The effect of 10% O2 on the continuous breathing induced by O2 or O2 plus cord occlusion in the fetal sheep.

Although the administration of 100% O2 alone or combined with umbilical cord occlusion induces continuous breathing and arousal in the fetal sheep (Baier, Hasan, Cates, Hooper, Nowaczyk & Rigatto, 1990a), the individual contribution of O2 and cord occlusion to the response have not been determined. We hypothesized that if O2 is an important factor in the induction of continuous breathing, administration of O2 low enough (10%) to bring fetal arterial PO2 to about 20 torr while the fetus is breathing continuously should reverse these changes. Thus we subjected 12 chronically instrumented fetal sheep to 10% O2 for 10 minutes after the establishment of continuous breathing by O2 (4 fetuses; 137 +/- 1 days) or by O2 plus umbilical cord occlusion (8 fetuses; 134 +/- 1 days). Arterial PO2 decreased from about 250 torr to 20 torr during 10% O2. This induced a significant decrease in breathing output (EMGdi x f) related primarily to a decrease in frequency (f). In 3/5 experiments in 4 fetuses, with O2 alone, apnoea developed within 4 +/- 0.6 min; in 12/13 experiments in 8 fetuses, with added cord occlusion it developed at 5 +/- 0.6 min. With the decrease in PaO2, electrocortical activity (ECoG) switched from low to high-voltage within 6 minutes in 5/5 experiments (O2 alone) and in 11/13 (O2 plus cord occlusion). The findings suggest that umbilical cord occlusion alone is not sufficient to maintain breathing continuously and an increased PaO2 is needed. We speculate that in the fetus there is a vital link between PaO2, breathing and ECoG with low PaO2 inhibiting and high PaO2 favouring breathing and arousal.     

Initiation of pulmonary gas exchange by fetal sheep in utero

The role of umbilical cord occlusion in the initiation of breathing at birth was investigated using unanesthetized fetal sheep that were provided with access to a tracheal supply of hyperoxic air. Near-term fetuses were studied in utero to eliminate extraneous sensory stimuli. Gasping movements began 1.4 +/- 0.1 min after cord occlusion. Breathing was irregular for several minutes before continuous breathing (greater than or equal to 40 min-1) began 6 +/- 1 min after cord occlusion (n = 10). Arterial PO2 rose significantly from 18 +/- 2 mmHg before occlusion and was 115 +/- 15 mmHg immediately before cord release at 15 or 30 min. Breathing continued even during high-voltage electrocortical activity. Cord release caused the breathing rate to decrease from 77 +/- 13 min-1 during the last 5 min of cord occlusion to 5 +/- 3 min-1 10 min after cord release (P less than 0.002; n = 7). Results indicate the change from placental to lung gas exchange can occur in the absence of sensory and thermal changes normally present at birth and that the transition is reversible.     

Umbilical cord occlusion stimulates breathing independent of blood gases and pH

The role of umbilical cord occlusion in the initiation of breathing at birth was investigated by use of 16 unanesthetized fetal sheep near full term. Artificial ventilation with high-frequency oscillation was used to control fetal arterial blood gas tensions. At baseline, PCO2 was maintained at control fetal values and PO2 was elevated to between 25 and 50 Torr. In the first study on six intact and four vagotomized fetuses, arterial PCO2 and PO2 were maintained constant during two 30-min periods of umbilical cord occlusion. Nevertheless, the mean fetal breathing rate increased significantly when the umbilical cord was occluded. In the second study on six intact fetuses, hypercapnia (68 Torr) was imposed by adding CO2 to the ventilation gas. When the umbilical cord was occluded, there was a significantly greater stimulation of breathing (rate, incidence, and amplitude) in response to hypercapnia than in response to hypercapnia alone. During cord occlusion, plasma prostaglandin E2 concentration decreased significantly. Results indicate that cord occlusion stimulates breathing possibly by causing the removal of a placentally produced respiratory inhibitor such as prostaglandin E2 from the circulation.     

The effects of gestational age and labour on the breathing and behaviour response to oxygen and umbilical cord occlusion in the fetal sheep.

