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Biomedical subjects

A B Froese

Publications and source records attributed to A B Froese.

At least 19 recordsLinked to original sources

[Physiological basis for the use of muscarine antagonists in bronchopulmonary dysplasia].

The rationale for the use of muscarinic antagonists in bronchopulmonary dysplasia (BPD) is based on the physiology and pharmacology of airway smooth muscle, the pathology of BPD, and the response of infants with BPD to bronchodilators, in vivo and in vitro studies of airway smooth muscle of newborn animals and humans indicate that vagal efferent airway innervation and/or muscarinic receptors are functional at birth, as well as early in gestation. Current concepts regarding muscarinic receptor subtypes suggest that M3 receptors mediate airway smooth muscle contraction, M2 receptors are autoinhibitory and limit vagally-mediated bronchoconstriction, and M1 receptors may play a facilitatory role in ganglionic transmission. Muscarinic receptor subtypes appear to be functionally expressed at birth but may undergo developmental regulation. Infants with BPD have an elevated pulmonary resistance that is accompanied by hypertrophy of airway smooth muscle, b2-agonists cause bronchodilation in BPD as does atropine in infants recovering from severe BPD. The synthetic congener of atropine, ipratropium bromide (IPB) causes bronchodilation in ventilator-dependent infants with BPD in a dose-dependent fashion. Nebulized IPB causes a decrease in respiratory resistance that reaches a maximum of 20% at 175 mg. The bronchodilation seen with muscarinic antagonists suggests that part of the elevated resistance associated with BPD is due to increased muscarinic tone, presumably vagal in origin. When IPB is combined with salbutamol (0.04 mg) the response is increased in magnitude and duration; reaching a slightly larger decreases in resistance (26%) that is now accompanied by an increase in compliance (20%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Ventilator pattern influences neutrophil influx and activation in atelectasis-prone rabbit lung.

Both ventilator pattern and neutrophil activation influence lung injury in adult respiratory distress syndrome (ARDS). We therefore questioned whether ventilator pattern independently affects neutrophil accumulation and function in early ARDS. Thirty-five New Zealand White rabbits were anesthetized, paralyzed, and prepared using sterile techniques. Fifteen surfactant-depleted animals were randomized and ventilated for 4 h using high-frequency oscillatory ventilation (HFO) at 15 Hz with an inspired O2 fraction = 1.0 and arterial PO2 (PaO2) > 400 Torr (a pattern known to reverse atelectasis) or conventional mechanical ventilation (CMV) with PaO2 = 80-100 Torr (a pattern with some atelectasis despite positive end-expiratory pressure). Eight normal animals on CMV with PaO2 > 400 Torr served as a reference group (NorCMV). NorCMV animals progressively increased circulating polymorphonuclear neutrophil (PMN) numbers and had minor pressure-volume curve alterations but no other significant changes. Lavaged CMV animals developed the characteristic gas exchange and marked pressure-volume curve abnormalities of ARDS. Circulating PMNs remained constant but developed decreased chemotactic activity, whereas lung neutrophil numbers increased significantly (P = 0.0002) and had substantially enhanced chemiluminescence (P = 0.0003 vs. NorCMV animals). Although lavaged HFO animals accumulated an intermediate number of lung neutrophils (lung myeloperoxidase > NorCMV animals; P = 0.003), the chemiluminescence and chemotaxis of these PMNs were the same as in cells from NorCMV animals. We concluded that both the degree of neutrophil activation and lung injury can be minimized by preventing cyclic alveolar/airway expansion and collapse in the surfactant-deficient lung by use of appropriate ventilator patterns.

Air Pressure

The association between preterm newborn hypotension and hypoxemia and outcome during the first year.

Ninety-eight newborn infants, less than 34 weeks at birth, were studied to examine the relationship between newborn hypotension and hypoxemia and brain damage. Heart rate, blood pressure and oxygen tension were recorded continuously during the 96 h following delivery. Outcome measures included neuropathology in children who died, and motor and cognitive development at one year corrected age in children who survived. There were 22 children with a minor and 27 with a major abnormal outcome. There was a relationship between newborn hypotension, newborn hypoxemia and low birth weight, and a major abnormal outcome. The probability of a major abnormal outcome increased from 8% in newborns with no hypotension or hypoxemia, to 53% in children with both hypotension and hypoxemia. These findings support the contention that combinations of sustained newborn hypotension and hypoxemia are important factors in the development of brain damage, accounting for a major abnormal outcome.

Acidosis

Dexamethasone therapy for bronchopulmonary dysplasia: improved respiratory mechanics without adrenal suppression.

