Biomedical subjects

T A Standaert

Publications and source records attributed to T A Standaert.

At least 55 records · Page 3Linked to original sources

PubMed1990

Regional pulmonary blood flow in piglets during group B streptococcal bacteremia.

Shunt fraction (QS/QT) and perfusion to hypoxic lung regions increase when pulmonary vascular driving pressure (PVDP) is raised by increasing pulmonary blood flow or enlarging the size of the hypoxic region. We hypothesized that perfusion to collapsed areas would similarly increase when PVDP was increased by a circulating pulmonary vasoconstrictor. Group B streptococci (GBS) were infused into 10 young piglets with left lung atelectasis to produce pulmonary vasoconstriction and determine if perfusion to collapsed regions (QL/QT) and intrapulmonary QS/QT increased as pulmonary vascular resistance (PVR) increased. Left lung collapse alone increased PVR from 11 +/- 3 to 18 +/- 10 mm Hg/L/min and QS/QT from 1.9 +/- 1.4% to 8.3 +/- 6.4%; QL/QT decreased from 44 +/- 1% to 10 +/- 7% of total pulmonary blood flow (p less than 0.02). Intravenous GBS increased PVDP from 11 +/- 3 to 27 +/- 4 mm Hg and further increased PVR from 18 +/- 10 to 33 +/- 12 mm Hg/L/min (p less than 0.02) but did not change cardiac output, QS/QT, or QL/QT. Changes in QL/QT and QS/QT are not predicted by changes in PVDP alone but also depend upon the site and nature of pulmonary vasoconstriction in infants with regional lung disease.

Animals↗

PubMed1990

Mechanisms for reduced total lung capacity at birth and during hyaline membrane disease in premature newborn monkeys.

To determine whether the cause of reduced total lung capacity (TLC) in hyaline membrane disease (HMD) is due to alveolar collapse, alveolar edema, or both, TLC was measured by N2-washout in premature Macaca nemestrina monkeys during the first 3 h of life. The TLC of animals with HMD was only one-third that of healthy premature monkeys over the first 3 h of life (p less than 0.01). At 3.5 h, lung tissue was rapidly frozen in situ during lung inflation to TLC. Samples of frozen lung tissue were freeze dried, embedded, sectioned, and examined by point counting. Animals with HMD had alveolar saccules filled with the residue of proteinaceous fluid, but little alveolar collapse was noted. The proportion of points falling on empty alveolar spaces was 74% in the healthy animals but only 18% in animals with HMD (p less than 0.01); there was a 70-fold increase in the residue present in alveoli of animals with HMD (p less than 0.05). In a separate experiment, rapid serial measurements of TLC by N2-washout showed that healthy premature monkeys, but not those with HMD, have a steady increase in TLC during the first few minutes of life, presumably due to clearance of lung liquid. Although the initial cause of reduced TLC in HMD appears to be inadequate clearance of fetal lung liquid, by 3 h of age proteinaceous alveolar edema is primarily responsible.

Animals↗

PubMed1990

Effect of aminophylline on diaphragmatic contractility in the piglet.

Minute ventilation, arterial blood gases, arterial pH, cardiac output, and transdiaphragmatic force generation, both during spontaneous ventilation and in response to phrenic nerve stimulation during airway occlusion at end expiration, were measured in nine anesthetized, tracheostomized piglets before and 30 min after parenteral infusion of 20 mg/kg aminophylline. Serum theophylline levels averaged 109 +/- 21 mumol/L (19.7 +/- 3.7 micrograms/mL) at 30 min postinfusion. No significant changes were noted in pH, blood gases, blood pressure, or ventilatory measures after aminophylline. Aminophylline infusion also had no effect on transdiaphragmatic force generation at any frequency of phrenic nerve stimulation studied. It is concluded that aminophylline has no effect on diaphragmatic contractility in the quietly breathing, nonfatigued piglet.

