Effects of graded focal cold block in rostral areas of the medulla.

Unilateral focal cold blocks (20 degrees C) in structures located ventrolaterally in rostral medulla consistently caused apnoea or deep depression of inspiratory motor output. The inhibitory effect could be correlated with the cooling temperature. Apnoeic response occurred either with complete absence of any inspiratory activity or combined with low level tonic inspiratory motor activity ('tonic apnoea'). The appearance of apnoea was CO2-independent, whereas the tonic component of the latter increased with increasing levels of PCO2. The results suggest that the structures in the deep, ventro-lateral aspect of rostral medulla, from which apnoea can be induced, correspond partly to the nucleus paragigantocellularis lateralis (nPGL) and the nucleus preolivaris. These structures appear to be relevant for the drive inputs necessary for respiratory rhythmogenesis. Unilateral focal cooling in the rostral medulla, including the 'Bötzinger Complex', caused increments in respiratory rate both in vagotomized and non-vagotomized animals. The increase in respiratory rate in response to cooling in the region of the 'Bötzinger Complex' was combined with either an enhancement or some depression of respiratory motor output. This area in the rostral part of the ventral respiratory group (VRG) seems not to be crucial for respiratory rhythmogenesis, but to play a role in determining both the intensity and timing of the respiratory activity. All effects of unilateral cold block were bilaterally symmetrical.

Effects of graded focal cold block in the solitary and para-ambigual regions of the medulla in the cat.

Unilateral focal cold blocks in the region of the nucleus tractus solitarius and the dorsal respiratory group of neurons, DRG, of anaesthetized cats consistently caused apneustic-type breathing. There was no concomitant change in the initial rate of rise of inspiratory activity. The apneustic prolongation of inspiratory duration, TI, was most pronounced in, but was not confined to, the DRG. The apneustic effects were more marked after vagotomy. In cats with intact vagus nerves being given artificial ventilation, focal cooling at certain sites of the DRG region could produce 'unlocking' of the respiratory rhythm from that of the respiratory pump. At other sites in this region, focal cooling could selectively block the effects of the inspiration-facilitating reflex induced by deflation without blocking the inspiration-inhibiting Hering-Breuer reflex. Unilateral focal cold blocks in the region of the intermediate part of the ventral respiratory group of neurons, VRG, generally caused depression of the rate of rise of inspiratory activity, but almost never apneustic effects. All effects of unilateral focal cooling both in the DRG and VRG were bilaterally symmetrical. No systematic differences between the effects on phrenic and external intercostal inspiratory activity were found in response to focal cooling either of the DRG or VRG suggesting that differential control of phrenic and external intercostal motoneurons is not exerted mainly at the level of these medullary structures. The results suggest that the DRG and VRG areas exert somewhat different effects on the respiratory pattern: DRG appears to be more concerned with integration of vagal and other inputs contributing to the inspiratory off-switch mechanisms which, however, are not confined only to the DRG. The VRG inspiratory mechanisms, on the other hand, appear to be more involved in the gain control of the inspiratory output intensity.

Release of expiratory muscle activity by graded focal cold block in the medulla.

Disinhibition or 'release' of expiratory muscle activity in response to focal cooling of various medullary structures was of two kinds: (1) release of rhythmic expiratory activity even when no such activity was recruited in the control situation and (2) release of tonic activity in the 'expiratory' muscles. Release of rhythmic expiratory activity was mainly elicited by focal cooling of structures in the intermediate part of the medulla and release of tonic activity was preferentially induced by cooling rostroventral structures, although a considerable overlap did occur. Release of rhythmic expiratory activity was not related to any changes in expiratory time (TE) or to any associated variations in the pattern of inspiratory activity. It showed a marked increase with increasing levels of PCO2. The release of tonic activity was not CO2-dependent. Both types of effects could be mimicked by focal microinjections of lignocaine and were reflected by corresponding changes in activity of a majority of the expiration-related neurons. These results suggest that complex and widespread neural substrates subserve the control of the intensity of rhythmic expiratory activity and of the tonic activity of the abdominal and intercostal muscles. These neural mechanisms can apparently operate independently from those controlling the inspiratory activity. The release of the tonic activity observed in the 'expiratory' muscles might reflect a disinhibition of mechanisms involved in non-respiratory functions of expiratory muscles.

Experimentally induced Cheyne-Stokes breathing.

We have studied the propensity for periodic breathing to occur in cats anaesthetized with pentobarbitone breathing either spontaneously or with the aid of a 'servo-respirator' governed continuously by the efferent phrenic nerve activity. Sustained periodic breathing could be induced increasing 'controller gain', either by increasing the gain of the respirator, or by lung deflation, which reflexly increased controller responses to both hypoxia and hypercapnia. Periodic breathing was potentiated both by hypoxia and by diminishing the central (CO2, H+)-drive by focal cooling at the ventral surface of the medulla, two procedures which increase the relative influence of hypoxic drive. Less hypoxia was needed to produce periodic breathing at high rather than low controller gains. Reducing controller gain to zero by constant artificial respiration always abolished periodic breathing. Periodic breathing was also eradicated when the relative importance of CO2 drive was enhanced by breathing the cats with CO2-enriched gas mixtures or with 100% O2. The results are consistent with theoretical predictions for the occurrence of oscillations in the mechanisms for the chemical control of breathing and indicate that increasing controller gas can produce periodic breathing. The results further emphasize the importance of the (CO2, H+)-drive in preserving ventilatory stability.

