Quantitation of myocardial perfusion by contrast echocardiography: analysis of contrast gray level appearance variables and intracyclic variability.

Hand-agitated diatrizoate meglumine/diatrizoate sodium (MD-76) was injected above the aortic valve in seven dogs during two-dimensional echocardiographic imaging to determine the ability of contrast appearance variables (i.e., peak background-subtracted gray level intensity, time to peak contrast appearance and maximal slope of the contrast appearance curve) to predict myocardial blood flow. Regional perfusion was altered by a critical coronary stenosis (around the left anterior descending coronary artery) or by administering intracoronary adenosine (into the left circumflex coronary artery), or both. Changes in regional blood flow between control and interventions were compared with the changes in the contrast appearance variables. In addition, the ability of intracyclic variability of gray level intensity to predict myocardial perfusion was assessed. In the determination of absolute myocardial perfusion, background-subtracted peak gray level intensity and the maximal slope of the appearance curve demonstrated a fair correlation (r = 0.67 and 0.51, respectively, p less than 0.0001). However, time to peak contrast appearance did not correlate (r = 0.14, p = 0.31). Intracyclic variability of gray level intensity at control (before contrast injection) and after contrast injection also did not correlate with perfusion (r = 0.18 and 0.06, respectively). In the evaluation of relative changes in myocardial blood flow, the percent change in the maximal slope of the appearance curve correlated with the percent change in blood flow (r = 0.77, p less than 0.0001). Seven of the eight regions with greater than 3.5-fold increase in blood flow were identified by an increase in maximal slope of greater than 50%.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug and fatty acid effects on serum thyroid hormone binding.

We directly compared the competitor potency for serum T4 binding of 11 nonsteroidal antiinflammatory drugs; the diuretics furosemide, ethacrynic acid, and bumetanide; diphenylhydantoin; the cholecystographic contrast agents iopanoate and ipodate; and six long-chain nonesterified fatty acids (NEFA) using equilibrium dialysis. To avoid artefacts that occur in competitor studies with diluted serum or isolated binding proteins, we used undiluted normal serum, with drugs added at concentrations that achieved high therapeutic total and free serum levels at equilibrium. Drug addition was based on the measured free fraction of each drug in serum. The free T4 fraction in normal serum (Tris buffer, pH 7.4; 37 C) was between 1.40 X 10(-4) and 1.53 X 10(-4). Drug-induced increases in T4 free fraction were: fenclofenac, 90%; aspirin, 62%; meclofenamic acid, 39%; diflunisal, 37%; mefenamic acid, 31%; and furosemide, 31%. Significant increases of 7-15% occurred with diclofenac, flufenamic acid, phenylbutazone, and diphenylhydantoin. Indomethacin, ketoprofen, tolmetin, ethacrynic acid, bumetanide, iopanoate, and ipodate were inactive at the concentrations studied. Addition of 2.0 mmol/L oleic acid had a negligible effect, but 3.5 mmol/L oleic acid inhibited T3 and T4 binding significantly. Other long chain NEFA (addition of 1.5 mmol/L) gave increases in free T4 fraction as follows: arachidonic acid, 26%; linolenic acid, 23%; and linoleic acid, 11%. Stearic and palmitic acids were inactive. The effect of 5 mmol/L oleic acid in serum could be reproduced by addition of 0.5 mmol/L to serum diluted 1:10, indicating that protein binding of NEFA is the major determinant that limits their competitor potency. These findings provide a basis for anticipating which potential inhibitors may cause important changes in serum thyroid hormone binding. The time course of such effects will be influenced by the pharmacokinetics of the inhibitor itself as well as the equilibrium findings described here.

Contrast media for CT. An analysis of the early pharmacokinetics.

Iohexol and meglumine-sodium diatrizoate were injected intravenously into 18 pigs as either a 99:1 or 1:99 mixture. Blood samples were taken for 30 minutes and the concentration of each of the two contrast media was measured by means of a double labeling technique with 125I and 131I. Relative concentrations of iohexol were significantly higher during the first 3 minutes when it was injected as a moderately hyperosmolar (99% iohexol) solution than when it was injected as a very hyperosomolar (99% diatrizoate) solution. The greater intravascular dilution of the 99% diatrizoate solution by extravascular water may explain this finding as well as the significantly longer rapid disposition phase and the slightly lower distribution volume of iohexol.

Cardiovascular radiology. Subcellular localization of uro-angiographic contrast by 125I-labeled media.

Various uro-angiographic contrast media have been injected in the rabbit. The partition at the organ level and in subcellular fraction has been studied. Blood enzymatic inhibition with specific enzymatic systems is reported.

