Personhood: a biological phenomenon.

Understanding the nature of the offspring from conception to birth is the fundamental requirement upon which clinical practice and laboratory research of Perinatal Medicine is based. Thus, definition of the person is essential, and "personhood" is not an arbitrary convention. Rather, it is a verity of nature, known and documented by biologists and understandable to all.

The alveolar surface network: a new anatomy and its physiological significance.

UNLABELLED: It is generally held that the terminal lung unit (TLU) is an agglomeration of alveoli that opens into the branching air spaces of respiratory bronchioles, alveolar ducts, and alveolar sacs and that these structures are covered by a continuous thin liquid layer bearing a monomolecular film of surfactants at the open gas-liquid interface. The inherent structural and functional instability given TLUs by a broad liquid surface layer of this nature has been mitigated by the discovery that the TLU surface is in fact an agglomeration of bubbles, a foam (the alveolar surface network) that fills the TLU space and forms ultrathin foam films that 1) impart infrastructural stability to sustain aeration, 2) modulate circulation of surface liquid, both in series and in parallel, throughout the TLU and between TLUs and the liquid surface of conducting airways, 3) modulate surface liquid volume and exchange with interstitial liquid, and 4) sustain gas transfer between conducting airways and pulmonary capillaries throughout the respiratory cycle. The experimental evidence, from discovery to the present, is addressed in this report. Lungs were examined in thorax by stereomicroscopy immediately from the in vivo state at volumes ranging from functional residual capacity to maximal volume (Vmax). Lungs were then excised; bubble topography of all anterior and anterolateral surfaces was reaffirmed and also confirmed for all posterior and posterolateral surfaces. The following additional criteria verify the ubiquitous presence of normal intraalveolar bubbles. 1) Bubbles are absent in conducting airways. 2) Bubbles are stable and stationary in TLUs but can be moved individually by gentle microprobe pressure. 3) Adjoining bubbles move into the external medium through subpleural microincisions; there is no free gas, and vacated spaces are rendered airless. Adjacent bubbles may shift position in situ, while more distal bubbles remain stationary. 4) The position and movement of "large" bubbles identifies them as intraductal bubbles. 5) Transection of the lung reveals analogous bubble occurrence and history in central lung regions. 6) Bubbles become fixed in place and change shape when the lung is dried in air; the original shape and movement are restored when the lung is rewet. 7) All exteriorized bubbles are stable with lamellar (film) surface tension near zero. 8) Intact lungs prepared and processed by the new double-embedding technique reveal the intact TLU bubbles and bubble films. Lungs were also monitored directly by stereomicroscopy to establish their presence, transformations, and apparent function from birth through adulthood, as summarized in the following section. ANATOMY: Intraalveolar bubbles and bubble films (the unit structures of the alveolar surface network) have been found in all mammalian species examined to date, including lambs, kids, and rabbit pups and adult mice, rats, rabbits, cats, and pigs. Rabbits were used for the definitive studies. 1) A unit bubble occupies each alveolus and branching airway of the TLU; unit bubbles in clusters correspond with alveolar clusters. 2) The appositions of unit bubble lamellae (films) form a network of liquid channels within the TLUs. The appositions are bubble to bubble (near alveolar entrances, at pores of Kohn, and between ductal bubbles), bubble to epithelial cell surface, and bubble to surface liquid of conducting airways. They rapidly form stable Newtonian black foam films (approximately 7 nm thick) under hydrodynamic conditions expected in vivo. 3) Lamellae of the foam films and bubbles tend to exclude bulk liquid and thus maintain near-zero surface tension. At the same time, the foam film formations--abetted by the constant but small retractive force of tissue recoil--stabilize unit bubble position within the network. 4) Unit bubble mobility in response to applied force increases as liquid accumulates within the network (e.g. (ABSTRACT TRUNCATED)

Intraalveolar bubbles and bubble films: III. Vulnerability and preservation in the laboratory.

