Biomedical subjects

R E Alvaro

Publications and source records attributed to R E Alvaro.

10 recordsLinked to original sources

PubMed1998

Effect of norepinephrine on fetal breathing in sheep.

We tested the hypothesis that the surge of norepinephrine at birth is associated with the establishment of continuous breathing. Therefore, we studied whether the administration of norepinephrine could enhance fetal breathing during administration of oxygen, or 100% O2 plus cord occlusion, and if phenoxybenzamine would reverse these changes. Fetal sheep were instrumented in late gestation to measure electrocortical activity and diaphragmatic electromyography. These parameters and blood gases were measured before and during in utero administration of nitrogen, 100% O2, 100% O2 plus umbilical cord occlusion, and subsequently during umbilical reperfusion and recovery. Nine fetuses (14 experiments) received continuous norepinephrine (0.13 microgram/kg/min) throughout the experiment while 9 other fetuses (18 experiments) underwent the same treatment without the hormonal infusion. We found that norepinephrine inhibited the breathing induced by 100% O2 plus cord occlusion, despite a significant increase in the duration of low-voltage electrocortical activity; phenoxybenzamine reverted these changes. The findings suggest that the surge of norepinephrine at birth is probably not the primary mechanism for establishment of continuous breathing.

Adrenergic alpha-Agonists↗

PubMed1997

Preliminary characterization of a placental factor inhibiting breathing in fetal sheep.

Previous studies have revealed a placental extract that inhibits breathing in fetal sheep. In the present study of 29 chronically instrumented sheep at 132+/-1 days of gestation, infusion of the 1-10 kDa extract inhibited breathing in 76% of the experiments whereas Krebs' solution inhibited it in 24%. It retained this activity after 6 months of freezing, after lyophilization, and upon lowering the pH during purification from 8.0 to 4.0, but it inhibited breathing in only 35% when the pH was lowered to 2.0. A significant dose-dependent effect was observed from a 16-fold dilution to a 4-fold concentration. Treatment of the extract with proteinase K or boiling reduced the activity to 30% or 26% inhibition, respectively. The activity was not adsorbed to an ion-exchange column at pH 7.0 or 8.0, but it was at pH 9.0 and it eluted with increasing NaCl concentrations. On a polyacrylamide gel the activity was eluted at a K(av) of 0.66 (82% inhibition), corresponding to between 2.5 and 4.5 kDa. These findings suggest that a peptide produced by the placenta, with a molecular mass between 2.5 and 4.5 kDa, inhibits fetal breathing.

Animals↗

PubMed1996

The biphasic ventilatory response to hypoxia in preterm infants is not due to a decrease in metabolism.

The mechanism underlying the biphasic ventilatory response to hypoxia in neonates is poorly understood. Because alveolar PCO2 (PaCO2) decreases and remains low during hypoxia, it has been argued that a decrease in metabolism may occur. We hypothesized that if the late decrease in ventilation during hypoxia is due to a decrease in CO2 production, an increase in PACO2 should abolish it. We studied 27 preterm infants [birth weight, 1,700 +/- 41 g (mean +/- SEM); study weight, 1,760 +/- 36 g; gestational age 32 +/- 0.2 weeks; postnatal age, 17 +/- 1 days]. A flow-through system and Beckman analyzers were used to measure ventilation and alveolar gases. Metabolism was expressed as changes in oxygen consumption. Infants were studied randomly during hypoxia alone (15% O2 + N2, n = 55) and during hypoxia plus CO2 (0.5% CO2, n = 30; 2% CO2, n = 10). Each experiment consisted of 2 minutes of control measurements (21% O2), 5 minutes of measurements during hypoxia alone or hypoxia plus CO2, followed by 2 minutes of recovery (21% O2). We found a biphasic response to hypoxia with or without CO2 supplementation, the percent change in ventilation from initial peak hyperventilation to late hypoventilation at 5 minutes being -16 +/- 2 on 15% O2; -9 +/- 3 on 15% O2 + 0.5% CO2; and -15 +/- 9 on 15% O2 + 2% CO2 (P < 0.05). The decrease in ventilation was primarily due to a significant decrease in frequency; tidal volume increased. Oxygen consumption decreased similarly with the various inspired gas mixtures during hypoxia. These findings indicate that the decrease in ventilation during hypoxia is unlikely to be solely due to a decrease in metabolism since the late decrease in ventilation following initial hyperventilation still occurred despite the elimination of a fall in PACO2. We speculate that the mechanism underlying the late decrease in ventilation is likely of central origin, probably mediated through the release of inhibitory neurotransmitters.

