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In the case of a nuclear accident or a terrorist attack by a "dirty bomb," there is a risk of external and internal contamination with radionuclides in addition to external irradiation. Internal irradiation as a consequence of radionuclide incorporation is associated with a higher risk of stochastic radiation effects (e.g., tumors). Decorporation treatment will enhance the elimination of radionuclides and reduce the committed effective dose as a metric of stochastic health effects. Although treatment efficacy is better when started early, beginning the therapy without knowing the committed effective dose may unnecessarily expose the patient to the side effects of the medication. The question is: Delay the therapy to wait for the results of internal dosimetry or start the therapy promptly on spec? To prove insight into this question, a selective review of the literature was conducted. The importance of the initiation time of treatment in the efficacy of decorporation treatment can be explained with pharmacokinetic laws and first order processes determining the disposition of xenobiotics in the organism. Nevertheless, there is no internationally accepted standard on when to start a decorporation therapy (exception: iodide). The "precautionary approach," emphasizing the importance of the committed effective dose for the indication of treatment, is competing with the "urgent approach" advocating the administration of medication "a priori" within several hours. A review of the literature actually indicates that the most important drugs used for decorporation are well tolerated with few adverse effects. In consideration of the higher efficacy and the low side-effects of a short-term treatment, initiating decorporation therapy as soon as possible after internal contamination, even before the committed effective dose has been assessed, appears to be a reasonable approach. The decision of continuation or discontinuation of the therapy should be taken after internal dosimetry is completed on the basis of the committed effective dose.

In the case of nuclear incidents, radioiodine may be liberated. After incorporation it accumulates in the thyroid and by internal irradiation enhances the risk of cancer occurrence. By administering a large dose of non-radioactive iodine the uptake of radioiodine into the gland can be inhibited (“iodine blockade”). Biokinetic models using first order kinetics are not suited to simulate iodine blockade, as the uptake into the gland is mediated by a saturable active transport. Therefore, we integrated an uptake mechanism described by a Michaelis-Menten kinetic into a simple ICRP biokinetic model. We moreover added a total uptake blocking mechanism representing the Wolff-Chaikoff effect becoming active when the gland is saturated with iodine. The validity of the model was ascertained by comparison with IMBA software. The competition of radioiodine and stable iodine at the membrane carrier site was modeled according to the rate law for monomolecular reactions for competing substrates. Our simulations show that competition for the uptake at the membrane carrier site accounts for about 60% and the saturation of the gland with iodine for over 35% of the total protective efficacy that exceeds 95%. Following acute radioiodine exposure, it is preferable to administer a single large dose of stable iodine. In the case of continuous radioiodine exposure, a single dose of stable iodine is less effective than after an acute exposure and splitting the total available dose and shortening the dosage intervals enhance efficacy. Model-based simulations may be a useful tool to develop antidote dosage schemes for uncommon emergencies.

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Left ventricular pressure or coronary flow were not significantly affected by either treatment (p > 0.05). Epicardial NADH-fluorescence area and intensity were, however, significantly enhanced by NE (+22%) (P < 0.05), although propranolol, phentolamine and vitamin C had no significant influence on MI (P > 0.05). SOD had no significant effect on MI in control hearts (P > 0.05) but completely prevented MI enlargement by NE (P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

In the case of a nuclear power plant accident, repetitive/prolonged radioiodine release may occur. Radioiodine accumulates in the thyroid and by irradiation enhances the risk of cancer. Large doses of non-radioactive iodine may protect the thyroid by inhibiting radioiodine uptake into the gland (iodine blockade). Protection is based on a competition at the active carrier site in the cellular membrane and the Wolff–Chaikoff effect, the latter being, however, only transient (24–48 h). Perchlorate may alternatively provide protection by a carrier competition mechanism only. Perchlorate has, however, a stronger affinity to the carrier than iodide. Based on an established biokinetic–dosimetric model developed to study iodine blockade, and after its extension to describe perchlorate pharmacokinetics and the inhibition of iodine transport through the carrier, we computed the protective efficacies that can be achieved by stable iodine or perchlorate in the case of an acute or prolonged radioiodine exposure. In the case of acute radioiodine exposure, perchlorate is less potent than stable iodine considering its ED 50. A dose of 100 mg stable iodine has roughly the same protective efficacy as 1000 mg perchlorate. For prolonged exposures, single doses of protective agents, whether stable iodine or perchlorate, offer substantially lower protection than after acute radioiodine exposure, and thus repetitive administrations seem necessary. In case of prolonged exposure, the higher affinity of perchlorate for the carrier in combination with the fading Wolff–Chaikoff effect of iodine confers perchlorate a higher protective efficacy compared to stable iodine. Taking into account the frequency and seriousness of adverse effects, iodine and perchlorate at equieffective dosages seem to be alternatives in case of short-term acute radioiodine exposure, whereas preference should be given to perchlorate in view of its higher protective efficacy in the case of longer lasting radioiodine exposures.

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