Scintigraphic monitoring of catheter-port systems in type I diabetics with continuous insulin therapy.

OBJECTIVE: We developed a non-invasive scintigraphic procedure to control the function of percutaneous catheter-port systems for continuous insulin therapy. The aim of the study was to evaluate the scintigraphic results and to compare the absorption kinetics of intraperitoneal and umbilical catheter-ports. MATERIAL AND METHODS: Seven patients with intraperitoneal and nine patients with umbilical catheter-port systems implanted into the partially redilated umbilical vein were investigated. All these patients had normal functioning catheter-ports. Additionally, three patients with intraperitoneal and three patients with umbilical catheter-port dysfunction confirmed either by radiography or laparoscopy were studied. After the injection of (99 m)TcO (4)(-) into the port a region-of-interest was drawn around the activity at the tip of the catheter and the half-life of tracer absorption (T(1/2)) calculated. RESULTS: The normal intraperitoneal catheter-port group showed a T(1/2) value of 6.7 +/- 3.2 min and the normal umbilical catheter-port group a T(1/2) of 6.6 +/- 2.0 min. There was no significant difference in T(1/2) between intraperitoneal and umbilicial systems. The dysfunctional catheter-port group (T(1/2) 19.3 +/- 6.7 min) differed ( p = 0.0005) from the normal catheter-port group (T(1/2) 6.7 +/- 3.2 min). On the basis of the normal group an upper threshold value of T(1/2) was calculated to be 11.8 min. CONCLUSIONS: Imaging with (99 m)TcO (4)(-) is an accurate, non-invasive, and quick method to assess the function of insulin catheter-ports. A T(1/2) value > 11.8 min is indicative of a catheter dysfunction. Umbilical and intraperitoneal catheter-ports show similar absorption rates of (99 m)TcO (4)(-).     

Do inhaled carbon nanoparticles translocate directly into the circulation in humans?

RATIONALE: Increased exposure to particulate air pollution (PM(10)) is a risk factor for death and hospitalization with cardiovascular disease. It has been suggested that the nanoparticulate component of PM(10) is capable of translocating into the circulation with the potential for direct effects on the vasculature. OBJECTIVE: The study's aim was to determine the extent to which inhaled technetium-99m ((99m)Tc)-labeled carbon nanoparticles (Technegas) were able to access the systemic circulation. METHODS AND MAIN RESULTS: Ten healthy volunteers inhaled Technegas and blood samples were taken sequentially over the following 6 h. Technegas particles were 4-20 nm in diameter and aggregated to a median particle diameter of approximately 100 nm. Radioactivity was immediately detected in blood, with levels increasing over 60 min. Thin-layer chromatography of whole blood identified a species that moved with the solvent front, corresponding to unbound (99m)Tc-pertechnetate, which was excreted in urine. There was no evidence of particle-bound (99m)Tc at the origin. gamma Camera images demonstrated high levels of Technegas retention (95.6 +/- 1.7% at 6 h) in the lungs, with no accumulation of radioactivity detected over the liver or spleen. CONCLUSIONS: The majority of (99m)Tc-labeled carbon nanoparticles remain within the lung up to 6 h after inhalation. In contrast to previous published studies, thin-layer chromatography did not support the hypothesis that inhaled Technegas carbon nanoparticles pass directly from the lungs into the systemic circulation.     

Portal hemodynamics in primary biliary cirrhosis as evaluated by per-rectal portal scintigraphy with Tc-99m pertechnetate

