Biomedical subjects

T A Standaert

Publications and source records attributed to T A Standaert.

At least 37 records · Page 2Linked to original sources

PubMed1994

Full-tidal liquid ventilation with perfluorocarbon for prevention of lung injury in newborn non-human primates.

Hyaline membrane disease (HMD), the most common life-threatening respiratory disorder of newborns, is associated with lung injury manifested by alveolar proteinaceous edema. The cause of the disease is thought to be elevated alveolar surface tension due to surfactant deficiency at birth. Treatment with exogenous surfactant may be unsuccessful due to problems in distribution of the surfactant, or inhibition of the surfactant by alveolar proteinaceous edema. Liquid ventilation with oxygen-saturated perfluorocarbon liquid has been proposed as a method to eliminate alveolar surface tension; little is known about the interfacial tension between perfluorocarbon liquids and the lung lining layer. Premature and term newborn monkeys were treated from birth with a pressure-limited, time-cycled liquid ventilator using oxygenated perfluorocarbon liquids (APF-145 and perflubron). Adequate gas exchange was achieved, and pilot experiments suggest long-term survival without adverse sequelae. Although many questions remain, liquid ventilation is a promising tool for the prevention and treatment of lung injury in newborns.

Animals↗

PubMed1993

Effect of amrinone during group B Streptococcus-induced pulmonary hypertension in piglets.

Intravenous infusion of group B Streptococcus (GBS) into neonatal animals produces pulmonary hypertension, ventilation/perfusion (VA/Q) mismatch, and an increase in serum levels of thromboxane B2 (TxB2) and tumor necrosis factor (TNF) alpha. The vasodilator amrinone (amr) is a cGMP-inhibited phosphodiesterase inhibitor and is reported to inhibit thromboxane A2 and TNF production. We hypothesized that infusion of amr would cause pulmonary vasodilation and reduce serum TxB2 and TNF levels in piglets with late phase GBS-induced pulmonary hypertension. The effect of amr on gas exchange was also determined. A continuous infusion of GBS was administered for 5 hr to 4 groups of anesthetized, mechanically ventilated neonatal piglets. An amr bolus of 8 mg/kg was given at 4 hr followed by a 1 hr continuous infusion of either 10 or 20 micrograms/kg/min of amr (amr 10 and amr 20, respectively). Control piglets received a bolus and 1 hr infusion of amr carrier. The infusion of amr, but not of carrier reversed late phase GBS-induced pulmonary hypertension. Piglets infused with amr 20 showed transient selective pulmonary vasodilation, based on a reduced ratio of pulmonary to systemic vascular resistance (PVR/SVR ratio) value at 30 min but not at 1 hr, compared to pre-amr treatment values. The PVR/SVR ratio values for amr 10 and control group did not change after treatment with either amr or carrier. Treatment with amr 10 or 20 did not decrease serum TxB2 or TNF levels or increase VA/Q mismatch.(ABSTRACT TRUNCATED AT 250 WORDS)

Amrinone↗

PubMed1993

Growth potential of the transplanted lung in the infant primate.

Success in neonatal lung transplantation depends on the growth of the transplanted lung. To study the effects of transplantation and denervation on primate lung growth without rejection or immunosuppression, an autotransplant model was chosen. Eight-week-old baboons underwent left lung autotransplantation (n = 5) or sham operation (n = 1). At age 13 weeks and 9 months, single lung volumes were calculated by nitrogen washout and computed tomography. Results were compared with those of 4 unoperated weight-matched controls (2 per age group). Over the growth period, mean total lung capacity in operated baboons increased 82% (137 to 249 mL) by nitrogen washout and 70% (182 to 309 mL) by computed tomography compared with 85% (128 to 237 mL) and 74% (141 to 245 mL) for the sham-operated baboon, respectively. Transplanted left lung volume increased 91% (53 to 101 mL) by nitrogen washout and 75% (68 to 119 mL) by computed tomography compared with 85% (54 to 100 mL) and 80% (56 to 101 mL) for the sham-operated baboon, respectively. In the absence of rejection and immunosuppression, normal volume growth occurs in the transplanted infant primate lung.

Animals↗

PubMed1993

Effect of inhaled nitric oxide during group B streptococcal sepsis in piglets.

