Reduction of ischemic reperfusion edema with corticotropin-releasing factor (CRF) in rat hind limb replantation.
Corticotropin-releasing factor (CRF), a peptide neurotransmitter, is suggested as a novel agent to reduce reperfusion edema following ischemia. In a rat hind limb replantation model, animals underwent amputation followed by 2.5 hours of ischemia with replantation and 2 hours of reperfusion. Animals were randomized to seven groups: a nonischemic control group and six experimental groups receiving treatment prior to reperfusion with (1) saline control, (2) alpha 9,41-CRF-a CRF receptor blocking agent (98 micrograms/per kilogram), (3) subcutaneous CRF (320 micrograms/per kilogram), (4) intravenous CRF (80 micrograms/per kilogram), (5) alpha-CRF and subcutaneous CRF, and (6) alpha-CRF and intravenous CRF. Comparison of preischemic amputated limb weight with weight after ischemia and reperfusion showed a reproducible and significant gain in limb weight after 2 hours (p = 0.004). A significant reduction in limb weight gain (49%) was achieved with both subcutaneous (p < 0.04) and intravenous CRF (p < 0.036). With the dose used in this model, alpha 9,41 CRF attenuated but did not completely block the effects of intravenous or subcutaneous CRF.
Whitney
T M
TM
Division of Plastic and Reconstructive Surgery, Lahey Hitchcock Clinic, Burlington 01805, USA.
Wang
K K
KK
Sternbach
Y
Y
Chaklis-Haley
D
D
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000503:physiopathology*; D006614:Hindlimb / Q000098:blood supply / Q000293:injuries* / Q000601:surgery; D006727:Hormone Antagonists / Q000494:pharmacology; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D007511:Ischemia / Q000503:physiopathology*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D015427:Reperfusion Injury / Q000503:physiopathology*; D012092:Replantation / Q000379:methods*
D006727:Hormone Antagonists; D010446:Peptide Fragments; D003346:Corticotropin-Releasing Hormone; C045089:corticotropin releasing hormone (9-41)