BACKGROUND: Having confirmed (Scarpelli et al. 1996. Anat. Rec. 244:344-357 and 246:245-270) the discovery of intraalveolar bubbles and films as the normal anatomical infrastructure of aerated alveoli at all ages, we now address three questions. Why have these structures been so elusive? Visible in fresh lungs from the in vivo state, can they be preserved by known laboratory methods? Can they be preserved intact for study in tissue sections? METHODS: Lungs of adult rabbits and pups were examined in thorax directly from the in vivo state to confirm normal bubbles both at functional residual capacity and at maximal volume; other lungs were permitted to deflate naturally to minimal volume. The fate of bubbles in situ (either intact, transected, or diced lung tissue) and of isolated bubbles was assessed (1) during conventional histopreparative processing, (2) during inflation-deflation after degassing, (3) after drying in air, (4) during and after quick freezing in liquid N2, and (5) after preservation in fixed and stained tissue sections prepared by a new double-impregnation procedure in which glutaraldehyde-fixed tissue was preembedded in agar, dehydrated and clarified chemically, embedded in paraffin, sectioned, and stained. Control studies included both blocking of bubble formation by rinsing the air spaces with Tween 20 prior to double impregnation and preparation of normal tissue without preembedding in agar. RESULTS: (1) Each of the following procedures in conventional processing dislocated and disrupted bubbles and films: osmium tetroxide and glutaraldehyde:formaldehyde:tannic acid mixture fixation; chemical dehydration (70-100% ethanol) and clarification (xylene and acetone); and embedding in paraffin or epoxy resin. Transection and dicing of the tissue aggravated the untoward effects. In contrast, bubbles and films remained stable in either glutaraldehyde or formaldehyde, which, however, did not protect against the other agents. (2) Degassing destroyed all bubbles as expected; however, bubbles and films re-formed immediately with reinflation. (3) Topography of fixed bubbles and films was retained after air drying. The dry polygonal configuration reverted to spherical-oval either in saline solution or in 50% ethanol, whereas vulnerability to upgraded ethanol concentrations was unchanged. (4) Normal topography and shape appeared to be retained during quick freezing and after thawing. (5) Intraalveolar and intraductal bubbles and films were preserved and photographed in sections from tissue prepared by the double-impregnation procedure; they were not seen either when bubble formation had been blocked (double-impregnation procedure) or when preembedding in agar had been omitted. CONCLUSIONS: (1) Whether or not fixed in glutaraldehyde or formaldehyde, preservation of intraalveolar and intraductal bubbles and films is not to be expected in tissue prepared by conventional histopreparative procedures, whereas product artifacts may be expected from bubble rupture in situ. (2) Degassing cannot be recommended for studies of alveolar structure-function interrelations because all natural bubbles are disrupted in the process, and bubble re-formation may not parallel their "natural history" in vivo. (3) Compared with glutaraldehyde or formaldehyde fixation, air drying offers no added protection against the untoward effects of conventional processing. (4) Quick-frozen tissue is equally at risk. (5) A new double-impregnation procedure does preserve bubbles and films during processing, sectioning, and staining.

Intraalveolar bubbles and bubble films: II. Formation in vivo through adulthood.

BACKGROUND: Intraalveolar bubbles and bubble films have been shown to be part of the normal alveolar architecture in vivo from birth through the first 2 days of extrauterine life of rabbit pups (Scarpelli et al., 1996a. Anat. Rec. 244:344-357). The intraluminal boundary between air-way free gas and alveolar bubbles at the level of respiratory bronchioles is established within 1 hour after birth. We now examine the lung through the rest of development, namely, 2 weeks, 1, 2, and 3 months, and adulthood. METHODS: In quick succession in anesthetized spontaneously breathing rabbits, the abdominal aorta was transected and trachea was occluded either after an end-tidal exhalation at functional residual capacity (FRC) or after volume expansion in vivo by a single inflation from FRC to 20 or 25 cm H2O pressure (V20, V25). Immediately the thorax was opened and lungs were examined (anterior, anterolateral) through a dissecting stereomicroscope while still in the chest, unperturbed (pleural surface temperature 34 degrees C). Heart and lungs were then removed en bloc and re-examined (anterior, lateral, posterior) to confirm that architecture had not changed (22-27 degrees C). After these immediate examinations, lungs were entered into one of the protocols enumerated in Results. RESULTS: Immediate examination revealed bubbles in all aerated subpleural and deep ("central") alveoli from apex to base at all ages and temperatures. Bubbles were confirmed from two views (top and tangential) and from their individual mobility in response to gentle microprobe pressure. A "common bubble" (> 30 microns to approximately 120 microns inside diameter at FRC) appeared to occupy a single alveolus, sometimes arranged in clusters and collectively accounting for approximately 84% of the total bubble population. Few "large bubbles" appeared to be intraductal. We concluded that "small bubbles" (< or = 30 microns; approximately 16% of the total population) were contracted common bubbles. The free gas-bubble film boundary of the airways was at the level of respiratory bronchioles. Subsequent protocols: (1) Common bubbles moved out of adjoining tissue following subpleural incision. Adjacent bubbles either moved into vacated spaces or into the outside liquid medium. Large bubble(s) followed common bubbles out of the tissue. Small bubbles were less mobile and distal common bubbles did not move. The sequence of bubble movement at V25 was the same. Isolated bubbles had normal surfactant content and surface tension according to "Pattle's stability ratio." Transection revealed analogous conditions in central alveoli. (2) Bubble size increased during inflation from FRC to V25. Airless spaces were aerated with bubbles during inflation. (3) The bubble surface was compressed during deflation to 81% of maximal volume (Vmax) and below, including deflation to minimal volume (Vmin). (4) Bubble/alveolar shape changed from spherical-oval to polygonal when the pleural surface dried at FRC and V25. The original shape was restored when the surface was re-wet. Dry tissue showed but did not emit bubbles when cut; re-wet tissue did. (5) Lung liquid content and volume-pressure were normal at FRC. (6) As expected, conventionally fixed, dehydrated, and embedded sections showed no bubbles. CONCLUSIONS: Bubbles and bubble films are fundamental to normal architecture of aerated alveoli at all lung volumes from birth through adulthood. As infrastructure, they sustain aeration and resist deformation. With ductal films, they may be expected to form an alveolar surface liquid (foam film) network (Scarpelli, 1988. Surfactants and the Lining of the Lung) that modulates liquid balance principally at Plateau borders. They expand and contract respectively during inflation and deflation, maintaining their closed film integrity. Films are compressed to "film collapse" in situ during deflation from volumes well above FRC to Vmin. At these volumes, intact films sustain aeration; some may disperse into t