Group B streptococcus (GBS), a common gram-positive pathogen, causes similar pathophysiologic changes in newborn humans and animals. Infusion of GBS into neonatal animals produces pulmonary hypertension and ventilation/perfusion (Va/Q) mismatch in both early-phase (< 1 h) and late-phase (2 to 6 h) responses. Contrary to early phase, late phase causes pulmonary vascular injury. Nitric oxide (NO) is an inhaled vasodilator whose effect on pulmonary hypertension and Va/Q matching during early and late phases of GBS sepsis is unclear. We hypothesized that inhaled NO (150 ppm) would: (1) reverse early-phase GBS-induced pulmonary hypertension; (2) demonstrate less effectiveness in reversing late-phase GBS-induced pulmonary hypertension because of vascular injury; (3) improve late-phase GBS-induced Va/Q mismatching. Anesthetized, mechanically ventilated piglets (n = 10; 14 +/- 4 days of age) received a 240-min infusion of GBS (1.5 x 10(9) CFU/kg/h). Piglets received 30 min of NO (Study) or N2 (Control) at 30 and 210 min of GBS infusion. We found that inhaled NO selectively reversed early- and late-phase GBS-induced pulmonary hypertension and that NO was equally as effective in each phase. Inhaled NO did not reverse Va/Q mismatching during late-phase GBS. We conclude that 4 h of GBS sepsis does not injure neonatal pulmonary vascular smooth muscle sufficiently to impair its response to inhaled NO.

Administration, Inhalation↗

PubMed1993

Effect of group B streptococcal sepsis on diaphragmatic function in young piglets.

Recent studies indicate that diaphragmatic pressure generation (Pdi) is impaired by bacterial infection. However, group B streptococcus (GBS) had no effect on Pdi when infused into 4-wk-old piglets. As responsiveness to GBS is age-dependent, we therefore studied the acute effect of GBS infusion on Pdi, using a younger, 2-wk-old piglet model. Using trans-Pdi with phrenic nerve stimulation, we studied the effect of continuous GBS infusion in seven anesthetized, spontaneously breathing 2-wk-old piglets. Pdi was measured under baseline conditions (50% O2/50% N2) and at 1, 2, and 4 h of GBS infusion. GBS was infused at a rate which caused a doubling of the pulmonary artery pressure but which avoided hypotension or acidosis--both of which can decrease Pdi. In addition, the piglets were kept hyperoxic [PaO2 > 13.3 kPa (100 torr)], and no piglet with hypercapnia [PaCO2 > 8.7 kPa (65 torr)] was included, as hypoxia and hypercapnia can also cause respiratory muscle dysfunction. For the GBS group, diaphragmatic contractility declined significantly by 1 h at 30-, 50-, and 100-Hz stimulation frequency and, by 2 h, was significantly decreased at all frequencies. We conclude that 2-wk-old piglets, in contrast to 4-wk-old piglets, demonstrate a decline in Pdi during GBS infusion. These data demonstrate an age-related response to GBS in the piglet.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Lung vascular responses and VA/Q matching after chronic hypoxia in neonatal piglets.

We hypothesized that exposure of neonatal swine to chronic alveolar hypoxia (CH) would cause increased PVR, blunt acute hypoxic vasoconstriction, and increase VA/Q mismatch. After exposure to either normobaric alveolar hypoxia (FIO2 = 0.10) or room air for 2 weeks, animals were anesthetized and ventilated first with room air and then with hypoxic gas (FIO2 = 0.12). PVR, and pressure-flow (P/Q) relations were measured between 15-100% of baseline cardiac output. VA/Q matching was measured by the multiple inert gas elimination technique. During room air breathing, the mean PVR and P/Q slope in the CH animals was significantly greater than in the control (C) animals. P/Q intercepts were similar and near the origin for both groups. The absolute PVR and P/Q slope were greater for CH compared to C animals during acute alveolar hypoxia. The fractional increase in PVR and P/Q slope in the response to acute hypoxia was similar for both groups. PaO2, intrapulmonary shunt, and SDQp (an index of VA/Q heterogeneity) were similar for both groups. We conclude that CH in neonatal swine causes pulmonary hypertension, but does not attenuate acute hypoxic pulmonary vasoconstriction, nor VA/Q matching.

