Use of 19F magnetic resonance imaging to measure local cerebral blood volume.
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Biomedical subjects
Publications and source records attributed to H A Sloviter.
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RATIONALE AND OBJECTIVES: Emulsions of perfluorocarbons (PFCs) have been tested as blood substitutes. However, evidence exists that there is long-term retention of some PFCs by the organs of the reticuloendothelial system (RES). The authors investigate organ retention of the blood substitute component, perfluorotripropylamine (FTPA), using fluorine-19 (19F) magnetic resonance imaging (MRI). METHODS: Various dosages of an emulsion of FTPA were administered to five rats. At intervals up to 86 weeks after infusion, 19F MRI was used to measure the amount of FTPA in liver and spleen. The data were fit to both linear and exponential elimination models, and organ retention half-lives were calculated. RESULTS: The exponential half-lives for combined liver and spleen FTPA ranged from 110 to 190 days. Linear half-lives ranged from 175 to 300 days. CONCLUSIONS: FTPA retained by the liver and spleen may be quantified by 19F MRI: The half-lives that were measured are longer than those reported previously for FTPA.
A stable emulsion of perfluorodecalin, made up of 34 percent (vol/vol) perfluorodecalin dispersed by sonication in isotonic Tyrode's buffer (pH 7.4) containing egg yolk lecithin, has been developed. The viscosity of the emulsion is the same as that of human blood, and the particle size is 0.2 microns in diameter. On storage at 5 degrees C, there was no change in viscosity for up to 60 weeks. At 21 degrees C, viscosity increased after 20 weeks of storage; this increase was considerably diminished by the presence of tocopherol in the emulsion. The accumulation of malondialdehyde indicated that there was continuous slow oxidation of the lecithin on storage of the emulsion at either 5 or 21 degrees C; this oxidation was markedly reduced by the presence of tocopherol.
The authors measured the level of blood oxygenation in vivo in a series of rats with implanted mammary adenocarcinoma. The technique used was 19F magnetic resonance imaging of a perfluorochemical blood substitute. The method is based on the effect of oxygen on the T1 relaxation time of the fluorochemical and allows the determination of mean vascular PO2 independent of the blood volume in the tissue. The PO2 levels in the liver, lung, and spleen also were determined and were consistent with previously reported results. When the rats breathed air, the tumor PO2 levels were somewhat lower than in the other organs and were in a range typical of venous blood. When the rat was given 100% oxygen to breathe, the tumor PO2 levels increased far less than the PO2 levels of the other organs. This may indicate a greatly diminished blood flow to this particular tumor.
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The bile duct was cannulated in rats that had been infused intravenously with an emulsion of perfluorodecalin at intervals from 2 to 34 weeks earlier. After injection of [14C]phenobarbital, urine and bile were collected during the next 24 hr and were analyzed for phenobarbital and its metabolites. There was a decrease in the biliary excretion of phenobarbital and its metabolites for several weeks after infusion of perfluorodecalin, but conjugation of the metabolites was not decreased. The reduced excretion returned to normal after about 20 weeks.
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Intravenous infusion of emulsified perfluorodecalin in rats caused a large increase in hepatic cytochrome P-450 concentration which persisted for many weeks. In contrast, hepatic cytochrome P-450 concentration was not changed significantly after infusion of perfluorotributylamine, but subsequent administration of phenobarbital caused the usual increase of cytochrome P-450. The cytochrome P-450 activity for demethylation of benzphetamine was decreased slightly after perfluorodecalin but was unchanged after perfluorotributylamine. The difference in the effects of these perfluorochemicals on hepatic cytochrome P-450 may be related to the difference in the time these compounds are retained in the liver.
The fluorine nuclear magnetic resonance spin-lattice relaxation rate (1/T1) of the perfluorochemical blood substitute perfluorotripropylamine (FTPA) is very sensitive to oxygen tension. This presents the possibility of measuring blood oxygen tension by 19F MR imaging. We obtained oxygen-sensitive 19F NMR images of the circulatory system of rats infused with emulsified FTPA. Blood oxygenation was assessed under conditions of both air- and 100% O2-breathing. T1 relaxation times were derived from MR images using a partial saturation pulse sequence. The T1 times were compared with a phantom calibration curve to calculate average blood pO2 values in the lung, liver, and spleen. The results showed marked, organ-specific increases in blood oxygen tension when the rat breathed 100% O2 instead of air.
