[Dyslexia, a serious disability].
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Biomedical subjects
Publications and source records attributed to C von Euler.
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Studies in cats and dogs have shown that the ventrolateral region of the medulla participates significantly in the shaping of the respiratory rhythm. The purpose of this study was to examine the effects of unilateral focal cooling (15-20 degrees C) in the ventrolateral medullary region on respiratory responses to hypercapnia and hypoxia in dogs. A cryoprobe was used to cool selected locations in the ventrolateral medulla in 9 anesthetized and vagotomized dogs. Diaphragmatic electromyogram (EMG) was measured with implanted electrodes. The animals were ventilated artificially at a constant rate with 100% O2 and the inspired gas was switched to 7% CO2 in O2 or 10% O2 in N2 to determine the response to hypercapnia or hypoxia. The sites cooled ranged 4.0-8.0 mm rostral to obex, 3.0-5.5 mm lateral to midline, and within 1.5 mm deep from the ventral surface of the medulla. Unilateral focal cooling in this region significantly decreased the responses of both the amplitude and the rate of rise of diaphragmatic EMG to hypercapnia and hypoxia. These results support the hypothesis that neural structures in the ventrolateral medulla are important in the respiratory responses to hypoxia and hypercapnia as well as for the setting of respiratory drive and timing.
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One hundred and one patients, nursed in an intensive care unit for at least 24 h, were monitored for bacterial colonization and infection. The infection rates were similar to those in other reports. Patients were not generally colonized with common environmental strains in the unit. Bacterial dissemination between patients was uncommon. No gentamicin resistant gram negative or Staphylococcus aureus strains were observed, nor methicillin resistant Staphylococcus aureus strains. The hypothesis that these favourable conditions are partly related to the excellent isolation and barrier nursing facilities in the unit cannot be fully substantiated.
Studies in cats have shown that, in addition to respiratory neuron groups in the dorsomedial (DRG) and ventrolateral (VRG) medulla, neural structures in the most ventral medullary regions are important for the maintenance of respiratory rhythm. The purpose of this study was to determine whether a similar superficially located ventral region was present in the dog and to assess the role of each of the other regions in the canine medulla important in the control of breathing, in 20 anesthetized, vagotomized, and artificially ventilated dogs, a cryoprobe was used to cool selected regions of the medulla to 15-20 degrees C. Respiratory output was determined from phrenic nerve or diaphragm electrical activity. Cooling in or near the nucleus of the solitary tract altered timing and produced little change in the amplitude or rate of rise of inspiratory activity; lengthening of inspiratory time was the most common timing effect observed. Cooling in ventrolateral regions affected the amplitude and rate of rise of respiratory activity. Depression of neural tidal volume and apnea could be produced by unilateral cooling in two ventrolateral regions: 1) near the nucleus ambiguus and nucleus para-ambiguus and 2) just beneath the ventral medullary surface. These findings indicate that in the dog dorsomedial neural structures influence respiratory timing, whereas more ventral structures are important to respiratory drive.
