Local release polymeric-controlled immunotherapy of cardiac transplants in rats
dc.contributor.author | Bolling, Steven F. | en_US |
dc.contributor.author | Lin, Hua | en_US |
dc.contributor.author | Ning, Xue-Han | en_US |
dc.contributor.author | Levy, Robert J. | en_US |
dc.date.accessioned | 2006-04-28T17:55:49Z | |
dc.date.available | 2006-04-28T17:55:49Z | |
dc.date.issued | 1992-10 | en_US |
dc.identifier.citation | Bolling, Steven F.; Lin, Hua; Ning, Xue-han; Levy, Robert J. (1992)."Local release polymeric-controlled immunotherapy of cardiac transplants in rats." Polymers for Advanced Technologies 3(6): 345-350. <http://hdl.handle.net/2027.42/38604> | en_US |
dc.identifier.issn | 1042-7147 | en_US |
dc.identifier.issn | 1099-1581 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/38604 | |
dc.description.abstract | Systemic immunosuppression frequently results in severe side effects. To evaluate a method of limiting the adverse effects of immunosuppression, we implanted controlled release matrices containing cyclosporine-A (Cy) embedded (0.2 or 1 mg/kg/day released), steroid embedded (2%, 0.2% and 0.02% dexamethasone, Dex) or both (Cy 0.2 mg and Dex 0.2%) locally around the transplanted heart at the time of rat heterotopic (neck) heart transplants. Controls received empty (non-drug) matrix implants. To elucidate a local effect, additional groups received Cy (0.2 mg) or Dex (0.2%) matrix implanted in a subdermal distal leg pouch at the time of heart transplant, without a local neck implant. Rejection was determined by the lack of transplanted heart contractions. Recipient animals received no other form of immunosuppression. The Cy (0.2 mg) animals had whole-blood Cy levels monitored for 6 weeks following transplantation. Cy levels peaked at 7–10 days after transplant (119 ± 26 ng/ml) and decayed to <50 ng/ml by day 42. At no time did whole-blood Cy levels reach clinically significant levels. Additional animals had whole-blood, heart and kidney Cy levels measured at day 6 post-transplant. Both doses of local Cy demonstrated good survival benefit and were well absorbed locally, resulting in high Cy levels in heart tissue (>9,000 ng/mg). Furthermore, while low-dose Cy (0.2 mg) demonstrated significant survival benefit, these animals had clinically negligible blood Cy levels on day 6 (<100 ng/ml) and very low kidney Cy levels. Interestingly, the lowest dose of Dex demonstrated no survival benefit, while the mid- and high-Dex doses demonstrated good survival benefit: however, the high-Dex dose had poor wound healing. Cy and Dex combination did not increase efficacy, perhaps due to release problems from physicochemical interactions. Local immunosuppression with a controlled release matrix resulted in a significant survival advantage and was effective in delaying rejection. This approach may prove advantageous clinically, in extending transplantation and lessening immunosuppression side effects. | en_US |
dc.format.extent | 672368 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | John Wiley & Sons, Ltd. | en_US |
dc.subject.other | Chemistry | en_US |
dc.subject.other | Polymer and Materials Science | en_US |
dc.title | Local release polymeric-controlled immunotherapy of cardiac transplants in rats | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Chemical Engineering | en_US |
dc.subject.hlbsecondlevel | Chemistry | en_US |
dc.subject.hlbsecondlevel | Materials Science and Engineering | en_US |
dc.subject.hlbtoplevel | Engineering | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Sections of Thoracic Surgery, University of Michigan Medical Center, Ann Arbor, MI 48109, U.S.A. ; Steven F. Bolling, M.D. +1 (313) 936-4981; | en_US |
dc.contributor.affiliationum | Sections of Thoracic Surgery, University of Michigan Medical Center, Ann Arbor, MI 48109, U.S.A. | en_US |
dc.contributor.affiliationum | Sections of Thoracic Surgery, University of Michigan Medical Center, Ann Arbor, MI 48109, U.S.A. | en_US |
dc.contributor.affiliationum | Pediatric Cardiology, University of Michigan Medical Center, Ann Arbor, MI 48109, U.S.A. ; Robert J. Levy, M.D. +1 (313) 9365-2850; addresses above. | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/38604/1/220030610_ftp.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1002/pat.1992.220030610 | en_US |
dc.identifier.source | Polymers for Advanced Technologies | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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