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Biomedical subjects

T W Morris

Publications and source records attributed to T W Morris.

At least 19 recordsLinked to original sources

Effects of radiopaque contrast media on calcium uptake and phosphatidylinositol metabolism in rat brain synaptosomes.

Radiographic contrast media (RCM) used in the subarachnoid space are associated with occasional adverse reactions. This study examines the possibility that RCM reactions are caused by interactions with the plasma membrane phosphatidylinositol (PI) second messenger system. Isolated nerve endings, known as synaptosomes, were produced from rat brain homogenates. The synaptosomes were then incubated with RCM to determine if 32Pi labeling of the PIs or the uptake of 45Ca were influenced in a manner consistent with known mechanisms. The RCM metrizamide, iopamidol, iodixanol, and iotrol (but not iohexol) increased the 32Pi labeling. Hyperosmolality produced large increases in phosphatidylinositol-4-phosphate (PIP) and phosphatidylinositol-4, 5,-bisphosphate (PIP2) labeling. In the non-depolarized state iodixanol, but not metrizamide or iohexol, caused a time-dependent increase in 45Ca uptake. Iodixanol, iohexol, and metrizamide also augmented the veratrine-stimulated uptake of calcium, but none of the RCM affected the uptake of Ca resulting from potassium depolarization. The increased 32Pi labeling of the PIs caused by RCM is not directly related to Ca uptake, because the direction of change is wrong. RCM perturbations of the plasma membrane may cause an inhibition of other membrane components and systems. Hyperosmolality also may cause inhibition of membrane components. It is not known if these effects are important in clinically observed RCM toxicity.

Animals

Changes in serum magnesium during excretory urography. A comparison of ionic and nonionic contrast media.

RATIONALE AND OBJECTIVES: It is known that ionic contrast media (CM) bind magnesium and that patients with asthma often benefit from magnesium injections. Similarly, asthmatics have a higher incidence of CM reactions. This work tests the hypothesis that ionic CM alter serum magnesium more than nonionic CM. METHODS: Ten patients were divided into two groups; one group received iothalamate and the other received iohexol. RESULTS AND CONCLUSIONS: The total magnesium level changed significantly from baseline in the iothalamate-treated group (P less than .01). Iothalamate produced a significant decrease in protein-bound magnesium (P less than .01) with a significant increase in filterable magnesium (P less than .01). Iohexol did not produce significant changes for any of the magnesium fractions. The patient with the most clinically significant adverse reaction (though minor) had the lowest baseline magnesium level. Further studies with larger groups including patients with asthma are needed.

Azo Compounds

The effects of gadolinium-DTPA and -DOTA on neural tissue metabolism.

Gadolinium DTPA and DOTA are being used extensively for imaging blood-brain barrier lesions. This study was performed to determine clinically relevant blood, cerebrospinal fluid (CSF), and neural tissue concentrations of these agents, and to determine if they alter neural tissue glucose metabolism. Bolus injections of 0.2 mmol Gd-DTPA/kg were made in rabbits, and blood, CSF, and neural tissue Gd concentrations were measured using atomic emission. Rat hippocampus slices were incubated for 6 hours in solutions of Gd-DTPA and Gd-DOTA, and effects on the production of carbon-14-labeled CO2 from glucose determined. Plasma concentrations reached a peak of 2.46 mmol at 1 minute postinjection, and dropped to 50% of peak in 6 minutes. The highest CSF concentration observed was approximately 0.1 mmol, and the mean lumbar cord concentration was approximately 8.5 mumol/g. Gd-DTPA and Gd-DOTA concentrations greater than 1.0 mmol caused significant increases in CO2 production. In areas of blood-brain barrier lesions, Gd-DTPA and Gd-DOTA may cause changes in tissue metabolism; however, in other areas it is much less likely.

Animals

Microangiography of the rabbit temporomandibular joint in the open and closed jaw positions.

