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Immunomodulatory Effects of Fentanyl or Dexmedetomidine Hydrochloride Infusion After Allogeneic Heart Transplantation in Mice
  1. Weili Chen, MD*,,,
  2. Ning Jin, MS,,§,
  3. Yingying Lin, MD,,
  4. Vincenzo Villani, MD,
  5. Akira Shimizu, MD, PhD**,
  6. Xia Zhao, MD*,
  7. FangNa Lu, MS,,
  8. Cheng Li, MD, PhD,,
  9. KeGong Chen, MD*,
  10. Zhi Lin, MD, PhD* and
  11. Zhongquan Qi, MD, PhD,
  1. *Xiamen Cardiovascular Hospital, Xiamen University
  2. Fujian Key Laboratory of Organ and Tissue Regeneration, Xiamen
  3. Organ Transplantation Institute, Xiamen University, Fujian
  4. §Shanxi Key Laboratory of Birth Defects and Cell Regeneration, Shanxi Medical University, Taiyuan, Shanxi, China
  5. Department of Surgery, Massachusetts General Hospital, Boston, MA
  6. **Department of Analytic Human Pathology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
  1. Address correspondence to: Weili Chen, MD, Xiamen Cardiovascular Hospital, Xiamen University, Xiamen, Fujian Province 361004, China (e-mail: forever_vicky1999{at}hotmail.com).

Abstract

Background and Objectives Postoperatively, transplant recipients receive immunosuppressants, as well as sedatives and analgesics. The immunomodulatory effects of these other agents during the induction period following transplantation remain unclear. We aimed to determine whether the agents dexmedetomidine hydrochloride (Dex) and fentanyl (Fen) have immunomodulatory effects during the induction period following heart transplantation (HTx).

Methods Fifty mice were used for antinociception tests after administration of Dex and Fen, and T cells from 3 naive animals were used for in vitro lymphocyte transformation test (study 1). Fifty-four B6 mice received HTx from BALB/c mice and were treated with Dex, Fen, or neither (study 2). Thirty-six recipients were used for graft survival data and were humanely killed at the time of cessation of heart graft contraction. The remaining 18 were humanely killed at either postoperative day (POD) 4 or 6 for histologic examination of graft survival, as well as in vitro analysis.

Results Based on the results of study 1, daily intraperitoneal administration of Dex at 30 μg/kg or Fen at 0.25 mg/kg was determined to be the optimal dose to induce analgesia without oversedation following HTx. Graft survivals in both Dex- or Fen-treated animals were statistically prolonged compared with control (P < 0.01). Graft survival of Fen-treated recipients was increased up to 15 days, and graft survival of Dex-treated animals was also increased up to 10 days, whereas control mice rejected heart grafts by POD 7. Mixed lymphocyte reaction responses on POD 4 showed statistically lower responses in Dex-treated recipients and Fen-treated recipients when compared with controls (P < 0.01). Cytokine profiles of splenocytes showed markedly fewer interferon γ–positive splenocytes in Fen-treated recipients on POD 4.

Conclusions These data suggest that both Dex and Fen have immunomodulatory properties in the induction period following transplantation.

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Footnotes

  • This research was supported by the Youth Foundation of Health Department of Fujian Province, China (2013-2-108, to Z.L.); Natural Science Fund of Fujian Province, China (2014D015, to Z.L.); Natural Science Fund of Fujian Province, China (2016JO414, to Z.Q.); and the joint research project of health and education of Fujian Province (WKJ2016-2-20, to Z.Q.).

    The authors declare no conflict of interest.

    Authors' contributions: W.C. primarily performed heart transplantation and antinociception test, participated in experimental design and histologic analysis, and wrote the manuscript. N.J. participated in mixed lymphocyte reaction assay, flow cytometry, mixed lymphocyte reaction, and writing the manuscript. Y.L. participated in flow cytometry, mixed lymphocyte reaction, and data analysis. V.V. participated in experimental design and writing the manuscript. A.S. primarily performed histopathologic analysis. X.Z. participated in data analysis. F.L. participated in flow cytometry and mixed lymphocyte reaction. C.D. participated in flow cytometric analysis. K.C. participated in experimental design. Z.L. participated in experimental design and is fully responsible for presented data and analysis and primary contact corresponding author. Z.Q. primarily participated in experimental design and is coresponsible for presented data and analysis.

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