We tested the hypothesis that the continuous breathing response to oxygen or oxygen plus umbilical cord occlusion, in the fetal sheep, could be modified by gestational age or labour. We studied 35 chronically instrumented fetal sheep on 84 occasions during late gestation (124 to 141 days), using our window model (Rigatto, 1984). After a resting cycle (1 low-voltage followed by 1 high-voltage electrocortical activity epoch), the fetal lung was distended via an endotracheal tube using mean airway pressure of about 30 cm H2O. Inspired nitrogen, and 100% O2 were given to the fetus during one cycle each. While on 100% O2 the umbilical cord was occluded using a balloon cuff. We found that: (1) the continuous breathing response to 100% O2 occurring in 8% of the experiments at a gestational age less than 130 days, in 25% from 130 to 134 days and in 45% at gestational ages greater than 134 days (P < 0.01); (2) at similar gestational age intervals the breathing responses to umbilical cord occlusion were 67%, 84%, and 100% (P < 0.01); and (3) in the presence of labour, 45% of the experiments responded to O2 with continuous breathing as compared to 23% in the absence of labour (P < 0.01). Cord occlusion did not affect these values. Because the highest PaO2 achieved increased significantly to 128 days but not thereafter it is unlikely that these results can be explained on the basis of an increase in PaO2 alone. We speculate that there is an age related maturation of the inhibition of breathing normally present in the fetus.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of bilateral vagotomy on oxygenation, arousal, and breathing movements in fetal sheep.

To investigate the effects of bilateral cervical vagotomy on arousal and breathing responses, we studied eight sham-operated and eight chronically instrumented unanesthetized vagotomized sheep fetuses between 136 and 144 days of gestation (term approximately 147 days). Each fetus was instrumented to record sleep states, diaphragmatic electromyogram, blood pressure, pH, and blood gas tensions. In a randomized order, fetal lungs were distended with four different O2 concentrations: 0 (100% N2), 21, 50, and 100% at a continuous positive airway pressure of 30 cmH2O via an in situ Y-endotracheal tube. Under control conditions, inspiratory time and the duration of the single longest breathing episode decreased from 598 +/- 99 (SD) ms and 24 +/- 10 min in sham group to 393 +/- 162 ms and 11.0 +/- 3.0 min in vagotomized group (P = 0.04 and 0.033), respectively. In response to lung distension with 100% N2, breathing time decreased from 44 +/- 17 to 20 +/- 18% (P = 0.045) in sham-operated fetuses, whereas it remained unchanged in the vagotomized group. In response to 100% O2, fetal arterial PO2 increased in five of eight fetuses sham-operated from 18.2 +/- 5.1 to 227 +/- 45 Torr (P = 0.0001) and in six of eight vagotomized fetuses from 18.5 +/- 4.4 to 172 +/- 39 Torr (P < 0.001). Although arousal was observed in all oxygenated fetuses at the onset of breathing, the duration of arousal was markedly attenuated in vagotomized fetuses (14 +/- 10 vs. 46 +/- 29 min in sham group; P = 0.024). Frequency and amplitude of breathing and respiratory output (frequency x amplitude) increased only in sham group (P = 0.02, 0.004, and 0.0002, respectively). We conclude that in response to lung distension and oxygenation, arousal and stimulation of breathing during active and quite sleep are critically dependent on intact vagal nerves.     

Fetal breathing is not initiated after cord occlusion in the unanaesthetized fetal lamb in utero.

We investigated the role of cord occlusion in the initiation of breathing at birth using an extracorporeal membrane oxygenator system to control fetal blood gases independently of the placenta in 12 chronically instrumented fetal lambs. In group IA (n = 9; exp = 12) PaCO2 was kept constant (5.62 +/- 0.21 to 5.70 +/- 0.23 kPa) during cord occlusion. Group IB (n = 7; exp = 8) were cord occlusion experiments from group IA in which no fetal breathing movements had occurred; CO2 flow to the membrane was increased and fetal PaCO2 rose significantly (5.45 +/- 0.24 to 8.27 +/- 0.56 kPa). In group II (n = 7; exp = 12) PaCO2 was allowed to increase from 5.98 +/- 0.24 kPa to 8.09 +/- 0.48 kPa after cord occlusion. Within 5 min of cord occlusion, FBM did not occur in 11 out of 12 experiments in group IA or in 11 out of 12 experiments in group II. In contrast in group IB breathing did occur in 5 out of 8 experiments. When they occurred, fetal breathing movements were always associated with low voltage electrocortical activity. Our results do not support the hypothesis that the initiation of breathing within 5 minutes of birth is dependent on an inhibitory factor of placental origin. Furthermore these data suggest an association between the presence of breathing and a substantial rise in PaCO2.     

