneic duration by 11% (PL: 250±58 vs. BR: 278±64s; P=0.04). In the longer maximal apneas in BR, the magnitude of the reductions in HR and SaO2 were greater than in PL (P≤0.05). The results suggest that acute dietary NO3− supplementation may increase apneic duration by reducing metabolic costs.

Cardiorespiratory pattern of rest-associated apnea in a Weddell seal: a case study at an ice hole in Antarctica

Seals are known to be periodic breathers with eupneic and apneic phases at rest. We video-recorded a resting Weddell seal (Leptonychotes weddellii) that appeared head up from an ice hole in McMurdo Sound, Antarctica. From the video recorded, the duration of each eupneic and apneic phase was extracted, and heart rate in apneic phase was obtained by counting ripples of the sea surface around the neck of a seal. The results indicated that the distribution of instantaneous heart rate was bimodal. In addition, the higher the apneic heart rate, the shorter the apneic duration as well as the combination of apneic duration and successive eupneic duration (A–E duration). From these analyses, we characterized the periodic breathing of a resting Weddell seal.

Effects of two weeks of daily apnea training on diving response, spleen contraction, and erythropoiesis in novel subjects

Three potentially protective responses to hypoxia have been reported to be enhanced in divers: (1) the diving response, (2) the blood-boosting spleen contraction, and (3) a long-term enhancement of hemoglobin concentration (Hb). Longitudinal studies, however, have been lacking except concerning the diving response. Ten untrained subjects followed a 2-week training program with 10 maximal effort apneas per day, with pre- and posttraining measurements during three maximal duration apneas, and an additional post-training series when the apneic duration was kept identical to that before training. Cardiorespiratory parameters and venous blood samples were collected across tests, and spleen diameters were measured via ultrasound imaging. Maximal apneic duration increased by 44 s (P < 0.05). Diving bradycardia developed 3 s earlier and was more pronounced after training (P < 0.05). Spleen contraction during apneas was similar during all tests. The arterial hemoglobin desaturation (SaO2) nadir after apnea was 84% pretraining and 89% after the duration-mimicked apneas post-training (P < 0.05), while it was 72% (P < 0.05) after maximal apneas post-training. Baseline Hb remained unchanged after training, but reticulocyte count increased by 15% (P < 0.05). We concluded that the attenuated SaO2 decrease during mimic apneas was due mainly to the earlier and more pronounced diving bradycardia, as no enhancement of spleen contraction or Hb had occurred. Increased reticulocyte count suggests augmented erythropoiesis.

Tumor necrosis factor alpha (TNFα) potentiates pulmonary chemoreflex responses in anesthetized rats

TNFa, a pro‐inflammatory cytokine, is involved in the pathogenesis of asthma and also known for its sensitizing effect on somatic nociceptive afferents. This study was carried out in anesthetized rats to test whether TNFa induces pulmonary C‐fiber hypersensitivity. Before intratracheal (i.t.) instillation of TNFa (~6.8 μg/kg; 1 μg = ~105 units), right atrial injection of a low dose of capsaicin (0.5 μg/kg) elicited a very mild respiratory and cardiovascular depression. Thirty min after the TNFa treatment, the same dose of capsaicin triggered a longer apnea; the apneic ratio (the ratio between apneic duration and average expiratory duration) increased from 180 ± 43% before to 633 ± 67% after TNFa (n = 6; P &lt; 0.005). This sensitizing effect of TNFa gradually declined, but lasted for &gt; 120 min. In contrast, vehicle administered in the same manner did not generate any increase in the responses to capsaicin at the same time point. Moreover, in single‐fiber recording experiments, inhalation of aerosolized TNFa (10 µg/ml; ~0.2 ml) caused a significant increase in the responses to injection of the the same dose of capsaicin. These results suggest that TNFα induces an acute, intense and reversible potentiating effect on the pulmonary chemoreflex to capsaicin, which is probably caused by an increase in the sensitivity of pulmonary C‐fibers. (Supported in part by NIH grant HL58686)

Respiratory syncytial virus infection in anesthetized weanling rather than adult rats prolongs the apneic responses to right atrial injection of capsaicin

