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Biomedical subjects

R A Delemos

Publications and source records attributed to R A Delemos.

9 recordsLinked to original sources

Frequency of chronic lung disease in infants with severe respiratory failure treated with high-frequency ventilation and/or extracorporeal membrane oxygenation.

OBJECTIVE: To assess the frequency of chronic lung disease and factors associated with its development in term infants with severe respiratory failure who receive high-frequency oscillatory ventilation, or high-frequency oscillatory ventilation, and extracorporeal membrane oxygenation (ECMO). DESIGN: Retrospective review of pulmonary outcome of all ECMO candidates admitted to Wilford Hall USAF Medical Center between July 1985 and September 1989. SETTING: A tertiary, level III, neonatal ICU accepting regional referrals for high-frequency ventilation and ECMO. PATIENTS: Ninety-four patients who were candidates for ECMO were studied. High-frequency oscillatory ventilation alone was used in 48 infants. Forty-six infants were treated with high-frequency oscillatory ventilation and ECMO. MAIN RESULTS: Twenty (24%) of 84 survivors developed chronic lung disease. There were no differences in gestational age, birth weight, or gender between those infants who developed chronic lung disease and those infants who did not. Arterial blood gas and ventilatory settings at initiation of high-frequency oscillatory ventilation were similar between those infants who did and those who did not develop chronic disease. Patients who developed chronic lung disease more often had lung hypoplasia (40% vs. 5%) and more often required ECMO (75% vs. 39%) than those patients who did not. In patients without lung hypoplasia, those patients who developed chronic lung disease were older at initiation of high-frequency oscillatory ventilation rescue than those patients who did not develop chronic lung disease (median 91 vs. 46 hrs). CONCLUSIONS: The frequency of chronic lung disease in ECMO candidates is clinically important. Factors associated with chronic lung disease in ECMO candidates are: the presence of lung hypoplasia, delayed referral, and the need for ECMO to support gas exchange.

Birth Weight

Pathophysiologic, morphometric, and biochemical studies of the premature baboon with bronchopulmonary dysplasia.

Pathophysiologic, morphometric, and biochemical (surfactant and coagulation-fibrinolytic parameters) features were studied in premature baboons with and without bronchopulmonary dysplasia (BPD). A total of 22 baboons were delivered by hysterotomy at 75% of gestation and randomized into two groups. Group 1 (PRN) animals were ventilated with high-frequency oscillation for 48 to 72 h and then changed to positive-pressure ventilation (PPV) while maintained on clinically appropriate oxygen for the 21-day experimental period. Group 2 (BPD) animals were ventilated with PPV and 1.0 FlO2 for 7 days followed by 0.8 FlO2 for 14 days. Group 3 (control) animals were delivered and immediately killed at 140 days gestation. Group 1 animals showed no significant airway or saccular lesions, and alveolarization of the saccules was present. Group 2 animals showed metaplastic or hyperplastic epithelial lesions in airways and an alternating pattern of atelectatic but more normal appearing saccules and alveoli interposed between foci of thickened overexpanded saccular walls with no alveolarization. Differences within and between the three study groups were analyzed morphometrically. When numerical densities were examined by comparing control, PRN, BPD-atelectatic areas, and BPD-overexpanded areas. Type II cells were significantly increased in the BPD-overexpanded sites above those of control and PRN values. The interstitial cells were significantly more numerous in the BPD-atelectatic blocks compared with control and BPD-overexpanded blocks. Endothelial cell numerical densities were significantly decreased in the overexpanded sites of the BPD animals compared with the control, PRN, and BPD-atelectatic values. Volume density data showed that the interstitial compartment of the BPD group was significantly larger than those of the control and PRN groups. This was seen as significant increases in the cellular, noncellular, and connective tissue fiber components. Vascular endothelium or lumen volume densities were not different between the BPD and PRN animals, but did differ from those of the 140-day gestation controls. Comparable levels of lavage plasminogen-dependent fibrinolytic activity, were detectable at the 21-day study interval. The phospholipid composition of pulmonary surfactant, including disaturated PC and total PG, was similar between BPD and PRN groups at 21 days. The pathologic, morphometric, and biochemical patterns in this study probably represent those seen in human neonates with mild to moderate clinical BPD who survive. At this time, it is not known if the destructive endothelial lesion and the lack of alveolarization in the overexpanded and fibrotic lesions will resolve over time in long-term BPD survivors.

