PubMed Health⌕ Search

Biomedical subjects

R P Geyer

Publications and source records attributed to R P Geyer.

At least 19 recordsLinked to original sources
PubMed1988

Pulmonary effects of blood replacement with a perfluorochemical emulsion followed by exposure to 85% oxygen or air.

Perfluorochemical emulsions (PCE) have been used as blood substitutes because of their high solubility coefficient for oxygen. However, concerns for their clinical use include both the hyperoxia required by PCE to improve oxygen delivery to tissues and the effects of PCE on lung tissue. We addressed 3 questions: (1) What are the combined effects on the lungs of PCE blood replacement and hyperoxia? (2) Does reduction of circulating white cells by PCE blood replacement modify the injurious effects of hyperoxia? (3) Does PCE alone alter the lungs? Adult rats received either partial or complete PCE blood replacement or no PCE and were then exposed to 85% oxygen for 5 days. Other rats received partial PCE or no PCE and breathed air for 5 days. Morphometric and morphologic analyses demonstrated that lung injury was primarily caused by hyperoxia, independent of PCE treatment. Statistical analyses of the data indicated no synergistic effects between PCE and hyperoxia; furthermore, transient reduction of blood inflammatory elements by PCE blood replacement did not modify the extent of injury that occurred later. Importantly, however, rats that received partial PCE and air exposure were virtually identical to those that received no PCE and air exposure. Five days after blood replacement, PCE components were most often seen within alveolar and interstitial macrophages and infrequently within endothelial and epithelial cells. Although PCE itself may have produced functional alterations in lung cells, direct effects were not morphologically evident. Our results suggest that, if PCE are used at moderate FIO2, such as 0.6 or less, structural changes in the lungs could be minimized.

Air↗
PubMed1988

Perfluorochemicals as oxygen transport vehicles.

Perfluorochemical liquids (PFC's) are good solvents for gases and as such, have significant relevance to the field of biology. Approximately 40 ml of oxygen will dissolve in 100 ml of most PFC's, and carbon dioxide is at least twice as soluble. This makes these compounds attractive as vehicles for these and other gases in-vivo and in-vitro. Although many have low viscosities and surface tensions, it is necessary to emulsify them for intravenous use and organ perfusion. The emulsion particles must be very fine, usually about 150 nanometers in diameter, and stable in the presence of blood and other biological fluids. Presently the two most used emulsifying agents are Pluronic F68 and phospholipids. Emulsions made with the former are now known to cause complement activation with accompanying transient decreases in circulating leukocytes and oxygen tension. This phenomenon is reversible and usually not severe. Phospholipid-stabilized PFC emulsions do not activate complement and should therefore, be advantageous. Areas of current research utilizing PFC emulsions are in tumor therapy, by increasing the oxygenation of otherwise hypoxic cells, in ischemic heart treatment, and in alleviating the effects of cerebral ischemia. Many other applications of PFC's are being pursued, and even more research activity in this field is likely.

Animals↗
PubMed1987

myo-inositol action on gerbil intestine: alterations in alkaline phosphatase activity upon phosphatidylinositol depletion and repletion in vivo.

The influence of phosphatidylinositol (PI) on intestinal alkaline phosphatase activity was studied in myo-inositol deficient gerbils. A reduction of membrane PI in intestinal mucosa to 30-40% of the control was produced by feeding female gerbils a myo-inositol-deficient diet containing coconut oil for 2 weeks. As expected, the animals developed typical intestinal lipodystrophy with abnormal fat accumulation. In the PI-depleted animal, intestinal alkaline phosphatase activity was reduced to 20-30% of the control group. The levels of both membranous and soluble enzymes in intestinal mucosa were affected, but there were no changes in liver, kidney and plasma levels. When the lipodystrophic gerbils were given dietary myo-inositol, the complete repletion of intestinal membrane PI to the control level occurred 36 h later, whereas membrane-bound alkaline phosphatase activity in intestine was not restored to the control level until 72 h later. Administration of cycloheximide or actinomycin D did not block this enzyme induction. Lymphatic output of triacylglycerol into the bloodstream was stimulated 10-fold at 18 h of myo-inositol repletion, but there was no parallel increase in the activity of alkaline phosphatase in plasma during this early phase of intestinal recovery. Thus, these data suggest a possible regulatory role of PI in the processing and/or turnover of alkaline phosphatase in vivo, but a negative role of alkaline phosphatase in lipid transport across gerbil intestine.