Graded changes in central chemoceptor input by local temperature changes on the ventral surface of medulla.

1. In cats under pentobarbitone anaesthesia the effects of focal temperature changes of the ;chemoceptive' areas on the ventral surface of medulla, described by Loeschcke and his associates, were studied with respect to tidal volume, V(T), tidal variation in efferent phrenic activity, Phr(T), and respiratory rate. The cats were either paralysed and ventilated at various constant P(A,CO2) and P(a,O2) levels, or breathing spontaneously.2. It was confirmed that focal bilateral cooling of the intermediate, ;I((S))', areas caused rapid depression of respiration even at constant artificial ventilation. In normocapnic and normoxic conditions apnoea usually ensued at brain surface temperatures of 20-22 degrees C.3. The effects were graded along continuous temperature-response curves with enhancements of ventilation above and depression below normal body temperature.4. The strongest effects on V(T) and Phr(T) were obtained from the I((S)) areas with no or only small effects on inspiratory or expiratory timing in the vagotomized animal. The Hering-Breuer inflation reflex and its effects on timing and amplitudes were not affected by cooling this area.5. Focal cooling of the caudal or the rostral ;chemoceptive' areas, ;C((L))' and ;R((M))' areas, caused smaller effects on V(T) and Phr(T) but produced significant effects on respiratory rate even after vagotomy.6. The effects of focal cooling of these areas could be mimicked by topical application of procaine solution which has been shown not to penetrate deeper than 100 mum from the surface.7. Moderate focal cooling of area I((S)) to temperatures above 28-30 degrees C caused a parallel shift in the CO(2)-response (V(T), Phr(T)) curves to the right with little change in slope. The P(CO2) thresholds for apnoea were correspondingly raised. These focal temperature effects could be compensated by changes in P(CO2) with, on the average, 2.7 torr/ degrees C. Focal temperatures below 28 degrees C usually caused some decrease in slope of the CO(2)-response curves in addition to further shifts.8. Added hypoxic stimulus or electrical stimulation of the carotid sinus nerves caused an almost parallel increase of Phr(T) at all P(CO2) levels and all focal temperatures suggesting an additive type of interaction between the input from the peripheral chemoreceptors and that from the central (CO(2), H(+)) sensing structures whether the latter was altered by changing P(CO2) or by focal temperature changes on the I((S)) areas.9. In contrast to these effects of hypoxia and stimulation of the carotid sinus nerves the reflex increase of inspiratory activity caused by lung deflation or by electrical stimulation of the glossopharyngeal nerve distal to the carotid sinus nerves was CO(2) dependent. These reflex effects decreased with focal cooling of the I((S)) areas as with hypocapnia, suggesting a mainly multiplicative or ;gain-changing' type of interaction with the central chemoceptive drive.10. The close similarities in effect of focal cooling and of hypocapnia on the different respiratory parameters even during constant artificial ventilation indicate that focal temperature changes of the I((S)) areas intervene effectively with the normal ventilatory response to CO(2) without changing the chemical or physical environment of those neural structures in the brain stem which set respiratory pattern.

[Failure of acupuncture anesthesia. A psychophysical study (author's transl)]. / Der Misserfolg der Akupunktur-Anästhesie. Eine psychophysische Studie

Four volunteers judged eight levels of thermal stimuli induced by a Hardy dolorimeter, varying in intensity from extremely painful to a low level seldom even perceived. Half of the 406 stimuli were applied during acupuncture and half either before the insertion or after removal of the needles. The experimental design minimized or eliminated factors other than the needles themselves; i.e. no medications were given; the subjects were scientists accustomed to objectivity and, on a preceeding day or days, all became experienced in assigning a number (individually chosen) to the sensation produced by the different stimuli. Galvanic skin resistance was also tested. The results did not show any influence of acupuncture on pain perception or galvanic skin resistance.

Evaluation of acupuncture anesthesia: a psychophysical study.

Four volunteers judged eight levels of thermal stimuli induced by a Hardy dolorimeter, varying in intensity from extremely painful to a low level seldom even perceived. Half of the 406 stimuli were applied during acupuncture and half either before insertion or after removal of the needles. The experimental design minimized or eliminated factors other than the needles themselves, i.e., no medication was given, the subjects were scientists accustomed to objectivity and, on a preceding day or days, all had become experienced in assigning numbers (individually chosen) to the sensations produced by the different stimuli. Galvanic skin resistance was also tested. The results did not show any influence of acupuncture on perception of pain or on galvanic skin resistance.

Vagal modulation of respiratory control during exercise.

Vagal modulation of chemical control of ventilation during rest and exercise was studied in 15 anesthetized mongrel dogs. Arterial chemical stimuli--hypoxic, hypercapnic or a combination of both, increased ventilation by increasing both rate and depth of breathing during rest and exercise in the intact dogs. After bilateral vagotomy chemical drive increased ventilation mostly by depth and little by rate. The ventilatory response to the chemical drive, therefore, reached a plateau when tidal volume approached its maximal value ata relatively unchanged breath frequency. Muscular exercise, however, largely restored frequency response in the vagotomized animals. Since the rate response to chemical stimuli but not to exercise was impaired by vagotomy, we concluded that hyperpnea of exercise could occur through a mechanism not shared by the chemical control of ventilation. The relationship between tidal volume and breath cycle during chemical stimulation was modulated by the volume related vagal reflex. During exercise, another mechanism, presumably bulbo-pontine, is activated to influence the relationship independent of the lung volume.