BACKGROUND/AIMS: Portal circulation can be evaluated in a relatively noninvasive manner by per-rectal portal scintigraphy. We used this method to evaluate portal hemodynamics in patients with primary biliary cirrhosis and idiopathic portal hypertension. We did the procedures simultaneously in some patients to examine the relation between portal circulation and hepatic functional reserve in these diseases. METHODOLOGY: Per-rectal portal scintigraphy with Tc-99m pertechnetate was done in 17 healthy subjects, 154 patients with chronic hepatitis, 447 patients with cirrhosis, 40 patients with primary biliary cirrhosis, and 20 patients with idiopathic portal hypertension. Eighty-three patients (14 with hepatitis, 48 with cirrhosis, 16 with primary biliary cirrhosis, and 5 with idiopathic portal hypertension) also underwent scintigraphy with Tc-99m galactosyl human serum albumin with 2 weeks. A solution containing Tc-99m pertechnetate was instilled into the rectum, and serial scintigrams were taken while radioactivity curves for the liver and heart were recorded sequentially. The per-rectal portal shunt index was calculated from the curves. A receptor index was calculated by dividing the radioactivity of the liver region of interest by that of the liver-plus-heart region of interest 15 min after the injection of Tc-99m galactosyl human serum albumin. The index of blood clearance was calculated by dividing the radioactivity of the heart region of interest at 15 min by that of the heart region of interest at 3 min. RESULTS: The shunt index was higher for more severe disorders, increasing in the order of chronic hepatitis, cirrhosis without varices, and cirrhosis with varices. The shunt indices in patients with primary biliary cirrhosis and idiopathic portal hypertension were higher than that in patients with chronic hepatitis. In terms of receptor index, the standard residuals were more than 0 in 10 of 16 patients with primary biliary cirrhosis and 4 of 5 patients with idiopathic portal hypertension. In terms of index of blood clearance, the standard residuals were more than 0 in 10 of 16 patients with primary biliary cirrhosis and 4 of 5 patients with idiopathic portal hypertension CONCLUSIONS: Abnormalities of portal hemodynamics in patients with primary biliary cirrhosis or idiopathic portal hypertension occur while hepatic functional reserve is still satisfactory as compared with patients who have chronic hepatitis or cirrhosis.     

Passage of intratracheally instilled ultrafine particles from the lung into the systemic circulation in hamster.

The mechanisms of particulate pollution-related cardiovascular morbidity and mortality are not well understood. We studied the passage of radioactively labeled ultrafine particles after their intratracheal instillation. Hamsters received a single intratracheal instillation of 100 microg albumin nanocolloid particles (nominal diameter < or = 80 nm) labeled with 100 microCi technetium-99m and were killed after 5, 15, 30, and 60 min. In blood, radioactivity, expressed as percentage of total body radioactivity per gram blood, amounted to 2.88 +/- 0.80%, 1.30 +/- 0.17%, 1.52 +/- 0.46%, and 0.21 +/- 0.06% at 5, 15, 30, and 60 min, respectively. Thin-layer chromatography showed only one peak of radioactivity corresponding to unaltered (99m)Tc-albumin nanocolloid. In the liver, radioactivity, expressed as percentage of total radioactivity per organ, amounted to 0.10 +/- 0.07%, 0.23 +/- 0.06%, 1.24 +/- 0.27%, and 0.06 +/- 0.02% at 5, 15, 30, and 60 min, respectively. Lower values were observed in the heart, spleen, kidneys, and brain. Dose dependence was assessed at 30 min following instillation of 10 microg and 1 microg (99m)Tc-albumin per animal (n = 3 at each dose), and values of the same relative magnitudes as after instillation of 100 microg were obtained. We conclude that a significant fraction of (99m)Tc-albumin, taken as a model of ultrafine particles, rapidly diffuses from the lungs into the systemic circulation.     

Metabolic clearance of insulin-like growth factor-II in sheep

The metabolic clearance of ovine insulin-like growth factor-II (IGF-II) was examined in sheep using 131I-labelled IGF-II. Following i.v. administration the tracer was distributed in a volume similar to that of the vascular space (58.5 +/- 3.3 ml/kg; mean +/- S.E.M., n = 5) and demonstrated a triphasic pattern of clearance. Size-exclusion chromatography of a plasma sample collected 1 min after injection revealed peaks of radioactivity corresponding to hormone complexed to binding proteins of 150 and 40-50 kDa (relative abundance 21 and 65% respectively), a high molecular weight binding protein (greater than 200 kDa; 5%) and 'free' tracer (9%). Chromatography of sequential plasma samples revealed different patterns of clearance for these constituents. Half-lives of 131I-labelled IGF-II complexed to the 150 and 40-50 kDa binding proteins, as calculated from rate constants for their decay, were 351 +/- 30 and 9.6 +/- 1.8 min respectively (n = 5). These differ markedly from estimates for the clearance of IGF-I (545 +/- 25 min, n = 8, and 34 +/- 2.3 min, n = 6) associated with carrier proteins of the same apparent molecular weights. This was reflected in calculated metabolic clearance rates for IGF-I (3.9 +/- 0.5 ml/min) and IGF-II (7.8 +/- 1.0 ml/min). Chromatography also revealed that free IGF-II was reduced to negligible levels by 12 min. In contrast, radioactivity eluting in the position expected for the greater than 200 kDa binding protein was cleared from the circulation very slowly.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fate of radioactive exocrine pancreatic proteins injected into the blood circulation of the rat. Tissue uptake and transepithelial excretion