Bicarbonate attenuates arterial desaturation during maximal exercise in humans.

The contribution of pH to exercise-induced arterial O2 desaturation was evaluated by intravenous infusion of sodium bicarbonate (Bic, 1 M; 200-350 ml) or an equal volume of saline (Sal; 1 M) at a constant infusion rate during a "2,000-m" maximal ergometer row in five male oarsmen. Blood-gas variables were corrected to the increase in blood temperature from 36.5 +/- 0.3 to 38.9 +/- 0.1 degrees C (P < 0.05; means +/- SE), which was established in a pilot study. During Sal exercise, pH decreased from 7.42 +/- 0.01 at rest to 7.07 +/- 0.02 but only to 7.34 +/- 0.02 (P < 0.05) during the Bic trial. Arterial PO2 was reduced from 103.1 +/- 0.7 to 88.2 +/- 1.3 Torr during exercise with Sal, and this reduction was not significantly affected by Bic. Arterial O2 saturation was 97.5 +/- 0.2% at rest and decreased to 89.0 +/- 0.7% during Sal exercise but only to 94.1 +/- 1% with Bic (P < 0.05). Arterial PCO2 was not significantly changed from resting values in the last minute of Sal exercise, but in the Bic trial it increased from 40.5 +/- 0.5 to 45.9 +/- 2.0 Torr (P < 0.05). Pulmonary ventilation was lowered during exercise with Bic (155 +/- 14 vs. 142 +/- 13 l/min; P < 0.05), but the exercise-induced increase in the difference between the end-tidal O2 pressure and arterial PO2 was similar in the two trials. Also, pulmonary O2 uptake and changes in muscle oxygenation as determined by near-infrared spectrophotometry during exercise were similar. The enlarged blood-buffering capacity after infusion of Bic attenuated acidosis and in turn arterial desaturation during maximal exercise.     

Fetal breathing and cardiovascular responses to graded methemoglobinemia in sheep

Graded methemoglobinemia (MetHb) was produced in unanesthetized fetal sheep to determine the effects on brain oxygenation. MetHb was induced by infusing methemoglobin-containing erythrocytes in exchange for fetal blood. During the hour after MetHb was established, fetal methemoglobin concentrations averaged 1.23 +/- 0.12 (mild MetHb), 1.71 +/- 0.13 (moderate MetHb), and 2.27 +/- 0.17 g/dl (severe MetHb). MetHb reduced mean arterial O2 content by approximately 19 (mild MetHb), 29 (moderate MetHb), and 39% (severe MetHb). The average preductal arterial PO2 fell by 1.6 (-7%), 2.8 (-11%), and 4.0 Torr (-16%) for mild, moderate, and severe MetHb, respectively. Fetal heart rate increased significantly during mild and moderate MetHb, and mean arterial pressure fell slightly during moderate and severe MetHb. The incidences of fetal breathing and eye movements were reduced in a dose-dependent manner when the calculated brain end-capillary PO2 was less than 14 Torr. We conclude that: 1) the effective capillary PO2 in the fetal brain can be significantly reduced by increasing the distance between non-methemoglobin-laden erythrocytes in capillaries and 2) hypoxic inhibition of fetal breathing probably arises from discrete areas of the brain having a PO2 less than 3 Torr.     