The purpose of the present study was to examine the pattern of changes in respiratory system mechanics induced by dexamethasone (Dex) in infants with bronchopulmonary dysplasia (BPD) and to determine whether dosages that produce these changes induce adrenal suppression. We examined mechanics in seven ventilator-dependent premature infants (age, 33 +/- 4.8 days) with BPD, before and daily during Dex therapy. Dex (0.5 mg/kg/day) was given intravenously for 7 days unless complications necessitated early termination. Respiratory system resistance (Rrs) and compliance (Crs) were measured by the passive expiratory flow-volume technique during the course of dexamethasone therapy or until extubation. Adrenocorticotrophic hormone (ACTH) stimulation tests were done at baseline and following Dex therapy to evaluate adrenal function. Dex therapy caused a 77 +/- 18% increase in Crs (from 0.97 +/- 0.09 SEM mL/cmH2O to 1.6 +/- 0.16 mL/cmH2O; P less than 0.025) and a 33 +/- 5% decrease in Rrs (from 0.20 +/- 0.02 cmH2O/mL/s to 0.14 +/- 0.01 cmH2O/mL/s; P less than 0.01). Concurrently, ventilator rate, mean airway pressure, and FIO2 all decreased significantly (P less than 0.025). Extubation occurred later in infants with the lowest Crs and highest Rrs at baseline. At extubation, all Crs values were greater than 1.33 mL/cmH2O and Rrs values were less than 0.15 cmH2O/mL/s. Systolic blood pressure increased from 61 +/- 6.3 mmHg to 84 +/- 17 mmHg, 72-96 h after the start of Dex (P less than 0.025). There were no episodes of culture-positive sepsis. Neither basal nor ACTH-stimulated levels of cortisol were suppressed as a result of Dex therapy (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands

Hypotension and hypoxemia in the preterm newborn during the four days following delivery identify infants at risk of echosonographically demonstrable cerebral lesions.

This prospective study of 130 preterm newborns at less than 34 weeks gestational age has examined the predictive value of abnormalities in continuously recorded newborn blood pressure, heart rate, and oxygen tension during the 4 d following delivery for echosonographically demonstrable cerebral lesions (EDCL) identified in the infant by six months corrected age. EDCL consisting of intraventricular hemorrhage, ventriculomegaly, or hyperechoic parenchymal lesions in the brain were identified in 44 preterm newborns (34%). The incidence of EDCL in preterm newborns with no hypotension or hypoxemia was 13%. The incidence of EDCL was significantly increased in preterm newborns with either hypotension or hypoxemia. The probability of EDCL exceeded 50% when the total exposure to either hypotension or hypoxemia during the 4 d exceeded 50 mmHg-hours, or when newborn hypotension and hypoxemia occurred concurrently. No relationship to hypertension, bradycardia, or tachycardia was detected. These findings indicate that hypotension and hypoxemia in the preterm newborn during the 4 d following delivery are useful risk markers of EDCL.

Brain Diseases

Blood pressure and heart rate of the preterm newborn following delivery.

Thirty-five preterm newborns were studied to determine the mean blood pressure and heart rate of preterm newborns less than 1500 gm and greater than or equal to 1500 gm at birth. Systemic blood pressure increased and heart rate decreased with increasing maturity at birth. Both systemic blood pressure and heart rate increased during the four days following delivery. The 95% prediction limits of stable preterm newborns less than 1500 gm and greater than or equal to 1500 gm at birth are useful criteria to define hypertension and hypotension, as well as tachycardia and bradycardia.

Aging

A clinical comparison of indices of pulmonary gas exchange with changes in the inspired oxygen concentration.

Several indices have been introduced as convenient alternatives to calculation of the physiological shunt fraction (Qs/QT) for the assessment of pulmonary gas exchange. These include: the arterial-alveolar oxygen tension ratio (a/APO2), the arterial oxygen tension-inspired oxygen concentration ratio (PaO2/FIO2), the respiratory index (RI), [A-a)DO2/PaO2) and the alveolar-arterial oxygen tension difference [A-a)Do2). These indices are in use clinically despite the fact that they may not accurately predict gas exchange in situations where FIO2, Qs/QT or arterial-venous oxygen content is changing. The clinical stability of each of these indices, relative to the behaviour of the physiological shunt, was therefore investigated prospectively in ten mechanically ventilated postoperative adults as FIO2 was varied from 0.30 to 1.00. None of the indices studied reliably reflected the behaviour of the physiological shunt. As FIO2 was increased incrementally from 0.30 to 1.00, 42 to 55 per cent of the measured changes in these indices were opposite in direction to the corresponding changes in the physiological shunt. The maximum magnitudes of the opposite changes were substantial; 24 and 22 per cent for the a/APO2 and PaO2/FIO2 ratio respectively, 67 per cent for the RI and 101 per cent for the (A-a)DO2. We conclude that the use of any of these indices for clinical assessment of a patient's gas exchange defect when FIO2 is varying can be substantially misleading.

