The Intravenous Injection of Bovine Crystalline Pancreatic Desoxyribonuclease into Patients1

Abstract

The intravenous injection of bovine crystalline pancreatic desoxyribonuclease (PD) into man in doses up to 2 million units, evoked no demonstrable toxic reactions either general, local, or of the hematopoietic system. The introduction of the enzyme intrathecally into adults and children with normal meninges, in an average dose of 50,000 units was accompanied by slight changes in the cytology and total protein of the cerebro-spinal fluid. An occasional transient reduction in the cerebro-spinal fluid pressure was also noted. No irritative effect was observed following intrathecal injections of PD into patients with meningitis. The blood level 1 hour following an intravenous injection of 1 million units averaged about 30 units/ml of serum and fell to near normal values within 24 hours. The measured level of PD in the serum was found to be partially dependent upon the amount of an inhibitor for PD present in the circulating blood of the patients. The inhibitor proved to be a heat labile, nondialyzable protein that combined reversibly with PD in a readily dissociable complex. PD in an active form was excreted in the urine following its injection intravenously in patients. Following rapid injections, about 8% of the intravenous dose was excreted 10-12 hours post-injection. The renal excretion of this protein of the albumin type presents certain unusual aspects which are discussed. Endogenous desoxyribonuclease was also found to be excreted in the urine of normal individuals. Intravenously injected PD diffused readily into the peritoneal and pleural fluids, wound exudates, and bronchial secretions. A dosage of 1 million units gave a range of diffusion of 0.1-3.2 units/ml. The enzyme also diffused into the cerebro-spinal fluid, but in smaller amounts and with some irregularity. In 13 patients serologically studied, no specific antibody was demonstrable in 10; in the remaining 3 patients, only low titers occurred. The potential therapeutic implications associated with the unusual excretion and diffusion of PD are discussed.