[35S]methionine or [35S]methionine-labeled exocrine pancreatic proteins were injected into the bloodstream of conscious rats. Samples of blood, urine, bile, and pancreatic juice were collected at varying intervals through 7 h. Injection of [35S]methionine resulted in the appearance of trichloroacetic acid--soluble radioactivity [( 35S]methionine) in bile and urine within 4 min and trichloroacetic acid-insoluble radioactivity in blood, bile, and pancreatic juice after 20 min. Analysis of these body fluids by two-dimensional isoelectric focusing/sodium dodecyl sulfate gel electrophoresis and fluorography indicated that rat serum, biliary, and pancreatic proteins were labeled, respectively. After the injection of [35S]methionine-labeled pancreatic proteins, half of the trichloroacetic acid-insoluble radioactivity disappeared from the serum in 10-15 min. Radioactive proteins appeared after 5 min in urine and bile, and, over the course of the experiment, accounted for 1%-2% and 0.3%-0.5% of the injected radioactivity, respectively. Analysis of individual radioactive proteins excreted into bile by two-dimensional isoelectric focusing/sodium dodecyl sulfate gel electrophoresis indicated preferential transhepatic transport of negatively charged pancreatic proteins. The majority of pancreatic proteins (approximately 97%) were taken up by a variety of body tissues, particularly kidney, liver, spleen, and lung. Trichloroacetic acid-soluble radioactivity, largely representing [35S]methionine, appeared sequentially in serum, urine, and bile within 2-12 min. At later experimental time points (greater than 60-90 min), radioactive rat serum, biliary, and pancreatic proteins appeared in blood, bile, and pancreatic juice, respectively. After the injection of 35S-labeled guinea pig pancreatic proteins into the blood circulation of the rat, trichloroacetic acid-insoluble radioactivity, observed in pancreatic juice after 60-90 min, exclusively represented rat exocrine pancreatic proteins as judged by the two-dimensional gel procedure. These studies indicate that pancreatic proteins are removed from the blood circulation by at least three separate pathways: (a) uptake and degradation by a variety of tissues in the body (approximately 97% of injected radioactivity), (b) excretion of intact proteins into urine (1%-2%), and (c) transport of intact proteins into bile (0.3%-0.5%). Transport of exocrine pancreatic proteins from the blood circulation to pancreatic juice could not be demonstrated.     

Hepatic and pulmonary clearance of exogenous vasoactive intestinal peptide in the rat.

1125-labeled vasoactive intestinal peptide (VIP) has been injected into the portal and systemic circulations of rats in an attempt to identify the distribution and fate of the circulating peptide. When VIP I125 was introduced into the portal circulation radioactivity was concentrated in the liver (415.5% +/- 57.2 at 10 min--counts per minute (cpm) per gram of tissue as percentage cpm per milliliter of plasma). Radioactivity in kidney and lung was 346.6% +/- 37.4 and 136.4% +/- 11.4, respectively. In contrast, if the liver was bypassed by performing a portacaval shunt or by injecting into the inferior vena cava, radioactivity was maximal in the lung (2,454.3% +/- 302.3 10 min after IVC injection) with activity in the liver of only 89.3% +/- 10.6. Analysis of the pattern of radioactivity in plasma and tissue extracts by gel filtration chromatography showed the presence of a number of fragments of smaller molecular weight than VIP with a progressive diminution of the amount of VIP-like radioactivity. Both liver and lung have the capacity to concentrate VIP from the circulation. Vasoactive intestinal peptide released into the portal circulation is probably taken up initially by the liver, and this may prevent subsequent uptake by pulmonary tissue. There is some evidence to suggest that the liver and the lung may handle VIP in different ways. If this is so, the enhanced pulmonary extraction of VIP when the liver is bypassed may have some significance for the cardiovascular complications of fulminant liver failure.     

beta-Endorphin: stability, clearance behavior, and entry into the central nervous system after intravenous injection of the tritiated peptide in rats and rabbits.

