Basal Ventilation Research Articles

Long-term intramuscular electrical activation of the phrenic nerve: efficacy as a ventilatory prosthesis.

The efficacy of a system for long-term intramuscular activation of the phrenic nerve as a ventilatory prosthesis was evaluated in seven dogs. (The safety and reliability of this system is addressed in a companion paper.) Five dogs underwent chronic bilateral intramuscular diaphragm stimulation (IDS) for 61 to 183 days at stimulus parameters selected to evoke at least 120% of the animal's basal ventilation. Two dogs maintained as controls did not undergo chronic stimulation. The ability of IDS to provide long-term ventilation without diaphragm fatigue was evaluated in terms of the ventilatory capacity of IDS, the effects of chronic IDS on diaphragm contractile properties, and the phrenic nerve recruitment properties of chronic IDS electrodes. Hemidiaphragms with electrodes placed within 2 cm of the phrenic nerve trunk could be completely activated by 25 mA pulses having a 100 microsecond pulse width. The tidal volume evoked by IDS in this study was 167% (+/- 48 s.d.) of that required for full-time basal ventilation without diaphragm fatigue. Evoked tidal volume increased after 8 to 9 weeks of chronic IDS for stimulus pulse intervals longer than 50 mS. Electrode recruitment properties were stable for both active and passive implanted electrodes. We conclude from these studies that with properly placed electrodes IDS is capable of providing reliable full-time ventilatory support without fatiguing the diaphragm.

Maintenance of ventilatory control by CO2 in the rat during growth and aging

The long-term adjustment of ventilation and blood gases throughout life was studied in halothane anaesthetized male Wistar rats of various ages (1.5-20 months). Basal metabolic rate (O2 consumption, CO2 production), ventilation and ventilatory response to CO2 changed significantly during growth and aging, whereas arterial partial pressure of CO2 (PaCO2) and pH remained unchanged. Changes in the rate of CO2 production were associated with proportional changes in alveolar ventilation and in the sensitivity of the ventilatory control system to a CO2 stimulus at various ages. Ventilatory equivalent (ratio of alveolar ventilation to CO2 production) and the slope of the CO2/ventilation response line normalized for CO2 production were maintained constant throughout life, despite significant changes in the breathing pattern. These findings suggest that PaCO2 homeostasis is maintained by ventilatory regulation coupled tightly with CO2 production throughout life.

Local application of somatostatin in the rat ventrolateral brain medulla induces apnea

Local injections of the tetradecapeptide somatostatin (SOM) into the brain stem region were performed in anesthetized and decerebrate rats. SOM administration (0.6-1.8 nmol) into the nucleus paragigantocellularis and the nucleus reticularis lateralis of the ventrolateral medulla oblongata induced ventilatory depression and apnea. The occurrence of apnea was dose dependent and attributed to the anesthetic depth, and it was seen within 60-240 s after injection. In anesthetized rats the apnea was seen as a termination or a continuous decrease in tidal volume while respiratory frequency remained unaltered. SOM-induced apnea was caused by depression of central inspiratory drive. SOM injections into the dorsal medulla were ineffective in eliciting apnea, although a ventilatory depression but no apnea was induced in the awake unanesthetized state. In addition to its effect on basal ventilation, SOM administration in the ventrolateral medulla resulted in a blunted ventilatory response to hypoxic and hypercapnic stimuli in anesthetized rats. We conclude that SOM has potent inhibitory effects on respiration that are specifically located in the nucleus paragigantocellularis and the nucleus reticularis lateralis.

Local effects of substance P on respiratory regulation in the rat medulla oblongata

The effect of substance P (SP) and the SP antagonist [D-Pro2,D-Trp7,9]-SP on basal ventilation was investigated in halothane-anesthetized rats. Microinjections of SP (0.4-1.5 nmol) into the ventrolateral medulla oblongata (VLM), (nuclei gigantocellularis, facialis, ambiguus, and reticularis lateralis) or into the dorsomedial medulla oblongata (DM, nucleus tractus solitarius) and its ventral surroundings dose dependently increased tidal volume (VT) and/or minute ventilation. In sensitive areas, the ventilatory stimulation was initiated within minutes, peaked around 8-10 min, and slowly returned to normal over 30-45 min after the injection. In the VLM sites, the increase in VT was generally accompanied by a decrease in respiratory frequency (f), whereas in the DM, f increased in parallel with VT. Furthermore, within the VLM, the respiratory response patterns differed with the definite location of the SP injection. A shortening of inspiratory time was observed in the ventromedial part, the ventrolateral portion of the nucleus paragigantocellularis and ventral to the nucleus facialis. In contrast, a lengthening of expiratory time was seen when SP was injected or applied more laterally along the ventral portion of nucleus facialis and near or directly on the ventral medullary surface. Application of [D-Pro2, D-Trp7,9]SP before or after SP completely antagonized the excitatory effects of SP on ventilation. The SP antagonist administered into the VLM decreased the ventilatory response to hypoxic breathing but caused no change during hyperoxic conditions.