Carbon Dioxide↗

PubMed1996

Specificity of a placental factor inhibiting breathing in fetal sheep.

We have found previously that the infusion of a placental extract inhibits breathing induced by 100% O2 plus umbilical cord occlusion in the fetal sheep, suggesting that a placental factor is responsible for the inhibition of fetal breathing. To test whether this factor is specific to the placenta and whether it also inhibits spontaneous fetal breathing (occurring in the absence of cord occlusion), we administered extracts from the placenta, muscle and liver of the pregnant ewe, extracts of fetal liver, and Krebs solution to 16 chronically instrumented fetal sheep at 135 +/- 5 days of gestation. Infusions were made during low-voltage electrocortical activity, 5 to 15 min after a switch from high voltage, when breathing was well established. Within 90 s of the infusion of the placental extract in the carotid artery of the fetus, breathing decreased in 79% (33/42) of the experiments and was completely abolished in 71% (30/42) of them (P < 0.0001 compared with the other infusates). No apnoeas were observed with the Krebs solution (0/19) and the maternal muscle (0/20). Extracts of maternal and fetal liver abolished breathing in only 17% (4/23) and 21% (6/29) of the experiments respectively (NS compared with Krebs solution). There were no significant changes in blood gas tensions, pH, blood pressure and heart rate associated with the infusion of the extracts. The electrocortical activity (ECoG) switched from low to high voltage in 50% of the experiments using placental extract compared with 0% with Krebs solution and maternal muscle, and with 9% and 17% with maternal and fetal liver respectively (P < 0.005). Breathing output (integral of EMGdi x f) during and after the infusions significantly decreased only with the placental extract. These findings indicate the presence of a factor produced by the placenta which inhibits fetal breathing and may be responsible for the normal inhibition of breathing observed in fetal life.

Animals↗

PubMed1996

Influence of sleep state and respiratory pattern on cyclical fluctuations of cerebral blood flow velocity in healthy preterm infants.

To examine the influence of sleep state, respiratory pattern, and ventilation on cyclical fluctuations (CF) in cerebral blood flow (CBF) velocity (CBFV), we studied 21 'healthy' preterm infants: birth weight 1,790 +/- 162 g (SEM), study weight 1,960 +/- 165 g, gestational age 32 +/- 1 weeks, postnatal age 20 +/- 4 (range 8-57) days. The CBFV was measured using on-line pulsed Doppler ultrasound by insonating the middle cerebral artery. Breathing was measured using a flow through system. The sleep state was monitored according to conventional criteria. Three hundred and seventy-five epochs of 1 min each were analyzed; 207 during quiet sleep (QS) and 168 during rapid eye movement (REM) sleep. CFs in CBFV were detected in all babies. The frequency of CF ranged from 0.5 to 6 cycles/min. The proportion of epochs showing CF was similar during both sleep states (56% QS vs. 59% REM; p = NS). Although the mean CBFV (cm/s) was similar in these two sleep states, the mean coefficient of variation, a measure of CF amplitude, was significantly higher during REM as compared with QS (6 +/- 0.5 vs. 4.3 +/- 0.2%; p < 0.05). Similarly, the mean CBFVs were similar with various respiratory patterns, but the coefficient of variation was significantly higher in periodic and apneic patterns as compared with regular and irregular respiratory patterns (5.6 +/- 0.6% periodic, 5.6 +/- 0.3% apneic, 3.6 +/- 0.3% regular, and 4.1 +/- 0.5% irregular, p < 0.05). The amplitude of CF was associated with the variability of the heart rate (p < 0.05), but not with the variability of the respiratory measurements. These findings suggest: (1) REM sleep is associated with a greater CBF variability than QS, and (2) periodic and apneic breathing are associated with a greater CBF variability than regular or irregular breathing. We speculate that sleep state and respiratory pattern do not determine but modulate the CBF. Our data suggest that in studies involving interpretation of CBFV data using the Doppler technique, breathing patterns should be taken into account in addition to sleep state.

