Participation of the arterial and portal drainage in the calculation of total hepatic blood flow in guinea pigs

Experiments were performed on partly isolated livers of guinea pigs. The hepatic outflow (HOF) was measured by an electromagnetic flowmeter placed on the inferior vena cava. Nutritive hepatic blood flow (HBF) was measured with ¹³³Xe bolus technique with the tracer injected into the portal vein or hepatic artery. Under unchanged perfusion conditions, three exponents could be demonstrated irrespective of the site of injection. Two of them observed during the first 5 min represent the intrahepatic, the third (slowest one) the extrahepatic blood flow. Occlusion of either the portal vein or the hepatic artery results in a monoexponential decrease during the first 5 min. Calculation of the HBF was based on an equation including both components of the washout curves obtained after arterial and portal application. The calculated HBF was equal to the value of the directly measured total outflow but overestimated HBF_f calculated from the first exponent of the washout curve obtained after intraportal tracer application.     

Validation of Doppler FloWire for measurement of coronary flow reserve in humans

Previous studies have validated the ¹³³Xenon (¹³³Xe) method to assess regional myocardial blood flow and coronary flow reserve (CFR). Doppler FloWire (DFW) has been used recently for measuring CFR to assess the physiological significance of coronary stenosis. Data obtained by DFW has never been correlated to ¹³³Xe. Our study compared data from DFW measurement of CFR to that obtained by ¹³³Xe in 31 consecutive patients with variable coronary stenosis. Regional myocardial blood flow was measured by assessing the rate constants of ¹³³Xe washout using multicrystal gamma camera after injection (20 millicuries) in the right or left coronary artery. CFR was assessed by measuring resting and hyperemic coronary blood flow by ¹³³Xe and DFW using IV adenosine (140 mcg/k/min × 3 min). CFR was also measured by DFW giving intracoronary (IC) adenosine (12 μg in the right coronary, 18 μg in the left). In both methods—¹³³Xe and DFW—coronary flow reserve was defined as the ratio of maximal hyperemic-to-baseline flow. DFW and ¹³³Xe assessment of CFR correlated highly, whether adenosine was used IC(r = 0.87; P = 0.0001) or IV(r = 0.78; P = 0.0001). CFR obtained by DFW following IC and IV adenosine correlated well (r = 0.79; P = 0.0001). IC adenosine has fewer side effects. Both DFW and ¹³³Xe are comparable in measuring CFR in humans. Cathet. Cardiovasc. Diagn. 45:382–385, 1998. © 1998 Wiley-Liss, Inc.     

Regional pulmonary function in patients with mitral stenosis in relation to haemodynamic data

Central haemodynamics in 23 patients with mitral stenosis and 7 control subjects were compared with the results of regional lung perfusion studied by ¹³³Xe, pulmonary scintigraphy with ⁹⁹mTc-labelled macro-aggregates of albumin, and regional ventilation by ¹³³Xe.     

High-frequency oscillatory ventilation may increase airway closure

In five seated, normal subjects, we measured closing volumes using 133Xe boluses inhaled at residual volume. High frequency oscillatory ventilation (HFOV) (15 Hz, 2 cc/kg) was applied during either inspiration to total lung capacity or the subsequent expiration. Closing volume was increased (P less than 0.001) when HFOV was applied during the latter half of expiration, but not when HFOV was applied during inspiration or the first half of expiration. Subsequently, in seven subjects, we measured the regional distributions of 133Xe boluses delivered during open-glottis breath-hold at 14% vital capacity after equilibration with N2O. HFOV was applied during bolus delivery for about 16 sec. These distributions were compared with those achieved by intravenous injections of 133Xe in saline. Regional perfusion (injected isotope) exceeded regional N2O uptake at the lung bases and this was significantly accentuated by HFOV, compatible with increased basal closure. We conclude that in normal subjects at low lung volumes, HFOV may enhance airway closure, though other explanations are possible.     

Possibilities, limitations, and technique for the study of regional myocardial perfusion in man by Xenon-133.

The theoretical possibilities and the practical limitations of the Xenon-133 (133Xe) method for the study of regional myocardial perfusion in man are discussed. The techniques for data acqusition and processing developed over the past 5 years are described in detail. Illustrative examples of experimental findings are reported. The practical interpretation of the data, at the light of the influence of injection site, initial tracer distribution, constancy of counting geometry, spatial resolution, and Xenon retention in fat, is presented.     