Rapid in vitro tests of surfactant film formation: advantages of the Exerowa black film method.

Based on our research, the natural configuration of surfactant from birth through adulthood takes the form of intraalveolar bubbles. Thus, bubble film analysis would seem to be the specific in vitro testing method for lung surfactant. In the present study we report a battery of five in vitro tests for assessing structural and functional properties of surfactant bubbles and bubble films from hydrophobic extracts, namely, the therapeutic surfactants Survanta (SU) and Infasurf (IN) (full strength and diluted to 3 mg phospholipid/mL) and from aqueous extracts from rabbit lung lavage at 3 mg phospholipid/mL (SAM). Each substrate was assessed by: 1) Shake test: stable bubbles from SU, IN, and SAM (50/50, v/v in 95% ethanol) covered the peripheral surfaces, indicating positive response; bubble production by IN and SAM always exceeded SU; 2) Click test: bubble clicking began immediately in all preparations except for undiluted SU, in which the onset of clicking was delayed more than 40 sec; 3) Pattle's stability test: diameters of SU, IN, and SAM bubbles were unchanged for more than 20 min in aerated solution, indicating stable very low surface tension; 4) bubble generation by gas dispersion from a single capillary: full-strength concentration of SU and IN produced relatively large bubbles-bubble rate (number/min) and size were comparable; all SU bubbles rupture in < 25 min, whereas IN bubbles were stable for > 30 min; and 5) Exerowa black film method: in contrast with each of the preceding methods for studying intact bubbles, the Exerowa method focuses on the contact between bubble films and permits direct observation of film formation and determination of film structure. Stable black films were formed spontaneously by both IN (full strength and diluted) and SAM. Conversely, SU (full strength) formed no black films but stable rheological films. Diluted SU films ruptured in 50% of trials. Since methods 1, 2, and 3 were nondiscriminatory and method 4 produced unphysiologically large bubbles for most mammals, we concluded that the black film method of Exerowa is the most discriminating of the tests studied here. It provides a unique visual record of foam film formation and stability and clearly defines differences relative to both the nature and concentration of the preparations.

Intraalveolar bubbles and bubble films. I. formation and development during the first 48 hours of extrauterine life in rabbits.

