P.J. Berger

Effect of venous oxygenation on arterial desaturation rate during repetitive apneas in lambs

While arterial oxygen desaturation during apnea is a common occurrence in adults and infants, the factors determining the rate of desaturation are poorly understood. We describe a theoretical model which suggests that arterial desaturation during an apneic episode occurs in two stages. In the initial stage (stage 1) the oxygen store in the lung is depleted, while in the second phase of the desaturation process (stage 2) tissue oxygen needs are met predominantly by depletion of the blood store. Our model predicts that preapneic venous oxygenation (SvO2) will strongly influence the rate of the desaturation in stage 1 but not in stage 2. We therefore examined the effect of changing preapneic SvO2 on the rate of arterial oxygen desaturation (SaO2) during stage 1 and stage 2 apnea in anaesthetised 10-20 day-old lambs. Preapneic arterial oxygen saturation was maintained constant. In agreement with the models prediction there were two stages to the desaturation process and during stage 1 a significant increase in SaO2 was observed when preapneic SvO2 was lowered; SaO2 was -3.1 +/- 0.4%.sec-1 when SvO2 = 47.4 +/- 2.1% increasing to -5.8 +/- 0.7%.sec-1 when SvO2 = 28.3 +/- 1.2%. During stage 2, SaO2 was -1.62 +/- 0.07%.sec-1 and was independent of preapneic SvO2, also in accord with the models prediction. In order to assess whether the accelerated desaturation rate we observed in stage 1 could have resulted from a decline in lung volume during apnea rather than lower levels of SvO2, we repeated the experiment with CPAP applied. Under these conditions SaO2 continued to be greater at lower preapneic SvO2 levels. In summary, lowered preapneic SvO2 has a potent influence on SaO2 during stage 1 of the desaturation process but not during stage 2.

Effect of lung liquid volume on respiratory performance after caesarean delivery in the lamb.

1. The volume of liquid in the lungs of the fetal lamb is reported to fall in the final days of gestation and during labour itself. We aimed to test the hypothesis that this fall in liquid volume adapts the lungs for air breathing and pulmonary gas exchange. 2. In twelve chronically catheterized fetal lambs we measured lung liquid volume at 140 days gestation (term is 147 days) and then delivered the fetuses by Caesarean section under maternal spinal anaesthesia. In five fetuses we removed approximately half the liquid contained in the lungs just before delivery (experimental group) while the remaining seven fetuses were delivered without change to their lung liquid (control group). 3. Lambs born with reduced lung liquid volume improved their arterial blood gas and acid‐base status more quickly than lambs born without alteration to lung liquid. 4. Carotid arterial blood gas values in the first 60 min of postnatal life were significantly related to the volume of liquid present in the lungs at birth, with higher arterial partial pressure of oxygen (Pa,02) and arterial oxygen saturation (Sa,02) and lower arterial partial pressure of carbon dioxide (Pa,CO2) levels being associated with lower lung liquid volumes. 5. We conclude that postnatal gas exchange is enhanced by a reduction in the volume of liquid remaining in the lungs when breathing starts.

Indirect relation between rises in oxygen consumption and left ventricular output at birth in lambs.

To examine the relation between increased newborn oxygen requirements and the postnatal rise in cardiac output, we measured left ventricular (LV) output, organ blood flows, and whole-body oxygen consumption using radioactive microspheres in late-gestation sheep fetuses and in the same animals 1 and 4 hours after cesarean section delivery. LV output rose from 264 +/- 23 ml.min-1.kg body wt-1 in fetuses to 444 +/- 33 ml.min-1.kg body wt-1 in lambs at 1 hour after delivery (p less than 0.005) and was unchanged at 4 hours after delivery. This rise in LV output was associated with a more than fourfold increase in the LV flow contribution to tissues situated distal to the ductus arteriosus (fetus, 51 +/- 9 ml.min-1.kg body wt-1; lamb, 226 +/- 22 ml.min-1.kg body wt-1; p less than 0.005), which were mainly perfused by the right ventricle in utero. However, average blood flow to body tissues was similar in fetuses (37 +/- 4 ml.min-1.100 g tissue-1), 1-hour lambs (39 +/- 4 ml.min-1.100 g tissue-1), and 4-hour lambs (40 +/- 5 ml.min-1.100 g tissue-1). Oxygen consumption increased by 58%, from 7.84 +/- 0.43 ml.min-1.kg body wt-1 in fetuses to 12.38 +/- 2.4 ml.min-1.kg body wt-1 in 1-hour lambs (p less than 0.01), and was unchanged in 4-hour lambs.(ABSTRACT TRUNCATED AT 250 WORDS)