Animals

Circulatory changes following premature delivery in a baboon model of hyaline membrane disease.

The premature baboon delivered by hysterotomy at 140 +/- 2 days (75%) gestation develops hyaline membrane disease (HMD) and left-to-right (L-R) shunting through the patent ductus arteriosus (PDA). To characterize hemodynamic changes that follow premature delivery, we measured systemic and organ blood flow, oxygen transport, and systemic vascular resistance over the first 96 h of life. We compared these measurements with those from more mature animals of the same species. Radiolabeled microspheres were used to measure organ blood flow (in ml.min-1.g-1) at 3 (n = 18), 23 (n = 17), and 96 h (n = 4) in the premature animals, and at 13 +/- 4 mo in the older animals (n = 5). Premature animals demonstrated over the first 96 h of life significant hemodynamic changes that included decreased systemic vascular resistance (P less than 0.001), increased systemic (P less than 0.05), intestinal (P less than 0.05), and hepatic blood flow (P less than 0.05), as well as resolution of L-R PDA shunting. These 96-h values were similar to those of the more mature infant baboons. Blood flow and oxygen transport to the kidneys and cerebrum did not significantly increase over the first 96 h in premature baboons and were significantly less than those of 13-mo-old animals (P less than 0.01, both). We speculate that low renal and cerebral blood flow in the 140-day premature baboon are manifestations of multisystem immaturity and, as such, may represent persistent physiological disturbances that are distinct from the severity of underlying lung disease in HMD.

Aging

Bacterial colonization and infection studies in the premature baboon with bronchopulmonary dysplasia.

Microbial colonization and infection patterns were prospectively evaluated in premature baboons with and without bronchopulmonary dysplasia (BPD) to assess if prolonged hyperoxia would predispose to a different pattern of microbial colonization and/or a higher risk of respiratory infection. Forty baboons were delivered by hysterotomy at 75% of gestation and randomized into two groups. Group I (control or PRN) animals were placed immediately on high-frequency oscillation at 15 Hz; I:E ratio 1:2, and changed to positive-pressure ventilation at 48 to 72 h. They were maintained on clinically appropriate oxygen at minimal ventilator settings for the remainder of the 21-day experimental period. Group II (oxygen-treated or BPD) animals were ventilated with PPV and FIO2 1.0 for 7 days followed by FIO2 0.8 for 14 days. All animals were treated with antibiotics during some portion of the 21-day course. Specimens from nose, oropharynx, trachea, and rectum were cultured for both aerobes and anaerobes throughout the neonatal intensive care unit (NICU) course. A subset of animals from both groups were killed at 21 days and lung, liver, spleen, and gastric contents were cultured quantitatively at autopsy. Findings showed that coagulase-negative staphylococci were the predominant organisms that colonized the neonate in the NICU. Lung infections were seen to evolve through sequential pathogenetic steps: colonization of the upper respiratory tract, with concomitant or subsequent colonization of the trachea with comparable organism and ultimate recovery of the same organisms at autopsy in the lungs of animals with pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Airway response to ultra short-term exposure to ozone.

To determine whether acute short-term exposure to oxidant pollutants can cause changes in respiratory mechanics, we gave 0.5 ppm ozone for 5 min to 7 baboons. We measured pulmonary resistance (RL) and obtained dose response curves to methacholine before and after the exposures. This brief insult increased resistance (control RL = 1.53 +/- 0.21 cm H2O.L-1 s; post-ozone RL = 3.53 +/- 0.54 cm H2O.L-1 s). On a second occasion, 6 of these animals were restudied before and after the administration of cromolyn sodium. Although this drug had no effect on the measurements of mechanics made in the control period, it significantly reduced the ozone-induced changes in mechanics. The increase in RL was 52% of that produced in the first study. The results demonstrated that the ozone injury with its acute and subacute airway sequelae occurs quite rapidly and after very brief exposure. The time course of the change in mechanics and the effects of cromolyn suggest the hypothesis that surface epithelial cells are disrupted, causing subsequent release of bronchoconstricting agents.

Air Pollutants

Oxygen toxicity in the premature baboon with hyaline membrane disease.

