Effect of cephalic pressure on fetal cerebral blood flow.

During vaginal delivery, the fetus is exposed to a variety of stresses including pressure applied to the fetal skull. In order to study the effects of this stress on fetal homeostasis, we monitored the response to external cephalic compression applied to the acutely prepared near-term fetal lamb. In response to cephalic pressure, we noted initial bradycardia followed by sustained tachycardia. Mean arterial pressure and pulse pressure rose during cephalic pressure and gradually returned to baseline levels. Cerebral blood flow fell approximately 95% early in the period of compression. This fall in total cerebral blood flow was accompanied by a redistribution of cerebral flow. During this time, a smaller percentage of cerebral blood flow was found in the cortex and a greater percentage was directed to the brainstem.

Altered gastric emptying and prevention of radiation-induced vomiting in dogs.

The relation between radiation-induced vomiting and gastric emptying is unclear and the treatment of this condition is not established. We explored, therefore, (a) the effect of cobalt 60 irradiation on gastric emptying of solids and liquids and (b) the possibility of preventing radiation-induced vomiting with the dopamine antagonist, domperidone. Twenty dogs were studied on two separate days, blindly and in random order, after i.v. injection of either a placebo or 0.06 mg/kg domperidone. On a third day, they received 8 Gy (800 rads) whole body irradiation with cobalt 60 gamma-rays after either placebo (n = 10) or domperidone (n = 10). Before each study, each dog was fed chicken liver tagged in vivo with 99mTc-sulfur colloid (solid marker), and water containing 111In-diethylenetriamine pentaacetic acid (liquid marker). Dogs were placed in a Pavlov stand for the subsequent 3 h and radionuclide imaging was performed at 10-min intervals. Irradiation produced vomiting in 9 of 10 dogs given placebo but only in 1 of 10 dogs pretreated with domperidone (p less than 0.01). Gastric emptying of liquids and solids was significantly suppressed by irradiation (p less than 0.01) after both placebo and domperidone. These results demonstrate that radiation-induced vomiting is accompanied by suppression of gastric emptying. Furthermore, domperidone prevents vomiting produced by ionizing radiation but does not alter the accompanying delay of gastric emptying.

Synthesis and evaluation of radioiodinated derivatives of 1-azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(4-iodophenyl)-alpha- phenylacetate as potential radiopharmaceuticals.

Two derivatives of (RS)-1-azabicyclo[2.2.2]oct-3-yl (RS)-alpha-hydroxy-alpha-(4-iodophenyl)-alpha-phenylacetate (1a) and three partially resolved (R)- or (S)-1-azabicyclo[2.2.2]oct-3-yl (RS)-alpha-hydroxy-alpha-(4-iodophenyl)-alpha-phenylacetates labeled with no carrier added iodine-125 (1b, 18, and 19) and iodine-123 (1c and 18a) were synthesized by the Wallach triazene approach. We have found that this approach is necessary to obtain no carrier added labeling and gives far better results than the direct electrophilic iodination. The obtained yields were 7 to 18% when using iodine-123 (yield dependent on the source of iodide) and up to 17% for iodine-123 (yield dependent on the source of iodide) and up to 17% for iodine-125 labeled compounds. Our preliminary distribution studies indicate that 1b localizes in the organs known to have a large concentration of muscarinic receptors and that this localization is due to binding to those receptors.

External imaging of cerebral muscarinic acetylcholine receptors.

A radioiodinated ligand that binds to muscarinic acetylcholine receptors was shown to distribute in the brain by a receptor-mediated process. With single-photon-emission imaging techniques, radioactivity was detected in the cerebrum but not in the cerebellum, whereas with a flow-limited radiotracer, radioactivity was detected in cerebrum and cerebellum. Single-photon-emission computed tomography showed good definition of the caudate putamen and cortex in man.

Regional pulmonary function after irradiation of the canine lung: radionuclide evaluation.

The pulmonary effects of neutron and gamma irradiation were compared in a group of beagle dogs that were subjected to hemithorax irradiation with cobalt-60 gamma rays or 15-MeV neutrons. Integral cobalt-60 doses of 3000, 4500, or 6750 rad (30, 45, or 67.5 Gy) and neutron doses of 1000, 1500, or 2250 rad (10, 15, or 22.5 Gy) were given on a therapy-type schedule of four equal fractions per week for 6 weeks. Serial Tc-99m-macroaggregated albumin perfusion, Tc-99m-Sn-phytate aerosol, and xenon-133 ventilation studies were performed before irradiation and at 3, 6, 9, 12, 18, and 24 months postexposure. Pulmonary damage was more severe and persistent with neutron than with gamma radiation, but the changes were dose-dependent for both types of radiation. The perfusion and radioaerosol imaging studies provided the best scintigraphic evidence of lung damage. Abnormalities in the xenon-133 studies were relatively minor and were more apparent on the single-breath than on the equilibrium or clearance studies. The scintigraphic studies provided evidence of radiation-induced ventilation perfusion inequalities with both types of radiation, but required several times less neutron radiation than gamma radiation to produce similar alterations in ventilation-perfusion relationships.

The influence of asphyxia on fetal lidocaine toxicity.

Local anesthetics have played an important role in modern obstetrics. Although reasonably safe, these agents have been shown to have detrimental effects in some fetuses. In the present study we examined the influence of acute asphyxia in the fetal lamb on the distribution and cerebral uptake of maternally infused lidocaine. Results demonstrate that asphyxia is associated with higher lidocaine concentrations in the fetal plasma, increased presentation of the drug to the fetal brain, and increased cerebral lidocaine uptake. These findings underscore the importance of evaluation of fetal status when considering the risks and benefits of maternal drug use.

The use of tritium labeled compounds to develop gamma-emitting receptor-binding radiotracers.

In an effort to evaluate receptor binding drugs for their potential as gamma labeled radiopharmaceuticals suitable for clinical heart scanning, in vivo data were compared with the results obtained from a theoretical model. The distribution of selected tritium-labeled, receptor-binding radiotracers was studied in animals to determine if the heart to blood ratios agree with those obtained using a theoretical model of receptor binding. In general, the in vivo studies agree with the theoretical model when the concentration of the radiotracer in the heart is due to specific receptor binding. The use of the theoretical model for a first approximation followed by in vivo biodistribution studies is an efficient strategy to select those few from among the large number of receptor binding compounds that will ultimately yield an efficacious radiopharmaceutical to study receptor changes in the intact human heart.

Experimental evaluation of Tc-99m sulfur colloid as a potential imaging agent in thromboembolic disease: concise communication.

Based on literature reports suggesting the possible incorporation of Tc-99m sulfur colloid (Tc-SC) into fibrin deposits, this study was undertaken to evaluate the potential of this radiopharmaceutical as an imaging agent in thromboembolic disease. Animal models of deep-vein thrombosis and pulmonary embolism were used. The mean thrombus-to-blood (T/B) uptake ratios were comparable for fresh and older thrombi (up to 72 hr). Thrombus uptake was significantly lower in a group of five control dogs that received pertechnetate instead of Tc-SC. Intravenous heparin administration (5,000 IU) 2 hr before injection of Tc-SC caused a depression in T/B ratios but did not totally block Tc-SC uptake. Gamma imaging with Tc-SC allowed demonstration of deep-vein thrombi, but imaging of pulmonary emboli as areas of increased activity was not satisfactory. This study supports the concept of thrombus detection with radiolabeled particles but not the extension of this principle to the imaging of pulmonary emboli.