BACKGROUND: Aeration of mature lungs at birth depends on formation of intraalveolar bubbles and bubble films (Scarpelli 1978. Pediatr. Res., 12:1070-1076). Bubbles establish immediately structural stability and pulmonary gas exchange. Given that air spaces are cleared in minutes of fetal liquid (the initial substrate for bubble formation), in formation possible beyond this period? If so, is this related to early development of pulmonary function and structure? METHODS: Mature, spontaneously breathing rabbit pups at 1-10 min and 1, 3, 8, 24, and 48 h after vaginal birth were anesthetized, trachea was occluded at "resting volume" (approximately functional residual capacity), and lungs were rapidly exposed to preserve in vivo intrapulmonary status. The entire lung was examined by stereomicroscopy. Other determinations included resting volume, lung wet weight, volume-pressure curves, histological sections, lung dry weight, tissue hydroxyproline (OH-Pro), and lavage phospholipids (PL). Bubble mobility in situ was tested. Bubbles were released into bathing liquid by incision of peripheral units and monitored over time. RESULTS: Pup activity and gross appearance of the lungs, together with septal thinning, secondary septal development, clearance of intraluminal liquid, increasing tissue OH-Pro, and PL distribution indicated normal postnatal development. Each aerated unit examined at resting volume (all lobes, all ages) contained intraalveolar bubbles. Transition to free gas exclusively in conducting airways and bubbles/bubble films in peripheral gas exchange units occurred within 1 h. Bubbles appeared to be exclusively within alveoli at 4 h and thereafter. Bubbles persisted and new bubbles were formed during subsequent inflation to maximal volume and deflation to atmospheric pressure (P0). Volume of intact lungs at P0 was maintained by the counterforce of rigid bubble films against tissue retraction. When bubbles were released either at resting volume or at P0, the bubble-free loci became airless. Constant size and stability of released bubbles support preferential incorporation of surfactants into bubble films and constant "near-zero surface tension" (Scarpelli 1978. Pediatr. Res., 12:1070-1076). CONCLUSIONS: We show the ubiquitous presence of intraalveolar bubbles and bubble films in vivo throughout the first 48 h of postnatal life. Bubble film rigidity sustains aeration and prevents collapse, while low surface tension of the films facilitate liquid removal from the air spaces. Bubbles in situ are stable and, within apparent limits, mobile; after birth they are quickly restricted to the alveolar spaces, leaving airways bubble free.

Maturation of undifferentiated lung epithelial cells into type II cells in vitro: a temporal process that parallels cell differentiation in vivo.

BACKGROUND: Formation of alveolar-like structures (ALS) by mature fetal rabbit type II pneumocytes (day 29 gestation) and long-term differentiation on Engelbreth-Holms-Swarm mouse tumor extract or EHS gel (Matrigel) were reported by our group (Blau et al., 1988. J. Cell Physiol., 136:203-214). We now describe structural organization and differentiation of immature lung epithelial cells, isolated at day 22 gestation, into mature type II cells in vitro. METHODS: Peripheral pulmonary tissue was pooled and undifferentiated epithelial cells isolated for primary culture on Matrigel. Cells were examined 12-16 h after plating and on days 1, 3, 5, and 7 of culture and assessed by phase contrast and by transmission electron microscopy after fixation in situ. RESULTS: Cells formed ALS 12-16 h after plating. Spherule diameter increased about four to eight times from day 1-7 in culture. There was rapid transformation of tall columnar cells to cuboidal, normal polarization of cells with respect to cell-free lumen of ALS, progressive reduction of glycogen zones, apparent gradual increase of cell organelles such as Golgi apparatus, rough endoplasmic reticulum and mitochondria, and apparent extrusion of lipidic figures into the lumen. These morphologic transformations in vitro temporally paralleled cell differentiation in vivo. The relative increase of 14C-acetate precursor into phosphatidylcholine in contrast to cardiolipin was consistent with these transformations. CONCLUSIONS: Under the conditions of our culture system, maturation of undifferentiated pulmonary epithelial cells is reproduced in vitro along the same time course and according to the same developmental sequence of fetal lungs in vivo.

Surface biophysics of the surface monolayer theory is incompatible with regional lung function.

The surface monolayer theory of Clements was tested on open surface films of calf lung surfactant extract in a leak-free vertical film surface balance in which alveolar area (A) changes in each lung zone were simulated in accordance with the theory. We found that: 1) physiologically necessary low surface tension (gamma), < 4 dyn/cm, was sustained only by continuous film compression ("expiration"); 2) compression from A equivalent to total lung capacity to functional residual capacity produced fleeting gamma reduction in all zones and quick reversal to high gamma with A changes that simulated tidal volume (VT) breathing at both 14 (adult) and 40 (neonatal) cpm; 3) phase differences between gamma and A axes of VT loops that indicate mixed surface film composition may be attributable to film inertia and viscoelasticity; 4) estimated alveolar retraction pressure due to gamma (P gamma) exceeds "net" transpulmonary pressure, i.e., favors alveolar collapse, under virtually all conditions of the theory in all zones; 5) return to transient, fleeting low gamma in successive VT cycles was determined by the inherent difference in compression and decompression rates, which results in exhaustion of available A in very few cycles; 6) the "sigh", which restores stable low gamma according to the theory, actually produced unstable high gamma during virtually all phases of the maneuver. In contrast, closed bubble films of the surfactant were structurally stable and produce stable near 0 gamma and P gamma.

