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Biomedical subjects

K Golman

Publications and source records attributed to K Golman.

90 records · Page 5Linked to original sources

The blood-brain barrier: effects of nonionic contrast media with and without addition of Ca2+ and Mg2+.

Trypan blue and 197HgCl2 were used as markers of the increased leakage through the blood-brain barrier which developed after selective injection of different contrast media formulations into the internal carotid arteries of rabbits. Interest was focused on a new, experimental, nonionic medium (C-29) and possible effects resulting from the addition of Ca2+ and Mg2+ to nonionic contrast media. Using 197Hg, it was possible to quantitate the increase in extravasation produced by the contrast media. C-29 caused less damage than either metrizamide or meglumine iothalamate. The addition of Ca2+ and Mg2+ to nonionic contrast media seemed to stabilize the blood-brain barrier.

Animals↗

Proteinuria produced by urographic contrast media.

All angiographic and urographic procedures expose the kidney to high contrast medium concentrations. The introduction of the triiodinated ionic contrast media has lowered the risk of contrast medium-induced renal damage. An increase in dose and use of "bolus urography" have, however, led to an increase in frequency of reports on renal damage following intravenous pyelography and angiography. The low general toxicity of the new nonionic contrast media should also include a lower toxicity towards the kidneys. The media are, however, concentrated in the kidney to twice the concentration of the ionic media, and this might blur the expected reduction in kidney toxicity. The authors examined this problem by studying enzymuria in rabbits and albuminuria in rats after injection of different ionic and nonionic contrast media. In the rabbit, the model should imitate a urography and in the rat, a nephroangiography. All contrast media resulted in enzymuria and albuminuria, but to different degrees. The time for maximum enzymuria differed from the time of maximum albuminuria. The proteinuria does not appear to be related to the osmotic pressure of the injected contrast medium. The clinical significance of these findings is discussed.

Acute Kidney Injury↗

Metabolism of urographic contrast media.

The metabolism of ionic and nonionic contrast agents was examined in the rabbit and in humans by specific measurement of iodide present in urine at different time intervals after injection of high contrast medium doses. Interest was focused on the experimental model compound C-29, which was investigated using a 125I-labeled compound, permitting a study of iodide release and the appearance of other metabolites in serum, bile, and urine from rabbits. Large, quantitative, individual variations were found, but in most cases th urine collected from both rabbits and humans contained more iodide than had been injected. A mean of 0.07% of total injected iodine was found within three days after injection of the ionic contrast medium metrizoate. The results with rabbits indicated that this figure may increase to 1% using the nonionic media tested. Direct evidence of metabolism of C-29 was found in bile, where up to 35% of the total radioactivity present in the bile 4-6 hours after injection was identified as a metabolite.

Animals↗

Contrast media-induced nephrotoxicity. Survey and present state.

Reports of renal failure induced by contrast media are increasing. Adverse effects of contrast media on kidney function include diuresis, changes in renal blood flow, osmotic nephroses, albuminuria, enzymuria and, most important, glomerular filtration rate. Animal studies indicate that the new nonionic contrast medium, iohexol, has fewer adverse effects on kidney function than the ionic media currently used. Three clinical studies offer some evidence of the effect of iohexol on renal function, but it is not yet possible to conclude that lower nephrotoxicity found in animals will also be found in man. Further clinical studies are warranted, and careful monitoring of contrast media clearance is recommended in all high-risk patients.

Acute Kidney Injury↗

Renal function following nephroangiography with metrizamide and iohexol. Effects on renal blood flow, glomerular permeability and filtration rate and diuresis in dogs.

The non-ionic ratio 3.0 contrast media metrizamide and iohexol used in high-dose unilateral nephroangiography in dogs produce homogeneous nephrograms and no marked effects on renal blood flow, glomerular filtration rate, and osmotic diuresis, in contrast to previously reported results using the same technique with iodine-equivalent doses of the ionic ratio 1.5 contrast medium diatrizoate (25). Iohexol affected glomerular permeability significantly less than metrizamide and diatrizoate.

