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Biomedical subjects

T A Standaert

Publications and source records attributed to T A Standaert.

90 records · Page 5Linked to original sources

Ventilation by high-frequency oscillation in rabbits with oleic acid lung disease.

The feasibility and efficiency of ventilation by high-frequency oscillation (HFO) were examined in animals with diffuse hemorrhagic lung disease. Twenty-four hours after injection with 0.12 ml/kg oleic acid, 11 spontaneously breathing rabbits had a mean (+/- SD) arterial O2 partial pressure (PaO2) of 65 +/- 16 Torr and arterial CO2 partial pressure (PaCO2) of 38 +/- 7 Torr [inspired fractional O2 concentration (FIO2) of 0.21]. Following paralysis animals were ventilated using a high-frequency oscillator for periods of 20 min followed by three successive hyperinflations to prevent atelectasis. Maintaining a constant mean airway pressure (MAP) of 6 cmH2O and fresh gas flow (FGF) of 2 1/min (FIO2 = 0.21), all combinations of frequency (5, 10, 20, and 30 Hz) and stroke volume (Vs) 2.6, 5.0, and 8.9 ml) were tested. At each frequency, an increase in Vs tended to lower mean PaCO2. At each Vs, CO2 elimination appeared maximal at 20 Hz, an effect attributable to decreasing effective Vs with increasing frequency. With constant Vs, MAP, and frequency, increasing FGF from 1 to 2 or 61/min decreased mean PaCO2 (P less than 0.05). With constant Vs, frequency, and FGF, increases in MAP from 2 to 10 cmH2O increased mean PaO2 (P less than 0.05). HFO, coupled with periodic hyperinflation, supports satisfactory gas exchange in rabbits with oleic acid lung injury. The efficiency of gas exchange is improved by independent increases in Vs, FGF, MAP, or frequency.

Animals↗

Development of CO2 sensitivity: effects of gestational age, postnatal age, and sleep state.

To determine the independent effects of sleep state, gestational age, and postnatal age on eucapnic ventilation and steady-state CO2 sensitivity, nine premature (146 +/- 3 days) and eight full-term (168 +/- 2 days) monkeys, Macaca nemestrina, from accurately timed conceptions were studied serially over the first 3 wk of life. Minute volume (VE)/kg,tidal volume (VT)/kg, and respiratory frequency were quantitated during rapid-eye-movement sleep (REM) and nonrapid-eye-movement sleep (NREM)in room air and when animals were breathing varied concentrations of cO2 in 21% O2. Eucapnic VE/kg and CO2 sensitivity [(deltaVE/kg)/delta PaCO2] increased progressively with advancing postnatal age during NREM sleep in grouped term and premature animals. CO2 sensitivity was not significantly different between REM and NREM sleep except in full-term animals at the highest postconceptual age studied (189 +/- 2 days) when [(delta VE/kg)/delta PaCO2] was lower in REM sleep than in NREM sleep (209 +/- 54 vs. 301 +/- 71 ml.min-1.kg-1.Torr-1; P less than 0.05, paired-t test). Gestational age had no measurable effect on eucapnic ventilation or CO2 sensitivity. These results support the hypothesis that REM sleep-induced depression of CO2 sensitivity develops in the neonatal monkey with advancing postconceptual age.

Aging↗

Occlusion pressures during the ventilatory response to hypoxemia in the newborn monkey.

End-expiratory airway occlusions were performed in eight unanesthetized premature newborn monkeys during acute hypoxemia to investigate mechanisms involved in the newborn's biphasic ventilatory response to hypoxia. Two-day-old monkeys demonstrated an immediate increase in minute ventilation (VI) and a decrease in PaCO2 followed within 5 min by a return of VI and PaCO2 to base-line levels. The decline in VI was associated with a decrease in tidal volume (VT) and inspiratory flow (VT/TI) and an increase in respiratory frequency. Occlusion pressures (PO.2) remained elevated throughout the hypoxic stimulus, and end-expiratory lung volume increased during the late response. "Effective" impedance (P0.1/V0.1, P0.2/V0.2, etc.) and "effective" elastance (Pmax/VT) were also elevated. At 21 days of age, the monkeys demonstrated a sustained ventilatory response as VI, VT, VT/TI, and P0.2 remained elevated throughout the period of hypoxemia. End-expiratory lung volume increases as on day 2, but effective impedance and effective elastance did not change. These data suggest that the biphasic response to hypoxia in the newborn may result from a change in respiratory timing and an alteration in respiratory mechanics and is not due to a decrease in central respiratory drive.

Airway Obstruction↗

Hypoxic ventilatory response in the newborn monkey.