Alkaline Phosphatase↗
PubMed1985

Limitations of fluorocarbons in reducing myocardial infarct size.

The effects of the oxygen-carrier fluorocarbons on myocardial infarct size were assessed in non-exchange-transfused dogs subjected either to a 3-hour occlusion of the left anterior descending coronary artery (LAD) followed by 2 hours of reperfusion (protocol I) or to a 5-hour permanent LAD occlusion (protocol II). Fluorocarbon administration was begun 30 minutes after LAD occlusion and was continued over the entire period of ischemia. After 5 hours, the hearts were excised and areas of necrosis were visualized by triphenyl tetrazolium chloride staining while risk regions were assessed by radiolabeled microspheres injected after coronary occlusion just before the onset of therapy, and further, in protocol I, by thallium-201 perfusion imaging performed at the end of fluorocarbon administration. In protocol I experiments, the ratio of necrotic area to area at risk was 81 +/- 35% (mean +/- standard deviation) in control saline-treated dogs (n = 6) and 67 +/- 27% in fluorocarbon-treated dogs (n = 6) (difference not significant). There was no significant difference between risk regions measured after and before fluorocarbon treatment. In protocol II, the ratio of necrotic area to area at risk was 47 +/- 30% in control dogs (n = 5) and 63 +/- 29% in fluorocarbon-treated dogs (n = 5) (difference not significant). However, in control dogs, the ratio of necrotic area to area at risk increased from 47 +/- 30% in the dogs that underwent permanent occlusion to 81 +/- 35% in the group that underwent reperfusion (p less than 0.001) while this ratio was similar in the corresponding subsets of fluorocarbon-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Platelet-derived growth factor stimulates rapid polyphosphoinositide breakdown in fetal human fibroblasts.

The addition of human platelet-derived growth factor (PDGF) to confluent, quiescent cultures of human diploid fibroblasts induced the rapid breakdown of cellular polyphosphoinositides. The levels of 32P-labeled phosphatidylinositol 4,5-bisphosphate (PIP2), phosphatidylinositol 4-phosphate (PIP), and phosphatidylinositol (PI) decreased by 30 to 40% within 1 min after exposure of the cells to PDGF. The levels of PIP and PIP2 returned to their initial values within 3 and 10 min, respectively, after PDGF addition. The level of PI continued to increase after it had returned to control values and was up threefold within 30 min after PDGF addition. In cells prelabeled with myo-[3H]inositol PDGF caused an eightfold increase in the levels of inositol trisphosphate (IP3) within 2 min. Lesser increases, twofold and 1.3-fold, respectively, were seen in levels of inositol bisphosphate (IP2) and inositol monophosphate (IP). Within 10 min after PDGF addition the levels of all three inositol phosphates had decreased to control values. The levels of IP3 measured 2 min after PDGF addition depended on the PDGF concentration and were maximal at 5-10 ng/ml of PDGF. Similar concentrations of PDGF stimulate maximal cell growth and DNA synthesis in these cells.

Cells, Cultured↗
PubMed1985

Enhanced cardioplegic protection by a fluorocarbon-oxygenated reperfusate: a phosphorus-31 nuclear magnetic resonance study.