Animals↗

PubMed1992

Acute changes in vasoactive lipid mediators in experimental hyaline membrane disease.

Endothelial release of the arachidonate derivative PGI2 may be increased in response to cyclic lung stretching. We therefore sought to determine if the stable metabolite of PGI2, 6-keto-PGF1 alpha, would be found in increased quantities in primates ventilated with conventional mechanical ventilation (CMV) compared to treatment with high frequency oscillatory ventilation (HFOV). We also sought to determine if other membrane-derived vasoactive substances such as LTC4, PAF and TXB2 would be elevated in plasma and lung tissue of animals developing hyaline membrane disease (HMD) and if the levels would correlate with the severity of the respiratory distress. Twenty prematurely delivered monkeys were treated with either CMV or HFOV from the first breath after Cesarean delivery until sacrifice at 6 h of age. We found a significant increase from birth to 5 min and from 5 min to 5 h in 6-keto-PGF1 alpha, and a significant increase from 5 min to 5 h in TXB2. We found a significant decline from cord blood to 5 min of LTC4, without further change by 5 h. PAF was present in all plasma samples but showed no upward or downward trend. There was no difference in the 5-h plasma level or in the lung homogenate level of any of the lipid mediators between the two types of assisted ventilation. There was no correlation between any lipid mediator level and severity of the HMD, as measured by gas exchange, radiographic or histologic criteria, when assessed by each ventilator group alone or with both groups combined. We conclude that the immediate postnatal increases in TXB2 and PGI2 and decrease in LTC4 are not altered substantially by use of HFOV.

6-Ketoprostaglandin F1 alpha↗

PubMed1992

Effect of inspiratory resistive loaded breathing and hypoxemia on diaphragmatic function in the piglet.

The combined effects of inspiratory resistive loaded breathing (IRL) and hypoxemia on transdiaphragmatic pressure (Pdi) in nine 1-mo-old Yorkshire piglets were studied. IRL was adjusted to increase spontaneously generated Pdi five to six times above baseline but maintain arterial PCO2 < 70 Torr to prevent hypercapnic depression of diaphragmatic contractility. Measurements of ventilation, blood gases and pH, Pdi, diaphragmatic electromyogram, Pdi during phrenic nerve stimulation, diaphragmatic blood flow, and end-expiratory lung volume were obtained at baseline, after 2 h of IRL, and then after 1 h of hypoxemia (arterial PO2 approximately 40 Torr) combined with IRL. Diaphragmatic muscle samples were obtained after study completion and immediately frozen in liquid nitrogen for determination of tissue ATP, phosphocreatine, lactate, and glycogen levels. Ten 1-mo-old piglets were subjected to IRL alone and served as controls. IRL alone resulted in significant impairment of Pdi generation. The addition of hypoxemia for 1 h did not further compromise Pdi in comparison to control animals who were subjected to IRL alone. Blood flow to both the costal and crural segments of the diaphragm increased significantly during IRL; the addition of the hypoxemic stress resulted in further significant augmentation of blood flow to both segments of the diaphragm. No differences were noted in diaphragmatic muscle tissue ATP, phosphocreatine, or glycogen between control and IRL animals or between control and IRL plus hypoxemia animals. Muscle lactate levels increased significantly in the IRL plus hypoxemia animals only. The data from this study suggest that moderate hypoxemia during resistive-loaded breathing in the piglet does not accentuate diaphragmatic fatigue.

Animals↗

PubMed1992

Group B streptococcus has no effect on piglet diaphragmatic force generation.

Recent studies indicate that diaphragmatic contractility is adversely affected by bacterial infection. Using transdiaphragmatic pressure (Pdi) with phrenic nerve stimulation, the effect of continuous Group B Streptococcus (GBS) infusion on diaphragmatic force output was studied in seven anesthetized, spontaneously breathing 1-month old piglets. Pdi was measured under baseline condition (50% O2/50% N2) and at 1, 2, and 4 h of GBS infusion. The GBS was infused at a level that caused a doubling of the pulmonary artery pressure and a 32% decrease in cardiac output but which avoided hypotension or acidosis--both of which can decrease diaphragmatic contractility. In addition, the piglets were kept hyperoxic (PaO2 greater than 100) and no piglet with hypercapnia (PaCO2 greater than 65) was studied, as hypoxia and hypercapnia also can cause respiratory muscle dysfunction. Pdi in response to phrenic nerve stimulation did not change during GBS infusion. We conclude that GBS infusion, in the absence of hypotension, hypercapnia, hypoxia, or acidosis, has no effect on diaphragmatic force generation in the piglet.