Intrapulmonary distribution of 99mtechnetium labelled ultrafine carbon aerosol (Technegas) in severe airflow obstruction

Technegas (TG), an ultrafine dispersion of carbon aggregates labelled with 99mTechnetium (99mTc), has been recently introduced for clinical imaging of lung ventilation. In 12 selected subjects with severe chronic airflow limitation (FEV1 = 0.89 +/- 0.22; mean +/- SD, l) we have studied the regional intrapulmonary distribution of TG and compared it quantitatively with that of 133Xenon (133Xe). A 133Xe equilibration image was acquired for 10-15 s during a breathhold at total lung capacity (TLC). Six subjects (Group 1) inspired 100 ml boli of TG or 133Xe from functional residual capacity (FRC) and another 6 subjects (Group 2) inspired 1.0 l of labelled gas from FRC followed by air to TLC at a constant flow rate less than 0.5 l.s-1. Lung images were then acquired with the chest position rigorously controlled. From the equilibration image, upper, middle, lower, central and peripheral regions were defined. Relative regional fractional concentrations (RFC) were then calculated using the equilibration image to correct for ventilated lung volume. In addition, in four of the Group 2 subjects, each lung image was divided into multiple regions (12-17 per lung). The RFC were then calculated as above (RFCM). The highest and lowest RFC were not significantly different between 133Xe and TG in either Group 1 or Group 2 subjects. Similarly the RFCM analysis showed no systematic difference between 133Xe and TG. The ratio of peripheral to central RFC constitutes a penetration index which for TG was 0.99 +/- 0.23 that of 133Xe. Our results indicate that even in the presence of severe airflow limitation the radiolabelled tracer TG mimics the regional distribution of a real gas.     

Early changes in capillary flow and transport following missile wounds

The local hemodynamic response to missile wounds in soft tissue has been studied on 31 mongrel dogs with a double isotope clearance technique using sodium iodide (Na¹³¹I) and xenon (¹³³Xe). Three different impact velocities with a small spherical projectile were used to vary the amount of energy absorbed by the tissues. The isotope was injected at a constant depth but at varying distances from the wound site. The flow responses (i.e., xenon clearance) were quite variable, but there was a tendency toward greater responses between 35 and 45 mm from the wound channel after high-velocity missile wounds. The same tendency was seen more clearly for iodide clearance values. The size of the damage by missiles hitting with the three velocities used is discussed. Because of irregularities in the volume of tissue absorbing the energy, variations in individual animals could be expected. However, the flow pattern recorded with the isotope clearance technique coincides in both time and localization with the hemodynamic and angiographic findings after wounds caused in a similar way and reported previously.     

A scintiphotographic method for measuring left ventricular ejection fraction in man without cardiac catheterization

A radioactive tracer method for the measurement of left ventricular ejection fraction in man without cardiac catheterization is described. The tracer (^99mtechnetium-labeled albumin) is injected intravenously. Images of the heart at end-systole and end-diastole are obtained using a scintillation camera and an electronic gate triggered by the patient's electrocardiogram. Each image is composed of 300,000 counts, representing a summation of 200 to 400 heartbeats at end-systole and end-diastole. An outline of the left ventricular free wall is drawn from each gated image. The position of the aortic and mitral valve planes is determined using a radionuclide angiogram obtained at the time of tracer injection. Left ventricular ejection fraction is calculated from the area and length of the long axis of the ventricular outline at end-systole and end-diastole. Determinations of ejection fraction in 20 patients using this tracer method were correlated with measurements obtained by contrast cineangiography with the following results: ejection fraction r = +0.92, P < 0.001; end-diastolic volume r = −0.76, P < 0.001; and end-systolic volume r = −0.75, P < 0.001.     

In vivo magnetic resonance vascular imaging using laser-polarized 3He microbubbles

Laser-polarized gases (³He and ¹²⁹Xe) are currently being used in magnetic resonance imaging as strong signal sources that can be safely introduced into the lung. Recently, researchers have been investigating other tissues using ¹²⁹Xe. These studies use xenon dissolved in a carrier such as lipid vesicles or blood. Since helium is much less soluble than xenon in these materials, ³He has been used exclusively for imaging air spaces. However, considering that the signal of ³He is more than 10 times greater than that of ¹²⁹Xe for presently attainable polarization levels, this work has focused on generating a method to introduce ³He into the vascular system. We addressed the low solubility issue by producing suspensions of ³He microbubbles. Here, we provide the first vascular images obtained with laser-polarized ³He. The potential increase in signal and absence of background should allow this technique to produce high-resolution angiographic images. In addition, quantitative measurements of blood flow velocity and tissue perfusion will be feasible.     

