Abstract
Background: Endothelin-1 (ET-1), a novel vasoconstrictor, possibly plays a role in the mediation
of ischemia/reperfusion (I/R) injury. Tacrolimus (FK506) and cyclosporin A (CsA) were
reported to maintain tissue microcirculation of the liver subjected to I/R. This study
investigated the effects of these immunosuppressants on intestinal I/R in terms of
intestinal tissue microcirculation associated with ET-1. Methods and Results: Male S-D rats were pretreated twice with FK506 (0.2 mg/kg), CsA (10 mg/kg) or only
saline solution (0.5 mL). The tissue microcirculation in the control was reduced after
I/R (29% ± 10%) accompanied by hypotension, increased tissue ET-1 expression (25.0%
± 6.4% to 67.9% ± 5.0% 60 minutes after reperfusion), and increased ET-1 level in
the portal blood (3.4 ± 0.9 to 23.6 ± 6.1 pg/mL). FK506 suppressed ET-1 expression
(27.3% ± 5.2%, 4.1 ± 2.2 pg/mL), maintained microcirculation (96% ± 16%), and blood
pressure, reduced histologic damage, and improved survival. CsA had a similar but
weaker effect compared with FK506. An additional experiment was performed with BQ485Na
(BQ), an ETA receptor antagonist, to evaluate the genuine role of ET-1. BQ showed almost the same
effects as FK506. Conclusions: FK506 and CsA, particularly the former, maintain microcirculation and protect the
tissue from I/R injury by suppressing the production and release of ET-1. (Surgery
1999;125:23-32.)
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Article info
Publication history
Accepted:
May 8,
1998
Footnotes
☆Reprint requests: Yukiko Soda, MD, Second Department of Surgery, Shimane Medical University, Izumo 693- 8501, Japan.
Identification
Copyright
© 1999 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