Animals↗

PubMed1992

Effect of pentoxifylline on cytokine- and eicosanoid-induced acute pulmonary hypertension in piglets.

The methylxanthine derivative pentoxifylline (PTF) demonstrates vasodilatory properties in vivo. We tested the hypothesis that PTF infusion would blunt or inhibit tumor necrosis factor-alpha (TNF alpha)-induced and U46,619-induced increases in mean pulmonary artery pressure and pulmonary vascular resistance (PVR) in the neonatal piglet and would do so by altering production of eicosanoid vasoactive mediators. Anesthetized, paralyzed piglets (age 10-29 d) were randomized and treated with a 30-min infusion of TNF alpha alone (n = 13 animals), with a combination of TNF alpha plus pretreatment and continuous infusion with PTF (n = 6), or with a combination of U46,619 for 30 min plus pretreatment and continuous infusion of PTF (n = 5). There was no difference in pulmonary or systemic hemodynamic indices between the three groups at baseline. PVR was significantly elevated at 15 min and at 2 h in the TNF alpha-only group. The TNF alpha-induced rise in mean pulmonary artery pressure and PVR was inhibited by the PTF until 2 h, by which time PVR was elevated above baseline and was comparable to the value found in animals treated with only TNF alpha. PTF produced no inhibition in the U46,619-induced elevation of PVR during the 30-min simultaneous treatment. In the PTF + TNF alpha group, mean systemic blood pressure declined to 50% of baseline value (p less than 0.02) by 2 h of age. No significant decline was noted in mean systemic arterial pressure of the TNF alpha-only or the U46,619-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1992

Effect of methylxanthines on diaphragmatic fatigue in the piglet.

Studies in adult animal and human subjects have suggested that the methylxanthine drugs can delay the onset or attenuate the severity of diaphragmatic fatigue. We have investigated the effect of aminophylline and caffeine on the pressure-generating capacity of the fatigued diaphragm in 1-mo-old piglets. Measurements of ventilation, transdiaphragmatic pressure, blood gases and pH, diaphragmatic electromyogram, diaphragmatic pressure-frequency curve (PdiFC), diaphragmatic blood flow, and end-expiratory lung volume were obtained at baseline, after 90 min of inspiratory resistive loaded breathing (IRL), and again 30 min after methylxanthine infusion while still on IRL. IRL resulted in a significant decrease in minute ventilation secondary to a fall in tidal volume. Spontaneously generated transdiaphragmatic pressure increased 7-fold from baseline. EMG activity increased to both segments of the diaphragm. Abdominal expiratory muscle activity was noted after the onset of IRL and was accompanied by a fall in end-expiratory lung volume. The PdiFC was significantly decreased from baseline after 90 min of IRL, demonstrating diaphragmatic fatigue. Aminophylline did not alter the PdiFC of the diaphragm. Diaphragmatic electromyogram and tidal volume increased. No change in diaphragmatic blood flow was demonstrated after infusion of aminophylline. Serum theophylline levels averaged 117 +/- 11 mumol/L (21 +/- 2 micrograms/mL). Caffeine administration did not alter the PdiFC or the diaphragmatic electromyogram during IRL. Blood flow to both segments of the diaphragm decreased after caffeine infusion. Serum caffeine levels averaged 86 +/- 30 mumol/L (16.6 +/- 5.9 micrograms/mL).(ABSTRACT TRUNCATED AT 250 WORDS)

Aminophylline↗

PubMed1991

Respiratory mechanics of the piglet during the first month of life.