Stimulation of breathing movements in fetal sheep by inhibitors of prostaglandin synthesis

We studied the effects of inhibitors of prostaglandin synthesis on fetal breathing movements on 17 occasions in 11 lambs (gestational age 125-141 days). We gave 12 h infusions of sodium mechlofenamate (8.6-22.2 mg.kg-1) in 13 studies and indomethacin (21.8-38.8 mg.kg-1) in four studies. Results were similar with both agents and did not correlate with drug dosage. There were no changes in fetal arterial blood pressure, pH or blood gas tensions. We assessed fetal breathing movements by measurements of tracheal pressure for a control period of 224 h prior to and 208 h during the infusion of inhibitors of prostaglandin synthesis; their administration caused a marked stimulation of fetal breathing movements judged from the following four variables: (1) incidence of fetal breathing movements increased from 38.4 to 69.2% of the time (P < 0.001); (2) average amplitude of change in tracheal pressure during fetal breathing movements increased from 4.1 to 6.0 torr (P < 0.01); (3) maximal amplitude of change in tracheal pressure during fetal breathing movements increased from 8.8 to 13.4 torr (P < 0.01); and (4) the duration of the longest continuous episode of fetal breathing movements increased from 37 to 229 min (P < 0.05). Two fetuses had electrocorticogram (ECoG) recordings. In control periods, fetal breathing movements occurred only during low voltage, high frequency ECoG activity; however, during infusions of inhibitors of prostaglandin synthesis, fetal breathing movements occurred also during high voltage, low frequency ECoG activity. We conclude that inhibitors of prostaglandin synthesis stimulate fetal breathing movement in fetal sheep. These results suggest that a component of the prostaglandin system is a factor which inhibits breathing movements during fetal life.     

Effect of increased arterial CO2 on fetal breathing and behavior in sheep

We studied breathing and behavioral response to increased arterial CO2 (PaCO2) in 12 fetal sheep between 130 and 145 days of gestation. Of these 12 fetuses, 10 had an increase in PaCO2 through maternal rebreathing of CO2; in the other 2 fetuses CO2 was increased via an endotracheal tube and application of continuous distending airway pressure. We used our window technique to observe and videotape fetal behavior. The experiments consisted of recording breathing activity and behavior during resting conditions (1 low- and high-voltage ECoG cycle) and during administration of CO2. We measured electrocortical activity (ECoG), eye movements (EOG), electromyography of the diaphragm (EMGdi) and neck muscles, tracheal (Ptr), amniotic, and carotid arterial pressures. Administration of CO2 by the rebreathing technique produced an increase in the amplitude of breathing activity as reflected by an increase in Ptr from 5.0 +/- 0.6 to 12 +/- 1.9 mmHg (P less than 0.01) and an increase in SEMGdi from 32 +/- 4 to 77 +/- 8% max (P less than 0.001). Frequency increased due to a decrease in inspiratory (TI) and expiratory duration. Ptr/TI increased from 11.0 +/- 2.0 to 37.4 +/- 9.0 mmHg/s (P less than 0.05) and SEMGdi/TI increased from 67 +/- 7 to 221 +/- 28% max/s (P less than 0.001). Although the response was at times prolonged into the transitional high-voltage zone, it did not persist during established high-voltage ECoG.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evidence for second metabolic pathway for O2 from PtiO2 measurements in denervated cat carotid body

O2 microelectrode studies were conducted in the cat carotid body (CB) to investigate the hypothesis that there is a second, low affinity metabolic pathway for O2 in addition to classical oxidative metabolism. Tissue PO2 (PtiO2) and O2 disappearance rates (dPO2/dt) after brief blood flow occlusion were measured with recessed cathode microelectrodes (tip diameter less than 5 microns) at 150 sites in 15 normal cats (controls) and at 154 sites in 5 cats in which one CB had been denervated 2 or 3 days before the experiments. Mean PtiO2 was slightly higher in denervated CBs: 79.6 +/- 1.6 (SE) Torr compared with 76.4 +/- 2.0 Torr for controls (P = not significant). Mean dPO2/dt was 8.4% faster: -8.42 +/- 0.28 Torr/s compared with -7.77 +/- 0.43 Torr/s for controls (P less than 0.05). The O2 consumption rate (VO2), calculated from dPO2/dt correcting for cat oxyhemoglobin, was 7.5% higher: 1.62 and 1.51 ml.100 g-1.min-1, respectively, for denervated and control CBs (P less than 0.05). The apparent Michaelis-Menten constant, Kmapp (defined as the PtiO2 where dPO2/dt decreased by 50% from the initial rate during the first 3 s after occlusion) was determined for each O2 disappearance curve. After denervation, Kmapp decreased significantly by -47%: 12.0 +/- 1.3 Torr compared with 22.6 +/- 2.5 Torr for controls (P less than 0.01). The data provide evidence for a second metabolic pathway for O2 in the CB that loses its influence on VO2 after denervation.     