Aminophylline↗

PubMed1989

Effects of digoxin on diaphragmatic contractility in the piglet.

Minute ventilation, arterial blood gases and pH, cardiac output, and transdiaphragmatic force generation were measured in eight anesthetized, tracheostomized piglets before and after administration of 40 micrograms/kg body wt of digoxin. No changes were noted in cardiac output, heart rate, tidal vol, respiratory rate, or minute ventilation. Blood pressure decreased from baseline to 60 min postinfusion. No change was noted in the force frequency curves at 30 and 60 min postinfusion. Serum digoxin levels averaged 10.4 ng/mL at 30 min and 5.6 ng/mL at 60 min. In seven control animals, no changes were noted in any ventilatory or hemodynamic parameter from baseline to 60 min. In contrast to the reported effects of digoxin on the diaphragm of adult humans and animals, digoxin did not augment diaphragmatic contractility in normal infant swine.

Animals↗

PubMed1989

The effect of aminophylline on diaphragm blood flow in the piglet.

The effect of aminophylline on diaphragmatic blood flow was investigated in two groups of newborn piglets. Six animals were studied during spontaneous breathing and seven additional animals were paralyzed and ventilated to assess the effect of aminophylline on blood flow to the nonworking diaphragm. Arterial blood gases and pH, cardiac output, and diaphragmatic blood flow were measured before and 20 min after infusion of 20 mg/kg aminophylline. Blood theophylline concentrations averaged 117 mumols/L (21 micrograms/mL) in both groups of animals. Heart rate increased significantly in all animals. Cardiac output increased significantly only in spontaneously breathing animals. Aminophylline had no effect on blood flow to the costal or crural portions of the diaphragm in either the paralyzed or spontaneously breathing animals.

Aminophylline↗

PubMed1988

Postnatal changes in lung phospholipids and alveolar macrophages in term newborn monkeys.

In order to better understand the postnatal sequence of surfactant secretion and establishment of the alveolar macrophage (AM) population in newborn primates, healthy Macaca nemestrina monkeys were sacrificed during fetal life at term gestation (n = 5), or at 2 days (n = 5) or 3-4 weeks (n = 5) after term vaginal delivery. Excised lung tissue and left lung lavage were analyzed for phospholipid (PL) content, surface active material (SAM) extract, PL components, surface activity, pressure-volume characteristics, and AM number. Compared to term fetal animals, 2 day old term newborn monkeys were found to have a several-fold increase in lavage PL and SAM, and this was associated with greater maximal lung volume and drier lungs, but not improved deflation stability. During the subsequent 3-4 weeks of life, a 42% reduction in lung tissue stores of PL and SAM, and an 87% reduction in lavage PL and SAM were noted. Despite these major changes in quantity, there were relatively minor changes in the composition of the PL synthesized and released. The reduced quantity of SAM in the 3-4 week old animals led to a small decline in deflation stability. The several-fold increase in lavage PL and SAM during the first 2 days of life was accompanied by a 33-fold increase in AM; there was an additional 4-fold increase in AM number by 3-4 weeks of age. The abundance of lavage surfactant at 2 days of age may play a role in the influx of AM.

Animals↗

PubMed1988

Ventilatory failure during loaded breathing: the role of central neural drive.