Piglets at 3, 14, and 30 days of age were studied to assess the postnatal changes in lung, chestwall, and total respiratory system compliance associated with normal growth. Static deflation compliance of the lung and total respiratory system increased significantly with age; there was no change in chestwall compliance. When normalized for body weight or lung volume, all measures of compliance tended to decrease with postnatal age. Measures of lung and chestwall compliance obtained with an end-inspiratory occlusion technique were less than the static compliance measures, but demonstrated the same relative changes with postnatal maturation. Chestwall compliance at 3 days of age was only 1.3 times greater than lung compliance and there was no significant change in this ratio with postnatal age. In contrast to the trend for the human infant, the piglet's chestwall at 3 days of age is stiff relative to the lung and does not become stiffer with age over the first 4 weeks of life.

Animals↗

PubMed1991

Diaphragmatic force and substrate response to resistive loaded breathing in the piglet.

Inspiratory resistive loaded (IRL) breathing results in hypoventilation and diaphragmatic fatigue in the piglet. We studied the effects of 6 h of IRL on ten 1-mo-old piglets. The load was adjusted to increase spontaneously generated transdiaphragmatic pressure five to six times baseline. Six 1-mo-old piglets acted as controls and were identically instrumented but were not subjected to IRL. Measurements of ventilation, blood gases and pH, diaphragmatic electromyogram, force-frequency curve, blood flow, and end-expiratory lung volume were obtained hourly. Diaphragmatic muscle samples were obtained after 6 h for determination of ATP, phosphocreatine, lactate, and glycogen levels. No changes occurred in the control animals. IRL resulted in a significant decrease in ventilation, an increase in diaphragmatic EMG, onset of abdominal expiratory muscle activity, and a fall in end-expiratory lung volume by 1 h. The force-frequency curve adjusted for lung volume change fell by 20% at all frequencies of stimulation at 1 h and by 40% at 6 h. Blood flow to the costal and crural diaphragm increased by 51 and 141%, respectively. No differences were noted in ATP, phosphocreatine, lactate, or glycogen between control and IRL animals. It is concluded that submaximal spontaneous contractions of the piglet diaphragm over a 6-h period cause a substantial decrease in its maximal force-generating capacity that is not related to substrate depletion.

Animals↗

PubMed1991

Effect of high-frequency ventilation on the development of alveolar edema in premature monkeys at risk for hyaline membrane disease.

High-frequency oscillatory ventilation (HFOV) permits adequate gas exchange but avoids the large phasic pressure-volume excursions of conventional mechanical ventilation (CMV); such avoidance may reduce the lung injury associated with hyaline membrane disease (HMD). We hypothesized that premature monkeys ventilated from birth with HFOV would have reduced lung injury compared to those assigned to CMV. Macaca nemestrina were delivered at 134 days (80% of term gestation) and ventilated from the first breath with either HFOV (n = 10) or CMV (n = 10). The mean airway pressure (Paw) was kept at 15 cm H2O pressure in HFOV animals; in CMV animals Paw was increased from 8 cm H2O at 2 h to 13 cm H2O at 6 h to prevent hypoxemia. At the conclusion of the 6-h experiment the HFOV animals had better oxygenation (p less than 0.05) and less evidence of HMD by chest radiograph (p less than 0.05). At 6 h of age a piece of the right middle lung lobe was removed, divided, and placed in fixatives for light and transmission electron microscopy. The lungs were subsequently inflated to 30 cm H2O pressure, and the right lower lobe was rapidly frozen in situ for morphometric studies. The proportion of peripheral lung tissue occupied by clear alveoli was greater in HFOV animals (66.3 +/- 14.8%) than in those assigned to CMV (44.2 +/- 16.9%, p less than 0.01); less alveolar debris and fluid was present in the HFOV animals (12.7 +/- 9.9%) compared with CMV animals (27.1 +/- 12.5%, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

The ventilatory pump: neonatal and developmental issues.

This review documents the current knowledge with regard to the structure and function of the developing ventilatory pump. We note that while the neonate's compliant rib cage and diaphragmatic configuration may predispose the newborn to pump failure, its diaphragmatic endurance properties and ability to recruit accessory muscles of respiration may protect against such impairment. We also share evidence that central neural failure can lead to an inability to defend minute ventilation during periods of heightened respiratory effort. Nevertheless, our fund of knowledge remains limited and at this juncture it is unclear which factors or interplay of factors contribute to the development of ventilatory failure in the human neonate and infant. The ventilatory pump is a vital component of the respiratory system. As such, our understanding of the pathogenesis and reversal of ventilatory pump impairment is crucial to improving our management of respiratory failure. We are only beginning to develop such an understanding within a neonatal and developmental context. Future research endeavors will enlarge our fund of knowledge regarding the thorax, the respiratory muscles, and the central neural respiratory-related neurons that control them. From such an understanding will emerge clinically relevant information that has therapeutic implications for the care of newborns and infants with respiratory disease.