Hemodynamic effects of periodic obstructive apneas in sedated pigs with congestive heart failure.

Because of similar physiological changes such as increased left ventricular (LV) afterload and sympathetic tone, an exaggerated depression in cardiac output (CO) could be expected in patients with coexisting obstructive sleep apnea and congestive heart failure (CHF). To determine cardiovascular effects and mechanisms of periodic obstructive apnea in the presence of CHF, 11 sedated and chronically instrumented pigs with CHF (rapid pacing) were tested with upper airway occlusion under room air breathing (RA), O(2) breathing (O2), and room air breathing after hexamethonium (Hex). All conditions led to large negative swings in intrathoracic pressure (-30 to -39 Torr) and hypercapnia (PCO(2) approximately 60 Torr), and RA and Hex also caused hypoxia (to approximately 42 Torr). Relative to baseline, RA increased mean arterial pressure (from 97.5 +/- 5.0 to 107.3 +/- 5.7 Torr, P < 0.01), systemic vascular resistance, LV end-diastolic pressure, and LV end-systolic length while it decreased CO (from 2.17 +/- 0.27 to 1.52 +/- 0.31 l/min, P < 0.01), stroke volume (SV; from 23.5 +/- 2.4 to 16.0 +/- 4.0 ml, P < 0.01), and LV end-diastolic length (LVEDL). O2 and Hex decreased mean arterial pressure [from 102.3 +/- 4.1 to 16.0 +/- 4.0 Torr (P < 0.01) with O2 and from 86.0 +/- 8.5 to 78.1 +/- 8.7 Torr (P < 0.05) with Hex] and blunted the reduction in CO [from 2.09 +/- 0.15 to 1.78 +/- 0.18 l/ml for O2 and from 2.91 +/- 0.43 to 2.50 +/- 0.35 l/ml for Hex (both P < 0.05)] and SV. However, the reduction in LVEDL and LV end-diastolic pressure was the same as with RA. There was no change in systemic vascular resistance and LVEDL during O2 and Hex relative to baseline. In the CHF pigs during apnea, there was an exaggerated reduction in CO and SV relative to our previously published data from normal sedated pigs under similar conditions. The primary difference between CHF (present study) and the normal animals is that, in addition to increased LV afterload, there was a decrease in LV preload in CHF contributing to SV depression not seen in normal animals. The decrease in LV preload during apneas in CHF may be related to effects of ventricular interdependence.     

Two-cytochrome metabolic model for carotid body PtiO2 and chemosensitivity changes after hemorrhage

O2 microelectrode measurements were made in the cat carotid body (CB) at normal control blood pressures (C) and after hemorrhage (H) to reduce mean arterial blood pressure [C, 98.7 +/- 4.6 (SE) mmHg; H, 58.1 +/- 1.8; P less than 0.001; paired t test; n = 9 cats]. Mean tissue PO2 (PtiO2) was significantly lower (C, 78.4 +/- 3.0 Torr; H, 65.3 +/- 4.8; P less than 0.01). Except for two experiments with good autoregulation, the decrease in PtiO2 correlated with the reduction in blood pressure (r = 0.791, P less than 0.005). Measurements of O2 disappearance curves (DCs) and sinus nerve discharge (ND) were obtained after blood supply was occluded for 30-45 s (56 C DCs, 44 H DCs). Disappearance rates (dPO2/dt) were significantly slower after hemorrhage (C, -7.52 +/- 0.47 Torr/s; H, -6.60 +/- 0.44; P less than 0.01), decreasing by 0.656 Torr/s for each 10 Torr fall in PtiO2 (r = 0.626, P less than 0.05). Resting ND before occlusion increased during hypotension (11.6 +/- 2.9% of control, P less than 0.01) and correlated with the decrease in PtiO2 (r = -0.792, P less than 0.005). A computer simulation was performed for a two-cytochrome metabolic model with a second, low-O2-affinity oxidase in addition to normal oxidative metabolism. The effects of cat oxyhemoglobin and blood pH on the O2 DC measurement were also taken into account. The simulation for the two-cytochrome model was consistent with our experimental data and predicts reductions in blood flow and O2 metabolism with hypotension after hemorrhage that have similarities, as well as aspects that disagree, with previous reports in the literature.     

