Tracheal instillation of pentamidine in a surfactant vehicle may be an effective direct method of antibiotic delivery to the lungs. In 10 healthy hamsters, we compared the pulmonary distribution of 99mTc sulfur colloid (TcSC) mixed with pentamidine, using as a vehicle either surfactant (n = 5) or saline (n = 5). Each animal was instilled with 0.25 ml/kg of suspension containing 0.0018 mCi TcSC and pentamidine mixed with either surfactant or saline. After 4 h of spontaneous respiration, the lungs were excised, inflated to TLC, dried, and sliced into 3-mm cross sections from apex to base. Autoradiographs were examined to evaluate 99mTc distribution. The surfactant group had detectable radioactivity in 93% of all slices compared with 72% in the saline group (p = 0.02). Six slices per animal (43% of total) and their corresponding autoradiographs were analyzed for distribution of radioactivity. Lung slice area was determined by planimetry, and autoradiograph area was determined by video densitometry. We calculated the fraction of each lung slice with detectable radioactivity. The surfactant group had 41% of the lung slice areas exposed compared with 21% in the saline group (p = 0.02). The coefficient of variation of radioactive intensities within each slice was used as an index of spatial uniformity. There was a trend towards more uniform distribution in the surfactant group, with a narrower range of variation of intensities (1.51 to 2.56) than the saline group (1.95 to 6.47). We conclude that a surfactant vehicle significantly increases airspace deposition of TcSC and pentamidine instilled intratracheally in normal hamster lungs, and may improve uniformity of spread.
We investigated the dynamic history dependence of lung surface area-to-volume ratio (S/V) during tidal breathing in live rabbits with use of our recently developed technique of diffuse optical scattering. We also examined the effect of methacholine (continuous intravenous infusion, 1-10 micrograms.kg-1.min-1) on lung micromechanics with the same technique. Animals were anesthetized, tracheostomized, and mechanically ventilated, and the left lung was exposed through a thoracotomy. An optical fiber delivering light from a He-Ne laser was attached normal to the pleural surface, producing a circular light pattern on the pleural surface from diffusively scattered light within the parenchyma. The pattern of light intensities was measured using a CCD video camera connected to a computer. S/V during tidal breathing changed in a manner qualitatively consistent with geometric similarity. There was a small but significant hysteresis in S/V vs. volume, with S/V inspiration greater than S/V expiration at the same volume. However, during methacholine challenge, the sense of hysteresis reversed; S/V inspiration was less than S/V expiration at isovolume points. Moreover, S/V during methacholine challenge systematically decreased at all lung volumes compared with control. These findings suggest that 1) during normal tidal breathing, stress hysteresis in ductal tissue is larger than septal stress hysteresis (septal tissue plus surface tension) and 2) the effect of methacholine on tissue in the septa is greater than the corresponding effect in ductal tissue.
At high oscillation frequencies (4 to 30 hertz), effective alveolar ventilation can be achieved with tidal volumes much smaller than the anatomic dead space. An explanation of this phenomenon is given in terms of the combined effects of diffusion and convection and in terms of data consistent with the hypothesis. Theory and experimental results both show that the significant variable determining the effectiveness of gas exchange is the amplitude of the oscillatory flow rate independent of the individual values of frequency and stroke volume.
The regional pleural surface expansion of an excised dog lung was measured during high-frequency ventilation (HFV) using synchronized stroboscopic photography to stop lung motion at 20 evenly spaced intervals over a respiratory cycle during ventilation at 1 Hz with a volume of 100 ml, 15 Hz with 100 ml, or 30 Hz with 50 ml. The lungs were also photographed during quasi-static deflation. The pleural surface was marked with ink dots to form 84 approximately square figures. The side lengths and areas of each of the 84 "squares" were measured for each frame of each photo sequence. At 1 Hz and during the quasi-static deflation the lung ventilated nearly synchronously, although minor nonuniformities were noted on both small and large length scales. At 15 and 30 Hz, the lung expanded asynchronously and nonuniformly, with a 78% increase in surface expansion per 100 ml of tracheal tidal volume, as frequency was increased from 1 to 30 Hz. These nonuniformities in expansion suggest marked interregional airflow and elastic wave propagation in the parenchyma during HFV.
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