Minute ventilation (VE), arterial blood gases, diaphragmatic electromyogram (EMG) activity, centroid frequency (Fc) and peak inspiratory airway pressures (Paw) were measured in five unanesthetized tracheostomized infant monkeys during various intensities of inspiratory resistive loaded breathing (IRL) until either 1) ventilatory failure occurred (failed trial) or 2) normocapnia was sustained for 1 h (successful trial). During successful trials VE and arterial PCO2 (PaCO2) were sustained at base-line levels, and an increase in peak integrated diaphragmatic EMG activity and peak inspiratory Paw occurred. In contrast, during ventilatory failure runs, VE decreased and PaCO2 rose compared with their respective base-line values. The fall in VE occurred secondary to a significant decline in breathing frequency. Tidal volume was sustained at base-line levels during all trials (both successful and failed groups). Inspiratory Paw's and peak moving time average EMG were sustained at elevated levels during ventilatory failure runs, suggesting that the respiratory muscles did not fail as pressure generators. Furthermore, the EMG Fc did not change from base line during either successful or failed trials. These data suggest that peripheral muscle fatigue did not occur, although in the absence of a more direct test of muscle performance, i.e., a force-frequency curve, we cannot rule out the possibility that a component of peripheral failure contributed to our results. Ventilatory failure during severe IRL in the infant monkey was most clearly associated with an alteration in the respiratory center timing mechanism, i.e., such failure was a function of a decline in respiratory frequency.

Animals↗

PubMed1988

Effect of hypercapnia and hypoxia on costal and crural diaphragm electromyograms in piglets.

We examined the separate effects of acute hypercapnia and acute hypoxia, on the electromyographic activity (EMG) of the costal and crural diaphragm in 6 anesthetized spontaneously breathing piglets (age 12-23 days, weight 3.00-4.37 kg). Bipolar wire electrodes were inserted into the anterior paratendinous costal diaphragm and the midportion of the crural diaphragm. EMG activity was quantified in arbitrary units (au) of peak moving time average while the animals breathed 50% O2/50% N2 (base-line) and after 30 min of either hypercapnia (12% CO2) or hypoxia (12% O2) exposure. After 30 min of hypercapnia, the peak moving time average EMG increased in both parts of the diaphragm with the increase in crural diaphragm EMG activity (from baseline: 20 +/- 2 au to 30 min 12% CO2: 83 +/- 20 au) not being significantly different from that observed in the costal diaphragm (from baseline: 21 +/- 2 au to 30 min 12% CO2: 72 +/- 20 au, p = 0.17). Similarly, the peak moving time average EMG increased in both parts of the diaphragm after 30 min of hypoxia with the increase in the crural diaphragm EMG activity (from baseline: 21 +/- 2 au to 30 min 12% O2: 28 +/- 6 au) not being significantly different from that observed in the costal diaphragm (from baseline: 21 +/- 1 au to 30 min 12% O2: 26 +/- 7 au, p = 0.51). These data indicate that the inspiratory EMG activity of the diaphragm is not differentially distributed between its costal and crural components during chemically stimulated breathing in piglets.

Animals↗

PubMed1987

Diaphragmatic function during hypercapnia: neonatal and developmental aspects.

The effect of acute hypercapnia on diaphragmatic force output was studied in 6 young (4-8 days) and 6 older (16-20 days) anesthetized, spontaneously breathing piglets. Diaphragmatic force output was assessed by analysis of the transdiaphragmatic pressure (Pdi) generated during phrenic nerve stimulation. Pdi was measured under base-line conditions (50% O2-50% N2) and after 10 min of hypercapnia induced by breathing 5, 10, or 15% CO2 balanced with N2 and 50% O2. Pdi was significantly less than base line during the 10 and 15% hypercapnic conditions in the young (P less than 0.05) but not the older piglets. End-expiratory lung volume was noted to decrease during 15% CO2 hypercapnia. Force output augmentation occurred at this lower end-expiratory lung volume and was significantly greater in the older piglet compared with its younger counterpart (P less than 0.05). When the effects of lung volume on Pdi were corrected for, there was no age-related difference in the response to 15% CO2 hypercapnia. We conclude that severe hypercapnia has a depressant effect on diaphragmatic force output in both young and older piglets, and a differential augmentation in diaphragmatic force-output gain occurs at lower end-expiratory lung volume between young and older piglets, with the greater output occurring in the more mature animal.

Animals↗

PubMed1987

Effects of hyperoxia on vasoconstriction and VA/Q matching in the neonatal lung.

