Abstract. Lagercrantz, H., Broberger, U., Milerad, J. and v. Euler, C. (Department of Paediatrics, Karolinska Hospital and the Nobel Institute of Neurophysiology, Karolinska Institute, Stockholm, Sweden). Ventilatory studies in two older infants with prolonged apnea. Acta Paediatr Scand 69:545, 1980.—Two infants, both born before term, were found apneic, cyanotic and limp at home when they were 9 weeks and 2 weeks old, respectively. Their respiration was monitored in the hospital and found to be remarkably periodic during sleep, and was in one case accompanied by pronounced bradycardia. The periodic breathing and apnea seemed to be caused by a decreased oxygen tension which can induce an instability of the central respiratory control mechanisms.

Vagally mediated, volume dependent excitatory effects on phrenic nerve activity have been recently described in anesthetized dogs and pigs, but could not be ascertained in rabbits and baboons (Bartoli et al. 1975, Huszczuk et al. 1977, Cross et al. 1980, Karczewski et al. 1980). Results presented here on cats confirm and further characterize a volume dependent facilitatory effect on inspiratory intercostal and phrenic activity in this species.

In twenty-four patients, undergoing a femoro-popliteal saphenous vein bypass graft for symptomatic atherosclerotic occlusion of the superficial femoral artery, oxygen saturation values for the femoral and popliteal veins were compared to the directly measured blood flows in the common femoral artery and in the bypass graft, respectively. Blood flow and venous oxygen saturation increased significantly after transfusion of 900 ml of blood. Pharmacological vasodilation caused a significant increase in blood flow both before and after transfusion, whereas the changes in venous oxygen saturation were significant only before blood transfusion. A close statistical relationship was found between initial femoral venous oxygen saturation and initial blood flow in the common femoral artery as well as between initial popliteal venous oxygen saturation and initial byapss blood flow. However, especially at low saturation values, the evaluation of blood flow was very uncertain. Whole leg and lower leg oxygen uptakes were not altered by intraoperative changes in blood volume. It is concluded that blood flow in the common femoral artery and the bypass graft can be roughly estimated from analysis of oxygen saturation in the femoral and popliteal veins, respectively. Furthermore, by determining leg venous oxygen saturation both before and after flow augmentation, induced by pharmacological vasodilation, a conception of the load on the vascular system may be obtained.

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, VT, tidal variation in efferent phrenic activity, PhrT, and respiratory rate. The cats were either paralysed and ventilated at various constant PA,CO2and Pa,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 °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 VT and PhrT 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 VT and PhrT 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 μm from the surface.7. Moderate focal cooling of area I(S) to temperatures above 28‐30 °C caused a parallel shift in the CO2—response (VT, PhrT) curves to the right with little change in slope. The PCO2 thresholds for apnoea were correspondingly raised. These focal temperature effects could be compensated by changes in PCO2 with, on the average, 2·7 torr/°C. Focal temperatures below 28 °C usually caused some decrease in slope of the CO2—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 PhrT at all PCO2 levels and all focal temperatures suggesting an additive type of interaction between the input from the peripheral chemoreceptors and that from the central (CO2, H+) sensing structures whether the latter was altered by changing PCO2 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 CO2 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 CO2 without changing the chemical or physical environment of those neural structures in the brain stem which set respiratory pattern.

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.

In order to obtain further information on the mechanisms controlling expiratory duration (TE) we have studied the effects of changes in body temperature on reflex characteristics of the TE-prolonging inflation reflex. In cats under light pentobarbitone anesthesia controlled volume changes were applied at various times in expiration and the changes in TE were measured from records of phrenic activity. Inflations falling in the last 20% of the control expiratory time were without effect. This reflex insensitive phase remained a constant fraction of expiratory time when respiratory rate was changed with temperature. The relative reflex responsiveness increased, and the volume threshold was reduced with increasing respiratory rate. The inflation reflex characteristics showed integration of the incoming pulmonary stretch receptor activity. The integrating mechanism exhibited a "leaky" character, the decay rate of which changed with body temperature. Functionally the duration of the inspiration-inhibiting activity controlling expiratory duration can be regarded as dependent on 3 main factors 1) the initial peak level of the inhibitory activity, 2) the amount and timing of the vagal afferent activity which adds to this inhibition, and 3) its rate of decay. The results suggest that all these factors are influenced by changes in temperature.

The effects of PCO2 and body temperature on the time course and peak amplitude of the central inspiratory activity (CIA) and the inspiratory "off-switch" threshold was studied in apneustic and non-apneustic cats. Apneusis resulted from lesions of the inspiratory inhibiting structures of the medial parabrachial nucleus (NPBM) and by interrupting vagal volume feedback. The cats were paralyzed and ventilated either proportionally to their phrenic output or at predetermined rate and volume. The dependence of the rate of rise and maximal amplitude of phrenic activity on PCO2 and body temperature were comparable in apneustic and non-lesioned animals. The Hering-Breuer volume threshold for inspiratory termination was increased following the rostral pontine lesions. Both hyperthermia and hypercapnia caused augmentation of the absolute rate of rise of inspiratory activity but hypercapnia, in contrast to hyperthermia, caused virtually no change in the fractional increment per unit time. With hypercapnia the inspiratory "off-switch" threshold was raised in the apneustic animals in intact ones, whereas hyperthermia did not seem to influence this threshold. In apneustic conditions expiratory duration remained constant, independent of the large variations in the inspiratory durations. Our results suggest that the NPBM merely provides an excitatory, threshold-lowering input to the inspiratory "off-switch" mechanism.

