Effect of Intracarotid administration of BCNU in rats

Abstract

Female Sprague-Dawley rats, weighing 212±21gm (SD) were used in the experiments. A chronic polyethylene cannula (PE 10) was inserted in the left common carotid artery and aortic arch for systemic BCNU administration and blood sampling. Besides a chronic cannula, an acutely placed PE 10 cannula in the internal carotid was used for BCNU administration into the brain. This cannula was removed after BCNU injection. The experimental animals received 10 mg/kg (0.68 ml) BCNU either into the internal carotid artery or systemically. The cannulated control animals received no drugs. Another group of the animals received only the BCNU solvent ethanol (0.6 ml of 10% solution). BCNU when injected either systemically or into the internal carotid artery decreased total white blood count (total WBC) with the largest drop occurring on the second day, reaching a level significantly lower than in control animals. Total WBC came back to normal values in both experimental groups after seven days. No thrombosis was found in the small vessels of the brain which we could interpret as being caused by the administration of the BCNU. A few vessels contained agglutinated erythrocytes both in the treated and in the control animals. This was interpreted as a post mortem change. After treatment with BCNU liver tissue was normal. The kidney tissue was necrotic, more so in systemically treated animals. Necrosis of the brain tissue was observed only after the internal carotid administration. Ethanol injected into the internal carotid did not induce any pathological changes in the brain tissue. The results indicated that the brain tissue in rats is more affected by intracarotid BCNU administration than when injected systemically and that internal carotid administration is less toxic to other tissues.