Exposure of adult animals to 48-72 h of 100% O2 breathing is associated with a blunting of hypoxic pulmonary vasoconstriction (HPV) (Newman et al. J. Appl. Physiol. 54: 1379-1386, 1983). It is unknown whether HPV is also diminished in neonates after hyperoxic exposure and if so to what extent such suppression might interfere with pulmonary gas exchange during hypoxic gas breathing. We tested the possibility that hyperoxia would suppress HPV and interfere with ventilation-perfusion (VA/Q) matching and therefore gas exchange in neonatal piglets. Twelve 2- to 4-wk-old piglets were exposed for an average of 68 h to greater than 90% inspired O2. A control group of eight piglets was exposed to room air for a similar period of time. Immediately after exposure the animals were anesthetized and instrumented. Pulmonary hemodynamics and respiratory and inert gas exchange were assessed while the animals inspired an O2 fraction of 1.0, 0.21, and 0.12. After 20 min of hypoxic gas breathing, pulmonary arterial pressure rose to a lesser degree in the hyperoxia (H)-exposed animals than in the control (C) animals (P less than 0.02). The increase in pulmonary vascular resistance was similarly blunted. Venous admixture of the insoluble inert gas, sulfur hexafluoride, an index of extremely low VA/Q areas, was increased during hypoxic gas breathing compared with room air breathing in the H-preexposed animals (P less than 0.02). Standard deviation of pulmonary blood flow was increased (P less than 0.02), indicating an increase in mismatching of VA/Q during hypoxic breathing in the H-preexposed animals compared with the C animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Developmental changes in the ventilatory response of the newborn to added airway resistance.

Postnatal development of the steady-state response to inspiratory resistive loading was studied in eight 48-hour-old and seven 24-day-old tracheostomized monkeys. The newborn subjects did not maintain minute ventilation (Vl) with increasing loads of from 2 to 6 times baseline respiratory resistance, whereas the older subjects kept Vl constant when challenged by the same added resistances. The response patterns in both groups were characterized by a prolongation of Tl and Tl/Ttot, a reduction of respiratory frequency, and increases in airway occlusion pressure and respiratory work output. Apart from Vl, tidal volume (VT) was the only other ventilatory variable that differed significantly between age groups during loading. Arterial CO2 and O2 did not change from baseline in either group during loading, indicating that both age groups defended blood gas values equally well. The increases in occlusion pressures, inspiratory work output, and the maintenance of PaCO2 in the newborns indicated the presence of load compensatory mechanisms despite the fact that Vl was not strictly defended.

Aging↗

PubMed1987

Effect of inspiratory resistive loading on costal and crural diaphragm electromyograms in piglets.

We examined the effect of inspiratory resistive loaded breathing (IRL) on the electromyographic (EMG) activity of the costal and crural diaphragm in nine anesthetized spontaneously breathing piglets (age 10-23 days, weight 2.8-4.4 kg). Bipolar wire electrodes were inserted into the anterior paratendinous costal diaphragm and the midportion of the crural diaphragm. EMG activity was quantified in arbitrary units (au) of peak moving time average while the animals breathed 50% O2/50% N2 (baseline) and during 30 min of IRL. Thirty min of IRL increased the peak moving time average of both parts of the diaphragm, with the increase in the crural EMG activity (from baseline: 22 +/- 2 to 30 min of IRL: 76 +/- 22 au) exceeding that of costal (from baseline: 23 +/- 2 to 30 min of IRL: 50 +/- 24 au), p less than 0.05. These results 1) suggest that the inspiratory EMG activity of the diaphragm can be differentially distributed between its costal and crural components and 2) document that crural inspiratory EMG activity undergoes greater augmentation under the condition of IRL than does the costal activity in piglets.

Animals↗

PubMed1987

Response to resistive loading in the newborn piglet.