Though the delivery of elemental oxygen to tissues ravaged by anaerobic infection may be useful, little data exists that suggests that such therapy may benefit ischemic tissue. We report the development of a model to test the question that peritoneal lavage with an oxygen containing solution may favorably influence occlusive intestinal ischemia. Adult Sprague-Dawley rats with Nembutal (sodium pentobarbital) anesthesia underwent midline laparotomy; a microvascular clamp was applied to the superior mesenteric artery (SMA); and an inflow and outflow lavage catheter was placed. Treatment groups included control rats undergoing SMA occlusion only without lavage, rats lavaged with albumin during SMA occlusion (medium control), and rats lavaged during SMA occlusion with oxygenated perfluorochemical FC-47 emulsified in albumin (O2-FC-47). The increase in serum L-lactate following occlusion was used as an index of intestinal injury whether the perfusate was maintained at room temperature (28 degrees C) or body temperature (37 degrees C). Beginning with time O, which corresponded to the time of unclamping, subsequent samples were collected at 15, 30, and 60 minutes after a 30-minute SMA occlusion. Sequential lactates in 13 control rats were 4.18, 4.10, 3.88, and 4.52 mmol/L. Albumin lavaged animals had values at 28 degrees C of 2.23, 1.35, 1.8, and 2.44 mmol/L and values at 37 degrees C of 2.22, 1.40, 2.07, and 3.21 mmol/L, respectively. With O2-FC-47 lavage the respective lactates were 1.89, 1.09, 1.32, and 1.44 mmol/L at 28 degrees C and 2.14, 2.19, 2.50, and 2.1 mmol/L at 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)
This study reports an assessment of a method of intestinal protection by the intraluminal administration of an oxygenated perfluorochemical, perfluorotributylamine, or gaseous oxygen in an attempt to provide oxygen for mucosal cells rendered ischemia. A model of acute arterial or acute arteriovenous ischemia was produced in adult female rats. All control ischemic animals died within 12 hours. To assess intestinal protection, the mortality rates in the experimental groups were compared with the 100 percent control mortality. Gaseous oxygen and oxygenated perfluorochemical administered intraluminally reduced mortality significantly in the acute arterial model but not in rats with arteriovenous occlusion. Electron microscopy demonstrated preservation of villi after 1 and 2 hours of occlusion in the oxygen-treated groups. Light microscopy revealed massive destruction in control animals with preserved architecture in both the gaseous oxygen and oxygenated perfluorochemical groups. These results demonstrate that the intraluminal delivery of oxygen to bowel rendered ischemic by arterial occlusion may significantly decrease anatomic bowel disruption and improve animal survival. Such techniques have a potential clinical application to facilitate salvage of ischemic intestine and to augment intestinal preservation.
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An MRI pulse sequence has been developed that enables the visualization of a perfluorocarbon (PFC) emulsion in the vascular system of rats. Images were made at 0.12T on a clinical imaging system using a small receiver coil, at intervals of approximately 2 hours, two days, two weeks, and two months after replacement of 50% of total blood volume. The most successful technique produced PA projections of the entire torso for both the fluorine and proton components. Direct comparison allowed identification of PFC in heart, lung, liver, spleen, and large vessels both in vivo and postmortem. Potential clinical applications to vascular imaging are discussed.
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A new emulsion of perfluorochemical, in which the emulsified particles are coated with lecithin, has been infused in rats. The retention of the emulsified perfluorochemical in the circulation has been prolonged more than 300% by injections of lecithin, which maintain a high concentration of lecithin in the plasma. This prolonged retention in the circulation resulted in a marked decrease in the amount of perfluorochemical retained in the liver and spleen.
An unanesthetized, isolated, perfused rat brain, consisting of the skull and its contents with nearly all other tissues removed, has metabolic and electrical activity similar to that of the brain of the intact rat with its blood-brain barrier intact. Its use yielded results that are difficult or impossible to obtain from in vitro preparations or in vivo. With the perfused brain it was shown that mannose can completely replace glucose as metabolic substrate, that insulin has no direct effect on the brain, that in the absence of added substrate glutamate is metabolized to aspartate, that the brain does not metabolize ethanol, and that morphine probably inhibits mitochondrial oxidative activity.