The hypoxic ventilatory response was determined in twelve unanesthetized newborn monkeys, Macaca nemestrina. Measurements of blood gases and ventilation were made during normoxia and hypoxia at the postnatal ages of 2, 7, and 21 days. Data were collected during quiet sleep. The infant monkey demonstrated a definite but transient hyperventilatory response following exposure to a FiO2 of 0.12 or 0.14 on the second day of life. Baseline ventilation increased 15% (Fi02=0.14) and 28% (Fi02=0.12) after 1 minute of hypoxia; p less than 0.05 in both instances. Return to baseline ventilation occurred between 3 and 5 minutes after hypoxic stimulus onset. This biphasic response to hypoxia converted to an adult-like, sustained hyperventilation during the ensuing three weeks of postnatal maturation. Episodes of periodic breathing and/or apnea were noted to occur during the induced hypoxemia. These data demonstrate that the infant subhuman primate has a ventilatory response to hypoxia that is similar to that of the human infant and is an excellent model for the study of the maturation of the respiratory control system.

Animals↗

Sleep and maturation of eucapnic ventilation and CO2 sensitivity in the premature primate.

The effects of sleep state and postnatal maturation on steady-state CO2 sensitivity, "inspiratory drive" (VT/TI), and the inspiratory "duty cycle" (TI/Ttot) were examined in nine unanesthetized premature Macaca nemestrina in the first 3 wk of life. Minute volume (VE) in room air was less in NREM sleep than in the awake state but there were no differences in VE, VT/TI, or TI/Ttot between REM and NREM sleep. VE and VT/TI corrected for body weight increased in REM and NREM sleep with postnatal maturation whereas TI/Ttot did not vary. Concomitant with this increase in room air VE and VT/TI, an increase in CO2 sensitivity (delta V/delta Paco2) with postnatal maturation was documented in NREM sleep. CO2 sensitivity was similar between REM and NREM states at each postnatal age. The increase in VE following inhalation of 2-5% CO2 was mediated by an increase in VT/TI, whereas TI/Ttot remained constant. The differences in the effect of sleep on CO2 sensitivity between neonates and adults are discussed and possible mechanisms for the observed developmental increase in CO2 sensitivity are proposed.

Animals↗

The immature monkey as a model for studies of bronchopulmonary dysplasia.

The monkey is a potential model for BPD since there is considerable background information on the normal-developing lung, the prematurely delivered infant is viable, HMD can be produced, the infant is large enough to permit physiologic measurements, and it should be possible to test the effects of positive pressure, oxygen, and pharmacologic agents. Clearly further information is needed on the cellular and subcellular changes occurring during the acute and recovery stages of HMD. The monkey has already proven to be of value in this inquiry. Studies on mechanisms of altered lung repair by various injurious agents are needed, and will require an animal model as well as in vitro systems. Basic understanding of the pathogenesis of bronchopulmonary dysplasia with establishment of the relative importance of the contributing factors should help in our efforts to prevent or minimize chronic lung disease in the newborn infant.

Animals↗

Oxygen-induced alteration of ventilation-perfusion relationships in rats.

The effect of oxygen breathing on shunt and ventilation-perfusion ratios (VA/Q) in anesthetized rats was studied using a modification of the multiple inert gas elimination technique. Base-line analyses showed hypoxemia in some animals breathing room air (arterial O2 tensions 48-70 Torr) associated with intrapulmonary shunts ranging from 0 to 22%, and variable low VA/Q lung regions as determined by calculation of the inert gas arterial-alveolar difference curve. Of nine rats that breathed 100% oxygen for 30 min, three showed increases in shunt (0% leads to 19%, 1.5% leads to 16%, 11% leads to 40%). These three animals had larger preexisting low VA/Q regions than the six that developed no shunt (0.48 +/- 0.15 vs. 0.17 +/- 0.03 (mean +/- SD); P less than 0.05). These data are compatible with the theory of absorption atelectasis. This study documents the usefulness of the inert gas elimination technique for studying pulmonary gas exchange problems in small animals.

Animals↗

Maturation of hypoxic ventilatory response of the newborn lamb.

The ventilatory response to acute hypoxia was studied in unanesthetized newborn lambs before and after carotid body denervation. Animals studied immediately following operative delivery were compared with a second group who were studied in the 2nd wk of postnatal life. Response time was defined as the interval between the decrease in oxygen saturation in the aortic arch and an increase in tidal volume or ventilatory rate. Animals in the older group demonstrated a significantly shorter response time than those studied immediately following delivery (1.8 s vs. 5.7 s). A ventilatory response was also elicited in carotid body-denervated animals in both study groups. Mean response time following denervation was 29.5 s for the younger and 12.5 s for the older animals. The data suggest that the development of a rapid, carotid body-mediated hypoxic ventilatory response occurs gradually during the first days of postnatal life, and that the central hypoxic response of the fetus (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 42:630-635, 1977) persists into postnatal life.

