Physiology, pathophysiology and (mal)adaptations to chronic apnoeic training: a state-of-the-art review.

Breath-hold diving is an activity that humans have engaged in since antiquity to forage for resources, provide sustenance and to support military campaigns. In modern times, breath-hold diving continues to gain popularity and recognition as both a competitive and recreational sport. The continued progression of world records is somewhat remarkable, particularly given the extreme hypoxaemic and hypercapnic conditions, and hydrostatic pressures these athletes endure. However, there is abundant literature to suggest a large inter-individual variation in the apnoeic capabilities that is thus far not fully understood. In this review, we explore developments in apnoea physiology and delineate the traits and mechanisms that potentially underpin this variation. In addition, we sought to highlight the physiological (mal)adaptations associated with consistent breath-hold training. Breath-hold divers (BHDs) are evidenced to exhibit a more pronounced diving-response than non-divers, while elite BHDs (EBHDs) also display beneficial adaptations in both blood and skeletal muscle. Importantly, these physiological characteristics are documented to be primarily influenced by training-induced stimuli. BHDs are exposed to unique physiological and environmental stressors, and as such possess an ability to withstand acute cerebrovascular and neuronal strains. Whether these characteristics are also a result of training-induced adaptations or genetic predisposition is less certain. Although the long-term effects of regular breath-hold diving activity are yet to be holistically established, preliminary evidence has posed considerations for cognitive, neurological, renal and bone health in BHDs. These areas should be explored further in longitudinal studies to more confidently ascertain the long-term health implications of extreme breath-holding activity.

Eight weeks of static apnea training increases spleen volume but not acute spleen contraction.

Splenic contraction is an important response to acute apnea causing the release of red blood cells into blood circulation. Current literature shows higher spleen volumes and greater spleen contractions in trained apnea divers compared to untrained individuals, but the influence of training is presently unknown. Thirteen subjects daily performed five static apneas for 8 weeks. Before, halfway through and after the apnea training period, subjects performed five maximal breath-holds at the laboratory. Baseline values for and changes in splenic volume and hemoglobin ([Hb]) were assessed. Although baseline spleen volume had increased (from 241 ±â€¯55 mL PRE to 299 ±â€¯51 mL POST training, p = 0.007), the absolute spleen contraction (142 ±â€¯52 mL PRE and 139 ±â€¯34 mL POST training, p = 0.868) and the acute increase in [Hb] remained unchanged. The present study shows that apnea training can increase the size of the spleen but that eight weeks of training is not sufficient to elicit significant training adaptations on the acute response.

Consequences of maternal omega-3 polyunsaturated fatty acid supplementation on respiratory function in rat pups.

KEY POINTS: Incomplete development of the neural circuits that control breathing contributes to respiratory disorders in pre-term infants. Manifestations include respiratory instability, prolonged apnoeas and poor ventilatory responses to stimuli. Based on evidence suggesting that omega-3 polyunsaturated fatty acids (n-3 PUFA) improves brain development, we determined whether n-3 PUFA supplementation (via the maternal diet) improves respiratory function in 10-11-day-old rat pups. n-3 PUFA treatment prolonged apnoea duration but augmented the relative pulmonary surface area and the ventilatory response to hypoxia. During hypoxia, the drop in body temperature measured in treated pups was 1 °C less than in controls. n-3 PUFA treatment also reduced microglia cell density in the brainstem. Although heterogeneous, the results obtained in rat pups constitute a proof of concept that n-3 PUFA supplementation can have positive effects on neonatal respiration. This includes a more sustained hypoxic ventilatory response and a decreased respiratory inhibition during laryngeal chemoreflex. ABSTRACT: Most pre-term infants present respiratory instabilities and apnoeas as a result of incomplete development of the neural circuits that control breathing. Because omega-3 polyunsaturated fatty acids (n-3 PUFA) benefit brain development, we hypothesized that n-3 PUFA supplementation (via the maternal diet) improves respiratory function in rat pups. Pups received n-3 PUFA supplementation from an enriched diet (13 g kg-1 of n-3 PUFA) administered to the mother from birth until the experiments were performed (postnatal days 10-11). Controls received a standard diet (0.3 g kg-1 of n-3 PUFA). Breathing was measured in intact pups at rest and during hypoxia (FiO2  = 0.12; 20 min) using whole body plethysmography. The duration of apnoeas induced by stimulating the laryngeal chemoreflex (LCR) was measured under anaesthesia. Lung morphology was compared between groups. Maternal n-3 PUFA supplementation effectively raised n-3 PUFA levels above control levels both in the blood and brainstem of pups. In intact, resting pups, n-3 PUFA increased the frequency and duration of apnoeas, especially in females. During hypoxia, n-3 PUFA supplemented pups hyperventilated 23% more than controls; their anapyrexic response was 1 °C less than controls. In anaesthetized pups, n-3 PUFA shortened the duration of LCR-induced apnoeas by 32%. The relative pulmonary surface area of n-3 PUFA supplemented pups was 12% higher than controls. Although n-3 PUFA supplementation augments apnoeas, there is no clear evidence of deleterious consequences on these pups. Based on the improved lung architecture and responses to respiratory challenges, this neonatal treatment appears to be beneficial to the offspring. However, further experiments are necessary to establish its overall safety.

