Early detection of extravascular lung water in an inhalation injury animal model.

A rabbit inhalation injury model using a dual tracer radioactive isotope technique (Rowland et al., 1986), has been utilized with small- and medium-sized molecular weight tracers. There is oedema formation at 2 h after smoke inhalation or fluid resuscitation and especially with the combination of inhalation injury and fluid resuscitation [corrected]. This oedema appears to have decreased by 24 h post-injury. There does not appear to be any difference between the small- and medium-sized tracers in the transit times of tracer in the lung vascular compartment. The increases in extravascular water volume have been confirmed by gravimetric analyses of the lungs. Thus the pulmonary oedema in the rabbit animal model is detectable within 2 h post-injury, with a return towards normal values some time within 24 h if fluid challenged for short periods. Fluid resuscitation exacerbates the amount of oedema that developed. The onset of pulmonary oedema may therefore be earlier than previously seen clinically, and fluid resuscitation modifications may be of benefit in smoke inhalation injury.

The lung as a metabolic organ.

Recently, the lung has received increasing attention as a metabolic organ. In this role, the lung modulates the composition of the arterial blood by several mechanisms: removing active substances from the plasma, releasing substances into the plasma, temporarily holding substances from circulation, and activating or inactivating substances that pass through the lungs. In this report, the procedures proposed by different investigators for in vivo noninvasive assessment of the lung metabolic functions are reviewed. Most procedures are based on an estimation of the clearance of plasma amines by the lung endothelial cells. This clearance is assessed by measuring the lung uptake or the extraction fraction of an intravenously (IV) injected radiolabeled amine. Our own procedure, which assesses the number of free pulmonary endothelial amine receptors, is discussed in detail. In our procedure, the number of receptors was computed using the number of injected molecules of amine and determining the lung extraction fraction of the amine during its first pass through the lungs. In goats, using N-isopropyl-p-iodoamphetamine labeled with 123I as the radiopharmaceutical, the total number of endothelial lung amine receptors was found to be 1.589 X 10(20). The methods for studying the lung metabolic functions, which are discussed in this report can be applied in humans to evaluate either physiological or pathological conditions.

Effect of region of interest selection on first-pass radionuclide cardiac output determination.

In principle, region of interest (ROI) selection should not affect the measurement of cardiac output by the first-pass technique with a radioactive intravascular indicator. Clinical application of the method requires that this theoretical hypothesis be tested. Sixty-eight left anterior oblique first-pass studies were acquired with a scintillation camera and computer using red blood cells labeled in vitro with 99mTc. Calculated mean cardiac output varied in the following order with respect to ROI: lung greater than right heart greater than left ventricle greater than whole heart (both ventricles) greater than aorta. Similar variations were observed in patients both with and without valvular regurgitation. Regions of interest over left ventricle or whole heart yielded the best correlations with cardiac output by thermodilution (r = 0.96, 0.95, respectively, n = 28) as well as the smallest interobserver variations (r = 0.994, 0.995, respectively, n = 33). First-pass studies with [99mTc]red blood cells labeled in vitro can yield accurate, reproducible determinations of cardiac output provided that the effect of ROI selection is recognized and that regions are properly selected.

A noninvasive procedure for in vivo assay of a lung amine endothelial receptor.

Lung endothelial N-isopropyl-p-iodoamphetamine (IMP) binding sites were assessed applying principles of competitive binding assay adapted for in vivo measurements obtained by digital imaging. Data were acquired following the method published by Rahimian et al., a modification of the dual indicator dilution technique of Chinard and Crone. Iodine-123 (123I) IMP, the test cellular tracer, and technetium-99m (99mTc) dextran, the reference vascular tracer were imaged during their first pass through the superior vena cava, right heart, lungs, and left heart in West African dwarf goats. The lung fractional extraction of IMP diminished progressively from 0.96 to 0.20 as the amount of IMP in the test tracer boluses was gradually increased from 0.6 to 150 mg. This demonstrated that lung extraction of IMP is by way of a saturable binding system, presumably receptors. The dissociation constant of IMP-lung binding sites reaction was calculated by Scatchard plot and found to be 11.7 mg. The amount of IMP bound at saturation (R), was found to be 30 mg. Assuming that a single molecule of IMP bound a single receptor, the total number of free receptors was computed as the Avogadro's number times R, divided by the IMP molecular weight, and found to be 6.04 X 10(19). Using a computer model, it was determined that the 20 mg per bolus isotherm was the most sensitive for measuring the number of total free receptors (binding sites). This is the first time, to our knowledge, that noninvasive in vivo assessment of receptors in lung has been accomplished. Basically, the method used can be applied in humans and, also, to assess receptors in organs other than the lungs.

Measurement of metabolic extraction of tracers in the lung using a multiple indicator dilution technique.

Selective pulmonary uptake of many natural and synthetic substances has been demonstrated by physiologists and pharmacologists using isolated perfused lung preparations or invasive techniques. It is difficult, however, to relate these laboratory studies to disease processes and to the study of problems encountered in a clinical environment. Our goal was to develop a noninvasive method for studying the pulmonary uptake of tracer substances using available radiotracers, gamma cameras, and computers that would give information similar, if not identical, to that from the invasive laboratory methods, and that could be applied in a clinical setting. The multiple-indicator dilution technique, modified for external counting, is well suited for such studies of pulmonary uptake of tracer substances. In this study, Tc-99m micro sulfur colloid (Tc-99m micro SC) was used as an intravascular reference tracer, N-isopropyl-p-[123I]iodoamphetamine (I-123 IMP) as a cellular test tracer amine, and In-111 DTPA as an extracellular tracer. Calculated first-pass lung uptakes of I-123 IMP and In-111 DTPA were 0.92 +/- 0.04 and 0.17 +/- 0.04, respectively, relative to the reference tracer. Using this approach, the first-pass pulmonary extraction of a variety of radiolabeled test tracers can be measured in a clinical environment in a variety of physiologic settings.