Penetration through the blood-brain barriers of cats after intracarotid injections of 125-I sodium diatrizoate, methylglucamine diatrizoate, or methylglucamine diatrizoate plus parabens and the retention of 131-I methylglucamine diatrizoate in the blood of rats.

Abstract

The experiments described below were performed in an effort to answer four questions: (a) To what extent does a tagged radiopaque diagnostic medium, injected into the carotid in a manner akin to that used for cerebral angiography in the clinic, penetrate the blood-brain barriers of cats? (b) Inferentially, would the degree of penetration be sufficient to account for toxic reactions occasionally encountered in the clinic? (c) Would parabens, a mixture of methyl and propyl parahydroxybenzoates, added as a preservative to a multidose container of such a medium, increase the degree of penetration of the blood-brain barrier? (d) Would the parabens delay the departure of intravenously injected medium from the blood of rats and perhaps increase thereby the ultimate uptake of medium by the brain? Methods Cats: The experiments were designed to measure the penetration of radioiodinated media from the blood stream into the brain. The media were labeled with iodine 125 (T∕2, fifty-seven and a half days) so that the tissues could be used for autoradiography. Cats rather than dogs were employed for the principal study because the anatomical arrangement of their cerebral arterial supply is closer to man's. Rats were used for supplemental experiments. Preliminary experiments made it clear the most troublesome problem was perfusing the cat's brain so it was completely free of blood before the tagged material in the brain itself was counted. Since most of the tagged material was still circulating in the blood, traces of blood in the brain would have given falsely high values for the amounts in its parenchyma. Eliminating all pressure on the cat's abdomen and elevating the head during the perfusion solved this problem by preventing gravitational drainage of facial or cervical venous blood into the cerebral venous system. Under these conditions the final milliliters of perfusate were water-clear, and no color of blood could be seen in the brain after it had been removed. Cats, anesthetized with sodium pentobarbital, received by way of the innominate artery 3 ml of a labeled radiopaque material, either 125I methylglucamine diatrizoate (125I MGD), 125I MGD plus parabens, or 125I sodium diatrizoate. The formulations of the media may be seen in Table I. Each injection lasted thirty seconds. Five minutes later a second 3 ml injection was made in the same way. Three minutes after the second injection, 1,000 units of heparin per kilogram was injected into the same site, and four minutes later a sample of blood was taken from the artery. A portion of this arterial blood was counted in a gamma spectrometer. The pump that had maintained respiration during this open chest maneuver was shut off, and the aorta was clamped off at the heart.