Electroconvulsive Therapy Considerations for Transgendered Patients.

As the transgender patient population continues to grow, health care providers will need to become aware of elements unique to the transgender community in order to provide the highest quality of care. Neuromuscular blockade with succinylcholine is routinely administered to patients undergoing electroconvulsive therapy (ECT). Decreased amounts or activity of pseudocholinesterase in serum can lead to prolonged duration of muscle paralysis. Causes of reduced action by pseudocholinesterase include genetically abnormal enzymes, reduced hepatic production, pregnancy, and various drug interactions. Estrogen supplementation taken by transitioning patients may affect the duration of neuromuscular blockade.This is a case of a 32-year-old male-to-female transgender patient with prolonged apnea following ECT treatment for severe, refractory depression. Further investigation revealed the patient was on estrogen therapy as a part of her transition and laboratory testing demonstrated reduced serum pseudocholinesterase activity. Further laboratory testing demonstrated reduced serum pseudocholinesterase activity. Succinylcholine dosing was titrated to an appropriate level to avoid prolonged apnea in subsequent ECT treatments. Physicians and other health care providers are faced with a unique population in the transgender community and must be aware of distinctive circumstances when providing care to this group. Of specific interest, many transitioning and transitioned patients can be on chronic estrogen supplementation. Neuromuscular blockade in those patients require attention from the anesthesiology care team as estrogen compounds may decrease pseudocholinesterase levels and lead to prolonged muscle paralysis from succinylcholine.

Preinduction incentive spirometry versus deep breathing to improve apnea tolerance during induction of anesthesia in patients of abdominal sepsis: A randomized trial.

BACKGROUND: Abdominal sepsis is associated with varied degree of hypoxemia and atelactasis in the lung and can enhance the onset of desaturation of arterial blood during apnea. AIMS: This study looked at methods to improve safety margin of apnea during induction of anesthesia in these high-risk patients. SETTINGS AND DESIGN: It was a randomized, single blind study on adult patients presenting for emergency laparotomy due to peritonitis in a university teaching hospital setting. MATERIALS AND METHODS: In group 1 (IS) (n = 32), three sessions of incentive spirometry (IS) were performed within one hour before induction of anesthesia. In group 2 (DB) (n = 34), patients were subjected to deep breathing sessions in a similar manner. All patients received preoxygenation (100%) by mask for 3 min, followed by rapid-sequence induction of anesthesia using fentanyl, thiopental, and suxamethonium and endotracheal intubation. Patients were subjected to a period of apnea by keeping the end of the endotracheal tube open to air till they developed 95% hemoglobin saturation (SpO 2) by pulse oxymetry. Positive pressure ventilation was resumed at the end. We observed for hemodynamic changes, apnea time, and SpO 2 (100%) recovery time on resuming ventilation. Arterial blood gas samples were taken before intervention, after IS or DB, after preoxygenation, and at the end of apnea. STATISTICAL ANALYSIS USED: One-way analysis of variance (ANOVA), X 2 test, Kaplan-Meier graph, and log-rank tests were applied to compare the two study groups. RESULTS: Oxygenation level in group 1 (265 ± 76.7 mmHg) patients was significantly (P < 0.001) higher than in group 2 (221 ± 61.8 mmHg)at the end of preoxygenation. The apnea time (median: lower bound - upper bound Confidence Interval apnea time) (272:240-279 s) in group 1 (IS) patients was significantly higher P < 0.05) than in group 2 (180:163-209 s) patients. Saturation recovery time (35:34-46 s) in group 1 (IS) patients was also quicker than in group 2 patients (48:44-58 s). CONCLUSIONS: IS in the preoperative period is superior to deep breathing sessions for improving apnea tolerance during induction of anesthesia in abdominal sepsis patients.