A manual therapy approach to evaluation and treatment of a patient with a chronic lumbar nerve root irritation.

The purpose of this case report is to familiarize the reader with the basic principles of the approach to manual therapy evaluation and treatment pioneered by Maitland, an Australian physical therapist. This approach involves a complete subjective examination to determine the severity, irritability, nature, and stage of the patient's complaints. In this way, the therapist may reach conclusions as to the amount and vigor of the physical examination and proceed with treatment in an analytical manner. Methodical reassessment is used to justify treatment progression. Comprehensive treatment and the rationale for this approach are discussed. Though most physical therapists are familiar with the straight-leg-raising test as a means of assessing low back pain and chronic lumbar nerve root irritation, they are often not familiar with other tests that examine neural tissues, such as the slump test. The proposed anatomical and biomechanical bases for these tests are discussed. The patient in this case study was a 50-year-old man with a physician's diagnosis of a chronic lumbar nerve root irritation. The patient was evaluated and treated in eight visits using techniques designed to evaluate neural tissues. Reassessment indicated significant symptom reduction, and the treatment was modified accordingly. Patient management, including home exercises, is discussed.

Fluid dynamics during initial aeration of mature fetal lung and effect of temperature.

Air volume-pressure (VP) curves were recorded simultaneously on pairs of mature rabbit fetuses from the same litter with one member of the pair at 37 degrees C and the other at 22 degrees C. Intrasaccular bubbles, formed primarily during inflation, were assessed for stability and surface tension (gamma). Average air flow rates (dV/dt) were calculated from the VP data. In separate experiments, liquid VP curves were recorded at 37 degrees and 22 degrees C: maximal liquid V was matched to maximal air V at 37 degrees and 22 degrees C, respectively. Fetal pulmonary liquid (FPL) viscosity (eta) and density (rho) were determined by standard methods. Both the effect of temperature on lung mechanics as reported previously, and the reliability of the rabbit model were confirmed in the paired fetuses. Analysis of fluid dynamics revealed that of the six parameters relevant to initial inflation-deflation of FPL-filled lungs, liquid rho, distensibility (recoil), and gamma were not altered significantly by temperature increase from 22 degrees to 37 degrees C. Enhanced lung mechanics at 37 degrees C (including enhanced inflation at lower P, higher maximal V, increased production of intrasaccular bubbles, and higher V at end-deflation) was primarily due to lowering of FPL eta at the higher temperature which appears to have an effect by augmenting bulk liquid flow and liquid drainage. Lower eta increases bulk flow through airways directly. Consequent recruitment and distention of these conducting units effectively increases radius (r) and further enhances flow. (The ultimate "brake" to airways flow at both temperatures is counter P from gamma at air/liquid menisci.).(ABSTRACT TRUNCATED AT 250 WORDS)

Surface tension of therapeutic surfactants (exosurf neonatal, infasurf, and survanta) as evaluated by standard methods and criteria.

Three commercial preparations for the treatment of neonatal respiratory distress syndrome (NRDS), Exosurf Neonatal (EX), Infasurf (IN), and Survanta (SU), were studied at 37 degrees C in both a pulsating bubble surfactometer and a vertical film surface balance. "Static" characteristics of adsorbed films were assessed with "bubble" at maximum radius (Rmax) and at minimum radius (Rmin). Adsorption time was time to stable film formation (gamma equilibrium). In dynamic experiments, the bubble was cycled (compressed-decompressed) between Rmax and Rmin at 20, 40, and 80 cpm. Spread films were cycled in the surface balance between maximum area (Amax) and minimum area (A(min)) at 1.5 cpm. In all experiments, maximum surface tension (gamma max) coincided with Rmax or Amax and gamma min with Rmin or A(min). All trials were continued until gamma max and gamma min were reproducible. Data were evaluated according to standard criteria for normal function both in vivo and in vitro of lipid mixtures (EX) or natural surfactants (IN, SU) prepared for treatment of NRDS. All preparations failed two of the four criteria, adsorption in the time of a deep breath and maintenance of stable, low gamma. Adsorption required 10 to 20 seconds and stable gamma was achieved only at equilibrium gamma, > 17 mN/m. IN and SU conformed in general to two criteria, gamma approaching zero on compression and low surface compressibility (< 0.09 m/mN), whereas spontaneously formed films of EX did not. EX was idiosyncratic in that these two criteria were met only after an apparent change of film conformation had been effected, possibly related to elimination of preparation additives from the surface.(ABSTRACT TRUNCATED AT 250 WORDS)

Temperature affects mechanics and stability during initial inflation-deflation of mature fetal lung.