Pharmacokinetics of lopamidol after intrathecal administration in humans.

The kinetics of iopamidol, a new nonionic radiocontrast agent, were evaluated in 10 patients undergoing lumbar myelography. The doses of iopamidol administered intrathecally were 11 and 15 ml of a 200-mg iodine per ml solution in one and nine patients, respectively. Radiographs were made within 30 to 40 min and CTs were taken at about 1, 6, and 23 hr after iopamidol administration. The diagnostic quality and usefulness of the conventional and CT myelograms were considered excellent. In the lumbosacral subarachnoid space, the densitometry CT readings were maximal at 1 hr, whereas in the cervical subarachnoid space, peak CT values were reached at 6 hr. Plasma and urine samples were taken at frequent intervals up to 48 hr after the contrast agent was administered. Peak plasma levels of iopamidol were observed at 2.9 hr and were no longer detectable at 48 hr. The 48-hr urinary recovery for all patients averaged 66 +/- 8% of the dose. In all but one patient, iopamidol was cleared almost completely from the CSF within 24 hr. Side effects after iopamidol administration were transient and minor, and were not related to the CT readings or its systemic clearance.

Absorbed dose in the presence of contrast agents during pediatric cardiac catheterization.

Administration of x-ray contrast agents during heart catheterization examination increases the absorbed radiation dose in tissue. To estimate the dose absorbed by the blood of children undergoing diagnostic heart catheterization and angiocardiography, a number of measurements and calculations were conducted. First, entrance and exit exposures to the patient were measured with thermoluminescent dosimeters calibrated for the diagnostic x-ray energy range. Second, a dose enhancement factor was calculated from mass energy absorption coefficients for various concentrations of the contrast media and at selected x-ray energies. Third, the dose enhancement factor was estimated from survival of peripheral blood lymphocytes suspended in varying concentrations of the contrast agent during exposure to graded doses of x-rays. Fourth, a mean absorbed dose to the patient's blood was calculated using (a) the dose enhancement factor determined above, (b) an estimate of the mean exposure in the irradiated body volume calculated from the entrance and exit exposure measurements, (c) an effective iodine concentration in the blood during the exposure time, and (d) a ratio correcting for the distribution and circulation of the blood. For eight pediatric patients monitored, absorbed doses to the blood ranged between 3 and 12 rad. These values were two to three times greater than the expected dose without administration of a contrast agent.

The binding of intravenous and oral biliary contrast agents to human and bovine serum albumin.

The binding of two homologous series of oral and intravenous biliary contrast agents to human and bovine serum albumin was investigated using the gel filtration technique. All intravenous compounds are bound to human serum albumin via one high affinity and several low affinity binding sites. Within the concentration range investigated, about 3--5 high affinity binding sites for the oral compounds were found on human serum albumin. In general, the intravenous compounds have a greater affinity for human serum albumin than the oral compounds. No significant differences were found for the binding of the oral compounds to human or bovine serum albumin, while the intravenous compounds have a higher affinity for bovine than for human serum albumin. The significance of the plasma protein binding of the biliary contrast agents for the hepatic uptake is discussed.

Optical studies on interaction of biliary contrast agents with native and modified human serum albumin.

The interaction of two homologous series of biliary contrast agents with native human and bovine serum albumin and with modified human serum albumin was investigated using circular dichroism and equilibrium dialysis. For most derivatives, extrinsic Cotton effects were observed for the interaction with both albumins. In some cases, these effects were strongly affected by only small changes in the chemical structure of the drugs. These large differences in extrinsic Cotton effects can be explained by definite effects of the chemical structures on the binding site selectivity of some drugs. For example, iopodate preferentially binds to the warfarin binding site of human serum albumin, while an ethyl group into the propionic acid side chain reduces the affinity for the warfarin site but strongly increases the affinity for the diazepam binding site of human albumin.

[The use of contrast media in computer tomography (author's transl)]. / Möglichkeiten der Kontrastmittelanwendung bei der Computertomographie.

There are a variety of applications for contrast media in CT. They can be used for better anatomic demonstration or for showing pathological processes. Nearly all available contrast media may be found useful. Intravenously injected renographic contrast media are most commonly employed. In addition to their inherent contrast, specific pharmaco-kinetic changes may be of diagnostic value. This adds some knowledge of function to the purely morphological information obtained by computer tomography. For this purpose, contrast has to be injected rapidly and a fast scanner must be used (so-called angio-CT).

The determination of commonly used iodinated contrast media in postmortem samples using HPLC and TLC.