Perivagal antagonist treatment in rats selectively blocks the reflex and afferent responses of vagal lung C fibers to intravenous agonists.

The terminals of vagal lung C fibers (VLCFs) express various types of pharmacological receptors that are important to the elicitation of airway reflexes and the development of airway hypersensitivity. We investigated the blockade of the reflex and afferent responses of VLCFs to intravenous injections of agonists using perivagal treatment with antagonists (PAT) targeting the transient receptor potential vanilloid 1, P2X, and 5-HT(3) receptors in anesthetized rats. Blockading these responses via perivagal capsaicin treatment (PCT), which blocks the neural conduction of C fibers, was also studied. We used capsaicin, α,ß-methylene-ATP, and phenylbiguanide as the agonists, and capsazepine, iso-pyridoxalphosphate-6-azophenyl-2',5'-disulfonate, and tropisetron as the antagonists of transient receptor potential vanilloid 1, P2X, and 5-HT(3) receptors, respectively. We found that each of the PATs abolished the VLCF-mediated reflex apnea evoked by the corresponding agonist, while having no effect on the response to other agonists. Perivagal vehicle treatment failed to produce any such blockade. These blockades had partially recovered at 3 h after removal of the PATs. In contrast, PCT abolished the reflex apneic response to all three agonists. Both PATs and PCT did not affect the myelinated afferent-mediated apneic response to lung inflation. Consistently, our electrophysiological studies revealed that each of the PATs prevented the VLCF responses to the corresponding agonist, but not to any other agonist. PCT inevitably prevented the VLCF responses to all three agonists. Thus these PATs selectively blocked the stimulatory action of corresponding agonists on the VLCF terminals via mechanisms that are distinct from those of PCT. PAT may become a novel intervention for studying the pharmacological modulation of VLCFs.

Effect of respiration on catheter-tissue contact force during ablation of atrial arrhythmias.

BACKGROUND: Catheter-tissue contact is important for effective lesion creation. OBJECTIVE: To assess the effect of respiration on contact force (CF) during atrial fibrillation and cavotricuspid isthmus (CTI)-dependent atrial flutter ablation. METHODS: Patients undergoing CTI ablation alone (n = 15) and pulmonary vein (PV) isolation alone (n = 12) under general anesthesia were recruited. Lesions were delivered under ventilation (30 seconds) alternating with lesions delivered under apnea (30 seconds) at an adjacent anatomical site at CTI or PV antra. The average force (F(av)), force-time integral (FTI), and force variability were measured in a region-specific manner by using a novel CF-sensing ablation catheter. Operators were blinded to CF data. RESULTS: F(av) and FTI were higher with apnea than with ventilation in all CTI and PV segments (P <.05), an effect attributed to drop in CF with each respiratory swing, resulting in greater force variability during ventilation (P <.05). Low FTI lesions (<500 g) were strongly associated with longer ablation time to achieve bidirectional CTI block (r(2) = .81; P <.001), left PVI (r(2) = .65; P = .009), and right PVI (r(2) = .41; P = .05). Sites with transient CTI block were associated with lower F(av) and FTI than were sites with persistent CTI block (P <.05). Sites of acute PV reconnection were associated with lower F(av) and FTI compared with non-reconnected sites (P <.001). CONCLUSIONS: Catheter-tissue CF is critically influenced by respiration; greater CF is observed with ablation during apnea. Poor CF is implicated in longer ablation time to achieve CTI block or PV isolation and in acute reconnection.

Characteristics of the respiratory mechanical and muscle function of competitive breath-hold divers.