Aging↗

Lung development in the fetal primate Macaca nemestrina. III. HMD.

Delivery of M. nemestrina at 80% of normal gestation provides a population of neonates at high risk for hyaline membrane disease (HMD). The diagnosis of HMD was made by the presence of reticulogranular densities and air bronchograms on chest radiographs. Patchy atelectasis was seen in the lungs of animals assigned by clinical and radiographic criteria to the HMD group and not in the normal lungs of animals matched for gestational and postnatal age. Total phospholipid and phosphatidylcholine in whole lung, airway lavage fluid, and surface-active materials were lower in animals with HMD. Amniotic fluid L/S ratios were lower in the group that developed HMD. Pressure-volume measurements indicated decreased distensibility and unstable terminal air spaces in the HMD group. Alveolar-arterial oxygen pressure differences were greater in animals with HMD. There were no differences between HMD and normal groups in body weight, lung weight, percent dry lung weight, gestational age, and postnatal age at death. This primate species, subjected to premature delivery, is a suitable animal model of HMD in human neonates.

Amniotic Fluid↗

Hemoglobin-ligand interaction in fetal and maternal sheep blood.

Hemoglobin-ligand interaction was studied in maternal and fetal sheep blood as a function of oxygen saturation. pH was changed by varying CO2 concentration (CO2 Bohr effect) or by addition of NaOH or HCl at constant PCO2 (fixed acid Bohr effect). For maternal blood, CO2 Bohr factor was -0.41 at 50% oxygen saturation, increasing in magnitude at lower saturation and decreasing in magnitude at higher saturation. For fetal blood, CO2 Bohr factor was -0.45 at 50% oxygen saturation, unchanging at lower saturation and decreasing in magnitude at higher saturation. Fixed acid Bohr factor was relatively saturation independent with a value of -0.36 for fetal blood and -0.27 for maternal blood. The pH-independent effect of molecular CO2 on oxygen affinity was markedly saturation dependent being greatest at low oxygen saturation. The CO2 effect was greater in maternal blood than fetal blood. However, the magnitude of the saturation dependency of Bohr factor is not great enough to have major physiological significance in oxygen transfer across the sheep placenta.

Animals↗

Nonrebreathing valve for spontaneously breathing or mechanically ventilated animals.

The design of a small dead space, nonbreathing valve suitable for use in small laboratory animals is presented. The design overcomes previous problems of condensation occurring at valve leaflets, and allows ongoing collection of expired gases should the animal require mechanical ventilation. The valve apparatus performs reliably when in operation for several hours at a time with a variety of small animals.

Animals↗

Ventilatory response in the fetal lamb following peripheral chemodenervation.

Carotid infusions of sodium cyanide solution and perfusions of hypoxemic or hypercapnic fetal blood were done before and after peripheral chemoreceptor denervation. Step changes in PaO2 ranged from -11 to -22 Torr; step changes in PaCO2 ranged from +17 to +42 Torr. The cyanide dose was 0.2 mg/kg per loop system. Control perfusions consisted of 25 ml of fetal blood without changes in pH and blood gases. A ventilatory response occurred in the majority of all experimental perfusions regardless of innervation status of the peripheral chemoreceptors. No response occurred with control perfusions. There was a marked variability in the time of onset of ventilatory activity with a delay of greater than 10 s occurring following most perfusions. These studies demonstrate that the fetus has an attenuated ventilatory response to chemical stimuli and that hypoxia stimulates ventilation in the absence of peripheral chemoreceptors.

Animals↗

Application of the hot-wire anemometer to respiratory measurements in small animal.

A hot-wire anemometer was evaluated to determine its suitability for measurement of small tidal volumes. Used with a constant background flow of gas, the output of the hot-wire anemometer was linear and independent of respiratory frequency, temperature, and humidity. The change in output with CO2 concentration was negligible within the physiologic range. The use of a background flow eliminates the need for one-way valves, minimizes dead space, and maintains the flow velocity past the hot wire within its range of linear response.

Animals↗

Diaphragmatic pressures in piglets: transvenous versus direct phrenic nerve stimulation.

We examined transdiaphragmatic pressure (Pdi) generation during both direct (DPNS) and transvenous (TVPNS) modes of phrenic nerve stimulation in anesthetized piglets of varying postnatal age. Pdi measurements during TVPNS were not statistically different from those obtained during DPNS (p greater than 0.10). Furthermore, a good correlation (r = 0.98, p less than 0.001) was obtained when the mean Pdi measurements obtained by both methods were compared. We conclude that TVPNS can be used in lieu of DPNS to generate Pdi. Furthermore, our data suggest that this technique can be used to study the effects of various experimental manipulations on diaphragmatic force output within a developmental context.

Age Factors↗