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Biomedical subjects

A J Mautone

Publications and source records attributed to A J Mautone.

25 records · Page 2Linked to original sources

Fourier transform infrared and differential scanning calorimetric studies of a surface-active material from rabbit lung.

A surface-active material with a chemical composition consistent with lung surfactant and with the ability to lower surface tension on a Wilhelmy balance to about 6 mN/m, has been isolated from rabbit pulmonary lavage. The thermotropic properties have been characterized with the techniques of Fourier transform infrared spectroscopy (FT-IR) and Differential Scanning Calorimetry (DSC). FT-IR melting curves were constructed from the temperature-dependence of the lipid CH2 symmetric stretching vibrational frequencies near 2850 cm-1. A broad gel-liquid crystal phase transition with an onset temperature of about 22 degrees C, and a completion temperature of about 38 degrees C was observed, with slight sample-to-sample variations in temperatures. A similar completion temperature was noted in DSC endotherms. Ca2+ (5-10 mM) increased the onset temperature of the lipid-melting event, and induced an ordering of surfactant and of its lipid extract at all temperatures studied. The effect on the lipids was suggestive of a Ca2+-induced phase separation caused by ion binding to phosphatidylglycerol and other acidic components. Evidence for a direct interaction between Ca2+ and the phosphate groups was suggested through small Ca2+-induced shifts in the 1090 cm-1 symmetric PO2 stretching frequency. Removal of most of the protein component from a 10:1 (lipid/protein, w/w) sample caused an ordering of the resultant lipid fractions. In contrast, removal of most of the protein component from a 20:1 sample resulted in no change in lipid order or thermotropic behavior. These observations are discussed in light of the roles played both by Ca2+ and protein in the spreading of surfactant. The power of FT-IR to acquire useful structural information from complex biological tissues is demonstrated.

Animals↗

Ventilation and pulmonary mechanics during high-frequency oscillation of immature lungs at birth.

Ventilation was initiated and maintained by high-frequency oscillation (HFO) in nine immature lambs not expected to survive for more than a few minutes out of the uterus. They were delivered to HFO (18 to 20 Hz) and ventilated only with air at the setting that yielded optimal blood gases and pH. Once removed from HFO, cardiorespiratory arrest occurred within minutes despite the return of previously inhibited natural inspiratory efforts. At autopsy, the lungs were liquid-filled (i.e., fetal). Thus, HFO had maintained viability without promoting either lung stability or fetal pulmonary fluid (FPF) absorption. Additional experiments on excised immature lungs showed that aeration is determined by distending pressure, which is regulated by the flow through the oscillator circuit and monitored most accurately as transpulmonary pressure (TPP). Once air-entry has begun, alveolar recruitment and negative compliance establish the limits of tolerable lung expansion via TPP. Within these limits, the immature lung can be ventilated effectively with air. However, since these lungs do not produce intrapulmonary foam, lung stability and FPF absorption are not effected. Complications of HFO (including pneumothorax, decreased arterial pressure and heart rate, and metabolic acidemia) can be related to overdistention of the lungs.

Animals↗

Acute responses to phosgene inhalation and selected corrective measures (including surfactant).

We exposed 22 mongrel dogs to 94 ppm phosgene for 20 min from a non-rebreathing system. We expressed exposure to phosgene as ppm X VI X min X kg 1, i.e., the amount of gas containing a known phosgene concentration that was actually inhaled per min standardized to body weight, the "exposure index" (EI). In contrast, the conventional expression of exposure, i.e., ppm X min, fails to take volume inhaled (VI) and body weight into account. Five dogs received no intervention and served as controls. Fourteen dogs received basic therapy of oral cortisone (40 mg/kg) and NaHCO3 (3 mEq/kg) plus 100% O2 (FiO2 = 1.0) for 30 min after the exposure period. These animals were further divided according to the following selected additional therapies, which were started 30 min after exposure: Theophylline, 5 mg/kg iv for 20 min followed by 1 mg/kg/hr for 70 min (n = 5). Three dogs of this group were given a trial of 5 cm H2O expiratory resistance during the period of basic therapy. Because of the untoward response, expiratory resistance was discontinued and not used in other experiments. PGE2-hi, [1 microgram/kg/min] iv for 90 min (n = 3). PGE1-lo, [0.04 microgram/kg/min] iv for 90 min (n = 3). Atropine, 0.5 mg/kg iv at 30 and 50 min after exposure (n = 3). Three dogs [group 5] received oral cortisone and NaHCO3 plus inhaled supplementary surfactant, 2.7 mg/min ultrasonically nebulized (FiO2 = 0.5; phosphate buffer), for 30 min after exposure. All treated dogs, groups [1] through [4] and the surfactant group [5], received cortisone (40 mg/kg/hr iv), NaHCO3 to correct base deficit, and O2 to correct hypoxemia from 30 min to 120 min after exposure. Because of its clearly beneficial effect in group [1], theophylline was also given to all other treatment groups during this period. At the end of the study, all lungs were excised, examined and prepared for light microscopy. We found that EI, which varied among subjects because of spontaneous variations of VI during exposure, correlated significantly with the changes in base deficit induced by phosgene inhalation. We also found that the change in minute ventilation, delta VI X kg-1, correlated significantly with changes in lung compliance, peak flow and base deficit. Evaluation of the various therapeutic modalities revealed the following: Immediate therapy with O2 is vital and and FiO2 of 0.4 to 0.5 is sufficient.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Intranasal↗

Intrasaccular bubbles of near-zero surface tension stabilize neonatal lungs.

Mature rabbit fetuses produce intrapulmonary foam at the onset of breathing at birth. Bubbles establish a minimal volume immediately and require relatively little distending pressure for their formation. Stability of bubbles that are formed during both rapid spontaneous breathing in vivo and slow inflation-deflation of excised lungs is determined by the surfactant content of fetal pulmonary fluid (FPF). Mature bubbles can be delivered at atmospheric pressure from all aerated saccules by microdissection. When observed in air-equilibrated normal saline solution (NSS), their stability with time indicates that film surface tension (gamma) is very low, i.e., near-zero. When mature FPF is replaced with NSS, stable bubble production is absent. Conversely, supplementation of immature FPF with a surfactant dispersion prior to aeration induces bubbles that are as stable (near-zero gamma) as those from mature lungs. Proper mixing of the supplement, e.g., by repeated inflation-deflation, is required for proper distribution of foam in the immature fetal saccules. From these findings, it may be concluded that bubbles establish the condition for production of near-zero gamma in situ. The latter stabilizes the lung by sustaining normal liquid transfers (Pattle theory). In addition, bubble films promote mechanical stability by providing a saccular infrastructure that resists collapse and retards surface spreading.

Animals↗

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)

Biological Products↗