Metal distribution patterns in tissues from implanted Sprague-Dawley rats

Abstract

Background: Injuries with fragments of embedded metal are a common occurrence in armed conflicts. Unfortunately, the list of metals encountered on the modern battlefield are practically endless while the short- and long-term health effects, especially when embedded as in a shrapnel wound, are not well understood. One of the major concerns with these types of injuries is the solubilization of the embedded metal and the translocation and deposition to various organs of the body. Methods: Using a rodent model system developed in our laboratory to assess the health effects of embedded metal fragments, we surgically implanted metal pellets into the gastrocnemius muscles of male Sprague-Dawley rats. Test metals were chosen from a list promulgated by the U.S. Department of Defense as “metals of concern” with respect to embedded fragment wounds and included tungsten, nickel, cobalt, iron, copper, aluminum, lead, and depleted uranium. Tantalum was used as a control metal. Cohorts of the metal-implanted rats were humanely euthanized at 1, 3, 6, and 12-months post-implantation and a variety of tissues collected and analyzed for metal content using inductively coupled plasma-mass spectrometry. Results: With few exceptions, the embedded metal fragments eventually released solubilized metal ions, with the metals deposited in numerous tissues in the rats. Not all of the embedded metals localized to all tissues at significant levels. Copper, iron, and aluminum were not found in statistically significant levels, versus control, in any of the tissues analyzed. The other metals tested all appeared in elevated levels in the kidney which is not surprising since previous research has shown that they are also excreted in the urine at appreciable amounts. Tungsten and nickel were found in only a small number of tissues, tungsten in spleen, and nickel in liver and testes. Cobalt, lead, and depleted uranium showed the widest distribution with significant levels in liver, spleen, testes, lung, tibia, fibula, and femur. Conclusion: In this study, we showed that embedded metal fragments, such as those suffered in a shrapnel wound, could solubilize and metals become deposited in tissues far from the original site of implantation. Tissue deposition was metal-specific and many of the metals were found to cross the blood-testes barrier and were also found in bone. Since standard surgical guidance recommends leaving embedded fragments in place except for certain circumstances, this report will expand the understanding of tissue deposition of the solubilized metals and will hopefully aid healthcare professionals in developing long-term treatment strategies for dealing with these types of wounds.