Hyperoxemia profoundly alters breathing pattern and arouses the fetal sheep.

We have recently shown that hyperoxemia alone or combined with umbilical cord occlusion causes continuous breathing and arousal in the fetal sheep (Baier, Hasan, Cates, Hooper, Nowaczyk & Rigatto, 1990). We have not however analyzed the changes in the pattern of breathing associated with these events. To do this, we measured the changes in breathing pattern, electrocortical activity and behaviour on 29 occasions in 15 fetal sheep in late gestation. Fetuses were studied during rest, and during lung distention (about 30 cm H2O) with 100% nitrogen (control), 17% oxygen, 100% oxygen and umbilical cord occlusion. Lung distention was obtained using a high frequency oscillator (Senko Co) and in some fetuses a stroke volume of 0 to 20 cm H2O was used to keep PaCO2 near-constant. We found that lung distention with nitrogen or 17% oxygen did not alter the pattern of breathing or behaviour. In 12 out of 34 (35%) experiments 100% oxygen induced continuous breathing, PaO2 increasing to about 250 torr. In the remaining 22 experiments, PaO2 increased to about 100 torr only and breathing was not continuous but it became continuous upon cord occlusion; with occlusion there was a further increase in PaO2 to 190 torr. The increased breathing with oxygen and occlusion was associated with an increase in breathing output (integral of EMGdi x f), an increase in inspiratory drive (integral of EMGdi/Ti), and a decrease in inspiratory (Ti) and expiratory (Te) times. In ten experiments PaCO2 was kept near-constant and the magnitude of the changes remained.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulmonary gas exchange and acid-base state at 5,260 m in high-altitude Bolivians and acclimatized lowlanders.

Pulmonary gas exchange and acid-base state were compared in nine Danish lowlanders (L) acclimatized to 5,260 m for 9 wk and seven native Bolivian residents (N) of La Paz (altitude 3,600-4,100 m) brought acutely to this altitude. We evaluated normalcy of arterial pH and assessed pulmonary gas exchange and acid-base balance at rest and during peak exercise when breathing room air and 55% O2. Despite 9 wk at 5,260 m and considerable renal bicarbonate excretion (arterial plasma HCO3- concentration = 15.1 meq/l), resting arterial pH in L was 7.48 +/- 0.007 (significantly greater than 7.40). On the other hand, arterial pH in N was only 7.43 +/- 0.004 (despite arterial O2 saturation of 77%) after ascent from 3,600-4,100 to 5,260 m in 2 h. Maximal power output was similar in the two groups breathing air, whereas on 55% O2 only L showed a significant increase. During exercise in air, arterial PCO2 was 8 Torr lower in L than in N (P < 0.001), yet PO2 was the same such that, at maximal O2 uptake, alveolar-arterial PO2 difference was lower in N (5.3 +/- 1.3 Torr) than in L (10.5 +/- 0.8 Torr), P = 0.004. Calculated O2 diffusing capacity was 40% higher in N than in L and, if referenced to maximal hyperoxic work, capacity was 73% greater in N. Buffering of lactic acid was greater in N, with 20% less increase in base deficit per millimole per liter rise in lactate. These data show in L persistent alkalosis even after 9 wk at 5,260 m. In N, the data show 1) insignificant reduction in exercise capacity when breathing air at 5,260 m compared with breathing 55% O2; 2) very little ventilatory response to acute hypoxemia (judged by arterial pH and arterial PCO2 responses to hyperoxia); 3) during exercise, greater pulmonary diffusing capacity than in L, allowing maintenance of arterial PO2 despite lower ventilation; and 4) better buffering of lactic acid. These results support and extend similar observations concerning adaptation in lung function in these and other high-altitude native groups previously performed at much lower altitudes.     