The purpose of this investigation was to test the hypothesis that jaw position significantly affects the vascular morphology of the temporomandibular joint (TMJ). The study was performed using intravascular perfusion with 30% Micropaque and 40% gelatin. Six anesthetized New Zealand white rabbits were divided into 2 groups of three. Group 1 rabbits were perfused in the resting, closed-jaw position and group 2 rabbits were perfused while the jaw was held open. The animals were killed with an overdose of pentobarbital and frozen. The heads were hemisected, fixed, decalcified, and embedded in Cedukol. Sagittal sections were cut at the level of the meniscus and radiographed with a specimen x-ray unit on high-resolution film. The 6 rabbits (12 TMJs) demonstrated consistent microvascular differences. In 83% of the jaws in group 2 rabbits the anterior condylar vein was not seen or appeared patchy whereas the same vein was readily seen in all jaws of group 1 (P less than .01). The superior condylar vasculature was distended in 83.3% of group 2 jaws and in 16.7% of group 1 jaws (P less than .05). This study demonstrates significant changes in vascular morphology when the jaw is placed in the open position.

Angiography

Ioxilan, a third generation low osmolality nonionic contrast medium. Systemic and renal hemodynamic effects.

The choice between high cost, low toxicity nonionic contrast media (CM) and low cost ionic CM poses a dilemma for radiologists. Ioxilan, a third generation nonionic CM, is obtained by simple conversion from an ionic CM. To examine how this economically promising, low osmolality CM (570 mOsm at 300 mgI/ml) affects canine systemic and renal hemodynamics, IV bolus injections of 350 mgI/ml at 2 ml/kg of Iohexol and Ioxilan were compared. Satisfactory nephrograms and pyelograms were produced by both agents, without significant differences. The effects on systemic and renal hemodynamics were minimal and statistically equal for both CM. The acute systemic and renal responses and radiographic image quality of Ioxilan and Iohexol confirm that the two compounds are biologically equivalent, and that the novel molecular design employed in Ioxilan to achieve very low osmolality also provides good biological tolerance.

Animals

Renal handling and physiologic effects of the paramagnetic contrast medium Gd-DOTA.

Gadolinium DOTA (Gd-DOTA) is a magnetic resonance (MR) contrast agent similar to Gd-DTPA but with greater stability in vitro. The effects of a high intravenous dose (0.5 mmol/kg) of Gd-DOTA (1360 mOsm/kg) on renal excretory function and its general systemic effects are examined in this animal study. This dose was selected to accentuate and better define the qualitative nature of these effects. A decrease in arterial pressure of 8% (131.9 +/- 6.8 at 120 minutes versus a control of 142.8 +/- 3.7 mm Hg, mean +/- standard error of mean, no significant change in electrocardiogram (ECG) lead II, a 16% increase in renal blood flow (106.0 +/- 5.4 at 7.5 minutes versus 91.2 +/- 3.2 ml/min), and a decrease in arterial hematocrit of 9% (38.9 +/- 1.5 at 120 minutes versus 41.9% +/- 1.7%) were noted. In general, qualitatively similar effects have been noted as a nonspecific effect of other hyperosmolar solutions. The filtration fraction decreased (0.23 +/- 0.01 at 7.5 minutes versus 0.28 +/- 0.02) followed by a rapid return to baseline values. No significant change was noted in glomerular filtration rate throughout the experimental protocol. Urine flow increased nearly 1.5-fold and osmolal clearance (Cosm) increased approximately 1.5 times. A natriuresis occurred as the fractional excretion of sodium (FENa+) increased from a control value of 3.5 +/- 0.3 to 5.2 +/- 0.5 at 7.5 minutes. The systemic and renal physiologic effects of high-dose intravenous Gd-DOTA on the kidney reflects a nonspecific, osmotically induced alteration. These data suggest that the main systemic and renal physiologic actions of Gd-DOTA are a nonspecific response to agent osmolality that is similar qualitatively to conventional, water-soluble contrast media.

Animals

Local glucose utilization changes caused by subarachnoid contrast media in the rabbit.

The glucose metabolism effects of six hour exposures to subarachnoid injections of metrizamide, iohexol, iodixanol and control solutions were studied in vivo in 18 rabbits. The brain tissue uptake of intravenously injected 14C labelled deoxyglucose was measured using autoradiographic techniques. Metrizamide and iodixanol caused significant (p less than 0.05) decreases in deoxyglucose uptake in the outer cortical areas where the contrast medium concentrations were highest. Iohexol and the control CSF solution did not cause significant effects. The results appear to indicate that iohexol has less effect on brain tissue glucose metabolism than either metrizamide or the new non-ionic dimer iodixanol.

Animals

Effects of contrast media on neural tissue glucose uptake in vitro.