Rabbits and rats were given intravenous injections of tritiated human beta-endorphin. The levels of beta-endorphin were followed by the decrease in radioactivity in the plasma of rats or rabbits and by the increase in radioactivity in the cerebrospinal fluid of the rabbit. The results were identical with the tritium label on either tyrosine-1 or -27. The plasma distribution times were 2 and 5 min in the rat and rabbit, respectively, with a later clearance time of approximately 1-8 hr. In the rat, approximately 50% of the radioactivity in the plasma was found to be intact human beta-endorphin 45 min after injection. Radioactivity appeared in the cerebrospinal fluid of the rabbit within 30 sec after injection and reached a plateau in approximately 60-90 min after injection. Approximately 75% of the radioactivity in the cerebrospinal fluid of the rabbit was intact human beta-endorphin. In the brain hemispheres of the rat and the rabbit, the only significant radiolabeled product was found to be radioactive tyrosine. Moreover, rat plasma levels of beta-endorphin decreased dramatically after hypophysectomy, which only slightly lowered the levels in the brain. It appears that beta-endorphin, upon entry into the plasma, is either not significantly taken up into the brain or is broken down with extreme rapidity upon entry into the brain, although it apparently does enter the cerebrospinal fluid.     

Distribution and degradation of two tritium-labelled corticotrophin analogues in the rat.

The distribution and degradation of corticotrophin-(1--24)-tetracosapeptide specifically labelled with tritium at Tyr2, Phe7 or Tyr23 and [D-Ser1, Lys17, Lys18]-corticotrophin-(1--18)-octadecapeptide amide labelled at Tyr2 were studied at various times after intravenous injection into rats. By characterizing the radioactivity in plasma and various tissues, an overall picture of the metabolic handling of the two peptides emerged. The peptides left the circulation rapidly, entering mainly muscle and skin where they were extensively degraded. The D-Ser1-containing analogue was less rapidly degraded and intact peptide persisted in muscle and skin for up to 1 h. This peptide probably returned to the circulation giving rise to the sustained plasma levels observed after injection of the D-Ser1-substituted octadecapeptide but not after injection of the tetracosapeptide. Although initially the kidneys did not clear such large amounts of peptide as did muscle and skin they played an important role by continuously and, on the basis of existing evidence, irreversibly clearing the peptides and peptide fragments from the circulation and degrading them.     

Measurement of lymphatic flow variation by noninvasive method cases of lymphedema.

The purpose of this study was to measure the variations of lymphatic flow. A noninvasive isotopic method was used to achieve a functional exploration of lymphatic circulation. Fifteen subjects were used in the study: 10 healthy subjects and 5 patients with lower extremity lymphedema. A first subcutaneous injection of technetium 99m rhenium sulfate (99mTc) was performed in the first interdigital space of both feet. The radioactivity was recorded in two places: the first one on the inguinal site by a gamma camera; the second, below the first, on the precordial site by a multichannel analyzer. With the two types of recording procedures, it was possible to obtain a curve that showed the amount of radioactivity in relation to time. In order to obtain a muscular activity fifty-five minutes after the injection, each subject or patient spent ten minutes on an ergometric bike. A second subcutaneous injection was performed one week later, but prior to the injection, the subject or patient took orally 1800 mg of heptaminol adenosine phosphate (HAP) per day for three days. The radioactivity recording was made under the same conditions as with the muscular activity. The statistical results of the experiment without treatment on the two types of recording show that in the healthy subjects the amount of radioactivity increased during muscular activity. Moreover, the treatment indicated higher radioactivity values, which remained at a higher level. However, the muscular activity performed by a patient was unable to increase the radioactivity. On the other hand, the drug gave radioactivity values that were higher than the previous values of the first curve.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of a second dose of thyrotropin on exocytosis and endocytosis in the rat thyroid gland