Competitive breath-hold divers (BHD) employ glossopharyngeal insufflation (GI) to increase intrapulmonary oxygen stores and prevent the lungs from dangerous compressions at great depths. Glossopharyngeal insufflation is associated with inflation of the lungs beyond total lung capacity (TLC). It is currently unknown whether GI transiently over-distends the lungs or adversely affects lung elastic properties in the long-term. Resting lung function, ventilatory drive, muscle strength, and lung compliance were measured in eight BHD who performed GI since 5.5 (range 2-6) years on average, eight scuba divers, and eight control subjects. In five BHD subsequent measures of static lung compliance (Cstat) were obtained after 1 and 3 min following GI. Breath-hold divers had higher than predicted ventilatory flows and volumes and did not differ from control groups with regard to gas transfer, inspiratory muscle strength, and lung compliance. A blunted response to CO2 was obtained in BHD as compared to control groups. Upon GI there was an increase in mean vital capacity (VCGI) by 1.75 +/- 0.85 (SD) L compared to baseline (p < 0.001). In five BHD Cstat raised from 3.7 (range 2.9-6.8) L/kPa at baseline to 8.1 (range 3.4-21.2) L/kPa after maximal GI and thereafter gradually decreased to 5.6 (range 3.3-8.1) L/kPa after 1 min and 4.2 (range 2.7-6.6) L/kPa after 3 min (p < 0.01). We conclude that in experienced BHD there is a transient alteration in lung elastic recoil. Resting lung function did not reveal a pattern indicative of altered lung ventilatory or muscle function.

Laryngeal apnea in rat pups: effects of age and body temperature.

In neonatal mammals of many species, including human infants, apnea and other reflex responses frequently arise from stimulation of laryngeal receptors by ingested or regurgitated liquids. These reflexes, mediated by afferents in the superior laryngeal nerves (SLNs), are collectively known as the laryngeal chemoreflex (LCR) and are suspected to be responsible for some cases of the sudden infant death syndrome (SIDS). The LCR is strongly enhanced by mild increases in body temperature in decerebrate piglets, a finding that is of interest because SIDS victims are often found in overheated environments. Because of the experimental advantages of studying reflex development and mechanisms in neonatal rodents, we have developed methods for eliciting laryngeal apnea in anesthetized rat pups and have examined the influence of mild hyperthermia in animals ranging in age from 3 to 21 days. We found that apnea and respiratory disruption, elicited either by intralaryngeal water or by electrical stimulation of the SLN, occurred at all ages studied. Raising body temperature by 2-3 degrees C prolonged the respiratory disturbance in response to either stimulus. This effect of hyperthermia was prominent in the youngest animals and diminished with age. We conclude that many studies of the LCR restricted to larger neonatal animals in the past can be performed in infant rodents using appropriate methods. Moreover, the developmental changes in the LCR and in the thermal modulation of the LCR seem to follow different temporal profiles, implying that distinct neurophysiological processes may mediate the LCR and thermal prolongation of the LCR.

Effects of fasting and carbohydrate consumption on voluntary resting apnea duration.

Breath holding is normally terminated due to the urge to breathe, mainly caused by the increasing carbon dioxide level. It was recently shown that a combination of 18 h of carbohydrate-free diet and prolonged exercise prior to breath holding lowered the respiratory exchange ratio (RER) and end-expiratory PO(2 )at maximal breath-hold break-point (MBP). Current hypothesis: fasting will result in longer breath-hold duration than will fasting followed by carbohydrate intake. It was also hypothesized that breath-holds during carbohydrate supplementation would be ended at a higher alveolar PO(2). Ten male non-divers performed multiple breath-holds either to the first diaphragmatic contraction (PBP), or to MBP. The breath-holds were performed during normal diet (control; C), twice during fasting (F14 h, F18 h), followed by post fasting carbohydrate consumption (PFCC) and a repetition of the breath-hold testing 1-2 h after ingestion of carbohydrates. Duration, RER, end-tidal PO(2) and PCO(2), SaO(2) and blood glucose were determined. RER and blood glucose increased after PFCC compared with fasting and control conditions (P < 0.001). PBP breath-hold duration increased from 129 +/- 34 s at C to 148 +/- 33 s at F18 h, and was reduced during PFCC to 122 +/- 30 s (P < 0.001). End-tidal PO(2) was higher at PFCC compared to F18 h (10.4 +/- 1.2 vs. 9.5 +/- 1.2 kPa at PBP, P < 0.05). Similar trends in breath-hold duration and physiology were seen in breath-holds that were terminated at MBP. Dietary restriction can affect breath-hold duration. The lower O(2) level at breakpoint during fasting suggests that breath holding may be less safe during fasting; the increased risk may be mitigated by ingestion of carbohydrates before breath holding.