Apnea is a common complication in infants infected by respiratory syncytial virus (RSV). A recent study has shown that intranasal inoculation of RSV in conscious weanling rats strengthens the apneic responses to right atrial injection of capsaicin (CAP), leading to 66% mortality. The objectives of the present study were to determine 1) whether RSV infection changes baseline minute ventilation (Ve) and arterial blood gases in anesthetized rats; 2) what the effects of RSV infection are on the respiratory responses to CAP; and 3) whether the RSV-strengthened apneic responses are age dependent. Our experiments were conducted in anesthetized and spontaneously breathing rats divided into four groups of weanling and adult rats that received either intranasal inoculation of RSV or virus-free medium. Two days after RSV infection (0.7 ml/kg), animal blood gases, baseline Ve, and Ve responses to right atrial injection of three doses of CAP (4, 16, and 64 microg/kg) were measured and compared among the four groups. Our results showed that RSV infection increased respiratory frequency (approximately 25%, P<0.05) in weanling but not adult rats, with little effect on arterial blood gases. RSV infection amplified the apneic responses to CAP in weanling but not adult rats, characterized by increases in the initial (40%) and the longest apneic duration (650%), the number of apneic episodes (139%), and the total duration of apneas (60%). These amplifications led to 50% mortality (P<0.05). We conclude that RSV infection increases respiratory frequency and strengthens the apneic responses to CAP only in anesthetized weanling but not adult rats.

Intratracheal Instillation of Lipopolysaccharide (LPS) Depresses Ventilatory Responses to Hypoxia and Hypercapnia in the Rat

Intravenous infusion of LPS blunted hypoxic ventilatory responses (HVR) in neonatal piglets and increased bronchopulmonary C-fibers (PCFs) activity in adult rats with inconsistent impacts on baseline ventilation. We hypothesized that intratracheal instillation of LPS depressed HVR and ventilatory responses to hypercapnia (HCVR), and prolonged the PCF-mediated apnea in both adult and weanling rats. LPS (1 mg/mL, serum type 0111:B4, Sigma L3012) and vehicle (0.5 mL for adult and 0.2 mL for weanling) were intratracheally instilled in two groups of adult and weanling rats, respectively. Three days later, rats were anesthetized and tracheotomized, and their ventilatory responses to 1 min of 10% O2 and 10% CO2, and subsequent apneic response to right atrial bolus-injections of capsaicin (CAP, 1 and 4 μg/0.1 mL) were measured. The results showed that compare to the vehicle, LPS: 1) did not affect baseline ventilation in both adult and weanling rats; 2) depressed HVR in both adult (229 ± 15% vs. 167 ± 11%, P < 0.01) and weaning rats (196 ± 14% vs. 132 ± 9%, P < 0.01); 3) attenuated HCVR (adult 291 ± 29% vs. 199 ± 16%, P < 0.05; weanling 281 ± 25% vs. 142 ± 6%, P < 0.01); and 4) did not alter CAP-induced apneic duration. We conclude that intratracheal instillation of LPS selectively depresses both HVR and HCVR with little effect on PCF-mediated respiratory responses. These responses are independent of the age of rats. (Supported by ALA CI-016N and NIH 74183)

Pill Swallowing by Adults With Dysphagia

To evaluate differences in swallowing physiology and safety in patients with dysphagia between conventional tablets and a new method of tablet transportation, orally disintegrating technology (ODT) (RapiTab; Schwarz Pharma Inc, Milwaukee, Wis). The study observed a single group, crossover design. Outpatient clinic within an academic teaching hospital. A total of 36 adult dysphagic patients referred to the clinic. All subjects underwent simultaneous nasopharyngeal endoscopic evaluation, surface electromyographic (sEMG) measurement, and respiratory monitoring during swallowing. Subjects were evaluated swallowing the ODT and a conventional tablet formulation. Tablets were randomly and blindly presented to each subject. Subjects completed a preference survey subsequent to swallowing both tablets. Significant differences included greater sEMG amplitude and longer apneic duration when swallowing a conventional tablet compared with the ODT (P<.001). Patients with dysphagia demonstrated significantly longer total swallow durations (P<.001), a higher number of swallows per tablet (P<.002), and the need for fluid to assist in the clearance of the conventional tablet (P<.001). No significant difference was noted between the 2 tablet preparations in amount of residue or airway compromise during or following the swallow. On a postevaluation survey, patients reported that they preferred the ODT preparation for most of the parameters assessed. Patients with dysphagia frequently complain of trouble swallowing medication. In this study, an ODT formulation provided a method of delivery that required less effort to swallow, did not result in increased levels of airway compromise, and was preferred by dysphagic patients. The ODT medication delivery technology may provide benefit to adults with dysphagia in convenience, compliance, and accuracy of dosing.

Increase of Hemoglobin Concentration After Maximal Apneas in Divers, Skiers, and Untrained Humans

Human splenic contraction occurs both during apnea and maximal exercise, increasing the circulating erythrocyte volume. We investigated the hematological responses to 3 maximal apneas performed by elite apneic divers, elite cross-country skiers, and untrained subjects. Post-apnea hemoglobin concentration had increased in all groups, but especially in divers. The increases disappeared within 10 min of recovery. Apneic duration across apneas also increased the most in divers. Responses in divers could be more pronounced as a result of apnea training.