VENTILATORY RESPONSE TO CARBON DIOXIDE DURING EXTRADURAL ANAESTHESIA WITH LIGNOCAINE AND FENTANYL

Twenty-seven patients undergoing extracorporeal shock-wave lithotripsy or knee arthroscopy received extradural anaesthesia with 2% lignocaine plus adrenaline 1 in 200,000. They were allocated randomly to three groups, one receiving no fentanyl (n = 6), the two others receiving fentanyl 50 micrograms either extradurally (n = 15) or i.v. (n = 6). Three tests of sensitivity to carbon dioxide (Read's method) were performed successively on each patient: before operation and at 1 and 2 h after the extradural injection. Whereas lignocaine and adrenaline alone had no significant effects on basal ventilation and the ventilatory response to carbon dioxide, extradural fentanyl caused a slight reduction in resting ventilatory rate and ventilation at 1 and 2 h with no change in resting end-tidal carbon dioxide concentration. In addition, the slope of the ventilatory response to carbon dioxide was reduced slightly at 1 h and ventilation at end-tidal PCO2 of 7.3 kPa was reduced also at 1 and 2 h. Conversely, the same dose of fentanyl i.v. had lesser and shorter effects on ventilation at rest and during carbon dioxide rebreathing. Our results show that fentanyl 50 micrograms given extradurally caused slight ventilatory depression which is probably clinically unimportant.

Substance P influences basal ventilation and ventilatory reflexes in the ventrolateral medulla oblongata of the rat

Substance P influences basal ventilation and ventilatory reflexes in the ventrolateral medulla oblongata of the rat

Effects of digoxin and acetyl-digitoxin on basal and CO2-stimulated ventilation.

Eight healthy volunteers were studied to ascertain the effect of digoxin and the relatively more lipophylic cardiac glycoside, acetyl-digitoxin on ventilation. Baseline ventilation as well as the response to the inspiration of 2.2% and 4.8% carbon dioxide were assessed. Digoxin produced a depression of minute volume and oxygen consumption whereas acetyl-digitoxin produced the opposite effect. This could be the result of a relatively greater vagomimetic effect with digoxin and a greater symphatomimetic effect with acetyl-digitoxin. These findings might have clinical implications in cardiac patients who have pulmonary disease.

Central respiratory and cardiovascular effects in the rat of some putative neurotransmitter amino acids.

Respiratory performance was studied in halothane anesthetized rats after intracerebroventricular (i.c.v.) injection of beta-alanine, taurine or glycine (0.01--1 mg). The amino acids induced a marked decrease in both respiratory frequency (f) and tidal volume (VT), which was immediate and longlasting. The respiratory depressant action of glycine could readily be reversed by strychnine, a glycine antagonist. Measurement of respiratory time intervals, inspiratory time (TI), expiratory time (TE) and total cycle duration (TTOT), after administration of the putative neurotransmitter amino acids revealed that the effects on f were due to prolongation of the duration of expiration. The duration of inspiration was principally unaltered, but mean inspiratory flow (VT/TI) and respiratory timing (TI/TTOT) decreased. In experiments employing the occluded breath technique, P0.1 was reduced in the same magnitude as the mean inspiratory flow (VT/TI). The results also showed a change in central (bulbopontine) setting for TE, while the setting to TI was unaltered. An inert amino acid, valine, which was administered i.c.v. in the same doses, had no effects on respiratory parameters. Apart from the effects on basal ventilation of beta-alanine, taurine and glycine, the CO2 induced respiratory response was blunted. These three amino acids also depressed heart rate and mean arterial pressure. Although relatively high doses were used to induce the respiratory effects, it may be hypothetised that the putative neurotransmitters beta-alanine, taurine and glycine may have a physiological role in the central regulation of breathing.

Effects of shape changes of the chest wall on distribution of inspired gas.