Paradoxical effect of oxygen administration on breathing stability following post‐hyperventilation apnoea in lambs

1 Oxygen administration is thought to suppress periodic breathing (PB) by reducing carotid body activity, and yet earlier experiments in neonates have shown that PB incidence may be increased following the application of hyperoxia. To clarify this paradox, we studied the changes in the pattern of PB that occur following administration of oxygen in a lamb model of PB. 2 PB was induced in eleven of seventeen anaesthetized lambs following passive hyper‐ventilation with air. When oxygen was administered during PB, the pattern was first enhanced, as evidenced by a sudden decrease in the ratio of the ventilatory duration to the apnoeic pause duration, and then suppressed, as evidenced by a progressive return to stable breathing which was associated with an increase in minute ventilation. 3 Five of the six lambs that did not show PB following passive hyperventilation with air could be made to do so if oxygen was substituted for air as the inspired gas following passive hyperventilation. 4 Five of the eleven lambs that showed PB following hyperventilation with air responded to the application of oxygen during PB by switching to a gross form of episodic breathing consisting of long apnoeic pauses followed by equally long periods of breathing during which minute ventilation fell progressively with time. 5 We conclude that when applied against a background of arterial hypoxaemia, oxygen has a destabilizing influence on ventilation in that (a) it accentuates the unstable breathing that occurs during PB, (b) it induces PB in lambs that exhibited stable breathing in air, and (c) it may precipitate episodic breathing.

Breathing at birth and the associated blood gas an pH changes in the lamb

We examined the relationship between the initiation of breathing at birth and the timing of delivery of the chest in a group of 13 lambs undergoing spontaneous unassisted delivery at term. In 8 of 11 lambs with a diaphragm electromyogram or intrapleural pressure signal the first breath occurred before chest delivery. The first breath was always followed by a period of irregular and often powerful inspiratory efforts. Some of these inspirations were followed by a forceful expiration. A regular respiratory rhythm never developed until the chest had delivered, suggesting that chest expansion is essential for the establishment of rhythm. Although PaO2 increased rapidly after birth, pHa declined and reached its lowest level approximately 20 minutes postnatally suggesting that considerable anaerobic metabolism occurs in the face of adequate arterial oxygenation. The level of respiratory activity in the first 30 min following birth did not appear to be related to arterial PO2, PCO2 or pH. Neither the appearance of the EMG activity of the first breath, nor blood samples taken from 2 lambs simultaneously with the first breath, suggested that the first breath was a gasp initiated by asphyxial blood gases. Our results therefore do not support the current hypothesis that the first breath is a gasp initiated by asphyxia accompanying delivery.

Easily-implantable electrodes for chronic recording of electromyogram activity in small fetuses

A method is described for the construction of simple, robust electrodes suitable for obtaining long-term chronic recordings of electromyogram activity from delicate muscles of small experimental animals. The electrodes are equipped with small, gold-plated barbed tips which have the form of harpoons that may be pushed directly into a muscle, where they remain without being sutured into place. These features greatly facilitate the instrumentation of muscles which are very thin or of limited accessibility. The electrodes have been used successfully to obtain chronic recordings of respiratory muscle activity from early gestation fetal lambs in utero.

Supraspinal Influence on the Development of Motor Behavior in the Fetal Lamb

To examine the involvement of supraspinal inputs in the maturation of motor activity patterns in the developing fetal lamb, we recorded spontaneous electromyographic activity from spinally innervated muscles at approximately 45, 65, and 95 days gestation (G45, G65, and G95; term = 147 days). At G45, fetal activity occurred in synchronized activity-inactivity cycles of approximately 2 min duration, with the activity phase lasting 22.2 +/- 4.8 s and the inactivity phase lasting 95.4 +/- 13.3 s (mean +/- standard error of the mean, n = 5). At G65 and G95, the organization of activity was clearly different from that at G45 in that it was no longer cyclic, nor was the discharge of different muscles synchronized. By contrast, after spinal cord transection at G62, synchronised cyclic activity occurred in muscles innervated by segmental levels below the transection, both at G65 and G95. At G65 the duration of the activity phase of the cycle was 53.5 +/- 6.0 s, while the inactivity phase lasted 171.6 +/- 22.1 s; these durations did not alter between G65 and G95. Since spinal cord transection leads to the motor behavior of the G65 fetus reverting to the cyclic pattern characteristic of the G45 fetus, we conclude that supraspinal inputs begin to modulate the output of the spinal pattern generators at some stage between G45 and G65. The observation that spinally transected fetuses generate identical behavior at G65 and G95, both in terms of its cyclic character and the duration of cycles, suggests that spinal circuits undergo little autonomous development over this period; that is, the altered behavior observed in the developing intact fetus reflects the influence of supraspinal inputs on the motor circuits of the spinal cord.