Changes in plasma adenosine during simulated birth of fetal sheep

Adenosine is known to inhibit nonshivering thermogenesis in adult brown fat. These experiments were undertaken to test whether fetal adenosine, normally present in high concentrations, suppresses lipolysis in utero and then falls after birth, permitting thermogenesis to begin. To test this hypothesis, we measured fetal plasma adenosine concentration [ADO] using high-performance liquid chromatography in 11 fetal sheep at 135-140 days gestation during simulated birth. During an initial control period, fetal [ADO] averaged 1.9 +/- 0.3 microM, about four times maternal [ADO] (0.4 +/- 0.1 microM, P less than 0.001). The fetus was then cooled by circulating cold water through a plastic coil encircled about the fetal torso. One hour later, when fetal core temperature had decreased 2.3 degrees C, fetal [ADO] averaged 2.8 +/- 0.5 microM, a 50% increase (P less than 0.05), while thermogenesis remained inactive. Next the fetal lungs were ventilated with O2 to raise arterial Po2 to greater than or equal to 150 Torr. Fetal [ADO] decreased only slightly, and thermogenic responses were modest. Finally, the umbilical cord was occluded. Fetal [ADO] decreased rapidly and 60 min later averaged 1.1 +/- 0.2 microM, 40% below initial control (P less than 0.05) and 57% below the previous period (P less than 0.001). As [ADO] fell, strong thermogenic responses became apparent, as indicated by seven- to eightfold increases in plasma glycerol (P less than 0.001) and a doubling in fetal O2 consumption (P less than 0.001). These results are consistent with the hypothesis that high fetal [ADO] inhibits thermogenesis before birth but then decreases after cord occlusion, allowing thermogenesis to begin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronic administration of sodium cyanate decreases O2 extraction ratio in dogs

It has been proposed that an increase in the affinity of hemoglobin for O2 may be beneficial in severe hypoxemia. To test this hypothesis, we compared the response to progressive hypoxemia in dogs with normal hemoglobin affinity (P50 = 32.4 +/- 0.7 Torr) to dogs with a left shift of the oxyhemoglobin dissociation curve (P50 = 21.9 +/- 0.5 Torr) induced by chronic oral administration of sodium cyanate. Animals were anesthetized, paralyzed, and mechanically ventilated. The inspired O2 fraction was progressively lowered by increasing the inspired fraction of N2. The lowest level of O2 transport required to maintain base-line O2 consumption (VO2) was 9.3 +/- 0.8 ml.min-1.kg-1 for control and 16.5 +/- 1.1 ml.min-1.kg-1 for the sodium cyanate-treated dogs (P less than 0.01). Other measured parameters at this level of O2 transport were, for experimental vs. control: arterial PO2 19.3 +/- 2.4 (SE) Torr vs. 21.8 +/- 1.6 Torr (NS); arterial O2 content 10.0 +/- 1.2 ml/dl vs. 4.9 +/- 0.4 ml/dl (P less than 0.01); mixed venous PO2 14.0 +/- 1.5 Torr vs. 13.8 +/- 1.0 Torr (NS); mixed venous O2 content 6.8 +/- 1.0 ml/dl vs. 2.3 +/- 0.2 ml/dl (P less than 0.01); and O2 extraction ratio 32.7 +/- 2.8% vs. 51.2 +/- 3.8% (P less than 0.01). We conclude that chronic administration of sodium cyanate appears to be detrimental to O2 transport, since the experimental dogs were unable to increase their O2 extraction ratios to the same level as control, thus requiring a higher level of O2 transport to maintain their base-line VO2 values.     