The diaphragmatic force generation and electromyographic response to long-term (1 h) inspiratory resistive loading was examined in the newborn piglet during the 3rd postnatal wk of life. Minute ventilation decreased to approximately 50% of baseline level within 5 min of imposition of a severe resistive load and remained at this level for the duration of loading. The decrease in ventilation was secondary to a fall in tidal volume at a constant frequency. There was a significant increase in central nervous system output to the diaphragm as manifested by integrated diaphragmatic electromyogram. Progressive augmentation of this index of central drive continued throughout the period of loading. Functional residual capacity fell significantly by 60 min of inspiratory resistive loading. This strategy should allow greater force generation by placing the diaphragm at a more optimal length-tension relationship. However, the force generating capability of the diaphragm was compromised as assessed by force-frequency curve analysis. These results suggest that the diaphragm of the neonatal piglet fatigues during prolonged inspiratory resistive loading.

Airway Resistance↗

PubMed1987

Spectral analysis of diaphragmatic EMG during the neonatal biphasic hypoxic ventilatory response.

The newborn infant monkey consistently demonstrates a biphasic ventilatory response to hypoxemia. We have previously shown that the ventilatory depression during the late portion of this biphasic response is secondary to a decline in inspiratory volume that cannot be explained solely by central neural depression. We hypothesized that hypoxemia caused the diaphragm to fatigue, thereby accounting for the late ventilatory depression during the biphasic neonatal hypoxic response. Diaphragmatic fatigue has been reported to be associated with a decrease in the centroid frequency (Fc) of the electromyogram derived through frequency spectral analysis. Therefore, we analyzed the power spectral density of the diaphragmatic electromyogram recorded from percutaneously implanted crural diaphragmatic electrodes in five 2-day-old infant monkeys while they breathed room air and after 5 min exposure to two levels of hypoxemia during the late ventilatory depression. A fast Fourier transform of EKG free diaphragmatic electromyogram was used to compute the power spectral density and the Fc. The Fc during room air breathing was statistically equivalent to the Fc observed after five minutes exposure to 12% FiO2 (p = 0.79), and 8% FiO2 (p = 0.74) when ventilation was falling. In conclusion, our data demonstrate that changes in the centroid frequency are not present during the biphasic ventilatory decline that occurs with the hypoxic ventilatory response in newborn monkeys. Thus, diaphragmatic fatigue, as defined by a decline in Fc, does not occur during the neonatal biphasic hypoxic response.

Animals↗

PubMed1987

Diaphragmatic muscle fiber type development in swine.

Diaphragmatic muscle fiber types were determined in the costal and crural segments of swine diaphragm at 4 postnatal ages (1 day, 1 month, 6 months, and between 3-6 yr of age). Fiber types were differentiated by enzyme histochemistry for adenosine triphosphatase and reduced nicotinamide adenine dinucleotide. A progressive increase in the number of type I fibers occurred in both costal and crural segments from birth to 6 months of age. The number of type IIA fibers decreased and type IIB fibers increased over the same time period. Type IIC fibers were present through 1 month of age, were rarely observed at 6 months, and were not found in older animals. Type I fibers were more numerous in the crural portion of the diaphragm. The cross-sectional area of all fiber types in both costal and crural segments increased significantly with age. No preferential fiber type growth was noted in either segment of the diaphragm. These data suggest that the pig diaphragmatic muscle is differentiated into its adult form by 6 months of postnatal age, but fiber cross-sectional area growth continues along with body growth.

Adenosine Triphosphatases↗

PubMed1986

Diaphragmatic function during hypoxemia: neonatal and developmental aspects.