Apnea↗

PubMed1996

Use of a magnified cardiac airflow oscillation to classify neonatal apnea.

Currently the classification of neonatal apnea relies upon an inference of airway closure based upon the presence of breathing efforts against such an obstruction. In this study we evaluate a new method of classification which utilizes the presence or absence of cardiac airflow oscillation to detect airway closure. Specifically, this evaluation consisted of an examination of the transmission characteristics of an artificially produced airflow oscillation through discrete airway narrowing in a model system; a confirmation that voluntary upper airway occlusion in adult volunteers uniformly induces complete loss of the oscillation; and a comparison of the cardiac oscillation method with the traditional method of apnea classification in a cohort of 4,309 apneas in 32 infants. We determined that the amplitude of the oscillation is negatively correlated with resistance (r = 0.97) and positively with the radius (r = 0.98) of narrowing in a model system, and that voluntary airway obstruction in adult subjects uniformly results in loss of transmitted cardiac oscillations. Moreover, although there was similarity in the frequency distribution of central, obstructive, and mixed apneas in our infants, there were statistically significantly greater obstructive events detected by the cardiac oscillation method. In addition, the cardiac oscillation method had the additional advantage of providing information regarding the timing of airway obstruction during apnea.

Adult↗

PubMed1995

Effects of central apnea on cerebral blood flow velocity in healthy term infants.

We evaluated a new method of monitoring cerebral blood flow velocity (CBFV) and described changes in CBFV in relation to central apnea in 17 healthy term infants. The area under the velocity curve during apnea did not change, whereas area under the velocity curve per the waveform showed a significant difference, suggesting that stability is maintained through an increase in CBFV with each heartbeat. The maintenance of cerebral hemodynamics during isolated central apnea supports the assumption that these episodes are benign.

Blood Flow Velocity↗

PubMed1993

A developmental study of the dose-response curve of the respiratory sensory reflex.

We have shown previously that inhalation of high concentration of CO2 (about 8%) inhibits breathing in preterm infants, presumably through an upper airway sensory reflex. To study the developmental aspects and the dose-response curve of this reflex, we studied eight preterm infants (body weight, 1.6 +/- 0.1 kg mean +/- SE; gestational age, 31 +/- 1 wk; postnatal age, 22 +/- 5 days) and eight term infants (body weight, 3.2 +/- 0.1 kg; gestational age, 39 +/- 1 wk; postnatal age, 8 +/- 6 days) using a flow-through system; eight adult subjects (weight, 67 +/- 5 kg; age, 30 +/- 4 yr) were studied during quiet sleep using a nasal mask. We gave 2, 4, 6, and 8% CO2 in 21+ O2 randomly for 20 to 30 s. A clear inhibition of breathing typically occurred during inhalation of 8% CO2 only in preterm infants, as reflected by the presence of an apnea of 11 +/- 1 s occurring at 7 +/- 2 s after the beginning of CO2 inhalation. Short apneas were occasionally observed with lower concentrations of CO2, but they were significantly fewer and shorter than with 8% CO2. No clear inhibition was observed in term infants or adult subjects, but pauses of 4 and 6 s were observed in the former group and a pause of 7 s was observed in the latter one. The associated changes in minute ventilation during inhalation of 2, 4, and 6% CO2 were not significantly different between the three groups. During inhalation of 8% CO2, minute ventilation decreased only in preterm infants (-26 +/- 10 compared with +32 +/- 10 in term infants and to +17 +/- 5% in adult subjects; p = 0.003 between groups).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

A respiratory sensory reflex in response to CO2 inhibits breathing in preterm infants.