Aged

Bronchodilator response to ipratropium bromide in infants with bronchopulmonary dysplasia.

Although the muscarinic antagonist Ipratropium bromide is used clinically as a bronchodilator in infants ventilated because of bronchopulmonary dysplasia (BPD), no studies have compared the response or efficacy of different dosages or its effectiveness in combination with beta-adrenergic agonists. We measured the response of respiratory system mechanics in 10 ventilated infants (25 +/- 2 days of age) to 75, 125, and 175 micrograms ipratropium bromide (IB), 125 micrograms IB plus 0.04 mg salbutamol (SAL), 175 micrograms IB plus 0.04 mg SAL, and saline vehicle, delivered via nebulizer into the ventilator circuit. Respiratory system resistance (Rrs) and compliance (Crs) were measured by the passive flow-volume technique. Rrs and Crs were measured before and at 1 to 2 h and at 4 h after delivery of the five drug dosages or saline. All six studies were completed within a 72-h period. Saline had no significant effect on mechanics. Significant responses to ipratropium alone were seen only after 175 micrograms where Rrs decreased 20 +/- 3% (SEM) (p less than 0.05) at 1 to 2 h and 16 +/- 5% (p less than 0.05) at 4 h. After 125 micrograms IB + SAL and 175 micrograms IB + SAL, Rrs was significantly decreased both at 1 to 2 h and at 4 h, and Crs was significantly increased 20 +/- 6% and 20 +/- 4%, respectively, at 1 to 2 h. The greatest decrease in Rrs (26 +/- 6%) was seen 1 to 2 h after 175 micrograms IB + salbutamol.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance

Lung volume recruitment during high-frequency oscillation in atelectasis-prone rabbits.

In diffuse lung injury, optimal oxygenation occurs with high-frequency oscillatory ventilation (HFO-A, where A is active expiratory phase) when sustained inflations (SI) are applied periodically to recruit lung volume. Theoretically pulsed pressures may be safer and more effective than static pressures for reexpanding alveoli. We compared the increases in lung volume and arterial PO2 (PaO2) induced by 30-s increases in mean airway pressure in six New Zealand White rabbits made atelectasis prone by saline lavage plus 1 h of conventional ventilation. Pulsatile SI's (HFO-A left on during increase in mean pressure) of delta PSI = 5, 10, and 15 cmH2O and static SI's (HFO-A off during SI) of delta PSI = 5, 10, 15, and 20 cmH2O were delivered in random order. Lungs were ventilated at 15 Hz, inspired fractional concentration of O2 = 1.0, and mean airway pressure 15-20 cmH2O between test periods and deflated to functional residual capacity before each SI to standardize volume history. With both maneuvers, increases in lung volume and PaO2 induced by SI's were proportional to the magnitude of the SI (P less than 0.001) in all cases. Pulsatile SI's consistently increased lung volume and PaO2 more than static SI's having the same delta PSI (P less than 0.005) such that any given target PaO2 or change in volume (delta V) was achieved at 5 cmH2O less mean pressure with the pulsatile maneuver. Respiratory system compliance increased after both types of SI. Oxygenation and lung volume changes at 5 min were related with r = 0.58 (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Lung volume maintenance prevents lung injury during high frequency oscillatory ventilation in surfactant-deficient rabbits.

Controversy exists whether high frequency oscillatory ventilation with an active expiratory phase (HFO-A) should be used at low ventilator pressures or high alveolar volumes to minimize lung injury in the atelectasis-prone lung. We therefore ventilated 20 anesthetized, tracheostomized rabbits made surfactant-deficient by lung lavage in 1 of 3 ways: HFO-A at a high lung volume (HFO-A/HI), HFO-A at a low lung volume (HFO-A/LO), or conventional mechanical ventilation (CMV); all received 100% oxygen for 7 h. We examined oxygenation, lung mechanics, and lung pathology. Arterial oxygenation in the HFO-A/HI rabbits was kept greater than 350 mm Hg. Mean lung volume above FRC in these animals was 23.4 ml/kg. In rabbits ventilated with HFO-A/LO and CMV, arterial oxygen tensions were 70 to 100 mm Hg. Mean lung volumes were 7.8 and 4.3 ml/kg, respectively. Total respiratory system pressure-volume curves (P-V curves) showed no change from baseline in the HFO-A/HI group after 7 h of ventilation. The low lung volume groups (HFO-A/LO and CMV) showed a diminution in hysteresis of their P-V curves, lower total respiratory system compliance, more hyaline membranes and severe airway epithelial damage. (All changes significant with p less than 0.05). We conclude that maintenance of alveolar volume is a key mechanism in the prevention of lung injury during mechanical ventilation of the atelectasis-prone lung. For optimal outcome using high frequency oscillatory ventilation, alveoli must be actively reexpanded and then kept expanded using appropriate mean airway pressures.