Adult↗

PubMed1990

Estimation of intrapleural pressure in the newborn.

We examined the changes in esophageal (Pes), proximal airway (Paw), and direct intrapleural (Ppl) pressure measurements following end-expiratory airway occlusion in anesthetized spontaneously breathing newborn piglets. Simultaneous occluded pressure measurements were obtained during resting ventilation, inspiratory resistive loaded (IRL) breathing, and bilateral transvenous phrenic nerve stimulation. During spontaneous resting ventilation, occluded Paw/Ppl averaged 104 +/- 4% and occluded Pes/Ppl averaged 89 +/- 3%. Similar values were found for occluded spontaneous breaths with IRL. During phrenic nerve stimulation at end-expiratory lung volume, occluded Paw/Ppl averaged 104 +/- 6% while occluded Pes/Ppl decreased to 70 +/- 22%. We conclude that proximal airway pressure more accurately reflects intrapleural pressure than esophageal pressure with occlusion in newborn swine. During phrenic nerve stimulation, esophageal pressure measures are grossly inaccurate estimates of intrapleural pressure with occlusion.

Airway Obstruction↗

PubMed1990

Developmental changes in the response of the newborn to sustained ventilatory elastic loads.

Postnatal development of the steady-state response to inspiratory elastic loading was studied in eight 48-h-old and eight 24-day-old unanesthetized, tracheostomized monkeys. Both age groups exhibited a fall in minute ventilation (VE) with loads of two to five times baseline respiratory elastance. There was no statistical difference in the ventilatory response between age groups. The response patterns of both groups were characterized by a fall in both tidal volume (VT) and mean inspiratory flow (VT/TI) associated with a prolongation of TI and TI/Ttot. All subjects demonstrated a significant load compensatory response both in terms of neural drive (diaphragmatic EMG output) and force output (inspiratory work production). Arterial CO2 increased significantly during loading in the older subjects in linear correlation with the decline in VE, but the newborns did not exhibit a statistically significant alteration in PaCO2 throughout the range of elastic loads. These data indicate that normal newborns are capable of responding to an external elastic load and that the newborn response is comparable to that of more mature subjects.

Animals↗

PubMed1990

Collagen synthesis during lung development and during hyaline membrane disease in the nonhuman primate.

To assess maturational changes in collagen synthesis, lung tissue was obtained from healthy Macaca nemestrina monkeys at different ages, ranging from 68% of term gestation to adulthood. We hypothesized that infants delivered prematurely have a greater rate of collagen synthesis than do older animals because of their greater rate of lung growth during gestation. Secondly, we hypothesized that lung repair in infants with hyaline membrane disease (HMD) is associated with an additional increase in lung collagen synthesis rate. Therefore, lung tissue was obtained during the first week of life from monkeys delivered at 82% of term gestation, a stage at which half of them developed HMD. The rate of total protein synthesis in lung samples was determined by measuring the incorporation of [3H]proline; the rate of collagen synthesis was determined by measuring the conversion of proline into hydroxyproline. Premature monkeys had a higher rate of collagen synthesis (9.9 +/- 2.7 nmol/mg DNA/h) than did term infants (5.3 +/- 1.1) or older animals (2.1 +/- 0.4, p less than 0.05). There was no additional increase in rate of collagen synthesis in animals with HMD from 3 h (14.3 +/- 6.9) to 7 days of age (15.1 +/- 6.1); control premature animals also had no significant change during the first week of life (10.9 +/- 3.0 at 3 h; 11.6 +/- 4.6 at 7 days). The early stage of recovery from HMD in premature monkeys does not appear to be associated with an increase in collagen production beyond the already increased synthesis rate associated with lung growth.

Analysis of Variance↗