Infusions of a novel calcitonin gene-related peptide (CGRP) derivative at the time of reperfusion to salvage ischaemic rabbit skin flaps.
Rabbit epigastric skin flaps were subjected to 21 h of ischaemia at 25 degrees C. In the first 40 min of reperfusion the flaps were infused intraarterially with either Hanks' balanced salt solution (controls), chicken CGRP or a derivative DADA-CGRP. Skin biopsies and blood specimens were taken immediately before and after 1-h reperfusion. The aim was to observe the effect of CGRP derivatives on compromised skin-flap survival and to help elucidate the critical biochemical mechanisms. It was found that chicken CGRP and DADA-CGRP produced a dose-dependent increase in blood flow, significant at and above 0.1 microgram/kg, but only the 0.1 microgram/kg DADA-CGRP infusion produced a statistically significant increase in flap survival (75.1%) as compared with controls (41.6%). CGRP infusions caused significantly more rapid restoration of tissue ATP levels and resulted in a smaller rise in blood thromboxane as compared with controls. However, CGRP caused no significant change in the tissue levels of myeloperoxidase, a measure of neutrophil infiltration, and lipid peroxidation, an indicator of free-radical activity. It is concluded that intraarterial CGRP infusions to ischaemic flaps at the time of reperfusion are indicated. However, an ideal infusion solution would also need to counteract free radicals and neutrophils which are believed to also play a major role in the inflammatory response leading to flap failure.
Knight
K R
KR
Department of Chemical Pathology, St Vincent's Hospital, Melbourne, Australia.
Lepore
D A
DA
Ritz
M
M
Bhattacharya
S
S
Martin
T J
TJ
Morrison
W A
WA
O'Brien
B M
BM
Shirai
T
T
D000818:Animals; D001706:Biopsy; D015740:Calcitonin Gene-Related Peptide / Q000008:administration & dosage* / Q000627:therapeutic use; D002465:Cell Movement / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D007261:Infusions, Intra-Arterial; D015227:Lipid Peroxidation; D017202:Myocardial Ischemia / Q000188:drug therapy*; D015425:Myocardial Reperfusion; D009504:Neutrophils / Q000166:cytology / Q000502:physiology; D011817:Rabbits; D012039:Regional Blood Flow; D016879:Salvage Therapy; D012867:Skin / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D013223:Statistics as Topic; D013929:Thromboxane B2 / Q000097:blood
D013929:Thromboxane B2; D015740:Calcitonin Gene-Related Peptide