Airway Resistance

High-frequency oscillatory ventilation in premature infants with respiratory failure: a preliminary report.

High-frequency ventilation has been used successfully to manage life-threatening complications in premature infants with lung disease. Here we report a preliminary assessment of the efficacy and safety of high-frequency oscillatory ventilation-(HFO-A, A = active expiratory phase) when used as a primary ventilator in 11 infants of 24-34 weeks gestation who required ventilatory support. HFO-A was initiated after no more than 5.5 hr of conventional mechanical ventilation (CMV). HFO-A at 15 Hz was used for 12-203 hr following a protocol designed for rapid reduction of FI02 requirements. CO2 elimination was easily achieved in all infants. Oxygenation was satisfactory, except in one infant with congenital pneumonia. There were four deaths during HFO-A: two pulmonary (one congenital pneumonia; one pulmonary hemorrhage) and two nonpulmonary. The HFO-A protocol utilized lung volume recruitment maneuvers plus mean airway pressures (MAwP) greater than those generally used early in the course of CMV. Therefore, in a subset of infants less than or equal to 29 weeks' gestation with respiratory distress syndrome (RDS), ventilator pressures and gas exchange were compared in infants treated with either HFO-A or CMV. Maximum MAwP levels were reached earlier in six infants on HFO-A (5.2 +/- 2.5 hr; mean +/- SD) than in a comparable group of 9 CMV-treated infants (36 +/- 1 hr). This earlier use of high MAwP lowered the FI02 to less than 0.4 by 18.9 +/- 11 hr with HFO-A as compared with 64 +/- 6 hr using CMV, without any evidence of an increase in pulmonary complications. There were 17 complications in the nine CMV-treated infants; and four in the six HFO-A treated ones. We conclude that HFO-A, instituted early and used with a protocol designed for early reduction in FI02 requirements, demonstrates sufficient efficacy and safety to warrant further clinical trials in the routine management of infant RDS.

Evaluation Studies as Topic

Effect of graded erythrocythemia on cardiovascular and metabolic responses to exercise.

The effects of graded induced erythrocythemia on cardiovascular and metabolic responses to intense treadmill running were studied in four highly trained endurance runners. Three autologous infusions of 1 unit (U) whole blood (450 ml/U) were administered sequentially 2-7 days apart. Maximal O2 consumption (VO2max) increased from 5.04 l/min at control (C) to 5.24 l/min after 2 U (R2) and 5.38 l/min after 3 U (R3). Cardiac output during treadmill running at 91% control VO2max was 28.2 l/min at C, 29.8 l/min at R2, and 33.1 l/min at R3. Corresponding heart rates were unchanged, and stroke volume was increased at R3. Peak lactate concentration was reduced, and arterial acid-base status improved at R2 and R3 after standardized bouts of intense exercise. Arterial blood pressures and electrocardiograms during exercise were not affected by erythrocythemia. We conclude that the reinfusion of up to 3 U of autologous blood into highly trained endurance runners who have normal hematology does not adversely affect their cardiovascular response to maximal exercise. In addition, the increases in VO2max following reinfusion of 2 U, and again after 3 U, suggest that the aerobic power of the working muscles was not surpassed at these levels of erythrocythemia.

Acid-Base Equilibrium

Validation of noninvasive maximal cardiac output measurement.

Due to the invasiveness of direct techniques and problems that constrain the use of popular indirect techniques during very heavy (non-steady-state) exercise, measurements of maximal cardiac output are seldom included in studies of exercise. The acetylene-rebreathing technique is well-suited for maximal exercise; however, until recent technological advances, difficulties involved in collecting and measuring alveolar acetylene samples have restricted its use. We compared cardiac output values measured via the acetylene-rebreathing technique (QA) (modified for use with a mass spectrometer) and the dye-dilution technique (QD) at rest and during light to maximal exercise in six moderately active males. Although QA consistently underestimated QD, the two techniques showed a significant correlation of 0.87 throughout all levels of exercise. During maximal exercise, QA and QD values were not significantly different (24.7 and 26.7 l X min-1, respectively). Modifications in the QA technique that reduce potential sources of error were also examined. We conclude that the acetylene-rebreathing technique, modified for use with a mass spectrometer, is a simple and valid procedure for measuring maximal cardiac output.

Adult