The effect of TSH on exocytosis and endocytosis in thyroid follicle cells was studied with electron microscopic stereology. Groups of rats, pretreated with T4 for 2 d, were injected iv with TSH (500 mU) 20 min, 2, 4, 6, and 8 h before perfusion fixation. Parallel groups were given a second dose of TSH 2, 4, 6 and 8 h after the first one and the thyroids were fixed after 20 min. In controls, injected with saline, the membrane surface area (msa) of exocytotic vesicles was about the same as that of the apical plasma membrane. Pseudopods and colloid droplets were not present. TSH induced exocytosis. The msa of exocytotic vesicles was reduced by about 85% already after 20 min and was even more reduced after 2 h. At later times after injection of TSH the msa of exocytotic vesicles increased gradually to reach control levels after 8 h. TSH also induced endocytosis. After 20 min the increase in msa of endocytotic structures (pseudopods, colloid droplets and micropinocytotic vesicles) corresponded to the decrease in msa of exocytotic vesicles during the same time interval. The msa of endocytotic structures remained high at 2 h but decreased gradually at later time intervals and after 8 h no pseudopods and colloid droplets remained in the apical cell region. A second injection of TSH given 2 h after the first one when few exocytotic vesicles were present did not influence the msa of endocytotic structures. At later time intervals a second dose of TSH stimulated exocytosis as well as endocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of SPECT using technetium-99m agents and thallium-201 and PET for the assessment of myocardial perfusion and viability

This report reviews the applications of tomographic imaging with current and new tracers in assessing myocardial perfusion and viability. Multiple studies with thallium-201 (TI-201) single photon emission computed tomography (SPECT) imaging for the detection of coronary artery disease (CAD) have demonstrated high sensitivity, high rates of normalcy and high reproducibility. In assessing viability, fixed defects are frequently detected in viable zones in 4-hour studies with TI-201 imaging. Redistribution imaging performed 18 to 72 hours after injection or reinjection of TI-201 before 4-hour redistribution imaging has been shown to improve accuracy of viability assessment. TI-201 SPECT studies are limited by the suboptimal physical properties of TI-201, which result in variable image quality. The 2 new technetium-99m (Tc-99m) - labeled myocardial perfusion tracers offer the ability to inject much higher amounts of radioactivity, making it possible to assess ventricular function as well as myocardial perfusion from the same injection of radiotracer. Tc-99m sestamibi has very slow myocardial clearance, which allows for prolonged imaging time and results in image quality superior to that obtained with TI-201 and Tc-99m teboroxime. The combination of minimal redistribution of Tc-99m sestamibi and high count rates makes gated SPECT imaging feasible, and also permits assessment of patients with acute ischemic syndromes by uncoupling the time of injection from the time of imaging. The combination of high image quality and first-pass exercise capabilities may lead to a choice of this agent over TI-201 for assessment of chronic CAD.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of technetium-99m sestamibi and thallium-201 retention characteristics in canine myocardium.

OBJECTIVES. The aim of this study was to compare the myocardial retention of technetium-99m (Tc-99m) sestamibi and thallium-201 over a wide range of blood flow at different time points after tracer injection. BACKGROUND. Technetium-99m sestamibi has been proposed as a new perfusion tracer with better physical characteristics than those of thallium-201 for scintigraphic imaging. However, no studies have simultaneously compared the ability of both tracers to assess myocardial blood flow during pharmacologic vasodilation. METHODS. The myocardial retention of Tc-99m sestamibi and thallium-201 were compared over a wide range of blood flow induced by regional coronary occlusion and dipyridamole infusion in an open chest dog model. Myocardial retention of both tracers was determined by in vitro tissue counting at 2, 5, and 20 min after tracer injection and was correlated with microsphere-determined blood flow. RESULTS: Thallium-201 demonstrated greater absolute tissue retention than did Tc-99m sestamibi. At 2 min after tracer injection, there was an almost linear relation between the retention of both tracers and myocardial blood flow over a wide flow range. However, this relation was not maintained over time. At 20 min after injection, the retention of both tracers underestimated myocardial blood flow at higher flow rates. At 2, 5 and 20 min after injection, increments of relative tracer retention between the different levels of flow were always greater for thallium-201 than for Tc-99m sestamibi. CONCLUSIONS. Thallium-201 displays more suitable physiologic characteristics as a flow tracer and may allow better differentiation of myocardial regions with different levels of coronary flow reserve. For both tracers, early cardiac imaging may minimize underestimation of blood flow at higher flow rates.     