Injury severity determines Purkinje cell loss and microglial activation in the cerebellum after cortical contusion injury.

Clinical evidence suggests that the cerebellum is damaged after traumatic brain injury (TBI) and experimental studies have validated these observations. We have previously shown cerebellar vulnerability, as demonstrated by Purkinje cell loss and microglial activation, after fluid percussion brain injury. In this study, we examine the effect of graded controlled cortical impact (CCI) injury on the cerebellum in the context of physiologic and anatomical parameters that have been shown by others to be sensitive to injury severity. Adult male rats received mild, moderate, or severe CCI and were euthanized 7 days later. We first validated the severity of the initial injury using physiologic criteria, including apnea and blood pressure, during the immediate postinjury period. Increasing injury severity was associated with an increased incidence of apnea and higher mortality. Severe injury also induced transient hypertension followed by hypotension, while lower grade injuries produced an immediate and sustained hypotension. We next evaluated the pattern of subcortical neuronal loss in response to graded injuries. There was significant neuronal loss in the ipsilateral cortex, hippocampal CA2/CA3, and laterodorsal thalamus that was injury severity-dependent and that paralleled microglial activation. Similarly, there was a distinctive pattern of Purkinje cell loss and microglial activation in the cerebellar vermis that varied with injury severity. Together, these findings emphasize the vulnerability of the cerebellum to TBI. That a selective pattern of Purkinje cell loss occurs regardless of the type of injury suggests a generalized response that is a likely determinant of recovery and a target for therapeutic intervention.

Consequences of capsaicin treatment on pulmonary vagal reflexes and chemoreceptor activity in lambs.

The aim of this study was to test the hypothesis that capsaicin treatment in lambs selectively inhibits bronchopulmonary C-fiber function but does not alter other vagal pulmonary receptor functions or peripheral and central chemoreceptor functions. Eleven lambs were randomized to receive a subcutaneous injection of either 25 mg/kg capsaicin (6 lambs) or solvent (5 lambs) under general anesthesia. Capsaicin-treated lambs did not demonstrate the classical ventilatory response consistently observed in response to capsaicin bolus intravenous injection in control lambs. Moreover, the ventilatory responses to stimulation of the rapidly adapting pulmonary stretch receptors (intratracheal water instillation) and slowly adapting pulmonary stretch receptors (Hering-Breuer inflation reflex) were similar in both groups of lambs. Finally, the ventilatory responses to various stimuli and depressants of carotid body activity and to central chemoreceptor stimulation (CO(2) rebreathing) were identical in control and capsaicin-treated lambs. We conclude that 25 mg/kg capsaicin treatment in lambs selectively inhibits bronchopulmonary C-fiber function without significantly affecting the other vagal pulmonary receptor functions or that of peripheral and central chemoreceptors.

The preoptic area in the hypothalamus is the source of the additional respiratory drive at raised body temperature in anaesthetised rats.

