Effects of cyclosporine on cerebral blood flow and metabolism in dogs

Thomas J.K. Toung, Frederick J. Bunke, Roger F. Grayson, George J. Kontos, Charles D. Fraser, William A. Baumgartner, Bruce A. Reitz, Richard J. Traystman

Research output: Contribution to journalArticle

Abstract

Neurological side effects associated with cyclosporine immunosuppressive therapy are generally believed to occur with CsA blood concentrations above the therapeutic range. The effects of high blood CsA levels on cerebral hemodynamics, metabolism, and electrophysiologic activity were studied in acute (no CsA prior treatment) and chronic (with CsA prior treatment) dogs. In acute animals, when parenteral CsA (10 mg/kg or 25 mg/kg) was administered intravenously (CsA blood level 2000-22,000 ng/ml), slight but significant time-dependent decreases in cerebral blood flow (CBF), prolongation of absolute latencies of somatosensory-cvoked potential (SSEP), and brainstem auditory-evoked responses (BAER) were noted. In the CsA chronically administered animals (oral CsA 25 mg/kg/24 hr for 14 days, CsA blood level 1077 ng/ml), baseline cerebral physiologic parameters were normal, and the cerebral responses to further administration of CsA (25 mg/kg, CSA blood level 56,000 ng/ml) intravenously were similar to those of the acute animals. Animals given Cremophor EL, the solvent for parenteral CsA preparation, showed similar cerebral responses to those observed in animals given CsA. Thus this study showed that CsA, regardless of the dose given, whether chronically or acutely administered, or the solvent for CsA all induced similar cerebral physiologic responses. We suggest that the cerebral physiologic and functional changes associated with parenteral CsA administration were small and were likely caused by its solvent, Cremophor EL, rather than CsA itself. Furthermore on the basis of our results, it is unlikely that high blood CsA per se can account for neurological side effects that occur in immunosuppressed patients.

Original languageEnglish (US)
Pages (from-to)1082-1088
Number of pages7
JournalTransplantation
Volume53
Issue number5
DOIs
StatePublished - May 1992

ASJC Scopus subject areas

  • Transplantation

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    Toung, T. J. K., Bunke, F. J., Grayson, R. F., Kontos, G. J., Fraser, C. D., Baumgartner, W. A., Reitz, B. A., & Traystman, R. J. (1992). Effects of cyclosporine on cerebral blood flow and metabolism in dogs. Transplantation, 53(5), 1082-1088. https://doi.org/10.1097/00007890-199205000-00021