Diurnal rhythms in plasma melatonin concentrations in the fetal sheep and pregnant ewe during late gestation

We have measured plasma melatonin (MT) concentrations in the pregnant ewe and fetal sheep during 24-h periods between 114 and 142 days gestation. There was a clear diurnal rhythm in the plasma MT concentrations in both the ewe and fetus from 114 days gestation. Blood samples were also collected from the pregnant ewe and fetus during the day every 2-3 days from 112 days gestation to term. There was no gestational age trend in maternal or fetal day time plasma MT concentrations during late pregnancy. To establish whether there was transplacental transfer of MT, pregnant ewes were injected with [3H]MT, and total radioactivity (disintegrations per min) was measured in maternal and fetal arterial plasma and in amniotic fluid collected before and for 1 h after the [3H]MT injection. Two minutes after [3H]MT injection, radioactivity was detected in both maternal and fetal sheep plasma. Extraction of fetal plasma with chloroform indicated that [3H]MT accounted for 48.0 +/- 7.2 (SE) % of total radioactivity at 2 min after the injection. In one pregnant ewe infused with unlabeled MT (0.3 microgram/ml saline.min for 20 min) maternal and fetal plasma MT concentrations increased within 6 min after the start of the MT infusion. We conclude that there is a diurnal rhythm in the plasma concentrations of MT in the fetal lamb and pregnant ewe between 114 and 142 days gestation, and that MT crosses the ovine placenta from the maternal to the fetal circulation. Therefore, the MT present in the fetal sheep circulation may be solely of maternal origin or it may be derived from both fetal and maternal sources.     

3H-estradiol distribution in female, androgenized female, and male rats at 100 and 200 days of age.

Tissue distribution of radioactivity was studied 48 h after gonadectomy and 1 h after iv injection of 3H-estradiol (1 mug/kg body wt) in 100- and 200-day-old normal female rats, female rats androgenized with 30, 100 or 1250 mug testosterone propionate (TP) at 5 days of age, and male rats. Receptor-mediated uptake of estradiol, as shown by diethylstilbestrol (DES) competition, was highest in preoptic area-anterior hypothalamus (POA-AH) and median eminence-basal hypothalamus (ME-BH), but also occurred in dorsal hypothalamus, pre-hypothalamic area, amygdala and septum in all groups. At 100 days of age there were no differences in brain radioactivity levels between females and androgenized females or males. At 200 days of age radioactivity levels in POA-AH and ME-BH tended to be lower in androgenized female and male rats than in normal females. Also, radioactivity levels in the amygdala were lower in the 1250 mug TP-treated females than in normal females. When expressed per unit fresh weight, uptake in the anterior pituitary tended to be lower in androgenized rats at 100 days of age and was higher in males at 200 days of age than in normal females, but did not differ among any of the groups when expressed as uptake per organ. Thus, the well-known differences among these groups in neural regulation of gonadotropin secretion and sex behavior were not correlated with consistent differences in specific estradiol binding by hypothalamic or other brain areas or pituitary. The uterus took up less estradiol in androgenized females than in control females at both ages. Estradiol receptor activity was demonstrated in kidney of all animals and in seminal vesicles. At both ages radioactivity levels in the toluene and ethanol extracts of lever and kidney were strikingly higher in males than in the female groups. Reviewing the data, it appears that despite some evidence of differences between groups, males, females and androgenized females all have relatively similar limited-capacity, estradiol-uptake systems in brain and pituitary, as measured under the conditions of the present study.     

