Biomedical subjects

D B Cates

Publications and source records attributed to D B Cates.

28 records · Page 2Linked to original sources

PubMed1992

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.

Animals↗

PubMed1991

Clinical and physiological responses to prolonged nasogastric administration of doxapram for apnea of prematurity.

We hypothesized that enteral doxapram would effectively treat apnea of prematurity without the appearance of major side effects. Of 16 infants, 10 (BW 1,520 +/- 102 g) received doxapram alone and 6 (BW 1,020 +/- 35 g) received doxapram plus theophylline. Apneas decreased from 16.7 +/- 1.9 to 2.1 +/- 0.6 in infants receiving doxapram alone, and from 38.2 +/- 4.4 to 7.9 +/- 2.2 apneas/24 h in those receiving doxapram plus theophylline. This was associated with an increase in alveolar ventilation, a shift of the ventilatory response to CO2 to the left, and no change in the immediate ventilatory response to 100% oxygen. Side effects included premature teeth buds corresponding to the lower central incisors, prevalence of occult blood in stool and necrotizing enterocolitis. The findings suggest that doxapram effectively controls apnea when given enterally, but should be used cautiously because of potentially harmful side effects.

Apnea↗

PubMed1991

The ventilatory response to endogenous CO2 in preterm infants.

The measurement of the ventilatory response to inhaled CO2 is unphysiologic because the CO2 that normally stimulates breathing is endogenous (tissue or venous CO2). We took advantage of the spontaneous changes in alveolar PCO2 and ventilation occurring in preterm infants during periodic breathing to calculate the ventilatory response to endogenous CO2. This response was obtained in 20 infants and compared with those obtained using the more conventional methods of steady-state inhalation of CO2 (12 infants) and rebreathing of CO2 (11 infants); it was also compared with a transient change in alveolar CO2 obtained by inhalation of 7% CO2 in air for 10 s (CO2 "bolus"; 11 infants). All groups of infants had similar birth weight and gestational ages. To calculate the response to endogenous CO2, delta PACO2 was measured as the difference between lowest and highest PaCO2 and delta VE was the difference between the corresponding instantaneous ventilation. To adjust for circulation time, values for PACO2 were made lowest for the last breath before apnea and highest for the first breath after apnea. The coefficient of variation of the method was 8%. The slope of the ventilatory response to endogenous CO2 was 0.067 +/- 0.009 (mean +/- SE) L.min-1.kg-1.mm Hg PACO2(-1), a value greater than that using steady-state and rebreathing methods (0.038 +/- 0.004 and 0.040 +/- 0.006 L.min-1.kg-1.mm Hg PACO2(-1), respectively), but similar to that of infants inhaling a CO2 "bolus" (0.051 +/- 0.009 L.min-1.kg-1.mm Hg PACO2(-1)).(ABSTRACT TRUNCATED AT 250 WORDS)

Apnea↗

PubMed1990

Effects of various concentrations of O2 and umbilical cord occlusion on fetal breathing and behavior.

To test the hypothesis that continuous fetal breathing could be induced by hyperoxemia alone or by hyperoxemia and umbilical cord occlusion, even in the absence of a rise in arterial PCO2 (PaCO2), we studied 18 chronically instrumented fetal sheep on 34 occasions using our window model (18). 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 approximately cmH2O. Inspired N2, 17% O2, and 100% O2 were given to the fetus during one cycle each. While 100% O2 was given, the umbilical cord was occluded (balloon cuff).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

The effects of naloxone on the changes in breathing and behaviour induced by morphine in the foetal sheep.