Gas mixing in the human upper airways

The longitudinal dispersion of gas in the upper airways (oropharynx and larynx) was studied in 5 healthy subjects by measuring the response after injection of a bolus of 133Xe into the inspired airstream. The radioxenon concentration was measured during inspiration and expiration with two counter probes, one in front of the lips and one under the glottis. Assuming that the output tracer concentration follows a Gaussian distribution, the dispersion is expressed by the variance. The dispersion coefficient for the upper airways can then be readily computed with a simple mathematical model. This coefficient is found to be a function of the Peclet number.     

The effect of vagal stimulation on the distribution of inspired gas in the lungs.

We investigated the direct effects of efferent vagal activity on the distribution of inspired gas by stimulating the vagus nerve of one lung and measuring the topographic distribution of a radioactive tracer (133Xe) to both lungs. The distribution of inspired (133Xe) boli was measured with NaI scintillation detectors placed apex-base over each posterior lung of intubated, paralyzed, anesthetized dogs. In 7 supine dogs vagal stimulation reduced the distribution of rapidly insufflated 133Xe boli (flow greater than 2.5 L/s) to the test lung (P less than 0.02), but not when boli were insufflated slowly (flow less than 0.5 L/s), suggesting that vagal stimulation affects pulmonary gas distribution primarily by increasing airway resistance and not through changes in lung compliance. The effect of vagal stimulation on the regional apex-base distribution of inspired gas (greater than 2.5 L/s) was measured in 7 supine and 5 upright dogs. In the supine position, vagal stimulation did not change the uniform apex-base bolus distribution, whereas in the upright position less of the bolus was distributed to the middle and lower lung regions (P less than 0.043), compared to control measurements. This indicates that the regional effects of vagal stimulation on the distribution of inspired gas are uniform in the supine position, but that vagal stimulation alters the distribution of inspired gas when the apex-base pleural pressure gradient is increased.     

The evaluation of an isotopic clearance technique for the measurement of skin blood flow in the pig

An isotope, Technetium-99m (^99mTc), clearance technique has been used for measuring skin blood flow in the pig. The isotope is injected id, and the blood clearance of the tracer from the injection site is measured by scintillation detectors placed over the site of injection. The results showed that the ^99mTc-clearance technique in the pig was reproducible for comparable sites on opposite sides of the animal. When measurements were made along the midlateral flank skin a pattern of uniform blood flow was indicated. When the volume of tracer injected was varied (0.02–0.3 ml), no significant difference in the blood flow parameters measured was obtained. This result is compared with published findings in man and other animal systems. The clearance curves obtained over a period of 1 hr has two exponential exponents; the significance of this is discussed.     

Distribution of inhaled 99mtechnetium labelled ultrafine carbon particle aerosol (Technegas) in human lungs

Using a gamma camera, we quantified the topographical intrapulmonary distribution of inhaled 100 ml boluses of Technegas (TG), an ultrafine dispersion of carbon aggregates labelled with 99mTc, and 133Xenon (Xe) in six seated, normal subjects, inhaling from residual volume (RV) and from within a 1 l volume range above functional residual capacity (FRC) at a flow less than 0.5 l.s-1. Following inspiration of air to total lung capacity (TLC) counts were recorded during a 20 s breathhold. Twenty min after administration of the final TG bolus (TGF) counts were again recorded (TG20). Upper (U), middle (M) and lower (L) zones, as well as central (C) and peripheral (P) regions were identified in each lung. The relative fractional concentration (Fr) of TG and Xe was calculated for all zones after RV and FRC boluses, using counts obtained during Xe equilibration. The U/M or U/L ratios for XeFr did not differ significantly from those for TGFr (paired t-test; p greater than 0.1). The P/C count ratio constitutes a penetration index, which for TG was 1.07 +/- 0.13 (mean +/- SD) that of Xe. After correction for radioactive decay, TG20 counts were no different from TGF counts. The results suggest that the intrapulmonary distribution and penetration of TG in normal lungs is no different from Xe and that stable deposition in the lung periphery makes TG suitable for multiple-view imaging of ventilation distribution.     

Capillary permeability of 99mTc-DTPA in canine myocardium determined by intracoronary bolus injection and residue detection