Breath holding during intense exercise: arterial blood gases, pH, and lactate

Seven healthy endurance-trained [maximal O2 uptake (VO2max) = 57.1 +/- 4.1 ml.kg-1.min-1)] female volunteers (mean age 24.4 +/- 3.6 yr) served as subjects in an experiment measuring arterial blood gases, acid-base status, and lactate changes while breath holding (BH) during intense intermittent exercise. By the use of a counterbalance design, each subject repeated five intervals of a 15-s on:30-s off treadmill run at 125% VO2max while BH and while breathing freely (NBH). Arterial blood for pH, PO2, PCO2, O2 saturation (SO2) HCO3, and lactate was sampled from a radial arterial catheter at the end of each work and rest interval and throughout recovery, and the results were analyzed using repeated-measures analysis of variance. Significant reductions in pHa (delta mean = 0.07, P less than 0.01), arterial PO2 (delta mean = 24.2 Torr, P less than 0.01), and O2 saturation (delta mean = 4.6%, P less than 0.01) and elevations in arterial PCO2 (delta mean = 8.2 Torr, P less than 0.01) and arterial HCO3 (delta mean = 1.3 meq/l, P = 0.05) were found at the end of each exercise interval in the BH condition. All of the observed changes in arterial blood gases and acid-base status induced by BH were reversed during the rest intervals. During recovery, significantly (P less than 0.025) greater levels of arterial lactate were found in the BH condition.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gas exchange during separate diaphragm and intercostal muscle breathing.

In patients with diaphragm paralysis, ventilation to the basal lung zones is reduced, whereas in patients with paralysis of the rib cage muscles, ventilation to the upper lung zones in reduced. Inspiration produced by either rib cage muscle or diaphragm contraction alone, therefore, may result in mismatching of ventilation and perfusion and in gas-exchange impairment. To test this hypothesis, we assessed gas exchange in 11 anesthetized dogs during ventilation produced by either diaphragm or intercostal muscle contraction alone. Diaphragm activation was achieved by phrenic nerve stimulation. Intercostal muscle activation was accomplished by electrical stimulation by using electrodes positioned epidurally at the T(2) spinal cord level. Stimulation parameters were adjusted to provide a constant tidal volume and inspiratory flow rate. During diaphragm (D) and intercostal muscle breathing (IC), mean arterial Po(2) was 97.1 +/- 2.1 and 88.1 +/- 2.7 Torr, respectively (P < 0.01). Arterial Pco(2) was lower during D than during IC (32.6 +/- 1.4 and 36.6 +/- 1.8 Torr, respectively; P < 0.05). During IC, oxygen consumption was also higher than that during D (0.13 +/- 0.01 and 0.09 +/- 0.01 l/min, respectively; P < 0.05). The alveolar-arterial oxygen difference was 11.3 +/- 1.9 and 7.7 +/- 1.0 Torr (P < 0.01) during IC and D, respectively. These results indicate that diaphragm breathing is significantly more efficient than intercostal muscle breathing. However, despite marked differences in the pattern of inspiratory muscle contraction, the distribution of ventilation remains well matched to pulmonary perfusion resulting in preservation of normal gas exchange.     

Fetal breathing and sleep state responses to graded carboxyhemoglobinemia in sheep

To investigate CO effects on brain oxygenation, graded carboxyhemoglobinemia (HbCO) was produced in nine unanesthetized fetal sheep by infusing CO-laden erythrocytes in exchange for fetal blood. For the 1st h after this procedure, the mean fetal carboxyhemoglobin levels were 16.5 +/- 0.4% [control (C) = 1.4 +/- 0.4%] for mild HbCO, 22.7 +/- 0.6% (C = 1.8 +/- 0.4%) for moderate HbCO, and 27.8 +/- 0.5% (C = 2.1 +/- 0.7%) for severe HbCO. This induction of HbCO significantly reduced mean preductal arterial PO2 values to 4.3 Torr below control for mild HbCO, 4.6 Torr below control for moderate HbCO, and 5.5 Torr below control for severe HbCO. The respective arterial O2 contents were decreased by 17, 21, and 29%. Mean arterial pH was lowered only during severe HbCO, and arterial PCO2 values were unchanged. HbCO produced a fetal tachycardia. Mean arterial blood pressure was only increased during severe HbCO. The incidences of rapid eye movements and breathing activity were decreased by HbCO in a dose-dependent manner. When related to calculated brain tissue PO2, these decreases were similar to those measured during hypoxic hypoxia and anemia, suggesting that carboxyhemoglobin effects result solely from diminished oxygenation. It is concluded that 1) the peripheral arterial chemoreceptors in the fetus apparently have little effect on hypoxic inhibition of breathing and 2) the carboxyhemoglobin concentrations required to inhibit fetal breathing are greater than those likely to be encountered clinically.