Albuminuria↗

Comparison between EEG and observation of rabbit behaviour in evaluation of subarachnoid neurotoxicity of metrizamide.

The non-ionic contrast medium metrizamide (370 mg I/ml) was injected into the cisterna magna of rabbits at 2 dose levels (0.1 ml/kg and 0.5 ml/kg) to investigate whether visually evaluated EEG can detect neurotoxicity at a lower dose level than a method based on observation and ranking of signs of excitation and depression in animal behaviour. Half of the metrizamide injections were made without anaesthesia, whereas the remaining injections were made during a short alphadolon/alphaxolon anaesthesia. EEG and animal behaviour were followed for 24 h after the injection of metrizamide. At the low 'clinical' dose, EEG could not detect statistically significant neurotoxicity, neither in anaesthetized nor in non-anaesthetized rabbits. Observation of animal behaviour, however, could detect statistically significant signs of depression in animals that had been anaesthetized. At the high dose level, both methods could detect significantly more serious symptoms of neurotoxicity than at the low dose level.

Anesthetics↗

Acute renal failure in rats. Interaction between a contrast medium and renal arterial occlusion.

Acute renal failure is a serious complication of reconstructive aortoiliac surgery. The question was raised whether its etiology includes interaction between preoperative angiographic contrast medium and intra-operative clamping of the renal arteries. Renal arteries of 180 rats were bilaterally clamped 10 to 120 min and serum urea was determined from 3 h to 7 days later. In 35 rats 40 min clamping alone produced an increase in urea reaching a maximum 1 day later (median increase 70%). In 3 groups of 12 rats intravenous injection of the contrast medium metrizoate alone in doses 1, 2 and 3 g I/kg body-weight produced no significant increase in urea. Intravenous injection of the same doses to 3 groups of 10 rats each followed 1 h later by renal arterial occlusion for 40 min produced median urea increases one day later of 110, 130 and 170 per cent, respectively, in the 3 groups. The increase was higher than that produced by contrast medium alone (p less than 0.01) or by renal artery clamping alone (p less than 0.05) indicating a potentiation of transient renal failure by the combination of contrast medium and renal arterial clamping.

Acute Kidney Injury↗

Metrizamide in experimental urography. IV. Effects of bilateral ureteric stasis on urine iodine concentration after intravenous infection of an ionic and a non-ionic contrast medium.

The non-ionic contrast medium metrizamide was compared to the sodium salt of diatrizoate to investigate the potential usefulness of metrizamide in clinical urography when ureteric stasis is applied. After intravenous injection of the contrast media to rabbits at dose level 175 mg I/kg, the kidneys were subjected to temporary bilateral ureteric stasis. Urine was collected through ureteric catheters and analyzed for its concentration of iodine, sodium and potassium. After metrizamide injection the urine iodine concentration was twice as high as after sodium diatrizoate injection. This difference between one non-ionic and one ionic contrast medium was larger than what has been reported earlier during free flow of urine at the same dose. Furthermore, during the periods of ureteric stasis metrizamide was excreted faster than diatrizoate. When diatrizoate was given as its sodium salt, the sodium given was excreted at about the same rate as the diatrizoate given.

Animals↗

Nephrotoxicity of cyclosporin A and contrast media. A comparison between diatrizoate and iohexol in rats.

Urine profiles (albumin, glucose, NAG, LDH, GGT and sodium) were followed for 22 h or 8 days after intravenous injection of diatrizoate, iohexol or saline in 30 adult Wistar rats in which nephrotoxicity was induced by daily peroral administration of 25 mg/kg body weight cyclosporin A over a 14-day period. Another 10 rats which had the vehicle of the cyclosporin A solution (placebo) and saline injected intravenously served as controls. The effect of iohexol and saline on the albumin excretion was similar, whereas diatrizoate increased it significantly. Both contrast media caused significantly increased excretion of all three enzymes. The contrast media had no effect on the excretion of glucose and sodium. Except for the fact that the excretion of NAG was significantly higher following iohexol than following diatrizoate 24 to 46 h after injection no significant differences between the two media were found from 24 h after injection among the rats given cyclosporin A. No contrast medium related changes were found by light microscopy of the kidneys. Neither iohexol nor diatrizoate potentiate acute cyclosporin A nephrotoxicity.

