Local blood-brain barrier penetration following systemic contrast medium administration. A case report and an experimental study.

The present study was initiated by a severe complication in a patient with renal dysfunction who developed cortical blindness and weakness of her left extremities 30 hours following renal and abdominal angiography. To evaluate the impact of prolonged high serum concentrations of contrast medium (CM) this clinical situation was simulated in a laboratory model using sheep with elevated serum levels of contrast medium maintained for 48 hours. The experimental data did not support the theory that the prolonged exposure to high circulating levels of contrast medium (4 ml/kg body weight of meglumine diatrizoate 60%) is sufficient alone to cause penetration of the blood-brain barrier.

CT enhancement after prolonged high-dose contrast infusion in the early stage of cerebral infarction.

To demonstrate the BBB break-down on the CT image in the acute stage of cerebral infarction, a 3 hour continuous drip infusion of 200 ml of meglumine amidotrizoate, rather than the conventional bolus injection, was used. In this study, 22 examinations were carried out in 18 patients in whom cerebral infarction due to temporary or permanent obstruction of the cerebral artery was diagnosed by CT and angiography on admission. With each examination, the first CT was obtained prior to contrast infusion, and second immediately after the end of 3 hours of continuous contrast infusion. The EMI number was calculated at 3 regions of interest in the infarction. Within 3 days after stroke episode, 4 out of 5 patients with temporary vascular obstruction demonstrated enhancement, as well as 6 out of 9 patients with permanent vascular obstruction. Between 4 and 14 days after the stroke episode, all of 8 patients showed enhancement. To further clarify the extravasation of the contrast medium during the first 3 days of a cerebral infarction, a third CT scan was performed 3-hrs after finishing the contrast infusion in 4 patients. In these latter patients, blood was sampled at the time of each of the 3 CT series. The EMI number of the blood samples was also measured. In all 4 patients, the Gado's tissue-blood ratio (the EMI number of the CT lesion divided by that of the blood sample) was higher than 17.2% in the second, and higher than 54.7% in the third CT scan. Thus break-down of the BBB which was demonstrated by prolonged contrast infusion is an earlier event in human cerebral infarction than is usually accepted.

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.

Contrast enhancement pharmacokinetics of six ionic and nonionic contrast media.

The contrast enhancement of six contrast media (CM) was compared in 13 tissues of the rat after rapid intravenous bolus injection. The rats were sacrificed at 0 and 40 seconds and 2, 5, and 15 minutes after contrast injection. 125I labeled diatrizoate, metrizamide, ioxaglate, iohexol, iopamidol, and a nonionic dimer, iodecol, were each injected at a dose of 612 mg iodine per kg body weight, and iodine concentration (IC) and contrast enhancement were calculated from radioactivity measurements. Higher blood IC values were obtained with the nonionic CM; similar enhancement patterns were seen in the spleen, heart, lungs, and brain. Renal IC was directly related to the number of iodine atoms per ion or molecule of CM. In consequence, renal IC was inversely related to the CM osmolality, but no such correlation was seen with the blood IC. Metrizamide produced the greatest IC in the organs of the gastrointestinal tract. There was no apparent correlation of IC with molecular structure of physicochemical parameters of the CM in any of the other tissues studied.

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.

Proteinuria following nephroangiography. III. Role of osmolality and concentration of contrast medium in renal arteries in dogs.

Nephroangiography in dogs, with renal artery injections of Urografin 76%, resulted in massive albuminuria. Unilateral nephroangiography causes massive albuminuria only from the injected kidney. Significantly less albuminuria was caused by renal artery injections of a corresponding volume of a sodium chloride solution of equal osmolality or intravenous injections of twice that volume of Urografin 76%. Thus, the hypertonicity of the contrast medium is not the main cause of the albuminuria. The degree of albuminuria is related to the concentration of medium in the renal arteries and not to the amount excreted.

Intra-arterial bolus of 125I labeled meglumine diatrizoate. Early extravascular distribution.

A mixture of 125I labeled meglumine diatrizoate and 131I labeled human serum albumin was injected into the lower abdominal aorta of 30 anesthetized, laparotomized male rats. Measurements of the activities in cardiac blood and in different tissues of the hindlimbs and tests were perfomed at six time intervals ranging from 5 seconds to 2 minutes after injection, the determine early uptake and distribution volumes of diatrizoate. Concentrations and distribution volumes were initially much greater than values obtained after intravenous injection, but these differences had considerably decreased or disappeared by 2 minutes.

Intravenous bolus of 125I labeled meglumine diatrizoate. Early extravascular distribution.

A mixture of 125I labeled meglumine diatrizoate and 131I labeled human serum albumin was injected into the femoral vein of 26 anesthetized male rats. Measurements of the activities in cardiac blood and in different tissues of the lower extremity and in the testis were performed at time intervals ranging from 5 s to 5 min after injection. The determination of tissue uptake and distribution volumes of diatrizoate showed widely differing accumulation of contrast medium. Over 50 per cent of the intravenous bolus of diatrizoate was extravascular at 40 s.