Metabolic development of the sheep diaphragm during fetal and newborn life

Several parameters indicative of whole muscle aerobic and anaerobic metabolism were compared in heart, diaphragm and two locomotory muscles of sheep (Ovis aries) ranging from 90 days gestation to adult animals. Aerobic metabolism was assessed from myoglobin content, anaerobic metabolism from the pH buffering capacity and the balance between the two from the properties of the lactate dehydrogenase isozymes. We expected the diaphragm and heart, as the two vital pumps of the body, to have substantial aerobic capacity at birth. For the left ventricular myocardium this appears to be true, with the myoglobin level at birth averaging 69% of the adult value. However, the diaphragm had only 15% of the adult myoglobin level, a level similar to that in vastus lateralis and medial gastrocnemius muscles. In the first 18 days postnatally, myoglobin levels in the diaphragm did not change. Anaerobic capacity, as indicated by pH buffering capacity, increased in all four muscles during fetal life, reaching from 69-96% of adult values on day 1 after birth. A rapid increase in pH buffering capacity occurred in all four muscles in the first 6 days postnatally suggesting that anaerobic glycolysis is important to the newborn. We conclude that the work done by the fetal heart leads to the development of a high aerobic capacity by birth, but the activity of the fetal diaphragm does not have this effect.

Electromyographic changes in the isolated rat diaphragm during the development of fatigue

SummaryTo investigate whether the power spectrum of the electromyogram of a fatiguing muscle can be used to infer the degree to which the muscle is fatigued, we recorded isometric tension and two monopolar electromyograms from eight isolated rat diaphragm preparations suspended in an organ bath containing a balanced salt solution. Each preparation was excited with a fixed phrenic nerve impulse pattern made up of a 70-Hz train of impulses of supramaximal voltage delivered for 170 ms with a 500-ms recovery period. Tension fell rapidly over the first 60 s of the fatigue run and more slowly for the remaining 60 s analysed. The duration of extracellular action potentials increased and their amplitude decreased as the tension developed by the diaphragm decreased; conduction velocity along muscle fibres also decreased. The centroid frequency (fcen) of the power spectrum of the first action potential elicited by each train of stimuli decreased rapidly until tension fell to approximately 70% of the initial value; thereafter little change infcen occurred, although tension continued to fall to 33% of its initial value. Our results demonstrated that under controlled conditions,fcen provided a sensitive index of fatigue in its early stages, but provided no information once fatigue was pronounced.

Differential recruitment of inspiratory muscles in response to chemical drive

Changes in the intensity of EMG activity in the costal diaphragm, crural diaphragm and external intercostal muscle during inspiration were assessed in intact, awake lambs following abrupt transitions in the composition of the inspired gases from air to either a hypoxic/hypoxic mixture (10% O2, 90% N2), a hyperoxic/hypercapnic mixture (40% O2, 6% CO2, 54% N2) or a hypoxic/hypercapnic mixture (10% O2, 6% CO2, 84% N2). A regression method was used to compare the dynamic responses of the three muscles over the 10-min period following each transition. The relationship between the dynamic response functions of the costal and crural diaphragm was the same in each of the three experimental conditions, indicating that these separate components of the diaphragm comprise a single functional unit during breathing. The relationship between the dynamic response functions of the external intercostal muscle and the costal diaphragm varied according to the composition of the inspired gas mixture. This result suggests that the central and peripheral chemoreceptors exert differential effects on the activation of the diaphragm and the external intercostal muscles during breathing, consistent with the hypothesis that sensory information from these receptors is processed, at least in part, in parallel pathways which project separately to the phrenic and external intercostal motoneurons.