Oleic acid-induced pulmonary injury in rats: potential role of sulfidopeptide leukotrienes

Lung injury following intravenous oleic acid is characterized by pulmonary edema, leukopenia and hypoxemia. Because leukotrienes can increase permeability and cause leukocyte adherence, we evaluated their potential role in oleic acid-induced lung injury in the anesthetized rat using a selective LTD4/E4 antagonist, LY171883. 99mTc-albumin and 99mTc-red blood cells (99mTc-RBC) were used to measure changes in the pulmonary permeability index and intravascular space by non-invasive scintigraphy. Intravenous oleic acid (0.06 ml/kg) increased the pulmonary permeability index 11 (P less than 0.01) and 5.8 fold (P less than 0.01) at 5 and 50 min after its injection compared to baseline, but had no effect on mean pulmonary arterial pressure or pulmonary distribution of 99mTc-RBC. Oleic acid also induced arterial hypoxemia, and increased bronchoalveolar lavage-fluid levels of immunoreactive (i) leukotriene LTC4 from 0.40 +/- 0.14 ng/ml to 2.27 +/- 0.55 ng/ml (mean +/- S.E.M., n = 4, P less than 0.05) and iLTB4 (from 0.42 +/- 0.05 ng/ml to 1.91 +/- 0.63 ng/ml, n = 5-7, P less than 0.01). LY171883 attenuated the elevated permeability by 24% and 68% at 5 (P less than 0.05) and 50 min (P less than 0.01), but did not alter the hypoxemia. These results support the hypothesis that oleic acid elevates leukotriene levels which may increase pulmonary vascular permeability. Furthermore, they suggest that the prevention of elevated pulmonary vascular permeability and edema may be necessary, but are clearly not sufficient to prevent arterial hypoxemia following oleic acid injury in the rat.     

Comparison between technetium-99m-teboroxime and thallium-201 dipyridamole planar myocardial perfusion imaging in detection of coronary artery disease.

Technetium-99m (TC-99m)-teboroxime is a new myocardial perfusion imaging agent. The purpose of this prospective study was to compare Tc-99m-teboroxime with thallium-201 imaging after the administration of dipyridamole. Thirty patients referred for the evaluation of chest pain were studied with both thallium-201 and Tc-99m-teboroxime dipyridamole scans (mean interval 2 days). Dipyridamole was administered at 0.142 mg/kg/min for 4 minutes. Planar imaging (3 standard views) was obtained at 5 and 240 minutes after the injection of 2.2 mCi of thallium-201. Tc-99m-teboroxime (18 to 25 mCi) was injected after dipyridamole infusion. A second injection, at rest, was repeated 4 hours later. Planar imaging (3 standard views of 1 minute/view for the first 2 views, and 90 seconds for the last view) was obtained 2 minutes after Tc-99m-teboroxime injection. Blinded reading was performed by 3 observers. Thallium-201 showed perfusion defects in 182 myocardial segments corresponding to 33 of 45 (73%) significantly stenosed coronary arteries (greater than or equal to 70% reduction in endoluminal diameter), and Tc-99m-teboroxime detected 160 abnormal segments corresponding to 29 of 45 (64%) stenosed arteries. Thallium-201 and Tc-99m-teboroxime studies were normal in 3 patients. In conclusion, this study shows that there is a good correlation in the imaging results found with thallium-201 and Tc-99m-teboroxime using dipyridamole infusion on both a segmental and a diagnostic comparison.     

Simultaneous test of ventricular function and myocardial perfusion, during exercise, using a new agent labeled with Tc99m

One a tribute of a Tc 99m labeled myocardial agent is the possibility to measure both ventricular function and myocardial perfusion with a single injection. To assess this, normal volunteers, 14 patients with coronary artery disease (CAD) and two suffering from cardiomyopathy with normal coronaries, were injected with 8-10 mci carbomethoxy-isopropyl-isonitrile or 20 mci Rp-30 Tc 99m at peak semi-recumbent bicycle exercise and again at rest. Thirty msec per frame first pass data, and 5 min static anterior, 40(0-) and 70(0-) left anterior oblique images were obtained. Standard Thallium 201 stress test were also done, within one month, and were at the same level of exercise. The left ventricular ejection fraction (EF) increased with exercise (69%-76%) in normal patients. All studies showed normal myocardial perfusion on exercise. In CAD patients the EF increased in some patients who had ischemia. Perfusion images with Tc 99m during exercise and at rest had an identical correlation with Thallium 201. The results support the concept of dual ventricular function and perfusion studies using a single Tc 99m labelled myocardial agent, and suggest that this could become the standard radionuclide stress tests in the future.     