Prolonged global ischemia results in a defect in oxygen extraction during early reperfusion. This study was thus undertaken to assess the effects of maintaining cardioplegia at the onset of reoxygenation in view of channeling available energy toward reparative cell processes rather than mechanical activity. Twenty-four isolated perfused rat hearts were subjected to 120 min of 15 degrees C ischemia. Group I (control) was reperfused with the standard Krebs perfusion medium whereas in groups II and III the initial reperfusate consisted of an oxygenated alkaline cardioplegic solution prior to the resumption of Krebs perfusion. Oxygenation of the cardioplegic reperfusate was ensured by fluorocarbons at a concentration of 10% (O2 content: 5.5 vol %; group II) or 20% (O2 content: 9 vol %; group III). In addition to hemodynamical determinations, high-energy phosphates and intracellular pH were monitored serially by phosphorus-31 nuclear magnetic resonance spectroscopy. After 30 min of reperfusion postischemic recovery of aortic flow was better in group II (74.0 +/- 5.9% of control) than in group I (59.1 +/- 5.4% of control, P less than 0.05). This functional improvement correlated with a higher postischemic increase in phosphocreatine levels (103.21 +/- 11.21% vs 74.12 +/- 3.59%, at 3 min of reperfusion, P less than 0.05) without significant differences in total ATP content. Group III hearts exhibited a slow recovery as evidenced by a severe depression in aortic flow, coronary arteriovenous difference, and total phosphate content during the 15 initial minutes of reperfusion. These results show that the protection provided by cardioplegia can be improved by a fluorocarbon-oxygenated cardioplegic reperfusate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1985

Fluorocarbons: a potential treatment of cerebral air embolism in open-heart surgery.

This study was designed to assess whether an oxygenated fluorocarbon solution could reduce ischemic brain damage related to arterial air embolism. Air embolism was produced by injecting air bubbles into the carotid artery of barbiturate-anesthetized rats breathing 100% oxygen. Results were assessed on electrocorticogram. In an additional set of experiments, mass spectrometry was used to provide continuous monitoring of intracerebral tissue oxygen (PO2) and carbon dioxide (PCO2) tensions and intermittent measurement of cerebral blood flow (CBF). Fluorocarbon or saline solution (containing the emulsifying agent of fluorocarbons) was given intravenously after the initial air embolism (0.2 ml), and injections of air (0.1 ml) were repeated thereafter every five minutes. The maximal amount of air required to achieve complete and irreversible flattening of the electrocorticogram was 1.60 +/- 0.06 ml (mean +/- standard error of the mean) in the saline-treated rats and 5.20 +/- 0.44 ml in the fluorocarbon-treated group (p less than 10(-7)). In the second experiment, air embolism caused CBF to rise in both groups, the average percent of increase being higher in treated (41.6%) than in control animals (38.3%) (p less than 0.02). However, in the control group, the increase in CBF did not prevent intracerebral tissue PO2 from decreasing by 7.4 +/- 7.0% over the same period; conversely, in the fluorocarbon group, PO2 levels fell by only 2.5 +/- 3.7% (p less than 0.001 versus controls), but this time-averaged percentage was calculated over a longer period of cumulative ischemia because of the greater number of air emboli tolerated by treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

31P-NMR study of high-energy phosphorylated compounds metabolism and intracellular pH in the perfused rat heart.

Using 31P-NMR and haemodynamical measurements, this work assesses different aspects of myocardial preservation improvement during a global ischaemia, based on a simultaneous and correlated study of high-energy phosphorylated compounds, intracellular pH and left ventricular function. Isolated perfused working rat hearts were subjected to 2 or 3 h of hypothermic ischaemia followed by 30 or 45 min of reperfusion. A study of the influence of pH and buffer used in cardioplegic solutions has demonstrated a better preservation of high-energy phosphates and an improved functional recovery when using a pH 7.0, glutamate - containing solution. Protection provided by cardioplegia can be enhanced by the appropriate use of a fluorocarbon-oxygenated cardioplegic reperfusate. The use of nifedipine, a calcium antagonist, in the cardioplegic solutions, does not provide any additional protection under hypothermic conditions.

Adenosine Triphosphate↗
PubMed1984

Reduction of myocardial infarct size by a fluorocarbon-oxygenated reperfusate.