In mammals that use the ventilatory system as the principal means of increasing heat loss, raising body temperature causes the adoption of a specialised breathing pattern known as panting and this is mediated by the thermoregulatory system in the preoptic area of the hypothalamus. In these species an additional respiratory drive is also present at raised body temperature, since breathing can reappear at low Pa,CO2 levels, when stimulation of chemoreceptors is minimal. It is not known whether the preoptic area is also the source of this additional drive. Rats do not pant but do possess this additional respiratory drive at raised body temperatures. We have therefore tested whether the preoptic area of the hypothalamus is the source of this additional respiratory drive in rats. Urethane anaesthesia and hyperoxia were used in eleven rats to minimise behavioural and chemical drives to breathe. The presence of the additional respiratory drive was indicated if rhythmic diaphragmatic EMG activity reappeared during hypocapnia (a mean Pa,CO2 level of 21+/-2 mm Hg, n = 11), induced by mechanical ventilation. The additional respiratory drive was absent at normal body temperature (37¿C). When the temperature of the whole body was raised using an external source of radiant heat, the additional respiratory drive appeared at 40.6+/-0.5 degrees C (n = 3). In two further rats this drive was induced at normal body temperature by localised warming in the preoptic area of the intact hypothalamus. The additional respiratory drive appeared at similar temperatures to those in control rats in three rats following isolation of the hypothalamus from more rostral areas of the brain. In contrast, the additional respiratory drive failed to appear at these temperatures in three rats after isolating the hypothalamus from the caudal brainstem, by sectioning pathways medial to the medial forebrain bundle. Since the preoptic area is known to contain thermoreceptors and to receive afferents from peripheral thermoreceptors, the results show that this area is also the source of the additional respiratory drive at raised body temperature in anaesthetised rats.

Factors related to the efficacy of an adjustable oral appliance for the treatment of obstructive sleep apnea.

AIM: The purpose of this study was to investigate whether any physiological or cephalometric parameters could be used to predict the efficacy of the Klearway oral appliance (OA) for the treatment of obstructive sleep apnea (OSA). METHODS: Forty-two male and 5 female patients with OSA were recruited on the basis of baseline polysomnography with a documented Apnea and Hypopnea Index (AHI) > 15 per hour. Repeat polysomnography was performed with the appliance in place. Baseline cephalometry was performed for each patient. Subjects were divided into 3 groups on the basis of the degree of change in AHI with OA therapy: good response (> 75% decrease in AHI), moderate response (25% to 75% decrease range in AHI), and poor response (< 25% decrease in AHI). RESULTS: Patients with a good response were younger and had smaller upper airways. A stepwise regression analysis revealed that a better treatment response with the Klearway appliance was obtained in patients who were younger and had a lower body mass index, a longer maxilla, a smaller oropharynx, a smaller overjet, less erupted maxillary molars, and larger ratio of vertical airway length to the cross-sectional area of the soft palate.

Tetrodotoxin infusion: nonventilatory effects and role in toxicity models.

OBJECTIVES: To determine the cardiovascular, autonomic, and neuromuscular effects of an IV infusion of tetrodotoxin (TTX) when ventilation is supported. METHODS: TTX was infused in 18 anesthetized beagles during conventional mechanical ventilation. TTX infusion continued at a rate of 9.3 micrograms/kg/hr until apnea occurred with 1 minute of ventilator disconnection. Measurements included intravascular pressures, heart rate (HR), cardiac output, blood gases, displacements of the rib cage and abdomen, O2 delivery, and responses to train-of-four and tetanic peripheral nerve stimulation. Results are expressed as mean +/- SD. RESULTS: During TTX infusion, all the dogs had discoordinate movements of the rib cage, abdomen, and limbs. Vomiting, urination, defecation, and increased salivation occurred. Nicotinic and muscarinic effects, neuromuscular blockade, and cardiovascular depression were produced by TTX. Apnea occurred in 72.0 +/- 17.0 minutes when a total of 119.0 +/- 17.4 micrograms of TTX was infused. At apnea, decreases in arterial pressure, cardiac index, HR, O2 delivery, and systemic vascular resistance occurred, while pulmonary artery pressure and pulmonary vascular resistance increased. Loss of response to tetanic stimulation was closely correlated with the dose of TTX that produced apnea. CONCLUSION: The clinical symptoms and signs of TTX poisoning are similar to those of anticholinesterase poisons, and TTX dosing as described by this model may serve as a surrogate for organophosphorus poisoning. The model may be useful to determine optimum therapies for TTX poisoning and, since TTX prevents sodium influx into cells, to investigate enhanced survival in animals suffering from ischemia.

The effect of the presentation of visual and auditory stimuli on the breathing patterns of two girls with Rett syndrome.