Traditionally, the increase in ventilation occurring after approximately 4 s of CO2 inhalation in preterm infants has been attributed to an action at the peripheral chemoreceptors. However, on a few occasions, we have observed a short apnea (2-3 s) in response to 3-5% CO2 in these infants. To test the hypothesis that this apnea reflects a respiratory sensory reflex to CO2, we gave nine preterm infants [birth wt 1.5 +/- 0.1 (SE) kg, gestational age 31 +/- 1 wk] 7-8% CO2 while they breathed 21% O2. To study the dose-response relationship, we also gave 2, 4, 6, and 8% CO2 to another group of seven preterm infants (birth wt 1.5 +/- 0.1 kg, gestational age 31 +/- 1 wk). In the first group of infants, minute ventilation during 21% O2 breathing (0.232 +/- 0.022 l.min-1.kg-1) decreased after CO2 administration (0.140 +/- 0.022, P < 0.01) and increased with CO2 removal (0.380 +/- 0.054, P < 0.05). This decrease in ventilation was related to an apnea (12 +/- 2.6 s) occurring 7.7 +/- 0.8 s after the beginning of CO2 inhalation. There was no significant change in tidal volume. In the second group of infants, minute ventilation increased during administration of 2, 4, and 6% CO2 but decreased during 8% CO2 because of the presence of an apnea. These findings suggest that inhalation of a high concentration of CO2 (> 6%) inhibits breathing through a respiratory sensory reflex, as described in adult cats (H. A. Boushey and P. S. Richardson. J. Physiol. Lond. 228: 181-191, 1973).(ABSTRACT TRUNCATED AT 250 WORDS)

Apnea↗

PubMed1992

Speed and profile of the arterial peripheral chemoreceptors as measured by ventilatory changes in preterm infants.

To measure the response time of the peripheral chemoreceptors, we studied 13 preterm infants [birth weight 1602 +/- 230 g (mean +/- SEM); gestational age 31 +/- 1 wk; postnatal age 15 +/- 1 d] during inhalation of 21% O2 (15 +/- 5 s) followed by 100% O2 (1 min). We used a flow-through system to measure ventilation and gas analyzers to measure alveolar gases. Hypoventilation was observed at 3.6 +/- 0.6 s and was maximal at 6.8 +/- 1 s after O2 began. This maximal response was always associated with an apnea (greater than 3 s). Alveolar PO2 increased from 13.5 +/- 0.1 kPa (101 +/- 0.8 torr) (control) to 28.0 +/- 1.2 kPa (210 +/- 9 torr) (1st O2 breath), to 42.0 +/- 2.4 kPa (315 +/- 18 torr) (1st hypoventilation), to 45.9 +/- 4.1 kPa (344 +/- 31 torr) (breath preceding maximal response), and to 53.6 +/- 4.1 kPa (402 +/- 31 torr) (at maximal response). Minute ventilation was 0.192 +/- 0.011 (control), 0.188 +/- 0.011 (1st O2 breath), 0.088 +/- 0.016 (1st hypoventilation; p less than 0.0001), 0.122 +/- 0.016 (breath preceding maximal response; p less than 0.0002), and 0.044 +/- 0.011 L/min/kg at maximal response (p less than 0.0001). This decrease in ventilation was due to a decrease in frequency with no appreciable change in tidal volume. The initial period of hypoventilation (19 +/- 4 s) was followed by a breathing interval (10 +/- 2 s) and a second period of hypoventilation (14 +/- 3 s) before continuous breathing resumed.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteries↗