The time course of the excitability of the inspiratory "off-switch" mechanism with and without phasic vagal stretch receptor feedback has been studied in cats under light pentobarbitone anesthesia by electrical stimulation in the rostral pons using brief tetanic stimulation (300 Hz for 0.2 s). The threshold strength required just to elicit inspiratory "off-switch" was high early in inspiration and fell steeply with time. The threshold curves were steeper with than without phasic vagal feedback, and the difference reflects the phasic vagal contribution to the excitability of the inspiratory "off-switch" the absence of phasic vagal vagal feedback the time course of this threshold curve usually corresponded closely to that of the "integrated" phrenic activity at all PCO2 levels and body temperatures tested indicating that the "integrated" phrenic activity can be used as an index of the centrally generated inspiratory activity. In response to a rise in PCO2 both the rate of change of excitability of the inspiratory "off-switch" mechanism and its initial threshold level was increased. Changes in body temperature caused no change in the initial threshold but produced marked changes in the rate of rise of the "off-switch" excitability; Following an "augmented breath" the inspiratory "off-switch" threshold was markedly reduced

Acta Physiologica ScandinavicaVolume 93, Issue 4 p. 560-562 Cyclic Excitability Changes of the Inspiratory 'Off-switch' Mechanism Curt von Euler, Curt von Euler Nobel Institute for Neurophysiology, Karolinska lnstitutet, Stockholm, SwedenSearch for more papers by this authorTeresa Trippenbach, Teresa Trippenbach Nobel Institute for Neurophysiology, Karolinska lnstitutet, Stockholm, Sweden *On leave of absence from the Laboratory of Neurophysiology, Polish Academy of Sciences, Warsaw, PolandSearch for more papers by this author Curt von Euler, Curt von Euler Nobel Institute for Neurophysiology, Karolinska lnstitutet, Stockholm, SwedenSearch for more papers by this authorTeresa Trippenbach, Teresa Trippenbach Nobel Institute for Neurophysiology, Karolinska lnstitutet, Stockholm, Sweden *On leave of absence from the Laboratory of Neurophysiology, Polish Academy of Sciences, Warsaw, PolandSearch for more papers by this author First published: April 1975 https://doi.org/10.1111/j.1748-1716.1975.tb05849.xCitations: 17 AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume93, Issue4April 1975Pages 560-562 RelatedInformation

AbstractBreath‐by‐breath analysis of tidal volume, VT, inspiratory duration, Tr, and expiratory duration, TE, was performed on cats under light pentobarbitone anesthesia or after decerebra‐tion before and after vagotomy. In response to step changes in inspired CO2 VT changes earlier and more rapidly than the corresponding changes in the timing. The VT–Tj points may thus form a ‘hysteresis loop’ embracing the volume threshold curve of Clark and Euler (1972). The transient responses were present also after peripheral chemodenervation and after bilateral vagotomy. In contrast to earlier papers vagotomized cats under pentobarbitone anesthesia often showed some decrease of T(with increased steady state CO2 levels. In decerebrate vagotomized cats T[was more independent of variations in steady state PCO2 levels, but after administration of pentobarbitone Ti showed some steady state shortening of Tj with increased CO2. It is concluded that the controller of depth and rate of breathing contains at least 2 functional components which depend on PCO2 in such a way that they exert opposite effects on Ti which cancel out to a great extent and that this relative match can be disturbed by pentobarbitone. It is postulated that the transient increase in mismatch is due to the fact that the 2 (or more) CO2 effects have slightly different dynamic features.

The time course of the volume threshold curve for the inspiratory off-switch, i.e. the relationship between volume, (Vx) and inspiratory duration (Tj) with intact vagus nerves, was determined in steady conditions at different inspired CO2 concentrations and body temperatures in lightly anesthetized cats by means of ‘ramp’-shaped inflations and deflations of different rise times. With intact vagal feedback the Vx–TT data points could be very well fitted to hyperbolas in all conditions studied. Changes in steady state FACO2 never caused any detectable influence on the volume threshold curves. Changes in body temperatures, in a range below the panting threshold, caused pronounced effects on the volume threshold curve which could best be characterized as a shift of the whole curve along the volume axis to lower values with increased temperature. Thus, at each rate of volume expansion the threshold for inspiratory off-switch was reached earlier the higher the temperature. Also in the absence of vagal volume feed-back Ti became correspondingly shorter with increased temperature which indicates that these temperature effects are mainly of central origin. The mechanisms for the CO2 and temperature effects on tidal volume and inspiratory duration are discussed.

Acta Physiologica ScandinavicaVolume 57, Issue 4 p. 481-482 Intercostal γ-Motor Activity By G. Eklund, By G. Eklund Nobel Institute for Neurophysiology, Karolinska Institutet, Stockholm 60, SwedenSearch for more papers by this authorC. von Euler, C. von Euler Nobel Institute for Neurophysiology, Karolinska Institutet, Stockholm 60, SwedenSearch for more papers by this authorS. Rutkowski, S. Rutkowski Nobel Institute for Neurophysiology, Karolinska Institutet, Stockholm 60, SwedenSearch for more papers by this author By G. Eklund, By G. Eklund Nobel Institute for Neurophysiology, Karolinska Institutet, Stockholm 60, SwedenSearch for more papers by this authorC. von Euler, C. von Euler Nobel Institute for Neurophysiology, Karolinska Institutet, Stockholm 60, SwedenSearch for more papers by this authorS. Rutkowski, S. Rutkowski Nobel Institute for Neurophysiology, Karolinska Institutet, Stockholm 60, SwedenSearch for more papers by this author First published: April 1963 https://doi.org/10.1111/j.1748-1716.1963.tb02611.xCitations: 12AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume57, Issue4April 1963Pages 481-482 RelatedInformation