Acetylglucosaminidase↗

Effect of diatrizoate on renal extraction of PAH in man.

The effect of diatrizoate on the renal extraction of para-amino hippurate (EPAH) was studied in 8 healthy male volunteers. The contrast medium was injected into an antecubital vein and into a renal vein in each individual. A single-injection technique for the determination of EPAH was used and EPAH was measured before and over a period of 30 min after each contrast medium injection. In addition, the renal extraction of diatrizoate was measured simultaneously. Small but significant and similar decreases in EPAH were observed after both antecubital and renal venous administrations of the contrast medium, with a duration of less than 30 min after the injection. The renal extraction ratio for the diatrizoate was 0.20. It is concluded that diatrizoate should not be used before the determination of EPAH, at least not until 30 min after the administration of the contrast medium. The decrease in EPAH caused by diatrizoate seems to be due to a direct tubular depressant effect.

Adult↗

Influence of urography on renal function in children. A double blind study with metrizoate and iohexol.

Thirty-two children were given either metrizoate or iohexol for urography in a double blind study. Mild to moderate adverse reactions were observed in all patients receiving metrizoate (15/15) and in 4 receiving iohexol (4/17). Alkaline phosphatase in urine was significantly increased 4 hours after the injection of both media, but had returned to pre-injection levels 16 hours later. The excretion of beta 2-microglobulin and albumin was not altered. In 9 children in the metrizoate group and 11 in the iohexol group the glomerular filtration rate (GFR) was determined before urography by the single injection 99Tcm-DTPA-technique and 3 to 4 hours after urography by measuring the plasma disappearance of the contrast medium with the x-ray fluorescence technique. No reduction of GFR was observed.

Adolescent↗

Acute renal failure in rats. Interaction between contrast media and temporary renal arterial occlusion.

It was demonstrated in rats that renal injury which follows transient renal hypoxia is potentiated by the contrast media metrizoate, ioxaglate, iopamidol and iohexol. Intravenous injection of 1 g I/kg of all four media alone to 82 rats caused no significant increase in serum urea 1, 3 and 7 days later. The percentage increase of serum urea is given in median values and interquartile range (in parentheses). Bilateral renal arterial occlusion alone for 40 minutes in 42 rats increased serum urea one day later by 40 per cent (20-130). Intravenous injection of the media followed in one hour by bilateral renal arterial occlusion for 40 minutes in 104 rats caused serum urea to increase one day later by 130 per cent (70-350) after metrizoate, by 220 per cent (50-380) after ioxaglate, by 290 per cent (60-420) after iopamidol and by 160 per cent (50-330) after iohexol. There were no significant differences between the potentiating effects of the various media on ischemic renal failure.

Acute Kidney Injury↗

Addition of local anesthetics to contrast media. I. Effects on patient discomfort and hemodynamics in aortofemoral angiography.

Effects of equiosmolar solutions (osmolality 1.35 mol/kg) of the ratio 1.5 contrast medium metrizoate (250 mg I/ml) containing either the local anesthetic mepivacaine or saline were evaluated on subjective discomfort, aortic blood pressure and heart rate in 17 patients referred for aortofemoral angiography due to intermittent claudication. Each patient was injected with 30 ml (15 ml/s) of each solution in random double-blind order. Each patient was then injected with 45 ml (12 ml/s) of the ratio 3 medium ioxaglate (320 mg I/ml, osmolality 0.58 ml/kg). Ioxaglate caused significantly less total discomfort, pain, heat, vocal reactions, involuntary movements and hemodynamic effects than metrizoate-mepivacaine and metrizoate-saline. The effects of the two metrizoate solutions did not differ significantly. Previous contradictory reports on the effects of anesthetics in contrast media were reviewed with regard to experimental design, different osmolality of the test and control solutions, premedication, and pH dependence of local anesthetics. Ratio 3 media are recommended because they produce a more reliable relief of patient discomfort and fewer hemodynamic changes than the addition of local anesthetics to ratio 1.5 media.