Capillary permeability of 99mtechnetium-diethylenetriaminepenta-acetic acid (99mTc-DTPA; MW 485.0) and 51chromium-ethylenediaminetetra-acetate (51Cr-EDTA; MW 340.2) was studied in an in vivo canine heart preparation by the single injection, residue detection (SIRD) method. In experiments on open chest dogs (group A) these indicators were administered separately as bolus injections into a cannulated diagonal branch of the left anterior descending coronary artery (LAD) and the curve of the response function was recorded by external activity registration. In further experiments on closed and open chest dogs (group B) 99mTc-DTPA was injected via a coronary angiography catheter into the ostium of the left coronary artery and the response curve was obtained by external registration. Regional myocardial perfusion coefficients were determined by the local 133xenon washout technique and from kinetic analysis of SIRD experiments. Plasma perfusion coefficients calculated by kinetic analysis of response curves from 99mTc-DTPA SIRD experiments (group A) were on average 98 v 102 ml.min-1.100 g-1 in 51Cr-EDTA experiments, in good agreement with the average plasma flow rate of 92 ml.min-1.100 g-1 determined by local 133Xe washout technique. Mean values of the extraction fractions (E) were 0.463 and 0.475 for 99mTc-DTPA and 51Cr-EDTA, and the permeability-surface area products (PdS) were 52.8 and 57.5 ml.min-1.100 g-1 respectively. At the conventional capillary surface area estimate of 500 cm2.g-1 the permeability coefficient (Pd) for 99mTc-DTPA was 1.76.10(-5) cm.s-1 and for 51Cr-EDTA 1.92.10(-5) cm.s-1.(ABSTRACT TRUNCATED AT 250 WORDS)     

In vivo imaging and quantitative analysis of insulin-receptor interaction in lean and obese Zucker rats

Summary Imaging and quantitative analysis of insulin-receptor interaction was studied in vivo in lean and obese Zucker rats, using a recently developed technique in which purified Tyr A14 ¹²³I-monoiodoinsulin is intravenously injected and the tracer followed by scintillation scanning. The obese rats were 72% overweight, had near normal blood glucose concentrations and an 11-fold increase in plasma insulin concentration. In both groups of rats, the tracer was rapidly taken up by the liver (by a receptor mediated mechanism) and the kidneys (by a non-receptor mediated process). Past this maximum, radioactivity decreased in both organs as ¹²³I-insulin was degraded and free ¹²³I-iodide was released into the plasma compartment. Heart radioactivity (i.e. blood pool) mirrored that of the liver and kidneys. The rapid initial decrease of blood radioactivity was concomitant with liver and kidney uptake of ¹²³I-insulin. Release of free iodide from these organs induced a slow secondary rise of blood radioactivity followed by a final decline corresponding to clearance of plasma iodide, mainly by urinary excretion. Liver radioactivity profiles of lean and obese rats were parallel. When expressed per g weight, liver radioactivity was significantly decreased in obese rats. However, due to hepatomegaly in obese rats, total liver radioactivity was significantly higher in homozygous fa/fa rats than in lean littermates. Furthermore, if the marked hyperinsulinaemia of the obese rats is taken into account, total bound insulin was enhanced in the liver of fa/fa rats whatever reference is used, either g weight or total liver. The kidney profile of radioactivity of both rats was not significantly different. In conclusion: (1) obese rats are insulin resistant as near normal glycaemia is achieved at the price of a marked hyperinsulinaemia; (2) liver uptake of insulin is enhanced in obese rats, and (3) the insulin resistance syndrome of fa/fa rats is not due to a decrease in liver insulin receptor number and/or affinity but rather to as yet unknown event(s) subsequent to receptor binding.     

Interactions of regional respiratory mechanics and pulmonary ventilatory impairment in pulmonary emphysema: assessment with dynamic MRI and xenon-133 single-photon emission CT

STUDY OBJECTIVES: Dynamic MRI and (133)Xe single-photon emission CT (SPECT) were used to directly evaluate the interaction of regional respiratory mechanics and lung ventilatory function in pulmonary emphysema. METHODS: Respiratory diaphragmatic and chest wall (D/CW) motions were analyzed by sequential MRI of fast-gradient echo pulse sequences during two to three respiratory cycles in 28 patients with pulmonary emphysema, including 9 patients undergoing lung volume reduction surgery (LVRS). The extent of air trapping in the regional lung was quantified by the (133)Xe retention index (RI) on three-dimensional (133)Xe SPECT displays. RESULTS: By contrast to healthy subjects (n = 6) with regular, synchronous D/CW motions, pulmonary emphysema patients showed reduced, irregular, or asynchronous motions in the hemithorax or location with greater (133)Xe retention, with significant decreases in the maximal amplitude of D/CW motions (MADM and MACWM; p < 0.0001 and p < 0.05, respectively). The removal of (133)Xe retention sites by LVRS effectively and regionally improved D/CW motions in nine patients, with significant increases in MADM and MACWM (p < 0.01 and p < 0.001, respectively). In a total of 40 studies of the 28 patients including post-LVRS studies, normalized MADM and MACWM correlated with percent predicted FEV(1) (r = 0.881, p < 0.0001; and r = 0.906, p < 0.0001, respectively), and also with (133)Xe RI in each hemithorax (r = -0.871, p < 0 0.0001; and r = -0.901, p < 0 0.0001, respectively.) CONCLUSIONS: This direct comparison of regional respiratory mechanics with lung ventilation demonstrated a close interaction between these impairments in pulmonary emphysema. The present techniques provide additional sensitivity for evaluating pathophysiologic compromises in pulmonary emphysema, and may also be useful for selecting resection targets for LVRS and for monitoring the effects.     