Volume-pressure (VP) curves of initial aeration of mature (0.94-0.97 term) rabbit fetuses were compared in three groups, respectively, at 37 degrees C, with maximal inflation pressure of 25 cm H2O (P25); 22 degrees C, P25; and 22 degrees C, P30. Anesthetized fetuses were delivered through uterotomy; chest was opened; trachea of fetal pulmonary liquid (FPL)-filled lungs cannulated; and lungs inflated-deflated in 5 cm H2O, 2 min steps under continuous microscopic observation. As distending pressure was increased, FPL moved peripherally with airways inflation by free gas and with saccular recruitment by free gas and bubbles. Saccular aeration continued during initial reduction of P from Pmax. At end-deflation, air was retained in saccules virtually exclusively as bubbles. Airways inflation required less P at 37 degrees C, though airways volume (V) was the same at both temperatures. Opening P was lower, and saccular aeration was larger and more rapid at 37 degrees C. The apparently higher distensibility at 37 degrees C was most likely due to temperature effects on fluid dynamics rather than on tissue elasticity. Maximal V attained during early P reduction in all groups, was total lung capacity (TLC) at 37 degrees C and less than TLC at 22 degrees C. Air retention at end-deflation, with films of near-zero surface tension, was greatest at 37 degrees C and least at 22 degrees C, P25. Lung stability, greater at 37 degrees C than at 22 degrees C, was best discriminated when V at P0 was taken into account.(ABSTRACT TRUNCATED AT 250 WORDS)

Cocaine exposure in utero: perinatal development and neonatal manifestations--review.

The question of whether cocaine exposure in utero increases the risk of major structural malformations remains controversial. Most animal studies have demonstrated that cocaine can have a teratogenic effect. The ultimate association between cocaine exposure and fetal development must be inferred from human data. The relative effects of cocaine exposure, exposure to other illicit drugs and alcohol and deficient prenatal care are difficult to assess. Little specific information is available about the amount, duration, and timing of cocaine use during the nine months of pregnancy. Unlike the case with many other teratogens, cocaine exposure at any point in pregnancy can result in some abnormality. The extent of damage and the organ involved depend on the particular stage of morphogenesis. A large scale prospective human study is needed to confirm the suggested teratogenic effects. Since it involves an illicit drug such a study is obviously difficult to perform.

Enhanced lung maturation in cocaine-exposed rabbit fetuses.

Because of cocaine's possible effect on the incidence of respiratory distress syndrome in offspring of cocaine-addicted mothers, we have studied the effects of maternal exposure to cocaine on the functional anatomy of fetal rabbit lungs. Pregnant dams were injected s.c. daily with either cocaine (18 mg/kg) or an equal volume of 0.9% NaCl at 24, 25, and 26 d gestation. Cocaine metabolites were confirmed both in urine of treated dams and in fetal amniotic fluid. Serum cortisol levels were higher in treated dams than in controls. Fetuses were delivered through hysterotomy at 27 d. Tracheas were cannulated and a volume-pressure diagram was obtained during initial lung inflation-deflation. Volume was measured for 2 min at each pressure (P) increment of 5 cm H2O. Body weights and dry lung weights were comparable between the two groups. In contrast, cocaine-exposed lungs differed from controls as follows: 1) wet lung weights were lower (0.79 versus 0.89 g, p less than 0.02); 2) opening pressure was lower (P25 versus P35); 3) volume (mL/kg) was higher in treated animals at each pressure step (p less than 0.05); 4) end-deflation volume at P0 was higher (30.4 versus 0.8 mL/kg, p less than 0.001); and 5) bubbles released from saccules by micropuncture, which were stable by Pattle's criteria, had estimated surface tension near zero (controls produced no stable bubbles). Light micrographs of cocaine-exposed fetuses revealed more secondary septa and thinner septal walls than controls.(ABSTRACT TRUNCATED AT 250 WORDS)