This investigation assesses whether the size of an acutely revascularized myocardial infarct (MI) could be reduced by altering the composition of the initial reperfusate. Nineteen open-chest dogs underwent 4-hour occlusion of the left anterior descending coronary artery and were then assigned to a treatment group: 12 dogs to selective intracoronary infusion of the modified reperfusate over 30 minutes before resumption of blood flow for 60 minutes and 7 to a control group (90 minutes of unmodified blood reperfusion). The modified reperfusate consisted of 500 ml of a fluorocarbon-oxygenated crystalloid solution (PO2 650 mm Hg; total O2 content 5.5 vol%) whose composition was adjusted by decreasing Ca++ (0.25 mM), increasing pH (7.60) and adding glucose (1.8 g/liter). Four hours after occlusion, technetium-99m-labeled microspheres were injected into the left atrium. After 90 minutes of reperfusion, the heart was removed and sliced transversely. Areas not perfused by microspheres (areas at risk) were traced, planimetered and compared with the areas of necrosis after incubation in triphenyltetrazolium chloride. Areas were then converted into weights. In control dogs, the weight of necrotic myocardium was not significantly different from the weight at risk (5.0 +/- 0.7 vs 7.0 +/- 0.8 g, respectively [mean +/- standard error of the mean]), whereas it was markedly reduced in treated dogs (5.9 +/- 0.5 vs 9.4 +/- 0.7 g, respectively, p less than 0.001). The weight of salvaged myocardium was 3.4 +/- 0.5 g in treated dogs vs 1.9 +/- 0.4 g in the control group (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

In vivo coronary angioscopy.

The feasibility of in vivo coronary angioscopy was tested utilizing a 1.8 mm angioscope in vessels where blood had been replaced by optically clear liquids, including a new perfluorocarbon emulsion. After trials in postmortem canine and human coronary arteries, in vivo intraluminal visualization was accomplished in the dog with a catheterization technique and in patients during open heart surgery. The results demonstrate the feasibility and potential clinical usefulness of direct visualization of intravascular anatomy and disease, analogous to endoscopy of other organ systems.

Animals↗
PubMed1983

Tissue content and metabolism of myo-inositol in normal and lipodystrophic gerbils.

Experiments were conducted to evaluate the effect of diet and sex difference on the development of an intestinal lipodystrophy due to myo-inositol deficiency. Tissue contents of free and lipid-bound myo-inositol as well as the activities of L-myo-inositol-l-phosphate synthase (EC 5.5.1.4) and phosphatase (EC 3.1.3.25), and myo-inositol oxygenase (EC 1.13.99.1) were determined in male and female gerbils under various conditions. The enzyme study proved that the essentiality of dietary myo-inositol for this species was not due to the lack of such enzyme activity. The lower susceptibility of male gerbils to myo-inositol deficiency could be explained by the contribution of the biosynthesis of myo-inositol in the testis, as shown by a difference between intact and castrated animals. Although feeding coconut oil to the myo-inositol-deficient female gerbils produced greater myo-inositol depletion as well as more severe intestinal lesion than the feeding of safflower oil, the difference in myo-inositol status could be only in part responsible for different degrees of lipodystrophy. Additionally, neither dietary type of fat nor exogenous myo-inositol altered the activities of either hepatic or intestinal synthase and phosphatase, or kidney oxygenase. Thus, this study indicates that both sex and dietary factors might influence myo-inositol status to varying extents, but the diet-induced change in tissue myo-inositol was not reflected by the enzyme activity as measured in vitro.

Animals↗
PubMed1983

A method for evaluation of blood substitutes in the conscious animal.

Physiological evaluation of new and potential blood replacement agents has not kept pace with the development of such agents. Current procedures involve partial or total blood replacement in the anesthetized animal. This introduces the variable of anesthesia and eliminates the ability to observe behavior changes during blood replacement. Clinically, many patients receive blood or will receive artificial agents while sedated or under anesthesia, whereas others will be conscious. It is essential that evaluative studies be performed on the awake animal using procedures that are nontraumatic and nonrestrictive. A technique for isovolumic exchange perfusion utilizing an indwelling, heparin-coated, double-lumen catheter in the right atrium of a conscious rat is described. This animal model system permits continuous pre- and postperfusion monitoring. Nearly total blood replacement with perfluorochemical blood substitutes causes no discerniable discomfort or adverse reactions in the animal. Such animals thrive and replace missing hematologic components in 1-3 wk. The technique described can, with minimal modification, be used for isovolumic exchange perfusion of larger animals.

Animals↗