Immaturity, pulmonary barotrauma, and oxygen toxicity have been implicated in the pathogenesis of bronchopulmonary dysplasia (BPD). Although the physiologic and biochemical consequences of oxygen toxicity have been described in newborn and adult animals, there have been no controlled observations in prematures. We compared the physiologic and morphologic effects of prolonged hyperoxia with those of clinically appropriate oxygen in premature baboons with hyaline membrane disease (HMD) supported with conventional positive pressure ventilation and continuous distending airway pressure (PPV/PEEP). Twenty-one premature baboons were delivered at 140 days gestation, intubated and resuscitated, and supported with PPV/PEEP and standard NICU techniques for 11 days. The FIO2, PaO2, PaCO2, pHa, ventilator and airway pressures, and blood pressure were intermittently measured and recorded. The physiologic observations could be divided into 3 distinct phases. During Phase 1 (0 to 42 h) there were no significant intergroup differences, and (a/A)PO2 and IO2 (oxygenation index; (a/A)PO2/Paw) remained stable. In Phase 2 (43 to 96 h) there was a rapid improvement in (a/A)PO2 and IO2 in both groups, but the response in the hyperoxic animals was significantly dampened. During Phase 3 (97 to 264 h) there was continued improvement in the "prn" animals, which contrasted with progressive deterioration in those exposed to FIO2 1.0. Five of 11 "prn" and 3 of 10 FIO2 1.0 baboons developed air leaks during Phase 1 or early Phase 2. Four of 10 of the hyperoxic animals died after the late onset of air leak. Pathologic changes of BPD were found in all FIO2 1.0 animals surviving more than 6 days but in none of the "prn" long-term survivors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Ventilatory management of infant baboons with hyaline membrane disease: the use of high frequency ventilation.

We tested the hypothesis that high frequency oscillatory ventilation (HFOV) would result in decreased pulmonary barotrauma in infants with hyaline membrane disease by comparing HFOV at 10 Hz to conventional positive pressure ventilation with continual distending airway pressure (PPV/PEEP) in premature baboons with hyaline membrane disease. Nineteen baboon fetuses were randomized to one of two treatment groups, delivered at 140 +/- 2 days, and, after stabilization and instrumentation of PPV/PEEP, placed in their respective ventilator group. Animals on conventional ventilation were managed by adjustment of tidal volume and frequency (to 1 Hz) to keep PaCO2 below 55 and by adjustment of the mean airway pressure. One of the "HFOV" group died of cardiovascular complications before going on HFOV and was eliminated from data analysis. The remaining HFOV baboons survived the 11-day experimental period without evidence of airleak. Six of the 11 prematures treated with PPV/PEEP developed pulmonary interstitial emphysema and/or pneumothorax and five of the animals died within 48 h. The intergroup differences in airleak were significant (p less than 0.05). Mean airway pressure (measured at the proximal airway) was higher initially with HFOV but then was lowered more rapidly than in the PPV/PEEP animals. The arterial to alveolar oxygen ratio rose and the FIO2 could be lowered more rapidly with HFOV than with conventional ventilation. These differences reached significance by 20 h. After 60 h there were no significant differences between HFOV and the PPV/PEEP survivors. HFOV resulted in more uniform saccular expansion, higher arterial to alveolar oxygen ratio, less oxygen exposure, and decreased acute barotrauma when compared to PPV/PEEP.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance

Pulmonary interstitial emphysema treated by high-frequency oscillatory ventilation.

Twenty-seven low birth weight infants who developed pulmonary interstitial emphysema (PIE) and respiratory failure while on conventional ventilation were treated with high-frequency oscillatory ventilation (HFOV). The mean birth weight was 1.2 kg (range 0.55 to 2) with gestational age of 28 wk (range 25 to 34). Ten patients died, six of whom had documented sepsis with shock and were therefore excluded from analysis. All patients showed initial improvement on HFOV. Surviving patients showed continued improvement in oxygenation and ventilation at increasingly lower fraction of inspired oxygen and proximal airway pressure with resolution of PIE, while nonsurvivors progressively developed chronic respiratory insufficiency with continued PIE from which recovery was not possible. Overall survival in nonseptic patients was 80% (16 of 20). We found HFOV to be effective in the treatment of PIE and hypothesize that interstitial airleak is decreased during HFOV because adequate ventilation is provided at lower peak distal airway pressures.

Critical Care