Effect of ischemia and postischemic dysfunction on myocardial uptake of technetium-99m-labeled methoxyisobutyl isonitrile and thallium-201

The myocardial uptake of a new technetium-99m-labeled myocardial perfusion agent, methoxyisobutyl isonitrile (Tc-99m MIBI), and thallium-201 was correlated with microsphere flow in an open chest canine model of low coronary flow and postischemic dysfunction. Eighteen dogs were given an injection of thallium-201 (0.5 mCi) and Tc-99m MIBI (5 mCi) either after 40 min of partial left anterior descending artery occlusion (Group I, 10 dogs) or during reperfusion after 15 min of left anterior descending artery occlusion (Group II, 8 dogs). Regional dysfunction was documented during injection in both groups by quantitative two-dimensional echocardiography. Regional blood flow was assessed by radiolabeled microspheres. The heart was excised 15 min after radionuclide injection and the left ventricle divided into 96 segments for gamma well counting. Among Group I dogs, central ischemic thallium-201 and Tc-99m MIBI activity (expressed as a percent of the activity in the corresponding nonischemic zone) was comparable, respectively, for endocardial (54 +/- 17% and 52 +/- 17%), mid-wall (71 +/- 20% and 69 +/- 17%) and epicardial (89 +/- 13% and 94 +/- 9%) segments and increased proportionally with flow. There was a good linear correlation among these endocardial segments between flow and both thallium-201 (r = 0.78) and Tc-99m MIBI (r = 0.85) activity. Among Group II dogs, central ischemic endocardial flow (59 +/- 14%) was comparable to thallium-201 (70 +/- 18%) and Tc-99m MIBI (74 +/- 12%) activity. Similarly, relative endocardial flow in the intermediate ischemic region (71 +/- 11%) was comparable to thallium-201 (77 +/- 11%) and Tc-99m MIBI (81 +/- 10%) activity. Thus, myocardial uptake of Tc-99m MIBI and thallium-201 is comparable under conditions of low coronary flow and postischemic dysfunction and closely parallels flow alterations.     

The fate and uptake of murine epidermal growth factor in the sheep

125I-Labelled murine epidermal growth factor (EGF) was injected or infused into conscious ewes through the jugular vein. Its disappearance from the circulation and the pattern of its distribution in other body tissues and compartments were observed. Single bolus injections of 125I-labelled EGF resulted in a transient peak of radioactive EGF in the circulation which occurred within 1 min of the injection. This was followed by a very rapid fall in radioactivity in the plasma (t1/2 approximately 1 min) and the gradual appearance of 125I-labelled EGF in the urine. Immunoprecipitable 125I-labelled EGF could be detected in urine within 5 min of the start of the experiment. 125I-Labelled EGF accumulated in the urine for several hours following the injection, although with increasing time a substantial amount of non-immunoprecipitable iodide was also found. The rate of disappearance of the 125I-labelled EGF from the plasma of the ewe was found to be faster than the rate of disappearance of free [125I]iodide that had been injected into the ewe. 125I-Labelled EGF was also administered by a continuous infusion following an initial bolus injection. This again resulted in a rapid initial fall in radioactivity in blood, followed by a slow rise throughout the period of the infusion. When the infusion was stopped, there was a 15-min period of rapid readjustment, after which the radioactivity in the blood fell at a much slower rate (t1/2 approximately 70 min) than was seen initially. Again, intact 125I-labelled EGF was transferred to urine throughout the experiment. At autopsy, 125I-labelled EGF was increased in bile, liver, thyroid and kidney. Although most of the 125I found in the thyroid was free iodide, some EGF-like material was also present. There was also EGF-like material found in both the kidney cortex and the kidney medulla. These results indicate that complex multi-compartment pathways for the uptake, distribution and clearance of 125I-labelled EGF exist in the sheep.