The authors previously showed that metrizamide causes an inhibition in CO2 production in rat neural tissue. The purposes of this work were to test if this inhibition was the result of a competitive inhibition of metrizamide with the D-glucose transport system and to test the effect of other contrast media. Deoxyglucose was used as a marker for glucose. The first cellular system using rat hippocampus slices was designed to examine the effect of 15 mM and 80 mM metrizamide on deoxyglucose uptake. The second cell-free system, using isolated rat brain synaptosomes, was designed to evaluate more accurately the mechanism and kinetics of metrizamide's inhibitory effect on the uptake of deoxyglucose and to compare metrizamide to other nonionic contrast media (iohexol, iopamidol, iotrol, and iodixanol). These experiments demonstrate that there is inhibition of D-glucose uptake only in hippocampus slices and that the inhibition is dependent on the concentration of metrizamide. This does not, however, appear to be a competitive inhibitory effect on the carrier such as that between D-glucose and 2-deoxy-D-glucose. In synaptosomes, none of the contrast media had a significant effect on the uptake of 2-deoxyglucose.

Animals

A comparison of the systemic responses to rapid intravenous injections of ioxilan, iohexol, and diatrizoate in rabbits.

Rapid intravenous injections of contrast media are used for angiocardiography, intravenous digital subtraction angiography (DSA), and rapid scan computed tomography procedures. These rapid intravenous injections have been shown to produce significant hemodynamic changes that appear related to contrast media osmolality. In this study the systemic responses to 2-second injections at a dose of 1.5 mL/kg were compared for a new nonionic agent, ioxilan (350 mgI/mL), and for iohexol (350 mgI/mL), meglumine/sodium diatrizoate (370 mgI/mL), and saline. Ioxilan has a lower osmolality and viscosity than iohexol and is formulated with a 3 mM sodium citrate as a buffer and anticoagulant. All of the test solutions produced statistically significant changes in arterial pressure and respiratory rate (P less than .05, Student's t-test). The decrease in arterial pressure seen with diatrizoate (20.1%) was significantly greater than the decrease seen with either ioxilan (10.2%) or iohexol (10.2%). All of the responses observed were transient and would not be of clinical concern in a healthy patient. Ioxilan, which contains the calcium binding agent, sodium citrate, and iohexol appear to cause less systemic effects then diatrizoate.

Animals

An in vitro study of the hemodynamic effects of catheter injections.

The injection jet from a catheter has been shown to elevate distal pressure and flow. These disturbances in flow present a problem for the application of digital arteriography to measure physiologic flow. The authors used an in vitro model to determine the primary factors responsible for the increases in distal flow with the goal that these disturbances might be estimated and minimized. Experiments were performed to evaluate the importance of the cross-sectional area of the catheter and vessel, the importance of absolute vessel flow, and the importance of distal resistance. A lumped resistance model predicted the flow changes to within 3% of the preinjection vessel flow. In the model system the elevation of distal flow in percent was equal to (the injection rate divided by the tube flow rate) multiplied by (the proximal resistance divided by the total resistance) multiplied by 100. Because the resistance ratio generally is small, injections at physiologic flow rates should produce acceptably small increases in distal flow. The use of a large diameter catheter or the presence of a proximal stenotic lesion would increase the ratio.

Catheterization, Peripheral

Role of angiotensin II in renal hemodynamic functions during the initial stages of acute ureteral obstruction.

This investigation examines the role of Angiotensin II in renal hemodynamic functions during acute unilateral ureteral obstruction (UUO) in a dog model. An electro magnetic flow probe was utilized to assess renal blood flow while the arteriovenous extraction technique of technetium 99m DTPA was utilized for the assessment of changes in filtration fraction and glomerular filtration rate. The effects of Angiotensin II receptor blockade on renal hemodynamic functions during acute UUO was evaluated in six dogs and compared to acute ureteral obstruction without receptor blockade in seven dogs. Angiotensin II blockade with (Sar1, Thr8)-Angiotensin II during UUO led to a striking increase in renal blood flow that was significantly different in comparison to normalized values from UUO alone (+delta 63 +/- 17 vs. +delta 22 +/- 6% at 30 min; p less than 0.05). There were, however, no significant differences in the magnitude of the decrease in filtration fraction and glomerular filtration rate in comparison to UUO alone. This investigation demonstrates that Angiotensin II has an inhibitory effect on the initial increase in renal blood flow with acute UUO. The possibility of successful pharmacologic intervention in the setting of UUO can be examined using animal models similar to the one described here. Pharmacologic treatment in the setting of acute UUO in patients might permit better preservation of renal function.

Angiotensin II