Abstract
Summary
Some biological properties of 3 batches of a multichain polyamino acid, multi-(copoly-L-glutamyl-L-aspartyl) poly-L-lysine, were examined in vivo in dogs and in rabbits. The polymer was administered intravenously as 2 to 3% solutions of its sodium salt by one or by repeated injections. In some animals hypovolemia was produced by arterial bleeding prior to infusion. A low-molecular weight fraction of the polymer, amounting to about 10 to 20%, was excreted in the urine within a few hours. The rest of the injected polymer was not excreted in the urine, and disappeared gradually from the blood, with a constant half-concentration time of about 48 hours. As shown by its influence on blood pressure and on hematocrit, the polymer was able to combat the manifestations of hypovolemic shock. However, severe toxic manifestations appeared in many animals, consisting of diarrhea, vomiting, loss of appetite, a transient drop in blood pressure and a tendency to capillary bleeding. Progressive weakness of the animals was observed, leading to their death. The cause of toxicity of these polypeptides has not been found. Possibly their multiple negative charges may be responsible. It appears worthwhile to examine non-charged or isoelectric polyamino acids with regard to their plasma expanding properties and their toxicity.
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