Since substance P (SP)-like immunoreactivity has been demonstrated in vagal sensory fibres of bronchopulmonary origin, it was considered of interest to (1) characterize the pattern of responses to SP injected into the pulmonary as well as the systemic arterial system, and (2) assess the types of vagal afferents that are affected by SP. Experiments were performed on 15 pentobarbital-anaesthetized, spontaneously breathing rabbits. Efferent phrenic nerve activity was monitored as an index of central respiratory neural output. Intra-atrial injections of SP into the pulmonary circulation (100 ng kg-1) increased the respiratory rate, and peak integrated phrenic amplitude by 47 +/- 8 and 40 +/- 4%, respectively, above the controls. In addition, SP elicited augmented breaths (ABs) within 2-3 s in 67% of the trials. In contrast to right atrial injections, no ABs and no significant changes in respiratory rate were observed in response to intra-aortic injections of SP (100 ng kg-1). Tidal phrenic activity rise after aortic injections of SP was significantly less as compared with right atrial administrations of SP. Since both routes of administration decreased the arterial blood pressure to the same extent, these respiratory responses were not likely secondary to cardiovascular changes. After administration of an SP antagonist (D-Arg-D-Trp7,9, Leu11, SP), respiratory responses to SP were significantly attenuated. Also, the rate of occurrence of ABs elicited by releasing the tracheal occlusions was reduced (control 95 vs. 14% SP antagonist). Bilateral vagotomy abolished the tachypnoeic response and reduced the magnitude of the phrenic nerve increments caused by right atrial injection of SP.(ABSTRACT TRUNCATED AT 250 WORDS)
Esophageal and gastric pressures during singing are measured in four male professional singers performing singing tasks requiring rapid changes of subglottal pressure. Evidence for a consistent use of the diaphragm is found in all subjects. Some subjects punctually activate the diaphragm when there is a need for a rapid decrease of subglottal pressure, such as when singing a falling octave interval, when shifting from a loud to a soft note, to save air during a /p/ explosion, and in performing a trillo involving a repeated switching between glottal adduction and abduction. The first three cases were observed in the beginning of the phrase, presumably over the period that the pressure generated by the passive expiratory recoil forces of the breathing system was higher than the intended subglottal pressure. In addition to this, one subject exhibited a diaphragmatic tonus throughout the entire phrase. The phonatory relevance of a diaphragmatic activity was evaluated in a subsequent experiment. The transdiaphragmatic pressure was displayed on an oscilloscope screen as a visual feedback signal for singers and nonsingers, who performed various phonatory tasks with and without voluntary coactivation of the diaphragm. In most subjects this activity tended to increase the glottal closed/open ratio as well as the amplitude of the glottogram (i.e., the transglottal volume velocity wave-form as determined by inverse filtering). These changes suggest that diaphragmatic coactivation tends to affect phonation. Also, it tended to reduce the formant frequency variability under conditions of changing fundamental frequency suggesting a better stabilization of the vocal tract.
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.
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.
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.
Thirty-three mechanically ventilated patients in an intensive care unit were studied in order to verify a claim that the Servo humidifier acts as a bacterial barrier. The Servo humidifier was used on all patients. It was changed once daily, and the connecting tubes were changed once weekly. Daily bacterial cultures were taken from the trachea of the patient as well as from the humidifier, the tubing and the ventilator. In 25 of the patients, the same bacterial strain as in the trachea of the patient could not be isolated from the outside of the humidifier, from the tubing or the ventilator. In eight patients a breakthrough of bacterial strains from the trachea through the humidifier could be demonstrated. In four of these eight patients the breakthrough strains appeared to establish themselves in the respirator environment, while in the other four they appeared only temporarily outside the humidifier. The clinical importance of the establishment of a bacterial strain in the ventilator is not clear, but it seems prudent that the introduction of the Servo humidifier should not lead to less stringent cleaning and/or disinfection routines of ventilators and tubing than before.
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The effect of the adenosine analogue L-N-phenyl-isopropyl-adenosine (L-PIA) and theophylline on the respiration of rabbit pups was studied. L-PIA (5 mumol/kg) administered intraperitoneally caused a marked respiratory depression in urethane-anaesthetized decerebrate pups and unanaesthetized intact animals during natural sleep. The effect could often be reversed with theophylline. When L-PIA was given after theophylline (20 mg/kg), the effect of L-PIA was considerably lower. L-PIA also caused respiratory depression when administered onto the exposed surface of the fourth ventricle. The effect of the adenosine analogue was more pronounced in younger than in older animals. We conclude that adenosine strongly inhibits respiration and that effect is antagonized by theophylline. The hypothesis is put forward that the therapeutic effect of theophylline on neonatal apnea might be exerted via adenosine antagonism rather than via inhibition of phosphodiesterase. Apnea in infants is often triggered by hypoxemia. It is possible that adenosine, which is released during hypoxia, mediates this effect.
