Contribution on the Thrombocytopenic Action of Urethane in Dogs*

Abstract

Thrombocytopenic purpura in dogs has been obtained by subcutaneous urethane administration (Cruz and Moussatch6, 1948). Suppurative reactions commonly occur in the skin ofthe experimental animals after a few injections. These reactions, possibly due to sensitization to the drug, are undesirable in experiments on the action ofurethane. The present paper deals with the results of urethane administration by vein, a route much more suitable for controlling the toxic doses. METHODSOur routine haematological technique has been described in a previous paper (Cruz, Silva, and Mello, 1945). We have estimated bleeding time according Duke's method (1910), coagulation time by Lee and White's method (1913), and clot-retraction by Macfarlane's method (1939). Urethane was used as a 60 per cent solution in distilled water. RESULTSWhen urethane is administered in high doses (0.4 g. or higher per kg. body weight) the animals usually eliminate faeces and urine immediately after the injections and show somnolentia followed by sound sleep for 10-15 minutes. This slight anaesthetic effect is of short duration, and animals become normal again after a drowsy period of about half an hour.No striking differences were observed between the action of urethane administered subcutaneously and intravenously so far as the time of the establishment of the purpuric picture or pathological findings are concerned.* Aided by a grant from Dr. Guilherme Guinle.The results of effective doses (0.4-0.5 g. per kg. body weight) administered to 5 dogs are shown in Table I. In 4 dogs platelets disappeared from the circulation between 6-9 days when bleeding time was already very much prolonged and the other signs of purpura were also present. The animals were sacrificed a few days later, and the haematological findings revealed a picture of severe anaemia. In one of these dogs platelets obtained by fractioned centrifugation of 50 c.c. of normal dog's blood were injected daily soon after the urethane administration in order to observe any eventual interference in the pathological picture. This preliminary experiment was completely negative. In another_dog (494-16) urethane was stopped after seven daily injections and blood changes were followed. Confirmation of other authors (Duke, 1911; Firket, 1922; and Tocantins, 1938) and our previous experiments concerning platelet regeneration have been verified. Normal platelet volume was attained 3-5 days after the beginning of the platelet regeneration, which only started 20 days after the absence of platelets in the peripheral blood. In one splenectomized dog (466-19) the evolution and the pathological picture were very similar to those of normal dogs treated with urethane (Table I).In order to ascertain the optimal doses to obtain the picture ofpurpura, higher and smaller doses than those described have been tried. As higher doses, we tried eight intravenous injections, each 0.4 g. per kg. body weight, within a period of 36 hours (dog 437-3) as well as two daily injections of a slightly higher dose (0.5 g. per kg...