The respiration patterns of individuals with Rett syndrome are known to be dysrhythmic during wakefulness, suggesting cortical involvement of brainstem respiratory control. To investigate this involvement further, the waking breathing patterns of two girls with Rett syndrome were analysed during three phases: a quiet phase, and two phases during which visual and auditory stimuli were presented in controlled intervals. Differences were noted between the two subjects' respiratory patterns in both the quiet and stimulation phases. The usual quiet respiration patterns became more dysrhythmic for both girls during stimulation, with shortened breathing cycles and lengthened apnoeic pauses for the one subject, and increased numbers of apnoeic pauses and shallower breaths for the other. These results suggest that the cyclical brainstem control of breathing patterns in Rett syndrome may be subject to disruption as a result of cortical influences, including arousal subsequent to the engagement of attention.

Improved recovery from laryngeal-stimulation-induced apnea by alpha-adrenergic blockade in adult rabbits.

The apnea triggered by laryngeal stimulation (LS) is associated with a redistribution of blood flow towards the heart and the brain that depends upon peripheral vasoconstriction. The circulatory component of the response to LS has been shown to be reduced following injection of large dose of beta-adrenergic agonist that more intriguingly blunted the ventilatory response as well. To test whether the reduction of LS-induced apnea could be related to the decreased magnitude of the peripheral vasoconstruction, the effects of the alpha-adrenergic antagonist urapidil on the ventilatory and blood pressure responses to LS were studied in 6 adult rabbits. alpha-Adrenergic blockade reduced both the rise in blood pressure and the magnitude of hypopnea induced by LS. These results suggest that the circulatory component of the laryngeal chemoreflex, i.e. the peripheral vasoconstruction, contributes to the magnitude of the ventilatory depression.

Modification of conditioned apneas in rats: evidence for cortical involvement.

Apneic patterns in breathing can be classically conditioned in rats by brief neonatal exposures to hypoxia, noise, and petting during sleep (A. J. Thomas, W. Austin, L. Friedman, and K. P. Strohl, J. Appl. Physiol. 73: 1530-1536, 1992); thus animals may acquire apneic patterns by exposure to not only respiratory but also nonrespiratory stimuli. We hypothesized that conditioned apneas in these animals can be reduced or abolished by presentation of counterconditioning stimuli, which would prevent the respiratory controller from being influenced by nonrespiratory stimuli and affecting breathing rhythmicity. In five female rats conditioned during neonatal life to exhibit apneic breathing during adulthood and in five female unconditioned control rats, the effect of a brief quiet repetitive auditory stimulus (white noise, 50 Hz, 30 dB) presented for periods of 20 min on and 20 min off was assessed. In conditioned apneic rats, white noise reduced the frequencies of apneas by approximately 79% (P < 0.01) but did not alter the number of apneas in unconditioned control rats. In either group, white noise had no effect on the number of apneas preceded by a sigh. In a second experiment, the effect of Equithesin anesthetic was examined in five female conditioned apneic rats. In contrast to the white noise effect, not only apneic breathing but also apneas preceded by a sign were completely abolished by anesthesia (P < 0.0001). These findings suggest a role for counterconditioning and cortical influences on respiratory rhythm in the adult mammal.

Transesophageal electroventilation. Optimization and improvement.

For electroventilation, short duration pulse trains (0.1 ms) were applied between two axillary pads (transchest) and compared with transesophageal electroventilation where pulses passed between the same pads to an esophageal electrode in apneic, pentobarbitone-anesthetized pigs. Significantly greater tidal volumes were produced by transesophageal electroventilation in comparison with transchest. As measured by maintained tidal volumes, duration of inspiratory air flow, peak flow, percentage hemoglobin oxygen saturation (%SaO2), and end tidal carbon dioxide concentration (ETCO2), the optimal requirements for transesophageal electroventilation were pulse frequency 40 Hz, 0.7 s duration pulses, at 60 to 100 V, pulse width 0.1 ms, with the esophageal electrode proximal to the gastroesophageal junction without producing brachial plexus stimulation. The efficiency of transesophageal electroventilation falls off rapidly following ventricular fibrillation. Thus, the application of this technique would be in respiratory arrest with maintained circulation, eg, in drug-induced respiratory depression, severe smoke inhalation, severe emphysema, high cervical cord lesion, and weaning from prolonged mechanical ventilation.