The configuration of the chest wall was measured with magnetometers applied at various levels of the rib cage and abdomen. Distribution of ventilation was measured in the supine position using a bolus of xenon-133 inspired at a flow rate of 0.1 liter per sec. Measurements were made during spontaneous breathing, during augmented abdominal breathing, after manual lateral compression of the lower part of the rib cage followed by a predominantly abdominal motion, and after similar compression followed only by increase of the lateral basal rib cage diameter. Basal compression gave a decrease in lateral diameter of 5 to 7 per cent. During spontaneous breathing, apical ventilation exceeded basal ventilation. During an inspiration with an increase of the lateral basal rib cage diameter after compression, the ventilation of basal peripheral regions increased somewhat. No other systematic effects of the changes in either chest wall diameter at the start of inspiration or the type of inspiration were found on distribution of inspired boli.

Inspiratory flow rate and ventilation distribution in normal subjects and in patients with simple chronic bronchitis.

1. Seated subjects stopped ventilation briefly at end expiration while a 5 ml bolus of 133Xe was injected close to the mouth. They then inspired air at different flow rates and the distribution of radioactivity in the lungs was measured with a scanning technique during a period of breath-holding at maximal inspiration. 2. In five normal subjects the dependent zones received a greater fraction of the 133Xe bolus than the apex during slow inspirations, but apical distribution exceeded basal for fast inspirations. The volume history of the lungs before the bolus injection had no effect on the slow/fast difference in four out of five subjects. 3. In five patients with clinical bronchitis but normal forced expired volume, dependent zone ventilation was much reduced on a slow inspiration compared with normals, but at fast flow rates the distribution was normal. 4. Insofar as the bolus in the fast inspiration was distributed according to regional airway conductances, these results suggest that in normal subjects differences in airway resistance exist between the upper and lower zones of the upright lung. An early abnormality in bronchitis appears to be a reduction of compliance in the dependent zones, as judged from the decrease in basal ventilation on a slow inspiration.

Ventilatory response of SCUBA divers to CO2 inhalations.

A study was made to compare the minute ventilatory response of SCUBA (self-contained underwater breathing apparatus) divers and nondivers to CO2 inhalations under ambient conditions at rest and during light exercise. Furthermore, other respiratory parameters and lung function measurements were made for comparison with published reports of apneustic divers. The SCUBA diver and the nondiver in this study were similar with respect to basal ventilation, divisions of the lung volume, and spirographic functions. There was some tendency for the SCUBA divers to have a slightly diminished ventilatory response to CO2 inhalations during rest compared to the nondivers, but this was not a clear-cut phenomena. Furthermore, the ventilatory response to CO2 bore no relation to time spent in diving. The respiratory adaptations which have been described in the literature for the apneustic diver under ambient conditions were not present in the SCUBA diver. Note: (With the Technical Assistance of Christa McReynolds, Mabel Pearson and Roy Engstrom) Submitted on June 3, 1960

Psychophysiological Relations in Cases with Head Injuries

Respiratory functions under basal conditions and during work, muscular tension and heart rate during endurance to pain and fatigue have been correlated with tests of intelligence and personality in five groups of patients. These consisted of 16 cases with brain disease, 29 cases with recent head injuries, 29 cases of post-traumatic syndromes and signs of brain damage, 28 cases of post-traumatic syndromes without signs of brain damage, and 30 cases with psychoneuroses. In addition, 15 normal controls were subjected to some of these tests. The post-traumatic syndromes without signs of brain damage resembled the psychoneuroses more than the post-traumatic cases with evidence of brain lesions. The cases with recent head injuries were in many respects the most normal of all the patients studied. Basal ventilation volume and tidal air increased proportionately with rising neurotic scores in the Minnesota Multiphasic Personality Inventory. The higher the basal ventilation volume, the smaller was the subsequent increase during work. Irregularity of breathing was measured by a new scoring method, which revealed that individuals with neurotic tendencies breathe irregularly, especially during work. Metabolism under basal conditions and during work was higher in cases with signs of brain damage than in cases without evidence of a lesion. The more intelligent subjects were apt to use less oxygen than patients with average or sub average intelligence. During examination of endurance to strain (work of the hand during complete ischemia), all the cases with head injuries showed a smaller rise in heart rate than either cases with brain disease, psychoneuroses, or normal controls. Return of the heart rate to the initial level following exercise was delayed in the acute head injuries. Muscular tension was greatest in cases with brain disease and smallest in the normal controls. Endurance to strain was smallest in the psychoneuroses. In conclusion, it can be said that there exists an antagonism between presence of brain damage and psychoneuroses. The more marked one component, the less obvious the other becomes. Cases with posttraumatic syndromes usually show presence of both components but with marked prevalence of the neurotic aspects.