Speed of spleen volume changes evoked by serial apneas

Diving mammals may enhance dive duration by injecting extra erythrocytes into the circulation by spleen contraction. This mechanism may also be important for apneic duration in humans. We studied the speed and magnitude of spleen volume changes evoked by serial apneas, and the associated changes in hematocrit (Hct) and hemoglobin (Hb) concentration, diving response and apneic duration. Three maximal apneas separated by 2 min rest elicited spleen contraction in all ten subjects, by a mean of 49 (27) ml (18%; P<0.001). During the same period, Hct and Hb rose by 2.2 and 2.4% respectively (P<0.01 and P<0.001), and apneic duration rose by 20 s (22% P<0.05). The mean heart rate reduction of the diving response was 15%, which remained the same throughout the apnea series. While the diving response was completely reversed between the apneas, spleen size was not recovered until 8-9 min after the final apnea corresponding with recovery of Hct and Hb. Thus, although the spleen contraction may be associated with the cardiovascular diving response, it is likely to be triggered by different mechanisms, and it may remain activated between dives spaced by short pauses. The two adjustments may provide a fast, quickly reversed, and a slow, but long-lasting, way of shifting to a diving mode in humans.

Commentary

HIGHLIGHTED TOPICScommentaryPublished Online:01 Apr 2001https://doi.org/10.1152/jappl.2001.90.4.1606MoreSectionsPDF (41 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmail The first Highlighted Topics article in this issue of the Journal of Applied Physiology, “Chemoreflex responses to CO2 before and after an 8-h exposure to hypoxia in humans,” by Fatemian and Robbins (p. 1607–1614), focuses on the effects of hypoxia on the respiratory control system. In a previous study (J Appl Physiol 85: 1922–1928, 1998), these authors demonstrated that an 8-h exposure to hypoxia altered the ventilatory sensitivity to CO2 under hyperoxic conditions. Although hyperoxia is thought to minimize the contribution from the peripheral chemoreflex to the overall ventilatory response, a peripheral component may still persist. The present study employed differences in the speeds of response between the peripheral and central chemoreflexes to separate their contributions to overall chemoreflex sensitivity. The authors extracted these contributions by fitting a dynamic model of the respiratory controller to the ventilatory responses. The intriguing result was that exposure to 8 h of hypoxia induced a significant increase in the rapid component of the ventilatory response to CO2, suggesting that at least part of this modulation of the hyperoxic chemoreflex sensitivity to CO2 is peripheral in origin. This study demonstrates how modeling of the respiratory controller can provide valuable insight regarding the physiological responses to hypoxia, particularly in a complex integrative system.The second Highlighted Topics article in this issue, “Variation in acute hypoxic ventilatory response is linked to mouse chromosome 9,” by Tankersley (p. 1615–1622), also explores the complexity of the hypoxic ventilatory response. In this study, potential candidate genomic regions that might underlie various respiratory traits were examined using two different mouse strains. The investigator performed a very careful segregation analysis, as the two mouse strains and their F1 progeny differed in their ventilatory response to hypoxia. Through controlled back-cross F2 progeny studies, a candidate region on chromosome 9 was identified that appears to affect the hypoxic ventilatory response by influencing tidal volume and inspiratory flow. Potential pitfalls associated with the use of certain markers of the hypoxic ventilatory response were considered by including additional markers in regions of increased log likelihood values. Taken together, this is a carefully designed study that yields novel information about the variations of the ventilatory response to hypoxia. This study is also an important illustration of the invaluable future contributions of physiological genomics in better understanding complex integrative systems.The final Highlighted Topics article in this issue, “Role of spleen emptying in prolonging apneas in humans,” by Schagatay et al. (p. 1623–1629), explores a completely different physiological effect of hypoxia. In this study, it was demonstrated that spleen contraction, resulting in erythrocyte release, is triggered by repeated apneas and conversely that spleen contraction may be a key factor in prolonging apneic duration. Apneas repeated at intervals of less than 10 min are known to lead to prolonged apneic duration in humans; however, the physiological basis is poorly understood. Spleen contraction, as observed in mammals such as horses and seals, leads to elevated hematocrit (Hct) and hemoglobin concentration (Hb) and improved gas transportation in the blood. By studying intact and splenectomized subjects, Schagatay et al. showed that the increase in Hct and Hb, as well as the increase of apneic duration seen in intact subjects, does not occur in healthy splenectomized subjects. The increases in Hct and Hb were reversed within 10 min. The human “diving response,” until now considered to be characterized mainly by heart rate reduction and selective peripheral vasoconstriction, may thus have an additional component, namely spleen contraction. Unlike the neurally mediated cardiovascular diving response, which occurs within seconds and is triggered by apnea and facial cold stimulation, the hematological response requires several apnea episodes to be fully expressed. Therefore, the triggering of spleen contraction could be neurally and/or humorally mediated, and a possible eliciting factor may be the intermittent hypoxia that results from apnea episodes. Like the two other articles featured in this issue, this selected article also exemplifies the complexities of the integrative physiological responses to hypoxia.This article has no references to display. Previous Back to Top Next FiguresReferencesRelatedInformation More from this issue > Volume 90Issue 4April 2001Pages 1606-1606 Copyright & PermissionsCopyright © 2001 the American Physiological Societyhttps://doi.org/10.1152/jappl.2001.90.4.1606History Published online 1 April 2001 Published in print 1 April 2001 PDF download Metrics Downloaded 76 times