In the foetal sheep, administration of morphine induces apnoea followed by hyperpnoea; during hyperpnoea the foetus arouses. We tested the hypothesis that naloxone, an opiate antagonist, would block these responses. In 14 foetal sheep between 123 and 140 days of gestation, we measured electrocortical activity (ECoG), eye movements (EOG), diaphragmatic activity (EMGdi), blood pressure and amniotic pressure. Morphine (1 mg/kg) was injected in the foetal jugular vein during low-voltage ECoG. Saline or naloxone (0.1, 0.5 and 2.0 mg) were given, in randomized order, before the morphine injection, shortly after morphine injection during apnoea, and during maximum hyperpnoea. Saline alone had no effect on breathing or behaviour. When saline and naloxone preceded the morphine injection the length of apnoea was 26.6 +/- 7.7 and 19.5 +/- 7.0 min (SEM, P = 0.25) while the length of sustained hyperpnoea was 104.8 +/- 11.4 and 29.6 +/- 8.4 min respectively (P = 0.001). When administered during the maximum breathing response, naloxone decreased the length of breathing from 92.2 +/- 8.4 (saline) to 8.8 +/- 2.9 min (P = 0.001). Respiratory output (fEMGdi x f) also decreased from 6545 +/- 912 arbitrary units post saline to 3841 +/- 629 arbitrary units after naloxone (P = 0.05). Arousal disappeared with the decrease in breathing response. The negligible effect of naloxone on apnoea and its strong inhibition of hyperpnoea suggest that morphine may act on two distinct central regions or on two subtypes of opioid receptors to produce apnoea, hyperpnoea and arousal.

Animals↗

PubMed1990

The effects of brain-stem section on the breathing and behavioural response to morphine in the fetal sheep.

In the unanesthetized fetal sheep the administration of morphine causes initial apnoea followed by hyperpnoea. We thought that a section of the brain at midcollicular level might separate these two effects. Therefore we sectioned the brain stem of five fetuses at 132 +/- 1 (SEM) days of gestation and compared their responses to morphine (17 experiments) with that observed in seven intact fetuses at similar gestational ages (15 experiments). Brain stem sections were confirmed morphologically and histologically. Morphine, 1 mg/kg was injected in the fetal jugular vein during low-voltage electrocortical activity (ECoG). We measured ECoG, eye movements, diaphragmatic activity, blood pressure and amniotic pressure. Sectioned fetuses before the administration of morphine had a complete dissociation between ECoG and breathing activity. With the administration of morphine we found: (i) the length of the apnoea was 139.8 +/- 15.5 min in sectioned fetuses and 17.0 +/- 5.8 min in intact fetuses (P less than 0.01); and (ii) there was no hyperpneic response in the sectioned fetus whereas the length of hyperpnoea in the intact group was 99.1 +/- 11.8 min (P less than 0.001). The results support the idea of two central distinct areas of action of morphine in the fetal brain. The absence of hyperpnoea in the sectioned fetuses suggests that neurons inhibiting the 'respiratory neurons' are located rostrally to the mid-collicular line.

Animals↗

PubMed1989

Hypoxic airway constriction in infants of very low birth weight recovering from moderate to severe bronchopulmonary dysplasia.

We hypothesized that infants recovering from severe bronchopulmonary dysplasia have airway constriction that is, at least in part, related to borderline hypoxia. If this hypothesis were correct, pulmonary resistance should decrease with the administration of oxygen. To test this hypothesis, we studied 10 infants recovering from severe bronchopulmonary dysplasia (study weight 2490 +/- 275 gm; birth weight 1010 +/- 89 gm; postnatal age 73 +/- 7 days; postconceptional age 38.5 +/- 1.6 weeks) and 10 matched control infants (study weight 2430 +/- 179 gm; birth weight 2320 +/- 195 gm; postnatal age 25 +/- 4 days; postconceptional age 37.5 +/- 0.8 weeks). Resistance and compliance were measured by means of a mask with a flowmeter and an esophageal balloon (with the PEDS computer program). Measurements in both groups were made in quiet sleep, without sedation, during the inhalation of room air and during the fifth minute of oxygen inhalation. We found that (1) total pulmonary resistance, significantly higher in infants with bronchopulmonary dysplasia than in control infants, decreased from 206.1 +/- 47 cm H2O.L-1.sec-1 during inhalation of room air to 106.5 +/- 20.9 during inhalation of 100% oxygen (p less than 0.05) and (2) pulmonary dynamic compliance, lower in infants with bronchopulmonary dysplasia than in control infants, increased significantly with the administration of 100% oxygen. The results suggest that infants with bronchopulmonary dysplasia have airway constriction and that this is alleviated by inhalation of oxygen.

