Antidotes for Ricin Intoxication. Effects of Ricin on the Vascular Neuroeffector System.

摘要

The i.v. 48 hour (and 7 day) LD50 and the minimum lethal dose (MLD) of ricin in male New Zealand White rabbits has been determined by the Up and Down procedure. A MLD and a toxic sub-lethal dose (TSD) lowered blood pressure after a 12 hour or greater lag period, but only the MLD did so significantly (p < 0.05). Heart rate was increased when blood pressure was reduced, which seems to be a reflex effect, but the ECG was not altered. Abnormal laboratory values correlated well with histological findings. Serum CPK, SGPT, LDH, and cholesterol concentrations were higher and serum calcium concentrations were lower in rabbits given ricin. Rabbits that died earliest (approximately 22 hours after ricin) had marked pulmonary damage, while those that died later (36-48 hours after ricin) showed much more heart and liver damage. Ricin increased total blood flow to most organs. Exceptions were the brain and lungs, where the MLD markedly reduced blood flow. Ricin administration decreased the sensitivity of the central ear artery to norepinephrine (NE) (i.e., increased the EC50). Ricin increased methacholine (endothelium-dependent) relaxations of aorta rings, but did not alter those to papaverine. Ricin did not alter the activity of monoamine oxidase or catechol-O-methyltransferase, which metabolize NE. Ricin in some studies increased the amount of NE released by nerve stimulation, but did not alter NE reuptake by the neuronal membrane. Ricin did not alter basal calcium uptake by the aorta, but depressed stimulated calcium uptake in some studies. ...Ricin, Ricin in rabbits, Ricin cardiovascular effects, Ricin vascular tissue, Ricin neuroeffector mechanism, Ricin toxicity, Ricin on blood vessels, RA I, BD.