Viruria has been demonstrated in many human and animal viral infections (1, 2). Preliminary studies in mice and rats by Schultz and Neva (3) established that virus passes from blood to urine within 30 minutes after intravenous injection under the conditions of their experiments. This viruria was referred to as "immediate viruria" and was considered to be distinct from the viruria that occurs during acute infections. In the present study, dogs were used in experiments that were technically too difficult to be carried out in smaller laboratory animals. Renal physiological and virological techniques were combined to study the mechanisms of virus clearance from the blood by the kidney and to establish the locus in the nephron where virus gains entry into the urine. Previous studies of a similar nature include those of Keller and Zatzman (4), who injected Bacillus megatheriumi phage and studied its renal excretion and distribution in the liver and spleen of dogs. Petrov (5) used injection of bacteriophage of Escherichia coli in dogs to establish clearance values for these virus particles. Although Schultz and Neva (3) were unable to determine the renal contribution to viruria in rats, they observed that the rat bladder is permeable to small numbers of virus particles.Our present studies demonstrate that Coxsackie B-1 virus (a small enterovirus) can pass rapidly * Submitted for publication May 3, 1965; accepted August 19, 1965. This investigation was supported by U. S. Public Health Service research grants H7057 and H5860 from the National Heart Institute, and AI 4760 from the National Institute of Allergy and Infectious Diseases.Presented in part before the Fifty-fifth Annual Meeting of the American Society for Clinical Investigation, Atlantic City, N. J., April 1963, and abstracted in J. dlin. Invest. 1963, 42, 931. t (7). The catheter within the right renal artery was attached to a constant infusion pump, and a 0.9% NaCl' solution containing 0.01 mg per ml heparin sodium was infused at 1.23 ml per minute.Through an abdominal incision, no. 240 polyethylene catheters (i.d., 0.066 inch; o.d., 0.095 inch) were placed in the upper portions of both ureters. After 60-to 90-minute intervals, urine specimens were examined for microscopic hematuria (more than a rare erythrocyte per high power field in a centrifuged specimen) before control periods were collected. The experiments to be reported were selected from an original total of 23 dogs. Reasons for discarding the experimental results from the other animals included gross hematuria (four animals), microscopic hematuria (two animals), questionable renal arterial catheter placement (two animals), and postmortem evidence of severe diffuse renal disease without hematuria (one animal). An infusion of 15% mannitol into a cephalic vein usually was given to insure good urine flow rates; in some of the stop-flow experiments this infusion rate was as high as 14 ml per minute.The virus inoculum described below was first introduced into the tubing leading to the renal artery...
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