The effect of acute hypoxemia on diaphragmatic force output was studied in five young (age 4-8 days, wt 1.3-2.2 kg) and five older (age 16-19 days, wt 2.8-3.3 kg), anesthetized, spontaneously breathing piglets. Diaphragmatic force output was assessed by analysis of the transdiaphragmatic pressure (Pdi) generated during an occluded inspiratory effort, at end-expiratory lung volume, triggered by supramaximal transvenous stimulation of both phrenic nerves at frequencies of 20, 30, 50, and 100 Hz. During pressure measurements, the piglets were fitted with a rigid plaster cast covering the abdomen and lower third of the chest to ensure a consistency in diaphragmatic shortening during phrenic nerve stimulation. Pdi was measured under base-line conditions [inspired O2 fractional concentration (FIO2) = 0.50] and after 10 min of hypoxemia induced by breathing 12-14% FIO2. Pdi was significantly less than base line during acute hypoxemia at all frequencies of stimulation in both young and older piglets. The decline in the older piglets' Pdi during hypoxemia was significantly greater than that seen in younger piglets. We conclude that acute hypoxemia impairs the capacity of the developing piglet diaphragm to generate force. Furthermore, our data suggest that the young piglet is more resistant to the depressant effects of hypoxemia when compared to its older counterpart.

Age Factors↗

PubMed1986

Role of endogenous opiates in hypoxic ventilatory response in the newborn primate.

The effects of opiate receptor antagonism by naltrexone hydrochloride on the biphasic hypoxic ventilatory response in the infant Macaca nemestrina have been investigated. Minute ventilation, tidal volume, and respiratory frequency were measured in six animals from timed gestations before and during inhalation of a hypoxic gas mixture. All studies were completed in non-rapid-eye-movement sleep. Arterial blood gases were obtained during each stimulus period. All animals demonstrated the typical biphasic ventilatory response to acute moderate-severe hypoxemia. After the administration of naltrexone hydrochloride to block opiate receptors, the animals still manifested a biphasic hypoxic response that was no different than that noted prior to drug administration. Naltrexone hydrochloride had no effect on room air resting ventilation in any of the animals. Our data suggest that endogenous opiates play no physiological role in the acute ventilatory response to moderate-severe hypoxia in the newborn subhuman primate.

Animals↗

PubMed1986

Effects of the thromboxane synthetase inhibitor, dazmegrel (UK 38,485), on pulmonary gas exchange and hemodynamics in neonatal sepsis.

Group B streptococcal (GBS) sepsis produces arterial hypoxemia in newborns. In piglets we previously found that hypoxemia develops because of increased ventilation perfusion heterogeneity, and reduced mixed venous pO2 occurring in association with decreased pulmonary blood flow. We hypothesize that increased thromboxane A2 (TxA2) synthesis mediates the immediate alterations in gas exchange found in GBS sepsis. We studied 18 anesthetized, ventilated piglets before, during, and after a 30-min infusion of 2 X 10(9) colony forming units/kg of GBS. Nine piglets were pretreated with 8 mg/kg of dazmegrel (DAZ), a TxA2 synthetase inhibitor, and nine animals received GBS without DAZ pretreatment. Pulmonary and systemic arterial pressures, pulmonary vascular resistance, pulmonary blood flow, respiratory gas tensions, intrapulmonary shunt, and SD of pulmonary blood flow, an index of ventilation perfusion mismatching, were measured. Systemic and pulmonary arterial levels of thromboxane B2 and 6-keto-PGF1 alpha were also measured. The sham-treated animals showed the expected rise in pulmonary arterial pressure from 12 +/- 3 to 29 +/- 7 torr, (p less than 0.02). By comparison, the animals pretreated with DAZ did not demonstrate pulmonary arterial hypertension and had a delay in the fall in pulmonary blood flow until 2 h postinfusion. Arterial PO2 did not decline significantly after the GBS infusion in the DAZ-pretreated animals; the untreated animals showed a significant fall in pO2 from baseline. There was no significant change in intrapulmonary shunt or SD of pulmonary blood flow compared to baseline in the DAZ-pretreated animals. The elevation in thromboxane B2 occurring with GBS sepsis did not occur in the DAZ-pretreated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