Adult↗

Estimating kidney function during urography. Comparison of contrast medium clearance and simultaneous 51Cr-EDTA clearance.

Blood samples were taken from 21 subjects at 2 to 4 hours after simultaneous injection of contrast medium (metrizoate) for urography and 51Cr-EDTA. Clearance calculations were performed using the single injection (single slope) technique. The plasma concentrations of 51Cr-EDTA and contrast medium were measured by gamma counting and X-ray fluorescence analysis, respectively. A good correlation was found between the clearance of 51Cr-EDTA and clearance of contrast medium (r = 0.94).

Adult↗

Addition of local anesthetics to contrast media. II. Increase of acute mortality in mice with intravenous contrast administration.

The acute intravenous toxicity (i.v. LD50) of solutions of the ratio 1.5 contrast media metrizoate or diatrizoate and the ratio 3.0 contrast medium metrizamide was determined in mice with and without the addition of local anesthetics to the solutions. The two local anesthetics mepivacaine or lidocaine were added to final concentrations up to 2.0 mg/ml of the contrast medium solutions. This corresponds to clinically used concentrations. All additions of local anesthetics to the solutions increased the mortalities caused by the contrast medium solutions. Addition of local anesthetics to a final concentration of 2 mg/ml approximately doubled the acute intravenous toxicity of the contrast media. The ratio 3 contrast media produce less hypertonic solutions than the ratio 1.5 contrast media and should be preferred for angiography because they cause less pain and do not require the addition of local anesthetics which increase the acute toxicity of the solutions.

Anesthetics, Local↗

Renal excretion mechanism of a nonionic contrast agent.

The renal excretion mechanism of a nonionic experimental contrast agent, C-29, was investigated in rabbits in comparison with the ionic contrast agent sodium diatrizoate under conditions of free urine flow and ureteral stasis. The two contrast agents were injected as a mixture of 125I-C-29 and 131I-sodium diatrizoate, in doses of 25 and 250 mg I/kg. The results indicate that, during the period relevant for urographic examinations, C-29 may have a renal clearance as low as 0.7 times that of sodium diatrizoate under conditions of both free urine flow and ureteral stasis. The biologic half-life of C-29 is 41-50 min.

Animals↗

Noninvasive estimation of kidney function by x-ray fluorescence analysis. Elimination rate and clearance of contrast media injected for urography in man.

A noninvasive method for the estimation of kidney function is described. The use of radioactive tracers and the sampling of plasma and urine are omitted. The method has been used in patients referred for urography and who had therefore been injected with routine amounts of iodine-containing urographic contrast medium. After urography, the elimination rates of urographic contrast medium from both serum and finger tissue were determined and compared during a 2-hour period that began two hours after injection of contrast medium. The elimination of iodine in finger tissue was measured noninvasively using x-ray fluorescence analysis. A strong degree of correlation was found between the elimination rates from serum and finger tissue and between the total clearances calculated from the serum and finger measurements. Thus, after urography estimation of kidney function may be obtained as a fringe benefit by x-ray fluorescence measurements of the elimination rate of an iodine-containing contrast medium from tissue or from serum.

Adolescent↗

Noninvasive estimation of kidney function by x-ray fluorescence analysis: biological half-time and clearance of contrast material in rabbits.

A noninvasive method for glomerular filtration rate-determination, in which the use of radioactive tracers and sampling of plasma and urine can be omitted, is described. After injection of iodinated contrast material in rabbits, the iodine content of tissue, serum, and urine is measured by means of x-ray fluorescence analysis. The disappearance rates of iodine in tissue and serum are found to be the same, and a strong correlation is found between clearance values calculated from serum and tissue measurements. This indicates the possibility of evaluating kidney function by x-ray fluorescence analysis of contrast material in tissue only.

Animals↗