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Distribution of 3H-Morphine after Lumbar Epidural Administration in Unanesthetized Rabbits
  1. B. C. Wang, M.D.*,
  2. D. E. Hillman, Ph.D.††,
  3. J. M. Hiller, Ph.D.##,
  4. C. Rosenberg, Ph.D.§,
  5. E. J. Simon, Ph.D. and
  6. H. Turndorf, M.D.*
  1. *From the Departments of Anesthesiology,
  2. **Psychiatry,
  3. Pharmacology,
  4. Physiology
  5. §Environmental Medicine, New York University School of Medicine, New York, New York.
  1. Address correspondence and reprint requests to Boardman C. Wang, M.D., Department of Anesthesiology, New York University School of Medicine, 550 First Avenue, New York, NY 10016.

Abstract

Background and Objectives. This study focused on the distribution of 3H-morphine in the spinal cord, roots, urine, and blood, after epidural administration in rabbits.

Methods. Under nitrous oxide, halothane, and oxygen endotracheal anesthesia, the cisterna magna of New Zealand albino rabbits was cannulated for cerebrospinal fluid sampling, and catheters were placed in the lumbar epidural space. Through the epidural catheter, 200 pmol of 3H-morphine contained in 500 μl of 1.3 mM (0.21 mg) morphine was injected. Arterial blood and cisternal CSF were sampled at 0, 5, 15, 30, 45, 60, 90, and 120 minutes after injection. Animals were killed with intravenous pentobarbital at the end of 120 minutes (n = 3), 6 hours (n = 4), and 12 hours (n = 2). In each animal the brain, spinal cord, spinal roots, liver, kidneys, and urinary bladder were removed.

Results. The injection site over the cord was identified and all tissues were immediately frozen at −70°C. Two-mm thick cross-sections, were taken from every centimeter of the spinal cord. Radioactivity in the series of sections was determined by scintillation spectroscopy. At 2 hours, 4.2% ± 1.1% of the injected radioactivity was recovered, and at 6 hours 1.6% ± 0.6% was recovered. Radioactivity was concentrated mainly around the lumbar injection site, and it decreased as the distance increased from the injection site and coincided with elapsed time after the injection.

Conclusion. Multiple linear regression analysis of radioactive labels showed the significant effect of time, distance from the injection site, and the time-distance interaction on the distribution of 3H-morphine in the spinal cord (p < 0.0001 for time and rostral and caudal distance from the injection site; and p < 0.0001 for interaction between time and distance.) A major portion of the injected radioactivity was recovered in the urine and a small amount in other tissues and body fluid: bladder, liver, spinal roots, kidney, plasma, and cerebrospinal fluid.

  • Rabbit model
  • epidural 3H-morphine
  • distribution
  • spinal cord
  • spinal roots
  • urinary excretion.

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Footnotes

  • The authors thank Dr. Bernard Pasternack, Professor of Environmental Medicine, New York University, for guidance in statistics, and Professor Sivam Ramanathan for help with computers.

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