Reflex apneic response evoked by laryngeal exposure to wood smoke in rats: neural and chemical mechanisms.

We investigated the neural and chemical mechanisms contributing to the immediate ventilatory responses to laryngeal exposure to wood smoke in anesthetized Sprague-Dawley rats. Five milliliters of wood smoke were delivered into a functionally isolated larynx at a constant flow rate of 1.4 ml/s while the animals breathed spontaneously. Within 1 s after exposure, laryngeal wood smoke consistently triggered an apnea in each of the 42 rats tested. The apneic duration reached 1,636.4 +/- 105.4 (SE) % (n = 42) of the baseline expiratory duration. This apneic response was not affected by denervation of recurrent laryngeal nerves (n = 6) or by removal of smoke particulates (n = 14), but it was totally eliminated by topical application of an anesthetic (n = 8; lidocaine hydrochloride, 8%) to the laryngeal mucosa or by sectioning of the superior laryngeal nerves (n = 42). Furthermore, laryngeal application of a hydroxyl radical scavenger (dimethylthiourea; 500 mg/ml; n = 8) greatly diminished or abolished the smoke-induced apneic response, but it did not affect the apneic response evoked by laryngeal exposure to air saturated with 6% ammonia. These results suggest that the immediate apneic response to laryngeal wood smoke is a reflex resulting from the stimulation of the superior laryngeal afferents by the gas phase of wood smoke and that the stimulation is mediated through a hydroxyl radical mechanism.

Involvement of the fastigial nuclei in vagally mediated respiratory responses.

Previous studies have demonstrated that the cerebellum, especially the fastigial nucleus (FN), is capable of modulating respiratory responses to chemical and mechanical stimuli. Because there is evidence to show projections from vagal afferents to the FN, the goal of this study was to determine the role of the FN in the respiratory reflexes elicited by activation of vagal afferents. Experiments were performed in anesthetized (chloralose), paralyzed, and artificially ventilated cats with an occipital exposure of the cerebellum. Administration of capsaicin (Cap; 5-10 micrograms/kg) via the right external jugular vein at the end of inspiration and application of lung inflation (LI; 10 cmH2O) during inspiration were carried out to stimulate nonmyelinated and myelinated vagal afferents, respectively. The phrenic neurogram was recorded as an index of the respiratory motor output. Control cardiorespiratory variables [expiratory duration (TE), arterial blood pressure] and their immediate responses to stimuli were compared before and after bilateral lesions of the FN. The results showed the following. 1) Cap injection and LI resulted in a dramatic increase in TE (apnea). 2) FN lesions did not significantly alter the control TE; however, the apneic duration induced by Cap injection was prolonged. 3) Neither FN lesions nor cerebellectomy affected the apneic duration that resulted from application of LI. 4) Cold blockade of the vagi (6-8 degrees C) eliminated the respiratory responses elicited by LI but not Cap injection; vagotomy abolished the responses to both stimuli. 5) FN lesions did not change the control ABP or its responses to either LI or Cap injection. It is concluded that the FN is involved in vagally mediated respiratory reflexes elicited by activation of nonmyelinated (C-fiber) vagal afferents.

Role of bronchopulmonary C-fiber afferents in the apneic response to cigarette smoke.