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Recent advances in several laboratories concerning the respiration-related medullary neurons, their locations, projections, interconnections, morphological and physiological properties, and patterns of inhibitory postsynaptic potentials, excitatory postsynaptic potentials, and discharge rate, on the one hand, and the "systems behavior," on the other, have provided the basis for new hypothesis concerning the neural mechanisms underlying the central pattern generator (CPG) for breathing and its different parts. The onset of the "ramp"-like increase in inspiratory activity is due to an abrupt release of inhibition and a subsequent progressively increasing synaptic excitation of inspiratory premotor neurons. The integration of the excitatory "drive" inputs underlying the ramp inspiratory activity seems to depend on structures in the ventrorostral medulla, including nucleus paragigantocellularis. The termination of this activity by the off-switch mechanisms is actuated when a critical threshold is attained by the excitatory inputs of 1) a slowly increasing inspiration-related activity and 2) the afferent input from the pulmonary stretch receptors. The nature of the former activity is discussed. During the expiratory phase, an inhibitory activity suppresses inspiration-facilitating inputs with a slowly decaying power that controls the expiratory duration. The postinspiration activity, which brakes the rate of exhalation during the first part of the expiratory phase, depends on mechanisms separate from those responsible for the inspiratory ramp activity. The respiratory CPG seems to be organized with considerable amount of redundancy, or "degeneracity."
The bilateral reflex actions of vagus nerve afferent signals on phrenic efferent activity have been tested by unilateral graded single shock electrical stimulation. An early excitation (latency 3-5 msec) was more prominent in the phrenic nerve contralateral to the stimulated vagus. Spinal cord hemisection at C3 eliminated both contralateral and ipsilateral responses: thus, both were mediated via descending tracts in the contralateral cord. A bilaterally symmetrical early inhibition (latency 8-12 msec) followed the early excitation. The electrical thresholds for evoking the early responses and the temperature for blocking these responses during graded vagal cooling were closely similar to the threshold and blocking temperature for pulmonary stretch receptor afferents. Higher stimulus strengths evoked a strong, bilaterally similar, late excitation (latency 12-20 msec) followed by a late inhibition. At very high stimulus strengths a third excitation (latency 25-30 msec) could appear. Sometimes these responses were followed by lowered phrenic activity for the remainder of inspiration. Single shock stimulation of the intact vagus nerve or of the peripheral end of the cut recurrent laryngeal nerve provoked, by the contraction of laryngeal muscles, a strong, short latency (12 msec) inhibition of phrenic activity mediated by superior laryngeal nerve afferents. The implications of these results with respect to the reflex pathways of the different responses and their possible integration in the central respiratory control mechanisms are discussed.
Seven patients were operated on for stenosis of the internal carotid artery (ICA) with endarterectomy under neurolept anesthesia. The ICA blood flow was found to be unchanged after reconstruction following an operative blood loss of one fifth of the patient's blood volume despite variations in cardiac output. The relationship between carbon dioxide tension and cerebral blood flow remained unchanged during hypovolemia. It is concluded that the autoregulation of the cerebral blood flow is maintained under neurolept anesthesia.
Central haemodynamics were studied before and during reconstructive vascular surgery in 18 patients receiving halothane or enflurane anaesthesia (nine patients in each group). In both groups cardiac output (CO), stroke volume (SV), oxygen uptake (VO2) and arterial blood pressure fell significantly after induction of anaesthesia, whereas the arterio-venous oxygen difference (AVD) and the total peripheral resistance (TPR) remained unchanged. In spite of an average intraoperative blood loss of 600 ml, which had not been substituted for, surgery brought about an increase in CO, SV and VO2, while the AVD and TPR remained unchanged. Following transfusion of 900 ml of blood, CO and SV showed a further significant increase in both groups, whereas VO2 was unchanged and the AVD and TPR fell significantly. The pulmonary capillary venous pressure (PPCV) was stable during induction of anaesthesia and surgery but increased after blood transfusion. The changes in SV and PPCV were analyzed in relation to the concept of ventricular function curves. It is concluded that there were no fundamental differences in central haemodynamics between halothane and enflurane anaesthesia either before or during surgery. In both groups the changes in CO and SV were due mainly to a reduced demand of oxygen transport and expected changes in sympatho-adrenergic tone rather than to myocardial depression.