A rapid micro method is described for the determination of diatrizoic, iothalamic, ioxaglic, and iopanoic acids in postmortem liver and blood. The compounds were extracted with methanol and analyzed by high performance liquid chromatography using a C18 column. The mobile phase consisted of methanol:PIC A with ultraviolet detection at 232 and 242 nm. Recoveries of about 85% were obtained. A thin layer chromatographic system is described which separates the four compounds. The spots were hydrolyzed and sprayed with a diazonium coupling reagent to produce colored spots with sensitivities of 0.02 to 0.1 micrograms. Postmortem levels are given for two deaths involving diatrizoic acid.

The interaction of iopanoic and iophenoxic acids with human serum albumin.

Iopanoic and iophenoxic acids are strongly bound to human serum albumin, as revealed from ultracentrifugation experiments. About two or three high affinity binding sites were found for both drugs. Within the concentration range investigated iopanoic acid is stronglier bound than iophenoxic acid. The binding to only one of the high affinity binding sites produces extrinsic Cotton effects. Further saturation of the high affinity binding sites decreases the extrinsic Cotton effects, possibly due to a binding induced change of the protein conformation.

Competition for binding to multiple sites of human serum albumin for cholecystographic agents and sulfobromophthalein.

The binding of two cholecystographic agents, iophenoxate and iopanoate, to human serum albumin was studied with 11 putative competitors; the results were qualitatively consistent with competitive binding to common sites. A more precise analysis of competition was achieved with four pairs of compounds for which the free and bound concentration of each was determined. The results were analyzed by a computer program and the dissociation constants calculated for both binder and competitor at specified sites on albumin. With numbering based on the rank order of dissociation constants for iophenoxate, the highest binding of the four compounds occurs at different sites: iophenoxate at site I; iopanoate at site II, sulfobromophthalein at site III; and bromphenol blue at site II. For a given compound, there is close agreement in the calculated affinities at different sites regardless of the competitor.

Volume of distribution of contrast media in blood.

The volume of distribution of diatrizoate and iodipamide in blood in relation to hematocrit and contrast concentration was measured using 125I-labeled compounds. In concentration obtained after intravenous injection, the percentage volume of distribution of both contrast media is 100 minus hematocrit, except for high hematocrit values, which may cause uneven distribution of contrast media in smaller concentrations. No evidence of intracellular penetration was obtained.

Opening of the blood-brain barrier by intravenous contrast media in euvolemic and dehydrated rabbits.

It has been suggested that intravenous injections of hypertonic contrast media when used in computed tomography and digital subtraction angiography might raise plasma osmolality sufficiently to open the blood-brain barrier (BBB). The current investigation establishes the threshold of plasma osmolality that causes the the opening of the BBB in euvolemic and dehydrated rabbits. Euvolemic rabbits were allowed food and water ad libitum. Dehydrated rabbits received 4.0 mg/kg of furosemide intramuscularly and were deprived of water for 72 hours. Meglumine/sodium diatrizoate 76 per cent (n = 28) or mannitol 20 per cent (n = 12) was administrated intravenously, at a rate of 25 mmol/kg body weight/hour for 2, 3 or 4 hours. Plasma osmolality, blood iodine concentration, blood pressure, heart rate and hematocrit were assessed at regular intervals. Evans blue and 99Tcm-DTPA were used simultaneously as tracers for BBB opening. Rating of BBB opening with 99Tcm-DTPA correlated well with Evans blue staining (r = 0.863, p less than 0.001; n = 42). BBB opening was related to plasma osmolality and was similar for both contrast media and mannitol. Widespread BBB opening occurred above 400 mmol/kg while focal BBB opening occurred above 370 mmol/kg. Dehydration per se increased plasma osmolality but did not reduce the threshold for BBB opening.

Continuous infusion urography in unilateral hydronephrosis.

In cases of unilateral hydronephrosis the urine concentration of contrast medium, for example diatrizoate, depends on the remaining renal function, the rate of turnover in the obstructed renal pelvis and the function of the contralateral kidney. Contrast medium for a single injection or a short infusion time is rapidly excreted by the normal contraleteral kidney, without allowing high enough plasma levels long enough for sufficient urine concentrations in the hydronephrotic kidney. This excretion rate can be compensated for by continuous infusion urography for several hours with large doses of contrast medium (up to 1,250 ml. 30 per cent diatrizoate). This method was theoretically computerized, tested in animals experiments and clinically used in 11 patients. It can improve the diagnostic possibilites of excretory urography, especially in cases of unilateral obstruction, and can minimize the need for retrograde pyelography with its known complications.