Changes in blood flow and permeability of vessels to protein preceding the development of cutaneous ulcers in the hind limb of the rabbit

The effect of sciatic nerve transection on the cutaneous and muscle nutritive blood flow in the hind limb of rabbits was studied. Vessel permeability to albumin was measured with ¹²⁵I-labeled human serum albumin periodically during the 2 weeks after transection. Cutaneous blood flow was measured with the ¹³³Xe washout technique. Two days after transection a decrease of blood flow was observed. The maximum drop in the blood flow occurred on the seventh day. A sharp increase in permeability to albumin was observed in the denervated leg starting on the fourth day after transection. Microscopic examination shows that peripheral nerve injury is responsible for structure disorders corresponding to the decrease of cutaneous blood flow and increase in the permeability to albumin.     

Measurement of right ventricular volumes using 131I-MAA

A method has been presented for determining the right ventricular residual ratio, that is, the ratio of the end-systolic volume to the end-diastolic volume during each cardiac cycle. ¹³¹I-MAA was injected as a bolus into the right ventricle, and the ratio of isotope remaining in the chamber during the succeeding cardiac cycles was determined with a collimated scintillation counter placed over the right ventricle. Since the counter detected the radioactivity from the entire right ventricular cavity, potential errors from incomplete mixing were minimized. The washout curve from the ventricle was distorted somewhat by the accumulation of isotope in intervening lung tissue. This distortion was eliminated by subtracting the build-up curve of radioactivity in the lung recorded simultaneously with a second scintillation counter positioned over the lateral chest wall.In 14 dogs anesthetized with chloralose, the right ventricular residual ratio was relatively constant at 40.4 ± 3.1 per cent. Duplicate measurements differed by less than 3 per cent indicating the good reproducibility of the method.Right ventricular stroke volume was determined from cardiac output (dye dilution) and heart rate. With this and the simultaneously determined residual ratio (¹³¹I-MAA), end-diastolic volume could be calculated. Stroke volume and stroke work were highly correlated with end-diastolic volume, in keeping with the Frank-Starling mechanism.     

On the accumulation of alloxan in the pancreatic β-cells

Summary Autoradiographic studies revealed that the radioactivity in the pancreatic islets was higher than in any other mouse tissue after intravenous injections of tracer doses of ¹⁴C-2-alloxan. The concentration of radioactivity in the endocrine pancreas concerned a great majority of the cells indicating that at least cells were involved. The uptake of the radioisotope in the pancreatic islets was considerably reduced when the small amounts of ¹⁴C-2-alloxan were complemented with carrier to bring up the total dose to the diabetogenic level or were proceeded by higher doses of non-radioactive alloxan. There was no accumulation of radioactivity in the islets after injection of the non-diabetogenic conversion products of ¹⁴C-2-alloxan obtained in an alkaline medium and only insignificant uptake was noted after exposure of the radioactive alloxan to the reactive SH-groups of glutathione. The absence of significant radioactivity in the islets of growing animals after tracer doses of ¹⁴C-2-alloxan suggests that the ability of the cells to concentrate alloxan is confined to the adult age.This study was supported by grants from the Swedish Medical Research Council, the United States Public Health Service (AM-05759-05) and Knut and Alice Wallenbergs Stiftelse.     

Clinical study of liver blood flow in man measured by 133Xe clearance after portal vein injection.

During the course of a clinical trial to assess the value of adjuvant liver perfusion of 5-fluorouracil after surgery for colorectal cancer, liver blood flow was measured in 14 patients. Access to the portal circulation was achieved by dilatation and cannulation of the obliterated umbilical vein. The clearance from the liver of a bolus of 133Xe was monitored using a gamma-ray camera so that blood flow from different areas of the liver could be calculated. The clearance curve of 133Xe was a double exponential of which the initial fast component accounted for a consistently high proportion of the total clearance. The perfusion studies have shown wide differences in blood flow to the various areas of the liver in the same patient, in addition to a wide variation in perfusion rate between the 14 patients. This technique of quantitative estimations of liver blood flow to different areas of the liver may have importance in planning operative procedures and understanding the haemodynamic mechanisms involved in liver disease.