Airway Obstruction↗

PubMed1988

Effect of morphine on breathing and behavior in fetal sheep.

To define the dose response of apnea and breathing to morphine we studied 12 fetuses at 116-141 days of gestation using our window technique. We instrumented the fetus to record electrocortical activity (ECoG), eye movements (EOG), diaphragmatic activity (integral of EMGdi), heart rate, carotid blood pressure, and amniotic pressure. Saline and morphine in doses of 0.03, 0.1, 0.5, 1, and 3 mg/kg were injected in random order in the jugular vein of the fetus during low-voltage ECoG. Fetuses were videotaped for evaluation of fetal behavior. We found 1) that saline did not elicit a response; 2) apnea, associated with a change from low- to high-voltage ECoG, increased from 2.2 +/- 1.5 (SE) min in two fetuses at a dose of 0.03 mg to 20 +/- 6.3 min in seven fetuses at 3 mg/kg (P less than 0.005); 3) the length of the breathing responses, associated with a change from high- to low-voltage ECoG, were 15 +/- 1.8 and 135.9 +/- 18.1 min (P less than 0.0005); 4) integral of EMGdi X frequency, an index equivalent to minute ventilation, increased from 1,763 +/- 317 arbitrary units to 10,658 +/- 1,843 at 1.0 mg/kg and then decreased to 7,997 +/- 1,335 at 3.0 mg/kg. These changes were related to a steady increase in integral of EMGdi, whereas frequency decreased at 3 mg/kg. There was an increase in breathing response to morphine plasma concentrations or morphine doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1981

Effect of periodic or regular respiratory pattern on the ventilatory response to low inhaled CO2 in preterm infants during sleep.

We wanted to know whether the ventilatory response to low concentrations of CO2 is measurable in the absence of change in alveolar PCO2, is sleep state dependent, and is dictated by the resting respiratory pattern. Therefore, we gave 11 preterm infants (birth weight, 1,565 +/- 122 g; gestational age, 32 +/- 1 wk; postnatal age, 28 +/- 5 days) 0.5 to 1.5% CO2 after a control period of breathing 21% O2. They were studied on 2 or 3 occasions, the aim being to have 5 infants in each of 2 categories, periodic to regular breathing, and regular to regular breathing, after administration of CO2 in both sleep states (n = 20). In both sleep states, when low CO2 increased ventilation, alveolar PCO2 also increased. The increase in ventilation was primarily due to an increase in breathing frequency if breathing was periodic, and to an increase in tidal volume if breathing was regular. This response was not affected by sleep state. We conclude that changes in respiratory pattern with low inhaled CO2 are fundamentally dependent on whether the baseline respiration is periodic or regular.

Carbon Dioxide↗

PubMed1981

Effect of feeding on the chemical control of breathing in the newborn infant.

To examine the influence of feeding on the chemical control of breathing in neonates, we studied the ventilatory response to 3% CO2 in air in nine bottle fed (BOT) and eight breast fed (BR) term infants during feeding while the infants were alert. Control responses were obtained either before or after feeding, VE, respiratory frequency, tidal volume, inspiratory time, expiratory time, and sum of inspiratory and expiratory time, VT/Ti/Ttot, PACO2 and slope (S) of CO2 response (liter/min/kg/mmHg) were determined. During 3% CO2 while resting BR had a lower VE, VT, VT/Ti than BOT and S in BR was 40% of BOT (P less than 0.05). During feeding and CO2 when compared to resting and CO2 there was no difference in either BR or BOT in VT/Ti but Ti/Ttot decreased in both groups. During feeding, S in BOT was reduced from 0.049 +/- 0.012 (mean +/- S.E.) to 0.013 +/- 0.002 (74% reduction) and in BR from 0.020 +/- 0.002 to 0.009 +/- 0.002 (55%). Thus, behavioral activity (either BR or BOT) markedly depresses the ventilatory response to chemical stimuli (CO2). This modification is primarily related to changes in "effective" respiratory timing (Ti/Ttot) rather than mean inspiratory flow (VT/Vi).

Bottle Feeding↗