The role of vagal bronchopulmonary C-fiber afferents in eliciting the immediate changes in breathing pattern after acute inhalation of cigarette smoke was assessed with a selective blockade of myelinated vagal afferents (innervating both stretch and irritant receptors) utilizing the method of differential cooling. In 15 of 17 chloralose-anesthetized dogs tested, spontaneous inhalation of cigarette smoke (19.7% avg conc, 500-700 ml vol) reproducibly caused the following immediate responses: apnea, bradycardia, and hypotension. These responses occurred within 1 to 2 breaths of smoke inhalation and were followed by a delayed hyperpnea. The apneic duration reached 326 +/- 33% (SE) (n = 15) of the mean base-line expiratory duration. Differential cold block of both vagi (coolant temperature 8.4 +/- 0.3 degrees C) abolished the reflex apnea induced by a positive-pressure (7-10 cmH2O) lung inflation but did not affect the apneic response to smoke inhalation (345 +/- 35%). The smoke-induced apnea was completely abolished by lowering the coolant temperature to -1.3 +/- 0.2 degrees C (n = 10) or by bilateral vagotomy (n = 5) and returned to the control level after both vagi were rewarmed. Based on these results, we suggest that the immediate apneic response to inhaled cigarette smoke is elicited by a stimulation of vagal C-fiber afferents in the lungs and airways.

Sleep apnea and autonomic cerebrovascular dysfunction.

Changes in common carotid blood flow (CCF) and resistance index (RI), calculated from velocity waveforms by a noninvasive pulsed Doppler technique, were measured during apneic episodes and voluntary breath holding in five sleep apnea patients (SA) and during breath holding in five normal subjects (N). During apneic episodes averaging 27 s, CCF was reduced by 9% and RI increased by 4%, both trends being related to apneic duration. Internal carotid artery measurements in one SA indicated more dramatic changes in blood flow and RI than noted in CCF. During breath holding, CCF decreased significantly in SA but not in N, and RI showed a smaller reduction in SA. These changes in CCF and RI during sleep apnea are similar to those noted in anesthetized dogs where vasomotor waves and associated apneas were induced by elevating intracranial pressure. Previously reported recordings of ventilatory and systemic cardiovascular responses in SA are similar to these recordings in dogs, and it is therefore proposed that vasomotor responses to intermittent cerebral ischemia and hypercapnia may be the principle event in SA and periodic breathing only a secondary consequence of the prevailing autonomic dysfunction.

Hexamethonium aerosol prevents pulmonary reflexes induced by cigarette smoke in dogs

The reflexogenic respiratory responses to spontaneous inhalation of cigarette smoke (500–750 ml, 12–20% concentration) were studied in chloralose anesthetized dogs before and after hexamethonium aerosol, a nicotinic receptor antagonist, was administered into the lungs. In 11 of 13 dogs studied, reproducible responses of either apnea (n = 9) or rapid shallow breathing (n = 2) were elicited immediately after the first or second breath of smoke inhalation: apneic duration reached 398 ± 47% (mean ± SEM) of the mean baseline expiratory duration. Pretreatment with hexamethonium aerosol (3–5 breaths, 10% concentration) completely abolished these immediate changes in breathing patterns, but did not significantly reduce the delayed hyperpnea induced by smoke inhalation. Hexamethonium aerosol alone did not cause any detectable systemic effects. To examine if a bronchoconstrictive effect of nicotine was involved, the response to cigarretet smoke was also studied after bronchodilation was induced by isoproterenol aerosol (15 breaths, 0.5% concentration) in 6 of these dogs. However, neither immediate nor delayed responses to smoke inhalation was significantly affected. These results suggest that: (1) these immediate respiratory responses to smoke inhalation are elicited by a nicotine-induced stimulation of vagal sensory of vagal sensory receptors in the lungs, and (2) bronchoconstriction is not responsible for causing these reflex effects.

Uvulopalatoplasty and obstructive sleep apnea.

We present results of uvulopalatoplasty (UPP) in 22 patients with obstructive sleep apnea who had preoperative and postoperative polysomnograms. Symptomatic improvement in daytime somnolence, snoring, and quality of sleep was reported by 20 patients. After operation, ten of 22 patients had more than a 50% improvement in the apnea index and apnea/sleep percentage, and the number of apneas, apnea index, apnea/sleep percentage, apneic duration, lowest oxygen saturation and longest apneas were significantly better (P less than .05). In the remaining 12 patients there was significant improvement in only the lowest oxygen saturation and longest apneic duration categories. We conclude that UPP is an effective alternative to tracheostomy in the treatment of obstructive sleep apnea; we observed symptomatic improvement in 91%, objective improvement in 46%, and cure in 36% of the patients. Because of the discordance in subjective improvement and objective assessment, we believe all patients should have follow-up polysomnograms after UPP.